BIOLOGICALS









Belimumab (Benlysta®)

Dosage form
Single-use vials
  • Comes in 120 mg and 400 mg vials

Dosing
Systemic Lupus Erythematosus
  • Starting: 10 mg/kg at 2-week intervals for 3 doses
  • Maintenance: 10 mg/kg every 4 weeks

Other
  • Benlysta is given by IV infusion over a period of 1 hour
  • Premedication (e.g. antihistamines, Tylenol, steroids) is recommended to prevent infusion reactions

Mechanism
  • B-cell depleting agent - B-lymphocyte stimulator (BLyS) is a growth factor required for B-cell survival, maturation, and activation. Belimumab is a fully humanized IgG monoclonal antibody that binds and inactivates soluble BLyS. By inactivating BLyS, belimumab inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.

FDA-approved indications
  • Systemic Lupus Erythematosus

Side effects
NOTE: Only side effects that occurred at incidence of ≥ 3% overall, and ≥ 2% more than placebo are listed

Side effect Belimumab Placebo
Nausea 15% 12%
Diarrhea 12% 9%
Fever 10% 8%
Nasopharyngitis 9% 7%
Bronchitis 9% 5%
Insomnia 7% 5%
Pain in extremity 6% 4%
Pharyngitis 5% 3%
Leukopenia 4% 2%
Gastroenteritis 3% 1%
Other
  • Infusion reactions - up to 17% of patients; common reactions include headache, nausea, and skin reactions


Contraindications / Precautions
  • Cyclophosphamide - DO NOT COMBINE. Benlysta has not been studied in patients receiving intravenous cyclophosphamide.
  • Biologicals - DO NOT COMBINE. Benlysta has not been studied in patients receiving other biologicals.
  • Serious infections - Benlysta may increase the risk of serious infections. In trials, serious infections occurred in 6% of Benlysta-treated patients and 5.2% of placebo-treated patients. The most frequent serious infections included pneumonia, urinary tract infection, cellulitis, and bronchitis.
  • Progressive Multifocal Leukoencephalopathy (PML) - JC virus infections resulting in PML and death have occurred. Consider PML diagnosis in patients with new-onset or deteriorating neurological signs and symptoms.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis and death have occurred. In trials, hypersensitivity reactions on the same day of infusion were reported in 13% of Benlysta-treated patients and 11% of placebo-treated patients. Reactions included rash, itching, angioedema, hypotension, and dyspnea.
  • Depression - in trials, psychiatric complaints including depression, anxiety, and insomnia occurred in 16% of Benlysta-treated patients and 12% of placebo-treated patients
  • Malignancy - Benlysta may increase the risk of malignancies. In controlled trials of IV Benlysta, malignancies (excluding non-melanoma skin cancers) occurred in 0.2% of Benlysta-treated patients and 0.3% of placebo-treated patients.
  • Immunizations - live vaccines should not be given 30 days before or concurrently with Benlysta
  • Benlysta antibodies - anti-Benlysta antibodies were detected in up to 4.8% of patients. It's unclear if antibody development is associated with reduced efficacy and/or an increase in hypersensitivity reactions.
  • Lupus nephritis - patients with severe lupus nephritis were excluded from trials. The effects of Benlysta in these patients are unknown.
  • CNS lupus - patients with CNS lupus were excluded from trials. The effects of Benlysta in these patients are unknown.
  • Kidney disease - dosage adjustment is not recommended
  • Liver disease - has not been studied. Dosage adjustment is not recommended.

Rituximab (Rituxan®)

Dosage form
Single-use vials
  • Comes in 100 mg and 500 mg vials
  • Drug concentration is 10 mg/ml

Dosing
Rheumatoid arthritis
  • Dosing: one course of Rituxan is two 1000 mg doses given 2 weeks apart
  • One course may be given every 24 weeks based on clinical response
  • Courses should not be given sooner than every 16 weeks
  • Rituxan should be given with methotrexate
Immune thrombocytopenia (off-label)
  • Dosing: 100 mg/week for 4 weeks OR 375 mg/m2/week for 4 weeks
  • Dosing is the same in children and adults
  • Response is highly variable. Only recommended as third- or fourth-line agent.
  • See immune thrombocytopenia for more
Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA)
  • Dosing 375 mg/m2 intravenous infusion once weekly for 4 weeks
  • Methylprednisolone 1000 mg IV per day for 1 to 3 days followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day and tapered per clinical need) are recommended to treat severe vasculitis symptoms. This regimen should begin within 14 days prior to or with the initiation of Rituximab and may continue during and after the 4 week course of Rituximab treatment.
  • Safety and efficacy of treatment with subsequent courses of Rituxan have not been established

Lab monitoring
Blood dyscrasias
  • In patients with RA, check CBC with platelets at 2 - 4 month intervals during Rituxan therapy
  • Recommendations in patients with malignancies differ.

Other
  • Rituxan is given as an IV infusion
  • Glucocorticoids administered as methylprednisolone 100 mg intravenous or its equivalent 30 minutes prior to each infusion are recommended to reduce the incidence and severity of infusion reactions

Mechanism
  • B-cell depleting agent - Rituxan is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen. Rituxan targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, Rituxan mediates B-cell lysis.

FDA-approved indications
  • Rheumatoid arthritis
  • Non–Hodgkin's lymphoma
  • Chronic Lymphocytic Leukemia (CLL)
  • Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA)

Side effects
NOTE: Only side effects that occurred at an incidence of ≥ 3% and ≥ 2% more than placebo are listed. Data is from RA trials.

Side effect Rituximab Placebo
Hypertension 8% 5%
Nausea 8% 5%
Arthralgia 6% 4%
Fever 5% 2%
Dyspepsia 3% < 1%
Other
  • Infusion reactions - up to 32% of patients during first infusion; reactions include fever, chills, rigors, pruritus, urticaria/rash, angioedema, sneezing, throat irritation, cough, bronchospasm, and hypertension; reactions decreased with subsequent infusions


Contraindications / Precautions
NOTE: Precautions presented here are for patients with RA. Precautions in patients with malignancies may differ.

  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting rituximab. Active TB should be treated completely before starting rituximab. [2]
  • Infusion reactions - fatal infusion reactions have occurred. Patients should be premedicated with methylprednisolone 100 mg IV or its equivalent 30 minutes prior to each infusion.
  • Mucocutaneous reactions - fatal mucocutaneous reactions have occurred. Reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis.
  • Hepatitis B reactivation - hepatitis B reactivation leading to death has occurred. Screen all patients for hepatitis B infection by measuring HBsAg and anti-HBc before initiating treatment with Rituxan. For positive results (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult hepatitis B expert before starting therapy. Monitor patients with current or prior infection closely.
  • Progressive Multifocal Leukoencephalopathy (PML) - JC virus infections resulting in PML and death have occurred. The majority of cases occurred in patients receiving chemotherapy or as part of a hematopoietic stem cell transplant. Consider PML in any patient presenting with new-onset neurologic manifestations.
  • Serious infections - Rituxan may increase the risk of serious infections including invasive fungal infections, bacterial infections, viral infections, and others. In RA trials, the rate of serious infections in Rituxan-treated patients was 4.31 per 100 patient-years. The most common serious infections were pneumonia or lower respiratory tract infections, cellulitis and urinary tract infections.
  • Use with other biologicals or DMARDs other than methotrexate - has not been studied. Use caution.
  • Cardiac reactions - cardiac reactions including arrhythmia and heart attack have occurred in patients treated with Rituxan. Susceptible patients should have cardiac monitoring during infusions.
  • Rituxan antibodies - in trials, anti-Rituxan antibodies were detected in up to 56% of patients. It's unclear if antibody development is associated with reduced efficacy and/or an increase in hypersensitivity reactions.
  • Vaccines - patients may receive non-live vaccines. Administer non-live vaccines at least 4 weeks prior to a course of Rituxan. Vaccine response may be lower in patients receiving Rituxan. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • Hypophosphatemia - in trials, newly-occurring hypophosphatemia (< 2.0 mg/dl) was observed in 21% of Rituxan-treated patients. The majority of the observed hypophosphatemia occurred at the time of the infusions and was transient.
  • Hyperuricemia - in trials, newly-occurring hyperuricemia (> 10 mg/dl) was observed in 1.5% of Rituxan-treated patients compared to 0.3% of placebo-treated patients.
  • Liver disease - has not been studied
  • Kidney disease - has not been studied



Anakinra (Kineret®)

Dosage form
Prefilled syringe
  • Comes in 100 mg dose
  • Comes in pack of 28 syringes

Dosing
Rheumatoid arthritis
  • Dosing: 100 mg once daily
  • Dose should be given at the same time every day

Lab monitoring
Neutropenia
  • Check neutrophil count before starting therapy
  • Check neutrophil count monthly for 3 months when starting therapy, and thereafter quarterly for a period up to 1 year

Other
  • Keep refrigerated
  • Allow syringe to warm to room temperature for 30 minutes before injecting
  • Solution should be colorless. There may be trace amounts of small, translucent-to-white amorphous particles of protein in the solution.
  • Inject subcutaneously in the thigh, abdomen, or outer upper arms. Rotate injection sites.

Mechanism
  • Interleukin-1-receptor inhibitor - Kineret is a recombinant, nonglycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra). Kineret binds to IL-1 receptors and blocks the activity of IL-1 alpha and beta.
FDA-approved indications
  • Rheumatoid arthritis
  • Cryopyrin-associated periodic syndromes

Side effects
NOTE: Only side effects that occurred at an incidence of ≥ 2% more than placebo are listed

Side effect Anakinra Placebo
Headache 12% 9%
Diarrhea 7% 5%
Other
  • Injection site reactions - up to 71% of patients; common reactions include erythema, ecchymosis, inflammation, and pain; reactions typically last 14 - 28 days; reactions typically occur within first 4 weeks of therapy


Contraindications / Precautions
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting anakinra. Active TB should be treated completely before starting anakinra. [2]
  • Serious infections - Kineret may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In trials lasting 1 year, the incidence of serious infections in Kineret-treated patients was 3% compared to 2% in placebo-treated patients. Patients with asthma may be at higher risk.
  • TNF inhibitors - DO NOT COMBINE. May increase risk of serious infection.
  • Neutropenia - in trials, 8% of Kineret-treated patients had a decrease in WBCs of at least one WHO toxicity grade compared to 2% of placebo-treated patients. See Lab monitoring for further recommendations.
  • Eosinophilia - in trials, 9% of Kineret-treated patients had an increase in eosinophils of at least one WHO toxicity grade compared to 3% of placebo-treated patients.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Malignancies - may increase the risk for malignancies
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • Kineret antibodies - in trials, anti-Kineret antibodies were detected in up to 49% of patients. It's unclear if antibody development is associated with reduced efficacy.
  • CYP enzyme activity - suppression of inflammatory mediators by Kineret may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease
    • CrCl < 30 ml/min: consider dosing every other day

Sarilumab (Kevzara®)

Dosage form
Single-dose pen
  • 150 mg
  • 200 mg
  • Comes in package of 2 pens
Single-dose syringe
  • 150 mg
  • 200 mg
  • Comes in package of 2 syringes

Dosing
Rheumatoid arthritis
  • Dosing: 200 mg SQ every two weeks
  • May be used as monotherapy or in combination with methotrexate or other conventional DMARDs

Lab monitoring
Neutropenia
  • Do not initiate in patients with ANC < 2000 cells/mm³
  • Check neutrophil count 4 - 8 weeks after starting therapy and every 3 months thereafter
Thrombocytopenia
  • Do not initiate in patients with platelet count < 150,000/mm³
  • Check platelet count 4 - 8 weeks after starting therapy and every 3 months thereafter
Elevated LFTs
  • Do not initiate in patients with AST or ALT > 1.5 X ULN
  • Check LFTs 4 - 8 weeks after starting therapy and every 3 months thereafter
Increased cholesterol
  • Check lipid parameters 4 - 8 weeks after starting therapy and every 24 weeks thereafter
Dose adjustments

Other
Syringe
  • Keep refrigerated
  • May be stored at room temperature up to 14 days
  • Inject subcutaneously in the thigh, abdomen, or outer upper arms. Rotate injection sites.

Mechanism
  • Interleukin-6-receptor inhibitor - Interleukin-6 (IL-6) is a pro-inflammatory mediator found in joints affected by inflammatory processes such as rheumatoid arthritis. Sarilumab is a human recombinant monoclonal antibody of the IgG1 subclass that binds to the IL-6 receptor. Sarilumab binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors.
FDA-approved indications
  • Rheumatoid arthritis

Side effects
NOTE: Only side effects that occurred at an incidence of ≥ 2% more than placebo are listed. Side effects are for the 200 mg dose.

Side effect Sarilumab Placebo
Neutropenia 10% 0.2%
ALT increase 5% 2%
Injection site erythema 4% 0.9%
Upper respiratory infection 3% 2%
UTI 3% 2%
Injection site pruritus 2% 0.2%
Leukopenia 2% 0%


Contraindications / Precautions
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). For another IL-6-receptor inhibitor (tocilizumab), the American College of Rheumatology recommends treating latent TB for at least one month before starting therapy. Active TB should be treated completely before starting therapy. [2]
  • Serious infections - sarilumab may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In 52-week trials, 4.3 serious infections per 100 patient-years occurred in sarilumab-treated patients compared to 3.1 serious infections per 100 patient-years in placebo-treated patients.
  • JAK inhibitors and other biologic DMARDs - sarilumab has not been investigated in combination with JAK inhibitors or biological DMARDs such as TNF antagonists. Avoid combination due to possible increased immunosuppression and risk of infection.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking sarilumab. Test patients before initiating therapy. Monitor infected patients closely.
  • Herpes zoster - reactivation of herpes zoster has occurred in patients using sarilumab
  • Gastrointestinal perforations - gastrointestinal (GI) perforations have been reported in trials. Most cases were reported as complications of diverticulitis. GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids.
  • Neutropenia - neutropenia (< 1000 cells/mm³) occurred in 6% of patients in trials. Do not initiate sarilumab in patients with ANC < 2000 cells/mm³. See Lab monitoring for further recommendations.
  • Thrombocytopenia - thrombocytopenia (< 100,000/mm³) occurred in 1% of patients in trials. Do not initiate sarilumab in patients with platelet count < 150,000/mm³. See Lab monitoring for further recommendations.
  • Elevated liver enzymes - elevated liver enzymes (> 3 X ULN) occurred in 43% of patients in trials. Do not initiate sarilumab in patients with AST or ALT > 1.5 X ULN. See Lab monitoring for further recommendations.
  • Elevated lipid parameters - average lipid increases of 16 mg/dl, 27 mg/dl, and 3 mg/dl in LDL, triglycerides, and HDL, respectively, were seen in trials. See Lab monitoring for further recommendations.
  • Hypersensitivity reactions - hypersensitivity reactions were reported in 0.3% of sarilumab-treated patients in trials. Injection site redness, rash, and urticaria were the most frequent hypersensitivity reactions.
  • Malignancies - sarilumab may increase the risk for malignancies
  • Sarilumab antibodies - in trials, anti-sarilumab antibodies were detected in up to 9.2% of patients. No correlation was observed between antibody development and either loss of efficacy or adverse reactions.
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (see list of live vaccines).
  • CYP enzyme activity - suppression of inflammatory mediators by sarilumab may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - DO NOT USE in active liver disease or hepatic impairment
  • Kidney disease
    • CrCl ≥ 30 ml/min: no dose adjustment necessary
    • CrCl < 30 ml/min: has not been studied

Tocilizumab (Actemra®)

Dosage form
Prefilled syringe
  • Comes in 162 mg dose
Single-use vial
  • 80 mg
  • 200 mg
  • 400 mg
  • Comes in 20 mg/ml concentration

Dosing
Rheumatoid arthritis
  • Prefilled syringe (subcutaneous)
    • Weight < 220 pounds (100 kg): 162 mg every other week. May increase to every week based on response.
    • Weight ≥ 220 pounds (100 kg): 162 mg every week
  • Infusion
    • Dosing: 4 mg/kg every 4 weeks
    • May increase to 8 mg/kg every 4 weeks based on response
    • Doses exceeding 800 mg per infusion are not recommended
Giant Cell Arteritis
  • 162 mg SQ once weekly in combination with a tapering course of glucocorticoids
  • A dose of 162 mg SQ once every other week in combination with a tapering course of glucocorticoids may be prescribed based on clinical considerations
  • Tocilizumab can be used alone following discontinuation of glucocorticoids
Polyarticular Juvenile Idiopathic Arthritis
  • Weight < 66 lbs (30 kg): 10 mg/kg every 4 weeks by IV infusion
  • Weight ≥ 66 lbs (30 kg): 8 mg/kg every 4 weeks by IV infusion
  • May be used alone or in combination with methotrexate
Systemic Juvenile Idiopathic Arthritis
  • Weight < 66 lbs (30 kg): 12 mg/kg every 2 weeks by IV infusion
  • Weight ≥ 66 lbs (30 kg): 8 mg/kg every 2 weeks by IV infusion
  • May be used alone or in combination with methotrexate
Cytokine Release Syndrome (CRS)
  • Weight < 66 lbs (30 kg): 12 mg/kg by IV infusion
  • Weight ≥ 66 lbs (30 kg): 8 mg/kg by IV infusion
  • May be given alone or in combination with corticosteroids
  • If no clinical improvement in the signs and symptoms of CRS occurs after the first dose, up to 3 additional doses may be administered. The interval between consecutive doses should be at least 8 hours.
  • Doses exceeding 800 mg per infusion are not recommended in CRS patients
  • Subcutaneous administration is not approved for CRS

Efficacy
Lab monitoring
Neutropenia
  • Do not initiate in patients with ANC < 2000 cells/mm³
  • Check neutrophil count 4 - 8 weeks after starting therapy and every 3 months thereafter
Thrombocytopenia
  • Do not initiate in patients with platelet count < 100,000/mm³
  • Check platelet count 4 - 8 weeks after starting therapy and every 3 months thereafter
Elevated LFTs
  • Do not initiate in patients with AST or ALT > 1.5 X ULN
  • Check LFTs 4 - 8 weeks after starting therapy and every 3 months thereafter
Increased cholesterol
  • Check lipid parameters 4 - 8 weeks after starting therapy and every 24 weeks thereafter
Dose adjustments

Other
Prefilled syringe
  • Keep refrigerated
  • Solution should be clear and colorless to pale yellow
  • Inject subcutaneously in the thigh, abdomen, or outer upper arms. Rotate injection sites.
Vials
  • Infuse over 60 minutes

Mechanism
  • Interleukin-6-receptor inhibitor - tocilizumab is a recombinant humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody of the immunoglobulin IgG1κ (gamma 1, kappa) subclass. Tocilizumab binds IL-6 receptors and inhibits the action of IL-6.

FDA-approved indications
  • Rheumatoid arthritis
  • Giant Cell Arteritis
  • Polyarticular juvenile idiopathic arthritis
  • Systemic juvenile idiopathic arthritis

Side effects
NOTE: Only side effects that occurred at an incidence of ≥ 2% more than placebo are listed

Side effect Tocilizumab Placebo
Nasopharyngitis 7% 4%
Headache 7% 3%
Hypertension 6% 3%
ALT increase 6% 1%
Other
  • Injection site reactions - up to 10% of adult patients and 41% of pediatric patients; common reactions include erythema, pruritus, pain, and hematoma
  • Infusion reactions - up to 8% of patients; common reactions include headache, hypertension, and skin reactions


Contraindications / Precautions
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting tocilizumab. Active TB should be treated completely before starting tocilizumab. [2]
  • Serious infections - Actemra may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In RA patients treated for 24 weeks, 3.6 serious infections per 100 patient-years occurred in Actemra-treated patients compared to 1.5 serious infections per 100 patient-years in placebo-treated patients.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking Actemra. Test patients before initiating therapy. Monitor infected patients closely.
  • Herpes zoster - reactivation of herpes zoster has occurred in patients using Actemra
  • Gastrointestinal perforations - in trials, a small number of patients developed gastrointestinal perforations while using Actemra. Most cases were reported as complications of diverticulitis.
  • Neutropenia - seen in 3.4% of adult patients and up to 26% of pediatric patients who weigh < 30 kg. Do not initiate Actemra in patients with ANC < 2000 cells/mm³. See Lab monitoring for further recommendations.
  • Thrombocytopenia - seen in up to 1.7% of patients. Do not initiate Actemra in patients with platelet count < 100,000/mm³. See Lab monitoring for further recommendations.
  • Elevated liver enzymes - seen in up to 48% of patients. Do not initiate Actemra in patients with AST or ALT > 1.5 X ULN. See Lab monitoring for further recommendations.
  • Elevated lipid parameters - elevated lipid parameters are seen in a significant number of patients. See Lab monitoring for further recommendations.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Malignancies - may increase the risk for malignancies
  • Demyelinating diseases (e.g. multiple sclerosis) - may exacerbate demyelinating diseases. Use caution.
  • Actemra antibodies - in trials, anti-Actemra antibodies were detected in up to 2% of patients. In some patients, antibody development was associated with the development of hypersensitivity reactions. It's unclear if antibody development is associated with reduced efficacy.
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by Actemra may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - DO NOT USE in active liver disease
  • Kidney disease - has not been studied



Ustekinumab (Stelara®)

Dosage form
Prefilled syringe
  • 45 mg
  • 90 mg
Single-use vial
  • 45 mg
Vial for intravenous use
  • 130 mg/26 ml (5 mg/ml)

Dosing
Psoriasis
  • Weight ≤ 220 lbs (100 kg): 45 mg SQ initially and 4 weeks later, followed by 45 mg every 12 weeks
  • Weight > 220 lbs (100 kg): 90 mg SQ initially and 4 weeks later, followed by 90 mg every 12 weeks
Psoriatic arthritis
  • Dosing: 45 mg SQ initially and 4 weeks later, followed by 45 mg every 12 weeks
  • Patients weighing > 220 lbs (100 kg) with moderate-to-severe plaque psoriasis: 90 mg SQ initially and 4 weeks later, followed by 90 mg every 12 weeks
Crohn's disease
  • Initial: single intravenous dose based on the table below

Weight Dose # of vials (130 mg/26ml)
≤ 55 kg 260 mg 2
55 - 85 kg 390 mg 3
> 85 kg 520 mg 4

  • Maintenance: 90 mg SQ every 8 weeks starting 8 weeks after the initial IV dose

Efficacy
Other
Prefilled syringe
  • Keep refrigerated
  • Inject subcutaneously in the thigh, gluteal regions, abdomen, or upper arms. Rotate injection sites.
Infusion
  • Infuse over at least one hour

Mechanism
  • Interleukin inhibitor - ustekinumab is a human IgG1қ monoclonal antibody that binds with specificity to the p40 protein subunit used by both the IL-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. Ustekinumab has been shown to disrupt IL-12 and IL-23 mediated signaling and cytokine cascades by disrupting the interaction of these cytokines with a shared cell-surface receptor chain, IL-12Rβ1. The cytokines IL-12 and IL-23 have been implicated as important contributors to the chronic inflammation that is a hallmark of Crohn's disease

FDA-approved indications
  • Crohn's disease - moderate-to-severe disease in patients who have failed treatment with immunomodulators, corticosteroids, or tumor necrosis factor inhibitors
  • Psoriasis - moderate-to-severe disease
  • Psoriatic arthritis - may be used alone or with methotrexate

Side effects
NOTE: Data is from 44-week study in Crohn's disease. Only side effects that occurred at an incidence of ≥ 3% overall and greater than placebo are listed.

Side effect Ustekinumab Placebo
Nasopharyngitis 11% 8%
Injection site erythema 5% 0%
Vulvovaginal candidiasis 5% 1%
Bronchitis 5% 3%
Pruritus 4% 2%
Urinary tract infection 4% 2%
Sinusitis 3% 2%


Contraindications / Precautions
  • BCG vaccination - DO NOT GIVE during treatment or within one year following the end of treatment. Do not give ustekinumab to patients who have received the BCG vaccine within the previous year.
  • Live vaccines - DO NOT GIVE live vaccines to patients receiving ustekinumab. Use caution when giving live vaccines to household members. Common live vaccines include MMR, shingles (zoster), varicella (chickenpox), rotavirus, oral polio, influenza nasal vaccine (Flumist), Yellow fever, and adenovirus.
  • Non-live vaccines - non-live vaccines may not elicit the appropriate immune response in patients receiving ustekinumab
  • Allergen immunotherapy - allergen immunotherapy may not elicit the appropriate immune response in patients receiving ustekinumab
  • Noninfectious pneumonia - cases of interstitial pneumonia, eosinophilic pneumonia and cryptogenic organizing pneumonia have been reported. Symptoms include cough, dyspnea, and interstitial infiltrates following one to three doses of ustekinumab. Patients typically improved with drug discontinuation and in some cases, corticosteroids.
  • Serious infections - ustekinumab may increase the risk of serious infections. In psoriasis trials lasting 13 weeks, serious infections were reported in 0.3% of ustekinumab-treated patients and 0.4% of placebo-treated patients.
  • Theoretical risk for particular infections - patients with genetic deficiencies of IL-12/IL-23 are vulnerable to disseminated infections from mycobacteria, salmonella, and the BCG vaccine. It is unknown if ustekinumab increases the risk of these infections.
  • Tuberculosis (TB) - test all patients for TB before use. Do not treat patients with active TB. Start treatment for latent TB before initiating ustekinumab. Monitor for signs of active TB during treatment.
  • Malignancies - ustekinumab may increase the risk for malignancies. In Crohn's disease trials lasting up to one year, malignancies other than nonmelanoma skin cancers were reported in 0.2% of ustekinumab-treated patients and 0% of placebo-treated patients.
  • Nonmelanoma skin cancers - ustekinumab may particularly increase the risk of nonmelanoma skin cancer. In psoriasis trials lasting a median of 3.2 years, nonmelanoma skin cancers were reported in 1.5% of ustekinumab-treated patients. Rapid appearance of multiple cutaneous squamous cell carcinomas have been reported in patients receiving ustekinumab.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported in a small number of patients. In Crohn's disease trials, 0.1% of patients receiving SQ ustekinumab and 0.08% of patients receiving IV ustekinumab reported hypersensitivity reactions.
  • Reversible Posterior Leukoencephalopathy Syndrome (RPLS) - in trials, one case of RPLS occurred in a patient receiving ustekinumab. Symptoms of RPLS include headache, seizures, confusion and visual disturbances.
  • Ustekinumab antibodies - in trials, anti-ustekinumab antibodies were detected in 6 - 12.4% of psoriasis patients and less than 3% of Crohn's patients. Antibody development was associated with reduced or undetectable serum ustekinumab concentrations and reduced efficacy. Antibody development was not associated with the development of hypersensitivity reactions.
  • CYP enzyme activity - suppression of inflammatory mediators by ustekinumab may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease - has not been studied



Intravenous immunoglobulin (IVIG)

Dosage form
In the U.S., available IVIG products include the following:
  • Bivigam®
  • Carimune®
  • Flebogamma® Dif
  • Gammagard®
  • Gammagard® S/D
  • Gammaplex®
  • Gamunex-C®
  • Octagam®
  • Privigen®

Dosing
NOTE: Dosing recommendations vary slightly by product. Doses presented here are general recommendations.
Primary humoral immunodeficiency
  • 0.3 - 0.8 grams/kg every 3 - 4 weeks
Immune thrombocytopenia
  • 1 gram/kg as a one-time dose. May repeat if necessary.
  • Alternatively, 0.4 grams/kg/day can be given on 2 - 5 consecutive days as needed
Kawasaki syndrome
  • 1 gram/kg as a one-time dose
  • Alternatively, 0.4 grams/kg/day for 4 consecutive days
  • Dosing from Gammagard S/D PI
Multifocal motor neuropathy
  • 0.5 - 2.4 grams/kg/month
  • Dosing from Gammagard PI
Chronic Inflammatory Demyelinating Polyneuropathy
  • Loading dose: 2 grams/kg
  • Maintenance: 1 gram/kg every 3 weeks
  • Dosing from Gamunex-C PI
Guillain–Barré syndrome
  • 0.4 grams/kg/day for 5 consecutive days [3]
Myasthenia gravis
  • 1 - 2 grams/kg/dose [3]
Kidney transplant (highly sensitized to HLA)
  • 2 grams/kg/month for 4 months before transplant [3]

Other
  • IVIG is typically given intravenously over the course of 1 - 5 days depending on the dose and the patient
  • Some products (e.g. Gammagard) can be infused subcutaneously through a pump

Mechanism
  • Primary humoral immunodeficiency - IVIG replaces deficient antibodies
  • Autoimmune disorders - there are a number of theories on how IVIG causes immunosuppression. Proposed mechanisms include the following:
    • Binding and neutralization of autoantibodies
    • Blockade of Fcγ receptors on macrophages thereby inhibiting phagocytosis
    • Up regulation of Fcγ receptor IIB on macrophages. Fcγ receptor IIB down regulates the inflammatory cascade.
    • Binding of complement components and blocking their activation
    • Decreasing the half-life of autoantibodies [3,4]

FDA-approved indications
  • Primary humoral immunodeficiency
  • Immune thrombocytopenia
  • Kawasaki syndrome
  • Multifocal motor neuropathy
  • Chronic Inflammatory Demyelinating Polyneuropathy

Side effects
NOTE: Information below is from a study in Privigen PI where median dose was 0.430 grams/kg in patients with primary humoral immunodeficiency. Placebo comparison is not available so strength of association is unknown.

  • Headache - 45%
  • Fatigue - 16%
  • Nausea - 14%
  • Chills - 11%
  • Vomiting - 11%
  • Back pain - 10%
  • Pain - 9%
  • Fever - 9%
  • Diarrhea - 8%
  • Cough - 6%
  • Stomach discomfort - 6%

Contraindications / Precautions
NOTE: General contraindications/precautions are listed below. See the individual product PI for specific product information.

  • Sensitivity reactions - severe sensitivity reactions may occur, even in patients who have tolerated previous infusions. Appropriate precautions should be taken.
  • IgA deficiency - all IVIG products contain small amounts of IgA. Patients with IgA deficiency may have antibodies to IgA. These patients are at increased risk of severe hypersensitivity reactions to IVIG. Gammagard S/D contains the least amount of IgA.
  • Kidney dysfunction/failure - IVIG can cause kidney dysfunction/failure in some patients. IVIG products that contain sucrose (e.g. Carimune) carry a higher risk. Use caution in susceptible patients (e.g. pre-existing kidney disease, diabetes, ≥ 65 years old, volume depletion, sepsis, paraproteinemia, concomitant nephrotoxic drugs).
  • Thrombosis - IVIG may increase the risk of venous and arterial thrombosis. Use caution in patients with risk factors for thrombosis (e.g. immobilization, hypercoagulable states, history of thrombosis, estrogen use, indwelling catheters, hyperviscosity).
  • Increased serum viscosity - IVIG infusions increase serum proteins which may increase serum viscosity. Ensure adequate hydration and check blood viscosity in at-risk patients (e.g. cryoglobulins, very high triglycerides, monoclonal gammopathies).
  • Hyperproteinemia and pseudohyponatremia - IVIG infusions increase serum proteins. The increase in serum proteins may cause pseudohyponatremia because the plasma water fraction in blood samples is reduced leading to false sodium concentration measurements. Providers should distinguish true hyponatremia from pseudohyponatremia in patients receiving IVIG, because treatment of hyponatremia may increase blood viscosity.
  • Aseptic meningitis - aseptic meningitis has occurred in patients receiving IVIG. Symptoms (e.g. severe headache, nuchal rigidity, photophobia, painful eye movements) usually begin within several hours to 2 days of receiving treatment. Discontinuation of IVIG typically leads to resolution within 2 days.
  • Hemolysis - blood group antibodies in IVIG may cause hemolysis. Higher doses of IVIG (≥ 2 grams/kg) and non-O blood types in recipients may be risk factors. Check hemoglobin levels in high-risk patients before therapy, within 36 hours of the start of therapy, and at 7 - 10 days.
  • Transfusion-related acute lung injury (TRALI) - TRALI, a syndrome of noncardiogenic pulmonary edema, has occurred in patients receiving IVIG. Symptoms typically occur within 1 - 6 hours following treatment. If TRALI is suspected, testing for anti-neutrophil antibodies and anti-human leukocyte antigen (HLA) antibodies in both the IVIG product and the patient's serum should be performed.
  • Live vaccines - IVIG infusions may impair the efficacy of live vaccines such as mumps, rubella, and varicella for up to 6 months and measles for up to a year
  • Volume overload - IVIG infusions often contain a large volume of fluid. Use caution in susceptible patients (e.g. CHF, kidney disease)
  • Potential for infection transfer - because IVIG is a blood product, the potential for the transmission of infectious agents exists
  • Blood glucose monitoring - some IVIG products (e.g. Octagam) contain maltose which can be falsely interpreted as glucose by some glucometers
  • Serologic antibody tests - passively transferred antibodies from IVIG may cause false-positive serological testing (e.g. infection/immunity testing, direct or indirect antiglobulin testing, detection of beta-D-glucans for diagnosis of fungal infections)
  • Liver disease - manufacturer makes no recommendation
  • Kidney disease - use caution. May worsen kidney disease.



Adalimumab (Humira®)

Dosage form
Single-use pen
  • 40 mg/0.4 ml
  • 40 mg/0.8 ml
  • Comes in carton with 2 pens
Syringe
  • 10 mg/0.1 ml
  • 10 mg/0.2 ml
  • 20 mg/0.2 ml
  • 20 mg/0.4 ml
  • 40 mg/0.4 ml
  • 40 mg/0.8 ml
  • Comes in carton with 2 syringes
Starter packs
  • Adult Crohn's, Ulcerative colitis, Hidradenitis Suppurativa - six 40 mg pens (40 mg/0.8 ml or 40 mg/0.4 ml)
  • Adult Crohn's, Ulcerative colitis, Hidradenitis Suppurativa - three 80 mg pens (80 mg/0.8 ml)
  • Psoriasis, Uveitis - four 40 mg pens (40 mg/0.8 ml or 40 mg/0.4 ml)
  • Psoriasis, Uveitis - one 80 mg/0.8 ml pen and two 40 mg/0.4 ml pens
  • Pediatric Crohn's - 40 mg/0.8 ml (6 syringes); 80 mg/0.8 ml (3 syringes); 40 mg/0.8 ml (3 syringes); 80 mg/0.8 ml (one syringe) and 40 mg/0.4 ml (one syringe)

Dosing
Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis
  • Dosing: 40 mg every other week
  • In rheumatoid arthritis, some patients not taking methotrexate may derive additional benefit from increasing the frequency to 40 mg once weekly
Crohn's disease
  • Adults
    • Day 1: 160 mg (given as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days)
    • Day 15: 80 mg
    • Day 29 and on: 40 mg every other week
    • Target trough concentration in IBD: ≥ 7.5 mcg/ml [5]

  • Pediatric (≥ 6 years)

Weight Induction Maintenance (start Day 29)
17 kg (37 lbs) to < 40 kg (88 lbs) 80 mg initially on Day 1 and 40 mg two weeks later (Day 15) 20 mg every other week
≥ 40 kg (88 lbs) 160 mg initially on Day 1 (given in one day or split over two consecutive days) and 80 mg two weeks later (Day 15) 40 mg every other week
Ulcerative colitis
  • Day 1: 160 mg (given as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days)
  • Day 15: 80 mg
  • Day 29 and on: 40 mg every other week
  • Target trough concentration in IBD: ≥ 7.5 mcg/ml [5]
Plaque Psoriasis or Uveitis
  • Day 1: 80 mg
  • Day 8 and on: 40 mg every other week
Juvenile Idiopathic Arthritis (≥ 2 years old)

Weight Dose
10 kg (22 lbs) to < 15 kg (33 lbs) 10 mg every other week
(10 mg Prefilled Syringe)
15 kg (33 lbs) to < 30 kg (66 lbs) 20 mg every other week
(20 mg Prefilled Syringe)
≥ 30 kg (66 lbs) 40 mg every other week
(Humira Pen or 40 mg Prefilled Syringe)
Hidradenitis Suppurativa
  • Day 1: 160 mg (given as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days)
  • Day 15: 80 mg
  • Day 29 and on: 40 mg every week

Efficacy
Other
  • Keep refrigerated
  • Humira may be stored at room temperature up to a maximum of 77°F (25°C) for a period of up to 14 days with protection from light
  • Humira is injected subcutaneously into the thigh or abdomen. Rotate injection sites.
  • May leave at room temperature for 15 - 30 minutes before injecting
  • Solution should be clear and colorless

Mechanism
  • Tumor Necrosis Factor inhibitor - Humira is a human monoclonal antibody (IgG) specific for human tumor necrosis factor alpha (TNF-alpha). Humira binds TNF-alpha and blocks its interaction with cell receptors. Humira may also lyse TNF expressing cells in the presence of complement.

FDA-approved indications
  • Rheumatoid arthritis
  • Juvenile Idiopathic Arthritis
  • Psoriatic Arthritis
  • Ankylosing Spondylitis
  • Crohn’s Disease (adult and pediatric)
  • Ulcerative Colitis
  • Plaque Psoriasis
  • Hidradenitis Suppurativa
  • Uveitis

Side effects
NOTE: Only side effects that occurred at an incidence ≥ 2% more than placebo are listed. Data below is from rheumatoid arthritis trials

Side effect Adalimumab Placebo
Upper respiratory infection 17% 13%
Headache 12% 8%
Rash 12% 6%
Sinusitis 11% 9%
Accidental injury 10% 8%
Urinary tract infection 8% 5%
Abdominal pain 7% 4%
High cholesterol 6% 4%
Back pain 6% 4%
Increased alk phos 5% 3%
Hypertension 5% 3%
Other
  • Injection site reactions - 20% of patients; common reactions include redness, itching, bleeding, pain, and swelling.


Contraindications / Precautions
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting a TNF inhibitor. Active TB should be treated completely before starting a TNF inhibitor. [2]
  • Serious infections - TNF inhibitors may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In controlled trials, the rate of serious infections was 4.4 per 100 patient-years in 7723 Humira-treated patients versus a rate of 2.9 per 100 patient-years in 4598 control-treated patients.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking TNF inhibitors. Test patients before initiating therapy. Monitor infected patients closely.
  • Malignancies - TNF inhibitors may increase the risk for certain cancers, particularly lymphoma. Concomitant immunosuppressants may increase the risk.
  • Demyelinating diseases (e.g. multiple sclerosis) - TNF inhibitors may exacerbate demyelinating diseases. Use caution.
  • Blood dyscrasias - blood dyscrasias including aplastic anemia have been reported
  • Abatacept and anakinra - DO NOT COMBINE. Increases risk of serious infection.
  • Heart failure - TNF inhibitors may cause new onset heart failure or worsen existing heart failure. Use caution.
  • Drug-induced lupus - TNF inhibitors have been associated with drug-induced lupus in a small number of patients
  • Autoantibodies - in controlled trials, 12% of Humira-treated patients and 7% of placebo-treated patients developed positive ANA titers during treatment
  • Elevated liver enzymes - in controlled trials, ALT elevations ≥ 3 x ULN occurred in 3.5% of Humira-treated patients and 1.5% of control-treated patients. Concomitant methotrexate may increase the risk.
  • Humira antibodies - anti-adalimumab antibodies have been found in up to 61% of patients treated with adalimumab. Antibodies have been associated with reduced serum adalimumab concentrations. The effects of antibody development on efficacy and safety are unknown.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by TNF inhibitors may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Certolizumab (Cimzia®)

Dosage form
Prefilled syringe
  • Comes in 200 mg dose
  • Comes in carton with 2 pens
Vial
  • 200 mg/ml
  • Comes in kit with vial of powdered drug that must be reconstituted before injecting

Dosing
Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis
  • Starting: 400 mg at Weeks 0, 2, and 4
  • Maintenance: 200 mg every other week or 400 mg every 4 weeks
Crohn's disease
  • Starting: 400 mg at Weeks 0, 2, and 4
  • Maintenance: 400 mg every 4 weeks
  • Target trough concentration in IBD: ≥ 20 mcg/ml [5]

Other
  • Keep refrigerated
  • Let medication warm to room temperature before injecting
  • Cimzia is injected subcutaneously into the thigh or abdomen. Rotate injection sites.

Mechanism
  • Tumor Necrosis Factor inhibitor - Cimzia is a recombinant, humanized antibody Fab' fragment with specificity for human tumor necrosis factor alpha (TNF-alpha). Cimzia binds TNF-alpha and neutralizes it.

FDA-approved indications
  • Rheumatoid arthritis
  • Psoriatic Arthritis
  • Ankylosing Spondylitis
  • Crohn’s Disease (adult)

Side effects
NOTE: Only side effects that occurred at an incidence of ≥ 5% and more than placebo are listed. Data below is from Crohn's disease trials.

Side effect Certolizumab Placebo
Upper respiratory infections 20% 13%
Urinary tract infections 7% 6%
Arthralgia 6% 4%


Contraindications / Precautions
  • Concomitant abatacept or anakinra - DO NOT COMBINE. Increases risk of serious infection.
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting a TNF inhibitor. Active TB should be treated completely before starting a TNF inhibitor. [2]
  • Serious infections - TNF inhibitors may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In controlled trials, the rate of serious infections was 3% per year in Cimzia-treated patients and 1% per year for placebo-treated patients. Serious infections included bacterial and viral infections, pneumonia, and pyelonephritis.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking TNF inhibitors. Test patients before initiating therapy. Monitor infected patients closely.
  • Malignancies - TNF inhibitors may increase the risk for certain cancers, particularly lymphoma. Concomitant immunosuppressants may increase the risk. In trials, malignancies were observed at a rate of 0.5 per 100 patient-years among 4,650 Cimzia-treated patients versus a rate of 0.6 per 100 patient-years among 1,319 placebo-treated patients.
  • Demyelinating diseases (e.g. multiple sclerosis) - TNF inhibitors may exacerbate demyelinating diseases. Use caution.
  • Elevated liver enzymes - Cimzia may raise liver enzymes. In trials, up to 4.3% of Cimzia-treated subjects had elevated liver enzymes compared to 2.5% of placebo-treated subjects.
  • Blood dyscrasias - blood dyscrasias including aplastic anemia have been reported
  • Heart failure - TNF inhibitors may cause new onset heart failure or worsen existing heart failure. Use caution.
  • Drug-induced lupus - TNF inhibitors have been associated with drug-induced lupus in a small number of patients
  • Autoantibodies - in controlled trials, 4% of Cimzia-treated patients and 2% of placebo-treated patients developed positive ANA titers during treatment
  • Cimzia antibodies - in long-term Crohn's disease trials, up to 23% of patients developed anti-Cimzia antibodies. In RA trials, 7% of patients developed anti-Cimzia antibodies. In the RA trials, antibody development was associated with lower drug plasma concentrations and reduced efficacy.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by TNF inhibitors may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Coagulation studies - Cimzia may cause an erroneously prolonged activated Partial Thromboplastin Time (aPTT)
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Etanercept | Enbrel® | Erelzi®

Dosage form
Enbrel® prefilled syringe
  • Comes in 25 mg and 50 mg doses
  • Comes in carton with 4 pens
Enbrel® SureClick autoinjector
  • Comes in 50 mg dose
  • Comes in carton with 4 autoinjectors
Enbrel® Mini prefilled cartridges
  • Comes in 50 mg dose
  • Comes in carton with 4 cartridges
  • For use with AutoTouch reusable autoinjector
Enbrel® Vial
  • Comes in 25 mg multi-use vial
  • Comes in carton with 4 vials
  • Drug must be reconstituted
Erelzi® prefilled syringe
  • Comes in 25 mg and 50 mg doses
  • Comes in carton with 1 or 4 pens
  • Erelzi is a biosimilar to Enbrel
  • Erelzi is etanercept-szzs
Erelzi® Sensoready Pen
  • Comes in 50 mg dose
  • Comes in carton with 1 or 4 pens
  • Erelzi is a biosimilar to Enbrel
  • Erelzi is etanercept-szzs

Dosing
Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis
  • Dosing: 50 mg once weekly
Plaque Psoriasis
  • Starting: 50 mg twice weekly for 3 months
  • Maintenance: 50 mg once weekly
  • Starting doses of 25 - 50 mg once weekly have also been shown to be effective

Other
  • Keep refrigerated
  • Let Enbrel/Erelzi warm to room temperature for 15 - 30 minutes before injecting
  • Inject subcutaneously in the thigh, abdomen, or outer upper arms. Rotate injection sites.
  • See medication guide and instructions for use for more information on storage and proper injection technique

Mechanism
  • Tumor Necrosis Factor inhibitor - Enbrel is a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton (p75) tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. Enbrel inhibits binding of TNF-alpha and TNF-beta to cell surface TNFRs.

FDA-approved indications
  • Rheumatoid arthritis
  • Polyarticular Juvenile Idiopathic Arthritis in patients ≥ 2 years old
  • Psoriatic Arthritis
  • Ankylosing Spondylitis
  • Plaque Psoriasis in patients ≥ 4 years old

Side effects
NOTE: Only side effects that occurred at an incidence of ≥ 2% more than placebo are listed. Data below is from RA trials.

Side effect Etanercept Placebo
Upper respiratory infections 38% 30%
Non-upper respiratory infections 21% 15%
Fever 3% 0%
Other
  • Injection site reactions - up to 37% of patients; reactions include redness, itching, pain, swelling, bleeding, and bruising; average duration of reactions is 3 - 5 days; reactions typically occurred in the first month and then decreased in frequency


Contraindications / Precautions
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting a TNF inhibitor. Active TB should be treated completely before starting a TNF inhibitor. [2]
  • Serious infections - TNF inhibitors may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In controlled trials, rates of serious infections were 1.4% in Enbrel-treated patients and 0.8% in placebo-treated patients. In rheumatological trials, serious infections included pneumonia, cellulitis, septic arthritis, bronchitis, gastroenteritis, pyelonephritis, sepsis, abscess and osteomyelitis.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking TNF inhibitors. Test patients before initiating therapy. Monitor infected patients closely.
  • Malignancies - TNF inhibitors may increase the risk for certain cancers, particularly lymphoma. Concomitant immunosuppressants may increase the risk.
  • Demyelinating diseases (e.g. multiple sclerosis) - TNF inhibitors may exacerbate demyelinating diseases. Use caution.
  • Blood dyscrasias - blood dyscrasias including aplastic anemia have been reported
  • Abatacept and anakinra - DO NOT COMBINE. Increases risk of serious infection.
  • Cyclophosphamide - DO NOT COMBINE. May increase risk of malignancy.
  • Sulfasalazine - combination may decrease neutrophil count
  • Heart failure - TNF inhibitors may cause new onset heart failure or worsen existing heart failure. Use caution.
  • Drug-induced lupus - TNF inhibitors have been associated with drug-induced lupus in a small number of patients
  • Autoantibodies - in controlled trials, 11% of Enbrel-treated patients and 5% of placebo-treated patients developed positive ANA titers during treatment
  • Wegener's granulomatosis - DO NOT USE. May increase risk of malignancy.
  • Alcoholic hepatitis - Use caution. May increase mortality.
  • Enbrel antibodies - in trials, anti-Enbrel antibodies were detected in up to 9% of patients. Antibody development did not appear to affect drug efficacy.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by TNF inhibitors may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Golimumab | Simponi® | Simponi Aria®

Dosage form
Simponi prefilled syringe
  • Comes 50 mg and 100 mg doses
Simponi SmartJect autoinjector
  • Comes 50 mg and 100 mg doses
Simponi Aria Vial
  • 50 mg/4 ml single-use vial

Dosing - Simponi syringe and autoinjector
Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis
  • Dosing: 50 mg once a month
  • For patients with rheumatoid arthritis, Simponi should be given with methotrexate
Ulcerative colitis
  • Starting: 200 mg at Week 0, followed by 100 mg at Week 2
  • Maintenance: 100 mg every 4 weeks

Dosing - Simponi Aria intravenous infusion
Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis
  • Starting: 2 mg/kg at Week 0 and 4
  • Maintenance: 2 mg/kg every 8 weeks
  • For patients with rheumatoid arthritis, Simponi Aria should be given with methotrexate
  • For patients with psoriatic arthritis or ankylosing spondylitis, Simponi Aria may be given with or without methotrexate or other non-biologic disease modifying antirheumatic drugs.

Other
Syringe and autoinjector
  • Keep refrigerated
  • Let Simponi warm to room temperature for 30 minutes before injecting
  • Inject subcutaneously in the thigh, abdomen, or outer upper arms. Rotate injection sites.
  • Simponi should be clear to slightly opalescent and colorless to light yellow
Simponi Aria
  • Keep refrigerated
  • Must be infused intravenously over 30 minutes
  • Solution should be colorless to light yellow. The solution may develop a few fine translucent particles.

Mechanism
  • Tumor Necrosis Factor inhibitor - Simponi is is a human IgG1қ monoclonal antibody specific for human tumor necrosis factor alpha (TNF-alpha). Simponi binds TNF-alpha and prevents it from binding with TNF-alpha receptors.

FDA-approved indications
Simponi
  • Rheumatoid arthritis (in combination with methotrexate)
  • Psoriatic Arthritis
  • Ankylosing Spondylitis
  • Ulcerative colitis
Simponi Aria
  • Rheumatoid arthritis in combination with methotrexate

Side effects
NOTE: Only side effects that occurred at an incidence of ≥ 2% more than placebo are listed. Data below is from trials where Simponi was given in combination with other DMARDs.

Side effect Golimumab Placebo
Upper respiratory infections 16% 13%
Viral infections (e.g. influenza and herpes) 5% 3%
Other
  • Injection site reactions - up to 6% of patients; most reactions were mild; most frequent reaction was redness
  • Infusion reactions (Simponi Aria) - 1.1% of patients; most common reaction was rash


Contraindications / Precautions
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting a TNF inhibitor. Active TB should be treated completely before starting a TNF inhibitor. [2]
  • Serious infections - TNF inhibitors may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In controlled trials, the incidence of serious infections was 5.7 per 100 patient-years in Simponi-treated patients and 4.2 per 100 patient-years in placebo-treated patients.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking TNF inhibitors. Test patients before initiating therapy. Monitor infected patients closely.
  • Malignancies - TNF inhibitors may increase the risk for certain cancers, particularly lymphoma. Concomitant immunosuppressants may increase the risk.
  • Demyelinating diseases (e.g. multiple sclerosis) - TNF inhibitors may exacerbate demyelinating diseases. Use caution.
  • Blood dyscrasias - blood dyscrasias including aplastic anemia have been reported
  • Abatacept and anakinra - DO NOT COMBINE. Increases risk of serious infection.
  • Heart failure - TNF inhibitors may cause new onset heart failure or worsen existing heart failure. Use caution.
  • Drug-induced lupus - TNF inhibitors have been associated with drug-induced lupus in a small number of patients
  • Autoantibodies - in controlled trials, 4% of Simponi-treated patients and 2.6% of placebo-treated patients developed positive ANA titers during treatment
  • Elevated liver enzymes - in controlled trials, ALT elevations ≥ 3 x ULN occurred in 2% of control-treated patients and 2% of Simponi-treated patients. Concomitant methotrexate may increase the risk.
  • Simponi antibodies - in trials, anti-golimumab antibodies have been detected in up to 38% of patients. Concomitant immunosuppressants lowers the risk of antibody development. A trend toward decreased drug concentrations and efficacy was noted in antibody-positive patients when compared to antibody-negative patients.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by TNF inhibitors may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Infliximab | Remicade® | Inflectra® | Renflexis®

Dosage form
Remicade® Vial
  • 100 mg single dose vial
Inflectra® Vial
  • 100 mg single dose vial
  • Inflectra is a biosimilar to Remicade
  • Inflectra is infliximab-dyyb
Renflexis® Vial
  • 100 mg single dose vial
  • Renflexis is a biosimilar to Remicade
  • Renflexis is infliximab-adba

Dosing
Crohn's disease (Adults)
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 8 weeks
  • May increase to 10 mg/kg in patients who respond and then lose their response
  • Target trough concentration in IBD: ≥ 5 mcg/ml [5]
Crohn's disease (≥ 6 years old)
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 8 weeks
Ulcerative colitis (Adults)
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 8 weeks
  • Target trough concentration in IBD: ≥ 5 mcg/ml [5]
Ulcerative colitis (≥ 6 years old)
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 8 weeks
Rheumatoid arthritis
  • Starting: 3 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 3 mg/kg every 8 weeks
  • Should be given with methotrexate
  • May increase dose to 10 mg/kg or shorten dosing interval to 4 weeks in patients with partial response
Ankylosing spondylitis
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 6 weeks
Psoriatic arthritis
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 8 weeks
Plaque Psoriasis
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 8 weeks

Efficacy
Other
  • Prior to infusion, may premedicate with antihistamine, acetaminophen, and/or corticosteroids
  • Infuse over a period of not less than 2 hours
  • Keep vials refrigerated
  • Unopened vials may also be stored at temperatures up to a maximum of 30°C (86°F) for a single period of up to 6 months
  • Upon removal from refrigerated storage, Remicade cannot be returned to refrigerated storage

Mechanism
  • Tumor Necrosis Factor inhibitor - Remicade is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions) specific for human tumor necrosis factor-alpha (TNF-alpha). Remicade binds TNF-alpha and prevents it from binding with TNF-alpha receptors.

FDA-approved indications
  • Crohn's disease (adult and pediatric)
  • Rheumatoid arthritis (in combination with methotrexate)
  • Psoriatic Arthritis
  • Ankylosing Spondylitis
  • Ulcerative colitis (adult and pediatric)
  • Plaque Psoriasis

Side effects
NOTE: Only side effects that occurred at an incidence of ≥ 2% more than placebo are listed. Data below is from RA trials.

Side effect Infliximab Placebo
Upper respiratory tract infection 32% 25%
Headache 18% 14%
Sinusitis 14% 8%
Pharyngitis 12% 8%
Coughing 12% 8%
Abdominal pain 12% 8%
Rash 10% 5%
Dyspepsia 10% 7%
Fatigue 9% 7%
Urinary tract infection 8% 6%
Hypertension 7% 5%
Fever 7% 4%
Itching 7% 2%
Yeast infection 5% 3%
Other
  • Infusion reactions - up to 18% of patients; serious reactions are rare


Contraindications / Precautions
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting a TNF inhibitor. Active TB should be treated completely before starting a TNF inhibitor. [2]
  • Serious infections - TNF inhibitors may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In RA patients treated for 1 year, 5.3% of Remicade-treated patients developed serious infections as compared to 3.4% of placebo-treated patients.
  • Elevated liver enzymes - in controlled trials, ALT elevations between 1 - 3 X ULN occurred in up to 51% of Remicade-treated patients. ALT elevations ≥ 3 X ULN occurred in up to 10% of Remicade-treated patients. Mild-to-moderate elevations typically decreased or resolved with either continuation or discontinuation of Remicade, or modification of concomitant medications. Discontinue Remicade if LFTs reach ≥ 5 X ULN.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking TNF inhibitors. Test patients before initiating therapy. Monitor infected patients closely.
  • Malignancies - TNF inhibitors may increase the risk for certain cancers, particularly lymphoma. Concomitant immunosuppressants may increase the risk.
  • Cervical cancer - In an observational study, the risk for invasive cervical cancer was increased in women receiving infliximab for RA. The risk was particularly high in women > 60 years old. Cervical cancer screening should continue in women receiving infliximab.
  • Vascular events during infusion - vascular events including stroke, MI, hypo/hypertension, transient vision loss, and arrhythmias have been reported during and within 24 hours of infliximab infusions. Discontinue infusion if events occur.
  • Demyelinating diseases (e.g. multiple sclerosis) - TNF inhibitors may exacerbate demyelinating diseases. Use caution.
  • Heart failure - Remicade may cause new-onset heart failure or worsen existing heart failure. Remicade at doses > 5 mg/kg should not be given to patients with moderate to severe (NYHA III and IV) heart failure.
  • Blood dyscrasias - blood dyscrasias including aplastic anemia have been reported
  • Abatacept and anakinra - DO NOT COMBINE. Increases risk of serious infection.
  • Tocilizumab - DO NOT COMBINE. Increases risk of serious infection.
  • Drug-induced lupus - TNF inhibitors have been associated with drug-induced lupus in a small number of patients
  • Autoantibodies - in controlled trials, 50% of Remicade-treated patients and 20% of placebo-treated patients developed positive ANA titers during treatment. Anti-dsDNA antibodies developed in 20% of Remicade-treated patients compared to 0% of placebo-treated patients.
  • Remicade antibodies - in trials, anti-Remicade antibodies were detected in up to 51% of patients. In some studies, antibody development was associated with reduced efficacy and an increased rate of infusion reactions.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by TNF inhibitors may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease - has not been studied



Abatacept (Orencia®)

Dosage form
Prefilled syringe
  • 50 mg/0.4 ml
  • 87.5 mg/0.7 ml
  • 125 mg/ml
  • Comes in package of 4 syringes
Single-use vials
  • Comes in 250 mg vial

Dosing
Rheumatoid arthritis and Psoriatic arthritis
  • Prefilled syringe (subcutaneous)
    • Dosing: 125 mg subcutaneously once weekly
    • Loading dose: In rheumatoid arthritis patients, may give IV loading dose per guidelines below. Loading dose is not recommended for psoriatic arthritis. If IV loading dose is given, initiate first subcutaneous dose within a day of IV loading dose.
    • If transitioning from IV therapy to subcutaneous, administer the first subcutaneous dose instead of the next scheduled intravenous dose
  • Intravenous
    • Starting: weight-based dose at Week 0, 2, and 4
    • Maintenance: weight-based dose every 4 weeks

Body weight (kg) Dose # of vials
< 60 kg 500 mg 2
60 - 100 kg 750 mg 3
> 100 kg 1000 mg 4
Juvenile idiopathic arthritis
  • Prefilled syringe - subcutaneous (≥ 2 years old)

Body weight (kg) Dose (once weekly)
10 to less than 25 kg 50 mg
25 to less than 50 kg 87.5 mg
≥ 50 kg 125 mg

  • Intravenous (≥ 6 years old)
    • Starting: 10 mg/kg at Week 0, 2, and 4
    • Maintenance: 10 mg/kg dose every 4 weeks
    • If weight is ≥ 75 kg, use adult dosing

Other
Prefilled syringe
  • Keep refrigerated
  • Solution should be clear and colorless to pale yellow
  • Let syringe warm to room temperature for 30 - 60 minutes before injecting
  • Inject subcutaneously in the thigh, abdomen, or outer upper arms. Rotate injection sites.
Intravenous infusion
  • Orencia is infused over 30 minutes

Mechanism
  • T-cell inhibitor - Orencia is a soluble fusion protein that consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc portion of human immunoglobulin G1 (IgG1). Orencia inhibits T-lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28. CD28 interaction is necessary for full activation of T-lymphocytes.

FDA-approved indications
  • Rheumatoid arthritis - as monotherapy or concomitantly with DMARDs other than TNF inhibitors
  • Psoriatic arthritis - with or without non-biologic DMARDs
  • Juvenile idiopathic arthritis - in patients ≥ 2 years old as monotherapy or with methotrexate

Side effects
NOTE: Only side effects that occurred at an incidence of ≥ 3% and ≥ 2% more than placebo are listed.

Side effect Abatacept Placebo
Headache 18% 13%
Nasopharyngitis 12% 9%
Dizziness 9% 7%
Hypertension 7% 4%
Dyspepsia 6% 4%
Other
  • Injection site reactions - 2.6% of patients; reactions include hematoma, pruritus, and erythema
  • Infusion reactions - 9% of patients; most common reactions include dizziness, headache, and hypertension


Contraindications / Precautions
  • TNF inhibitors - DO NOT COMBINE. May increase risk of serious infection.
  • Infusion reactions - rare cases of anaphylaxis have been reported with Orencia infusion. Administer under medical supervision.
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting abatacept. Active TB should be treated completely before starting abatacept. [2]
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking Orencia. Test patients before initiating therapy. Monitor infected patients closely.
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG) concurrently with Orencia or within 3 months of discontinuation.
  • COPD - patients with COPD had a greater number of adverse events (COPD exacerbations, cough, rhonchi, dyspnea) while using Orencia. Use caution in this population.
  • Serious infections - Orencia may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In trials, the incidence of serious infections in Orencia-treated patients was 3% compared to 1.9% in placebo-treated patients. The most common serious infections were pneumonia, cellulitis, urinary tract infection, bronchitis, diverticulitis, and acute pyelonephritis.
  • Malignancies - Orencia may increase the risk for certain cancers, particularly lymphoma and lung cancer
  • Orencia antibodies - in trials, anti-Orencia antibodies were detected in up to 10% of patients. It's unclear if antibody development is associated with reduced efficacy and/or an increase in hypersensitivity reactions.
  • Blood glucose test strips (infusion) - maltose in the Orencia infusion may cause falsely elevated blood glucose readings on the day of infusion with certain test strips and monitors.
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Natalizumab (Tysabri®)

Dosage form
Single-use vials
  • Comes in 300 mg vial

Dosing
Crohn's disease
  • Dosing: 300 mg every 4 weeks
  • If benefit is not seen by 12 weeks, discontinue
  • For patients using steroids, begin tapering steroids as soon as benefit from Tysabri is seen. If steroids cannot be tapered within 6 months, discontinue Tysabri.
  • Tysabri is given by IV infusion over 1 hour
  • Because of the risk of PML, providers must be enrolled in the Tysabri CD TOUCH program in order to prescribe Tysabri
Multiple sclerosis
  • Dosing: 300 mg every 4 weeks

Efficacy
Mechanism
  • T-cell inhibitor - Tysabri is a recombinant humanized IgG4ϰ monoclonal antibody that binds to the α4-subunit of α4β1 and α4β7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4-mediated adhesion of leukocytes to their counter-receptor(s). Inhibiting this interaction prevents transmigration of leukocytes across the endothelium into inflamed parenchymal tissue

FDA-approved indications
  • Crohn's disease
  • Multiple sclerosis

Side effects
NOTE: Only side effects that occurred at an incidence of ≥ 2% more than placebo are listed. Data is from Crohn's disease studies.

Side effect Natalizumab Placebo
Headache 32% 23%
Upper respiratory infection 22% 16%
Nausea 17% 15%
Fatigue 10% 8%
Arthralgia 8% 6%
Throat pain 6% 4%
Rash 6% 4%
Dyspepsia 5% 3%
Constipation 4% 2%
Vaginal infections 4% 2%
Urinary tract infections 3% 1%
Cough 3% <1%
Other
  • Infusion reactions - in Crohn's trials, up to 11% of patients; most common reactions include headache, nausea, urticaria, pruritus, and flushing


Contraindications / Precautions
  • Progressive Multifocal Leukoencephalopathy (PML) - JC virus infections resulting in PML and death have occurred. Longer duration of treatment (> 2 years), prior treatment with other immunosuppressants, and presence of anti-JCV antibodies are all risk factors for PML. Baseline MRI may help to distinguish new lesions in the future. Consider PML diagnosis in patients with new-onset or deteriorating neurological signs and symptoms.
  • Herpes encephalitis and meningitis - Tysabri increases the risk
  • Acute retinal necrosis - Tysabri increases the risk of acute retinal necrosis, a fulminant herpes virus infection of the eye
  • Hepatotoxicity - cases of acute hepatitis and liver failure have occurred.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have occurred. Reactions are more common in patients who develop anti-Tysabri antibodies. See Tysabri antibodies below.
  • Serious infections - Tysabri may increase the risk of serious infections including invasive fungal infections, bacterial infections, viral infections, and others. In Crohn's trials, the incidence of serious infections in Tysabri-treated patients was 3.3% compared to 2.8% in placebo-treated patients.
  • Tysabri antibodies - in Crohn's trials, anti-Tysabri antibodies were detected in up to 10% of patients. Antibody development was associated with reduced efficacy and an increase in hypersensitivity reactions. Patients who receive 1 - 2 infusions of Tysabri followed by an extended period without exposure are at greater risk of developing antibodies and experiencing hypersensitivity reactions. Before restarting therapy, antibody testing may be appropriate.
  • TNF inhibitors - DO NOT COMBINE. May increase risk of PML.
  • Immunosuppressants - DO NOT COMBINE. May increase risk of PML.
  • Corticosteroids - taper corticosteroids when starting Tysabri.
  • Increase in blood counts - Tysabri increases circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Levels return to normal when Tysabri is discontinued.
  • Decrease in hemoglobin - Tysabri induces mild decreases in hemoglobin levels (mean decrease of 0.6 g/dl) that are frequently transient
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Vedolizumab (Entyvio®)

Dosage form
Single-use vials
  • 300 mg vial

Dosing
Crohn's disease
  • Starting: 300 mg IV at Weeks 0, 2, and 6
  • Maintenance: 300 mg IV every 8 weeks
  • Entyvio is given by IV infusion over 30 minutes
  • Discontinue if no effect seen after Week 14
Ulcerative colitis
  • Starting: 300 mg IV at Weeks 0, 2, and 6
  • Maintenance: 300 mg IV every 8 weeks
  • Entyvio is given by IV infusion over 30 minutes
  • Discontinue if no effect seen after Week 14

Efficacy
Mechanism
  • T-cell inhibitor - Vedolizumab is a humanized monoclonal antibody that specifically binds to the α4β7 integrin and blocks the interaction of α4β7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue
FDA-approved indications
  • Crohn's disease - treatment of active disease in patients who did not respond to or tolerate tumor necrosis factor inhibitors, immunosuppressants, or corticosteroids
  • Ulcerative colitis - treatment of active disease and maintenance of remission in patients who did not respond to or tolerate tumor necrosis factor inhibitors, immunosuppressants, or corticosteroids

Side effects
NOTE: Only side effects that occurred at an overall incidence of ≥ 3% and at an incidence ≥ 2% more than placebo are listed. Data below has been combined from Crohn's disease and ulcerative colitis studies.

Side effect Vedolizumab Placebo
Nasopharyngitis 13% 7%
Arthralgia 12% 10%
Fever 9% 7%
Fatigue 6% 3%
Cough 5% 3%
Influenza 4% 2%
Itching 3% 1%
Sinusitis 3% 1%
Oropharyngeal pain 3% 1%
Pain in extremities 3% 1%
Other
  • Infusion reactions - up to 4% of patients; most common reactions include nausea, headache, pruritus, dizziness, fatigue, pyrexia, urticaria, and vomiting


Contraindications / Precautions
  • Natalizumab (Tysabri) - DO NOT COMBINE. May increase risk of PML.
  • TNF inhibitors - DO NOT COMBINE. May increase risk of serious infection.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have occurred. In trials, 1 patient out of 1434 had an anaphylactic reaction during Entyvio infusion.
  • Serious infections - Entyvio may increase the risk for serious infections. In trials, the rate of serious infections was 0.07 per patient-year in Entyvio-treated patients compared to 0.06 per patient-year in placebo-treated patients. Serious infections were more frequent in Crohn's disease patients than ulcerative colitis patients. Anal abscesses were the most frequently reported serious infection in Crohn's patients.
  • Progressive Multifocal Leukoencephalopathy (PML) - another integrin inhibitor (Tysabri) has been associated with JC virus infections resulting in PML. In Entyvio trials lasting at least 24 months, no cases of PML were observed. An association between Entyvio and PML cannot be ruled out. Consider PML diagnosis in patients with new-onset or deteriorating neurological signs and symptoms.
  • Hepatotoxicity - in rare cases, hepatotoxicity has occurred with Entyvio. In controlled trials, AST and ALT elevations ≥ 3 X ULN occurred in < 2% of patients.
  • Vaccines - patients may receive non-live vaccines. The risks of administering live or attenuated vaccines with Entyvio therapy are unknown. Ideally, all vaccines should be brought up to date before initiating Entyvio.
  • Malignancies - Entyvio may increase the risk of malignancy
  • Entyvio antibodies - in trials, anti-Entyvio antibodies were detected in up to 13% of patients. Antibody development was associated with reduced efficacy.
  • Liver disease - has not been studied
  • Kidney disease - has not been studied



Pregnancy safety studies

Pregnancy Outcomes After Exposure to Certolizumab Pegol: Updated Results From a Pharmacovigilance Safety Database, Arthritis Rheumatol (2018) [PubMed abstract]
  • Design: Prospective cohort study (N=538, length - pregnancy and birth) in women exposed to certolizumab during pregnancy
  • Exposure: Certolizumab exposure during pregnancy
  • Primary outcome: Pregnancy outcomes including miscarriages, stillbirths, and congenital malformations
  • Findings: This analysis represents the largest cohort of pregnant women exposed to an anti-TNF agent for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a teratogenic effect of certolizumab, compared to the general population, nor an increased risk of fetal death. The data are reassuring for women of childbearing age considering treatment with certolizumab.

Continuous Anti-TNFα Use Throughout Pregnancy: Possible Complications For the Mother But Not for the Fetus. A Retrospective Cohort on the French National Health Insurance Database (EVASION), Am J Gastroenterol (2018) [PubMed abstract]
  • Design: Retrospective cohort study (N=8726, length - pregnancy through 1 year postpartum) in women with IBD
  • Exposure: TNF inhibitor exposure during pregnancy
  • Primary outcome: Composite of disease-, treatment- and pregnancy-related complications during pregnancy for the mother, and infections during the first year of life for children
  • Findings: Anti-TNFα treatment during pregnancy increased the risk of maternal complications compared to unexposed; however, discontinuation before week 24 increased the risk of disease flare. There was no increased risk for children exposed to anti-TNFα up to 1 year of life.

Use of Biologic Therapy by Pregnant Women With Inflammatory Bowel Disease Does Not Affect Infant Response to Vaccines, Clin Gastroenterol Hepatol (2018) [PubMed abstract]
  • Design: Registry cohort study (N=179, length - 7 months)
  • Exposure: Biologic therapy during pregnancy
  • Primary outcome: Protective antibody titers to Hib tetanus toxoid
  • Findings: Vaccination of infants against HiB and tetanus toxin, based on antibody titers measured when infants were at least 7 months old, does not appear to be affected by in utero exposure to biologic therapy

Concentrations of Adalimumab and Infliximab in Mothers and Newborns, and Effects on Infection, Gastroenterology (2016) [PubMed abstract]
  • Design: Prospective cohort study (N=80, length - 12 months)
  • Exposure: Adalimumab, infliximab, and/or thiopurine during pregnancy
  • Primary outcome: Rates of clearance of adalimumab and infliximab in newborns after birth and risk of infection during the first year of life
  • Findings: In a prospective study of infants born to mothers who received anti-TNF agents during pregnancy, we detected the drugs until 12 months of age. There was an inverse correlation between the time from last exposure during pregnancy and drug concentration in the umbilical cord. Infliximab was cleared more slowly than adalimumab from the infants. The combination of an anti-TNF agent and thiopurine therapy during pregnancy increased the relative risk for infant infections almost 3-fold compared with anti-TNF monotherapy. Live vaccines therefore should be avoided for up to 1 year unless drug clearance is documented, and pregnant women should be educated on the risks of anti-TNF use.

Cancer risk with TNF inhibitors

Tumor Necrosis Factor Inhibitors and Cancer Recurrence in Swedish Patients With Rheumatoid Arthritis: A Nationwide Population-Based Cohort Study, Ann Intern Med (2018) [PubMed abstract]
  • Design: Prospective registry cohort study (N=2631, length - 7.9 years) among patients with RA who started TNF inhibitor after being diagnosed with cancer
  • Exposure: Treatment with TNF inhibitors
  • Primary outcome: First recurrence of cancer
  • Findings: The findings suggest that TNF inhibitor treatment is not associated with increased risk for cancer recurrence in patients with RA, although meaningful risk increases could not be ruled out completely.

Malignant Neoplasms in Patients With Rheumatoid Arthritis Treated With Tumor Necrosis Factor Inhibitors, Tocilizumab, Abatacept, or Rituximab in Clinical Practice: A Nationwide Cohort Study From Sweden, JAMA Intern Med (2017) [PubMed abstract]
  • Design: Prospective registry cohort study (N=100,000+, length - 9 years)
  • Exposure: Treatment with tocilizumab, abatacept, rituximab, or TNF inhibitors
  • Primary outcome: First invasive solid or hematologic malignant neoplasm, or skin cancer
  • Findings: The overall risk of cancer among patients with RA initiating TNFi as first or second bDMARD, tocilizumab, abatacept, or rituximab does not differ substantially from that of biologic drug-naive, csDMARD-treated patients with RA, although altered risks for specific cancer types, or those with longer latency, cannot be excluded.

Association Between Use of Thiopurines or Tumor Necrosis Factor Antagonists Alone or in Combination and Risk of Lymphoma in Patients With Inflammatory Bowel Disease, JAMA (2017) [PubMed abstract]
  • Design: Retrospective registry cohort study (N=189,289, length - 6 years)
  • Exposure: Thiopurine monotherapy, anti-TNF monotherapy, or combination therapy, or being unexposed
  • Primary outcome: Incidence of lymphoma
  • Findings: Among adults with IBD, the use of thiopurine monotherapy or anti-TNF monotherapy was associated with a small but statistically significant increased risk of lymphoma compared with exposure to neither medication, and this risk was higher with combination therapy than with each of these treatments used alone. These findings may inform decisions regarding the benefits and risks of treatment.

Association between tumor necrosis factor-α antagonists and risk of cancer in patients with inflammatory bowel disease, JAMA (2014) [PubMed abstract]
  • Design: Retrospective registry cohort study (N=56,146; length = 3.7 years)
  • Exposure:TNF inhibitors vs None in patients with IBD
  • Primary outcome: Rate ratios (RRs) for incident cancer (overall and site-specific)
  • Findings: In this Danish nationwide study, exposure to TNF-α antagonists among patients with IBD was not associated with an increased risk of cancer over a median follow-up of 3.7 years among those exposed. An increased risk associated with longer-term accumulated doses and follow-up cannot be excluded.

Biosimilar studies

Outcomes of Patients With Inflammatory Bowel Diseases Switched from a Biosimilar to Remicade, Clin Gastroenterol Hepatol. (2019) [PubMed abstract]
  • Design: Cohort study (N=174, length = 24 weeks) in patients with UC or Crohn's disease (CD) who were switched from a biosimilar(CT-P13) to Remicade
  • Primary outcome: Clinical remission and serum drug trough levels and anti-drug antibodies
  • Findings: We collected data from a real-life cohort of patients with CD or UC who were switched from maintenance therapy with a biosimilar to Remicade or were treated with only Remicade. No significant changes were observed in remission, trough levels, or antidrug antibodies in patients switched from the biosimilar to Remicade. No new safety signals were detected.

Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial, Lancet (2017) [PubMed abstract]
  • Design: Randomized controlled trial (N=482, length - 52 weeks)
  • Treatment: Brand Remicade (infliximab originator) vs Biosimilar (CT-P13)
  • Primary outcome: Disease worsening during 52-week follow-up
  • Findings: The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15%. The study was not powered to show non-inferiority in individual diseases.

Tocilizumab vs Placebo in Giant Cell Arteritis, NEJM (2017) [PubMed abstract]
  • The trial enrolled 251 patients with active giant cell arteritis
Main inclusion criteria
  • ≥ 50 years of age
  • Active giant-cell arteritis within 6 weeks before baseline
  • ESR > 30 mm/hour or CRP ≥ 1 mg/dL (including a presenting history of ESR> 50 mm/hour)
  • Cranial symptoms of GCA or symptoms of polymyalgia rheumatica
  • Evidence of GCA on imaging or temporal artery biopsy
Main exclusion criteria
  • Major ischemic event, related or unrelated to GCA, within 12 weeks of screening
  • History of GI disease (e.g. diverticulitis, Crohn's, ulcerative colitis) that might predispose a patient to perforations
  • Serum creatinine > 1.4 mg/dL
  • Total bilirubin > ULN
  • ALT or AST> 1.5 X ULN
Baseline characteristics
  • Average age - 69 years
  • Newly-diagnosed GCA - 48%, Relapsing GCA - 52%
  • Average duration of disease - 296 days
  • Symptoms of PR - 61%
  • Average ESR - 24 mm/hr
Randomized treatment groups
  • Group 1 (100 patients): Tocilizumab 162 mg SQ once weekly + 26-week prednisone taper
  • Group 2 (50 patients): Tocilizumab 162 mg SQ every other week + 26-week prednisone taper
  • Group 3 (50 patients): Placebo + 26-week prednisone taper
  • Group 4 (51 patients): Placebo + 52-week prednisone taper
  • Prednisone was initiated at a previously used dose or continued at current dose and then tapered weekly
Primary outcome: Rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper
Results

Duration: 52 weeks
Outcome Group 1 Group 2 Group 3 Group 4 Comparisons
Primary outcome 56% 53% 14% 18% 1 or 2 vs 3: p<0.001
  • The incidence of adverse events was similar in all the trial groups, but fewer patients reported serious adverse events in Group 1 (15%) and Group 2 (14%) than in Group 3 (22%) and Group 4 (25%)

Findings: Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab.

Ustekinumab vs Placebo in Patients with Crohn's Disease who Failed TNF Inhibitors, NEJM (2012) [PubMed abstract]
  • The study enrolled 526 adults with Crohn's Disease who had failed TNF inhibitor therapy
Main inclusion criteria
  • Crohn’s disease of at least 3 months’ duration
  • Disease confirmed by radiography and/or endoscopy
  • Failed infliximab, adalimumab, or certolizumab pegol
  • Active disease, defined as CDAI score of ≥ 220
Main exclusion criteria
  • Crohn’s complications (e.g. strictures, stenoses, short gut syndrome)
  • Bowel resection, diversion, or placement of a stoma within 6 months
Baseline characteristics
  • Average age - 39 years
  • Average duration of disease - 12 years
  • Average CDAI - 323
  • Receiving corticosteroids at baseline - 50%
Randomized treatment groups
  • Group 1 (131 patients): Ustekinumab 1 mg/kg IV one time
  • Group 2 (132 patients): Ustekinumab 3 mg/kg IV one time
  • Group 3 (131 patients): Ustekinumab 6 mg/kg IV one time
  • Group 4 (132 patients): Placebo
  • Patients were permitted to continue other drug therapies for Crohn's disease
  • After 6 weeks, 145 patients who had a response to ustekinumab underwent a second randomization to receive ustekinumab 90 mg SQ or placebo at weeks 8 and 16
Primary outcome: Clinical response (defined as ≥100-point decrease from the baseline CDAI score) at week 6
Results

Duration: 6 weeks
Outcome Group 1 Group 2 Group 3 Group 4 Comparisons
Primary outcome 36.6% 34.1% 39.7% 23.5% 1 vs 4: p=0.02 | 2 vs 4: p=0.06 | 3 vs 4: p=0.005
Clinical remission at 22 weeks (maintenance phase) Ustekinumab - 41.7%, Placebo - 27.4%, (p=0.03)

Findings: Patients with moderate-to-severe Crohn’s disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo. Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy.

GEMINI 2 Study - Vedolizumab vs Placebo for Moderate to Severe CD, NEJM (2013) [PubMed abstract]
  • The GEMINI 2 study enrolled 1093 patients with CD
Main inclusion criteria
  • ≥ 18 years old
  • 3 months of moderate to severe disease (CDAI 220 - 450)
  • No response or unacceptable side effects from steroids, immunosuppressants, or TNF inhibitors
  • One of the following: C-reactive protein > 2.87 mg/L, colonoscopy showing ≥ 3 large ulcers or ≥ 10 aphthous ulcers, Fecal calprotectin > 250 mcg/g + radiological findings of CD
Main exclusion criteria
  • Adalimumab within previous 30 days
  • Infliximab or certolizumab within 60 days
  • History of extensive intestinal surgery
Baseline characteristics
  • Average age 36 years
  • Average CDAI score - 324
  • Treatment with steroids only - 34%
  • Treatment with immunosuppressants only - 16%
  • Treatment with steroids + immunosuppressants - 17%
  • No steroids or immunosuppressants - 33%
  • Prior TNF inhibitor - 62%
Randomized treatment groups:
Induction phase
  • Patients were randomized to one of two groups:
    • Group 1 (148 patients) - Placebo infusion
    • Group 2 (220 patients) - Vedolizumab 300 mg at Weeks 0 and 2
Maintenance phase
  • Patients were randomized to one of three groups:
    • Group 1 (153 patients) - Placebo infusion
    • Group 2 (154 patients) - Vedolizumab 300 mg every 8 weeks
    • Group 3 (154 patients) - Vedolizumab 300 mg every 4 weeks
    • Stable doses of oral prednisone (≤30 mg per day) or budesonide (≤9 mg per day), immunosuppressive agents, mesalamine, and antibiotics were permitted
    • The induction phase also had an open-label vedolizumab arm that included 747 patients
    • Vedolizumab-responders from the induction phase (randomized and open-label) were re-randomized into the maintenance phase
Primary outcome:
  • Induction phase - clinical remission (CDAI score of ≤ 150 points) at week 6
  • Maintenance phase - clinical remission (CDAI score of ≤ 150 points) at week 52
Results

Duration: Induction phase - 6 weeks | Maintenance phase - 52 weeks
Outcome Group 1 Group 2 Group 3 Comparisons
Primary outcome (induction phase) 6.8% 14.5% N/A p=0.02
≥ 100-point decrease in the CDAI score at week 6 (induction phase) 25.7% 31.4% N/A p=0.23
Primary outcome (maintenance phase) 21.6% 39% 36.4% 1 vs 2: p<0.001 | 1 vs 3: p=0.004
  • More serious adverse events occurred in the vedolizumab groups than in the placebo groups (24.4% vs 15.3%)
  • More serious infections occurred in the vedolizumab groups than in the placebo groups (5.5% vs 3%)

Findings: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with vedolizumab.

ENACT 1 and 2 Studies - Natalizumab vs Placebo for Moderate to Severe CD, NEJM (2005) [PubMed abstract]
  • The ENACT 1 and 2 studies enrolled 905 patients with CD
Main inclusion criteria
  • ≥ 18 years old
  • 6 months of moderate to severe disease (CDAI 220 - 450)
  • Disease confirmed within previous 36 months by endoscopy, surgery, or imaging
Main exclusion criteria
  • TNF inhibitors within previous 3 months
  • Active obstructing stricture, fistula, or abscess
Baseline characteristics
  • Average age 38 years
  • Average CDAI score - 302
  • Treatment with steroids only - 38%
  • Treatment with immunosuppressants only - 33%
  • Treatment with steroids + immunosuppressants - 14%
Randomized treatment groups
  • Group 1 (724 patients) - Natalizumab 300 mg IV every 4 weeks
  • Group 2 (181 patients) - Placebo IV every 4 weeks
  • Immunosuppressants were continued at current doses
  • Steroids were continued until Week 10, at which point, patients were required to attempt tapering
  • ENACT-1 lasted 12 weeks. In ENACT-2, patients from ENACT-1 who had a response were randomized to natalizumab or placebo for an additional 44 weeks.
Primary outcome:
  • ENACT 1 - proportion of patients with response (defined by a decrease in the Crohn’s Disease Activity Index (CDAI) score of at least 70 points) at week 10
  • ENACT 2 - proportion of patients with sustained response through Week 36. Loss of response was defined by an increase in the CDAI score of at least 70 points after Week 12 and by an absolute score of at least 220 or the need for intervention after Week 12.
Results

Duration: ENACT 1 - 10 weeks | ENACT 2 - 36 weeks
Outcome Group 1 Group 2 1 vs 2
Primary outcome (ENACT 1) 56% 49% p=0.05
Primary outcome (ENACT 2) 61% 28% p=0<0.001
  • The rates of serious infections were similar between groups in both studies
  • In an open-label extension study, one patient treated with Natalizumab died of PML

Findings: Induction therapy with natalizumab for Crohn's disease resulted in small, nonsignificant improvements in response and remission rates. Patients who had a response had significantly increased rates of sustained response and remission if natalizumab was continued every four weeks. The benefit of natalizumab will need to be weighed against the risk of serious adverse events, including progressive multifocal leukoencephalopathy.

SONIC Study - Infliximab vs Azathioprine vs Both for Moderate to Severe Crohn's Disease, NEJM (2010) [PubMed abstract]
  • The SONIC study enrolled 508 patients with CD
Main inclusion criteria
  • ≥ 21 years old
  • Moderate to severe disease (CDAI 220 - 450)
  • One of the following: corticosteroid-dependent, considered for 2nd course of steroids within 12 months, no response to mesalamine after 4 weeks, no response to budesonide after 4 weeks
Main exclusion criteria
  • Previous treatment with azathioprine, 6MP, methotrexate, or anti-TNF
  • Decreased TPMT activity
  • Abdominal surgery within the previous 6 months
Baseline characteristics
  • Median age 34 years
  • Average CDAI score - 287
  • Median disease duration - 2.3 years
  • Treatment with oral steroids - 27%
  • Receiving budesonide - 14%
  • Receiving 5-Aminosalicylic compounds - 54%
Randomized treatment groups
  • Group 1 (170 patients) - Azathioprine 2.5 mg/kg/day
  • Group 2 (169 patients) - Infliximab 5 mg/kg at Weeks 0, 2, and 6, then every 8 weeks
  • Group 3 (169 patients) - Azathioprine + infliximab
  • Oral mesalamine was continued at a stable dose
  • Steroids (oral and budesonide) could be used up to Week 14, then they had to be tapered
  • Colonoscopy was performed at baseline and Week 26
  • At Week 30, patients were given the option to continue on current treatment while maintaining blinding to Week 50
Primary outcome: Rate of corticosteroid-free clinical remission (CDAI < 150) at week 26
Results

Duration: 26 weeks
Outcome Group 1 Group 2 Group 3 Comparisons
Primary outcome 30% 44% 57%, 3 vs 2: p=0.02 | 3 vs 1: p<0.001 | 2 vs 3: p=0.006
  • Mucosal healing after 26 weeks: Group 1 - 16.5%, Group 2 - 30%, Group 3 - 44%
  • Clinical remission at Week 50 (only patients who entered extension): Group 1 - 55%, Group 2 - 61%, Group 3 - 72%
  • There was no significant difference in the incidence of serious infections between the groups (Group 1 - 5.6%, Group 2 - 5%, Group 3 - 4%)
  • There were significantly fewer serious adverse events in Group 3 than in Group 1 and 2 (Group 1 - 27%, Group 2 - 24%, Group 3 - 15%)

Findings: Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy.



Periprocedural recommendations

Overview
  • In 2017, the American College of Rheumatology and the American Association of Hip and Knee Surgeons issued guidelines for the periprocedural management of biologicals and immunosuppressants in patients undergoing hip or knee replacement surgery
  • A pdf version of the guidelines is available at this link - management of periprocedural biologicals and immunosuppressants
    • Important pages:
      • Population definitions - page 1113
      • Table with specific recommendations for each drug - page 1114

General recommendations
  • Patients with rheumatic diseases undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) are at increased risk for periprosthetic joint infection
  • Appropriate management of antirheumatic medication in the perioperative period may provide an important opportunity to mitigate risk.
  • Nonbiologic disease-modifying antirheumatic drugs may be continued throughout the perioperative period in patients with rheumatic diseases who are undergoing elective THA and TKA.
  • Biologic medications should be withheld as close to 1 dosing cycle as scheduling permits prior to elective THA and TKA and restarted after evidence of wound healing, typically 14 days, for all patients with rheumatic diseases.

Studies
Perioperative Timing of Infliximab and the Risk of Serious Infection After Elective Hip and Knee Arthroplasty, Arthritis Care Res (Hoboken) (2017) [PubMed abstract]
  • Design: Retrospective cohort study (N=4288 | length - 12 months)
  • Exposure: Timing of infliximab dosing before elective hip or knee replacement
  • Primary outcome: Association of infliximab stop timing with hospitalized infection within 30 days or prosthetic joint infection (PJI) within 1 year
  • Findings: Administering infliximab within 4 weeks of elective knee or hip arthroplasty was not associated with a higher risk of short- or long-term serious infection compared to withholding infliximab for longer time periods. Glucocorticoid use, especially > 10 mg/day, was associated with an increased infection risk.



Pricing legend
  • $ = 0 - $50
  • $$ = $51 - $100
  • $$$ = $101 - $150
  • $$$$ = > $151
  • Pricing based on one month of therapy at standard dosing in an adult
  • Pricing based on information from GoodRX.com®
  • Pricing may vary by region and availability