PSORIASIS AND PSORIATIC ARTHRITIS



























  • Reference [2]
CASPAR Criteria for Diagnosing Psoriatic Arthritis
  • A diagnosis of psoriatic arthritis may be considered in patients with inflammatory articular disease (joint, spine, or entheseal) who score ≥ 3 on the criteria listed below. The presence of inflammatory articular disease has no defining feature and is left to the discretion of the provider. Patient gets one score for each criteria.
Criteria Finding Points
Psoriasis
  • Current psoriasis defined as skin or scalp disease diagnosed by a dermatologist or rheumatologist
2
  • History of psoriasis (patient-reported or health professional diagnosed)
1
  • Family history of psoriasis in a first- or second-degree relative
1
Psoriatic nail dystrophy
  • Presence of psoriatic nail disease (e.g. pitting, onycholysis, hyperkeratosis) on exam
1
Negative rheumatoid factor 1
Dactylitis
  • Current dactylitis with swelling of an entire digit on physical exam
1
  • History of dactylitis as recorded by a rheumatologist
1
Juxtaarticular new bone formation
  • Ill-defined ossification near joint margins (excluding osteophytes) on hand and foot X-rays
1

  • Reactive arthritis typically occurs 2 - 4 weeks after an infection with Shigella, Salmonella, Campylobacter, Chlamydia, or Strep throat
  • Reference [2,4,5,6]
Features of Different Arthritis Syndromes
Finding Psoriatic arthritis Rheumatoid arthritis Lupus Gout Ankylosing spondylitis Reactive arthritis IBD-associated arthritis
Age of onset
Male:Female
30 - 40s
1:1
35 - 50s
1:3
20 - 30s
1:9
30 - 60s
3:1
17 - 30s
3:1
20 - 30s
5:1
30s
2:1
Distal joints
Fingers and toes including DIP
Asymmetric
≤ 4 joints
Fingers and toes, spares DIP
Symmetric
> 4 joints
Hands, wrists, knees
Symmetric
> 4 joints
Great toe, foot, ankle, knees, elbow
Asymmetric
< 4 joints
Lower limbs (30 - 50%)
Asymmetric
< 4 joints
Knees, ankles, hips
Asymmetric
< 4 joints
Hands and knees
Asymmetric
Spine disease Axial joints - 50%
Sacroiliitis - 40%
Uncommon Uncommon Absent 100% Sacroiliitis - 50%
Back pain - 50%
30%
Enthesitis 30 - 50%, Plantar fascia and Achilles's tendon Absent Absent Absent Common Common, Achilles tendon and plantar fascia Uncommon
Dactylitis 40 - 50% Absent Absent Uncommon Uncommon Common Absent
HLA-B27 positive 40 - 50% Not associated Not associated Not associated 90 - 95% 75% 30%
Eye disease Uveitis - 8% Dry eyes - 20% Dry eyes - 15% Absent Uveitis - up to 30% Conjunctivitis (common)
Anterior uveitis - 25%
Uveitis - up to 7%
Other features Psoriasis - 100%
Nail disease - 85%
Positive RF and Anti-CCP Positive ANA
Joint disease is non-erosive
Elevated uric acid Primarily affects the spine and pelvis Preceding infection
Urethritis (common)
Self-limited - 80%
Occurs in 10 - 20% of patients with IBD



Psoriatic arthritis drugs
Biologicals
  • IL-12 / IL-23 inhibitor
    • Ustekinumab (Stelara®)

  • IL-17 inhibitors
    • Ixekizumab (Taltz®)
    • Secukinumab (Cosentyx®)

  • IL-23 inhibitors
    • Guselkumab (Tremfya®)
    • Risankizumab (Skyrizi®)

  • TNF inhibitors
    • Adalimumab (Humira®)
    • Certolizumab (Cimzia®)
    • Etanercept (Enbrel®)
    • Golimumab (Simponi®)
    • Infliximab (Remicade®)

  • T-cell agents
    • Abatacept (Orencia®)
Immunosuppressants
  • Janus kinase inhibitors
    • Tofacitinib (Xeljanz®)
    • Upadacitinib (Rinvoq®)

  • PDE4 inhibitor
    • Apremilast (Otezla®)

  • Dihydrofolate reductase inhibitors
    • Methotrexate (Trexall®, etc.)

  • Aminosalicylates
    • Sulfasalazine (Azulfidine®)

  • Calcineurin inhibitors
    • Cyclosporine (Neoral®)

  • Other
    • Leflunomide (Arava®)


  • Reference [10]
2018 ACR/NPF Recommendations for the Treatment of Psoriatic Arthritis
Therapy classes
Oral small molecules
  • Methotrexate
  • Sulfasalazine
  • Cyclosporine
  • Leflunomide
  • Apremilast
TNF inhibitors
  • Etanercept
  • Infliximab
  • Adalimumab
  • Golimumab
  • Certolizumab
IL-12/23 inhibitor
  • Ustekinumab
IL-17 inhibitors
  • Secukinumab
  • Ixekizumab
T-cell agent
  • Abatacept
JAK inhibitor
  • Tofacitinib
  • Upadacitinib (Rinvoq®)

  • Only apremilast is FDA-approved to treat psoriatic arthritis
All patients
  • Weight loss if overweight
  • Exercise
  • Smoking cessation
Treatment-naïve patients
  • TNF inhibitor (first-line)
  • Oral small molecule (second-line)
  • IL-17 inhibitor (third-line)
  • IL-12/23 inhibitor (fourth-line)
TNF inhibitor failure
  • Switch to different TNF inhibitor (first-line)
  • IL-17 inhibitor (second-line)
  • IL-12/23 inhibitor (third-line)
Oral small molecule failure
  • TNF inhibitor (first-line)
  • IL-17 inhibitor (second-line)
  • IL-12/23 inhibitor (third-line)
IL-17 failure
  • TNF inhibitor (first-line)
  • IL-12/23 inhibitor (second-line)
IL-12/23 failure
  • TNF inhibitor (first-line)
  • IL-17 inhibitor (second-line)
TNF inhibitor + MTX failure
  • Switch to different TNF inhibitor + MTX
  • IL-17 inhibitor monotherapy
  • IL-12/23 inhibitor monotherapy

Psoriasis drugs
Biologicals
  • IL-12 / IL-23 inhibitor
    • Ustekinumab (Stelara®)

  • IL-17 inhibitors
    • Brodalumab (Siliq®)
    • Ixekizumab (Taltz®)
    • Secukinumab (Cosentyx®)

  • IL-23 inhibitors
    • Guselkumab (Tremfya®)
    • Risankizumab (Skyrizi®)
    • Tildrakizumab (Ilumya™)

  • TNF inhibitors
    • Adalimumab (Humira®)
    • Certolizumab (Cimzia®)
    • Etanercept (Enbrel®)
    • Infliximab (Remicade®)
Immunosuppressants
  • Calcineurin inhibitors
    • Cyclosporine (Neoral®) oral
    • Tacrolimus (Neoral®) topical
    • Pimecrolimus (Elidel®) topical

  • Dihydrofolate reductase inhibitors
    • Methotrexate (Trexall®, etc.)

  • Janus kinase inhibitor
    • Deucravacitinib (Sotyktu®)

  • PDE4 inhibitor
    • Apremilast (Otezla®)

  • Retinoids
    • Acitretin (Soriatane®) oral
    • Tazarotene (Tazorac®) topical

  • Other topicals
    • Corticosteroids
    • Vitamin D analogs (e.g. calcipotriene)
    • Salicylic acid
    • Coal tar








  • Steroid-sparing agents include vitamin D analogues, topical retinoids, and calcineurin inhibitors
  • Reference [7]
AAD / NPF 2020 Guidelines for Topical Therapy in Psoriasis
Plaque psoriasis
  • Steroids and vitamin D analogues
    • Class 1 - 5 topical steroids twice daily (see topical steroid table) for up to 4 weeks is recommended. Topical steroids for > 12 weeks can be considered if under close supervision of a physician.
    • Use of combination treatments with vitamin D analogues and potent Class II and Class III topical steroids up to 52 weeks is recommended for the treatment of psoriasis
    • The application of morning high potency topical steroids and evening topical vitamin D analogues is an effective treatment regimen
  • Tacrolimus
    • The combination of Tacrolimus 0.1% and 6% salicylic acid for 12 weeks may be considered
  • Tazarotene
    • Topical tazarotene can be used for the treatment of mild to moderate psoriasis. The use of mid-potency or high-potency topical steroid in combination with tazarotene for 8 - 16 weeks is more effective than monotherapy with tazarotene and is recommended for the treatment of mild to moderate psoriasis. The use of topical steroids along with tazarotene is recommended to decrease the duration of treatment as well as increase the length of remission
  • Salicylic acid
    • Topical salicylic acid can be used for 8 - 16 weeks for the treatment of mild to moderate psoriasis
    • The combination of salicylic acid with topical corticosteroids can be used for the treatment of moderate to severe psoriasis (BSA ≤ 20%)
  • Other
    • Non-medicated moisturizers (i.e., creams, ointments, lotions, gels, etc.) can be used with steroids to help reduce itching, desquamation, and total body surface area and prevent quick relapse of psoriasis when topical corticosteroids are discontinued
    • Coal tar preparations are recommended for the treatment of mild to moderate psoriasis
Maintenance therapy regimens
  • Steroid-sparing agent twice daily on weekdays and steroid twice daily on weekends is one regimen that may prevent relapses. Twice weekly treatment of areas that are prone to flares is another approach that may be effective.
  • The long-term use of topical vitamin D analogues (up to 52 weeks) including calcipotriene, calcitriol, tacalcitol, and maxacalcitol is recommended for the treatment of mild to moderate psoriasis. Tacalcitol and maxacalcitol are not available in the U.S.
Scalp psoriasis
  • Class 1 - 7 topical steroids (see topical steroid table) for a minimum of up to 4 weeks is recommended as initial and maintenance treatment of scalp psoriasis
  • Use of calcipotriene foam and calcipotriene plus betamethasone dipropionate gel is recommended for 4 - 12 weeks for the treatment of mild to moderate scalp psoriasis
  • Foams and solutions may be preferred on the scalp because they are less greasy than ointments and creams
Intertriginous (inverse) psoriasis
  • Tacrolimus 0.1% or Pimecrolimus 1% for up to 8 weeks. Long-term use can be considered.
Facial psoriasis
  • Tacrolimus 0.1% for up to 8 weeks
  • Topical tacalcitol ointment or calcipotriene combined with hydrocortisone for 8 weeks can be used for the treatment of facial psoriasis
Nail psoriasis
  • Topical vitamin D analogues combined with betamethasone dipropionate can be used
  • Topical tazarotene can be used for the treatment of nail psoriasis
In combination with systemic therapies
  • Biologics
    • The addition of an ultra-high potency (Class 1) topical corticosteroid to standard dose etanercept for 12 weeks is recommended for the treatment of moderate to severe psoriasis
    • The addition of calcipotriene/betamethasone to standard dose adalimumab for 16 weeks is recommended for the treatment of moderate to severe psoriasis to accelerate clearance of psoriatic plaques
    • All topical steroids can be used in combination with any biologics for the treatment of moderate to severe psoriasis
  • Methotrexate
    • The addition of topical calcipotriene to standard dose methotrexate therapy is recommended for the treatment of moderate to severe psoriasis. It may lead to lower cumulative doses of methotrexate and increased time to relapse following methotrexate discontinuation.
  • Cyclosporine
    • The addition of calcipotriene/betamethasone dipropionate ointment to low dose (2 mg/kg/day) cyclosporine can be used for the treatment of moderate to severe psoriasis
  • Acitretin
    • The addition of calcipotriene to standard dose acitretin is recommended for the treatment of moderate to severe psoriasis.




Biologics for the Treatment of Plaque Psoriasis (PP) and Psoriatic Arthritis (PA)
Drug PP/PA approved Effect (PP: 75% or 90% improvement in PASI | PA: ACR20 response)
TNF inhibitors
Adalimumab (Humira®) PP / PA PP: Placebo - 7%, Adalimumab - 71% (16 weeks) [PMID 17936411]
PP: MTX - 35.5%, Adalimumab - 80% (16 weeks) [PMID 18047523]
PP: Guselkumab - 79%, Adalimumab - 70% (16 weeks) [PMID 26154787]
PP: Risankizumab - 91%, Adalimumab - 72% (16 weeks) [PMID 31280967]

PA: Placebo - 14%, Adalimumab - 58% (12 weeks) [PMID 16200601]
PA: Ixekizumab - 57.9%, Adalimumab - 57.4% (24 weeks) [PMID 27553214]
PA: Tofacitinib - 50%, Adalimumab - 52% (3 months) [PMID 29045212]
PA: Upadacitinib - 71%, Placebo - 36%, Adalimumab - 65% (12 weeks) [PMID 33789011]
Certolizumab (Cimzia®) PP / PA PP: Placebo - 9.9%, Certolizumab - 82% (16 weeks) [PMID 29660421]
PP: Etanercept - 53.3%, Certolizumab - 66.7% (12 weeks) [PMID 29660425]
PA: Placebo - 24.3%, Certolizumab - 58% (12 weeks) [PMID 23942868]
Etanercept (Enbrel®) PP / PA PP: Placebo - 4%, Etanercept - 49% (12 weeks) [PMID 14627786]
PP: Secukinumab - 77.1%, Etanercept - 44% (12 weeks) [PMID 25007392]
PP: Tofacitinib (5 mg) - 39.5%, Tofacitinib (10 mg) - 63.6%, Etanercept - 58.8% (12 weeks) [PMID 26051365]
PP: Ixekizumab - 89.7%, Etanercept - 41.6% (12 weeks) [PMID 26072109]
PP: Infliximab - 72%, Etanercept - 35% (24 weeks) [PMID 27416891]
PP: Tildrakizumab - 61%, Etanercept - 48% (12 weeks) [PMID 28596043]
PP: Certolizumab - 66.7%, Etanercept - 53.3% (12 weeks) [PMID 29660425]
PP: Apremilast - 39.8%, Etanercept - 48.2% (16 weeks) [PMID 27768242]
PA: Placebo - 15%, Etanercept - 59% (12 weeks) [PMID 15248226]
PA: MTX - 50.7%, Etanercept - 60.9%, Etanercept + MTX - 65% (24 weeks) [PMID 30747501]
Golimumab (Simponi®) PA PA: Placebo - 9%, Golimumab - 51% (14 weeks) [PMID 19333944]
Infliximab (Remicade®) PP / PA PP: Placebo - 6%, Infliximab - 88% (10 weeks) [PMID 15389187]
PP: MTX - 42%, Infliximab - 78% (16 weeks) [PMID 21910713]
PP: Etanercept - 35%, Infliximab - 72% (24 weeks) [PMID 27416891]

PA: Placebo - 11%, Infliximab - 58% (14 weeks) [PMID 15677701]
Interleukin-17 inhibitors
Brodalumab (Siliq®) PP PP: Placebo - 3%, Brodalumab - 83% (12 weeks) [PMID 26914406]
Ixekizumab (Taltz®) PP / PA PP: Placebo - 2.4%, Ixekizumab - 89.7% (12 weeks) [PMID 26072109]
PP: Etanercept - 41.6%, Ixekizumab - 89.7% (12 weeks) [PMID 26072109]
PP: Ustekinumab - 59%, Ixekizumab - 76.5% (52 weeks) [PMID 29969700]
PA: Placebo - 30.2%, Ixekizumab - 57.9% (24 weeks) [PMID 27553214]
PA: Adalimumab - 57.4%, Ixekizumab - 57.9% (24 weeks) [PMID 27553214]
Secukinumab (Cosentyx®) PP / PA PP: Placebo - 4.5%, Secukinumab - 81.6% (12 weeks) [PMID 25007392]
PP: Etanercept - 44%, Secukinumab - 77.1% (12 weeks) [PMID 25007392]
PP: Ustekinumab - 57.6%, Secukinumab - 79% (16 weeks) [PMID 26092291]
PP: Guselkumab - 84%, Secukinumab - 70% (48 weeks) [PMID 31402114]
PA: Placebo - 15%, Secukinumab - 54% (24 weeks) [PMID 26135703]
PA: Adalimumab - 62%, Secukinumab - 67% (52 weeks) [PMID 32386593]
Interleukin-23 inhibitors
Guselkumab (Tremfya®) PP / PA PP: Placebo - 5%, Guselkumab - 79% (16 weeks) [PMID 26154787]
PP: Adalimumab - 70%, Guselkumab - 79% (16 weeks) [PMID 26154787]
PP: Secukinumab - 70%, Guselkumab - 84% (48 weeks) [PMID 31402114]
PA: Placebo - 18%, Guselkumab - 58% (24 weeks) [PMID 29893222]
Risankizumab (Skyrizi®) PP / PA PP: Placebo - 4.9%, Risankizumab - 75% (16 weeks) [PMID 30097359]
PP: Ustekinumab - 42%, Risankizumab - 75% (16 weeks) [PMID 30097359]
PP: Adalimumab - 72%, Risankizumab - 91% (16 weeks) [PMID 31280967]

PA: Placebo - 34%, Risankizumab - 57% (24 weeks) [PMID 34911706]
Tildrakizumab (Ilumya®) PP PP: Placebo - 6%, Tildrakizumab - 61% (12 weeks) [PMID 28596043]
PP: Etanercept - 48%, Tildrakizumab - 61% (12 weeks) [PMID 28596043]
Interleukin-12/23 inhibitor
Ustekinumab (Stelara®) PP / PA PP: Placebo - 4.9%, Ustekinumab - 42% (16 weeks) [PMID 30097359]
PP: Risankizumab - 75%, Ustekinumab - 42% (16 weeks) [PMID 30097359]
PP: Ixekizumab - 76.5%, Ustekinumab - 59% (52 weeks) [PMID 29969700]
PP: Secukinumab - 79%, Ustekinumab - 57.6% (16 weeks) [PMID 26092291]
PA: Placebo - 14%, Ustekinumab - 42% (12 weeks) [PMID 19217154]
T-cell agent
Abatacept (Orencia®) PA PA: Placebo - 22.3%, Abatacept - 39.4% (24 weeks) [PMID 28473423]




  • Reference [9,10]
Nonbiologic Systemic Therapies for Psoriasis
FDA-approved therapies
Methotrexate (MTX)
  • MTX is FDA-approved for the treatment of psoriasis
  • The ACR/NPF guidelines list MTX as a possible treatment for psoriatic arthritis
  • MTX has a cheap generic
  • Dosing
  • Efficacy (PASI 75% for PP | ACR20 for PA)
    • PP: Adalimumab - 80%, MTX - 35.5% (16 weeks) [PMID 18047523]
    • PP: Infliximab - 78%, MTX - 42% (16 weeks) [PMID 21910713]
    • PA: Etanercept - 60.9%, MTX - 50.7%, Etanercept + MTX - 65% (24 weeks) [PMID 30747501]
  • Contraindications / Precautions / Drug interactions
    • Patients with psoriasis are more susceptible to liver toxicity from methotrexate, and monitoring recommendations differ from other indications
    • See methotrexate
  • Side effects
Apremilast (Otezla®)
  • Apremilast is FDA-approved for the treatment of psoriasis and psoriatic arthritis
  • Apremilst is an oral small-molecule inhibitor of phosphodiesterase 4
  • Apremilast has no generic, and it is very expensive
  • Dosing
  • Efficacy (PASI 75% for PP | ACR20 for PA)
    • PP: Placebo - 6%, Apremilast - 41% (16 weeks) [PMID 22748702]
    • PP: Etanercept - 48.2%, Apremilast - 39.8% (16 weeks) [PMID 27768242]
    • PA: Placebo - 19%, Apremilast - 40% (16 weeks) [PMID 24595547]
  • Contraindications / Precautions / Drug interactions
  • Side effects
Cyclosporine (Neoral®, Sandimmune®)
  • Cyclosporine is FDA-approved for the treatment of psoriasis
  • The ACR/NPF guidelines list cyclosporine as a possible treatment for psoriatic arthritis
  • Cyclosporine has many side effects and is only recommended in severe, recalcitrant psoriasis
  • Cyclosporine has a generic
  • Dosing
  • Efficacy (PASI 75%)
    • A systematic review found that cyclosporine doses of 5 mg/kg produced PASI 75 responses in 50 - 97% of patients and doses of 2.5 mg/kg produced a response in 28 - 85% [PMID 21388455]
  • Contraindications / Precautions / Drug interactions
  • Side effects
Tofacitinib (Xeljanz®)
  • Tofacitinib is FDA-approved for the treatment of psoriatic arthritis
  • Tofacitinib is a janus kinase (JAK) inhibitor
  • Tofacitinib does not have a generic and is expensive
  • Dosing
  • Efficacy (PASI 75% for PP | ACR20 for PA)
    • PA: Adalimumab - 52%, Placebo - 33%, Tofacitinib (5 mg) - 50%, Tofacitinib (10 mg) - 61% (3 months) [PMID 29045212]
    • PP: Etanercept - 58.8%, Placebo 5.6%, Tofacitinib (5 mg) - 39.5%, Tofacitinib (10 mg) - 63.6% (12 weeks) [PMID 26051365]
  • Contraindications / Precautions / Drug interactions
  • Side effects
Upatacitinib (Rinvoq®)
  • Upadacitinib is FDA-approved for the treatment of psoriatic arthritis
  • Upadacitinib is a janus kinase (JAK) inhibitor
  • Upadacitinib does not have a generic and is expensive
Acitretin (Soriatane®)
  • Acitretin is FDA-approved for the treatment of psoriasis
  • Acitretin is a retinoid much like the drug isotretinoin (Accutane®) that is used to treat acne
  • Acitretin has a generic, but is still somewhat expensive (> $200/month)
  • Dosing
    • 10 - 50 mg once daily
  • Efficacy (PASI 75%)
    • PP: Acitretin 25 mg/day - 47%, Acitretin 35 mg/day - 69%, Acitretin 50 mg/day - 53% (12 weeks) [PMID 22816881]
  • Contraindications / Precautions / Drug interactions
  • Side effects
    • Like isotretinoin, acitretin can have a significant drying effect
    • See Soriatane PI
Non-FDA approved therapies
Dimethyl fumarate
  • The AAD/NPF guidelines list dimethyl fumarate as a possible treatment for psoriasis
  • Dimethyl fumarate activates the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. Nrf2 activation leads to a reduction in the release of inflammatory cytokines, and it also has antioxidant effects.
  • Dimethyl fumarate is FDA-approved to treat multiple sclerosis but not psoriasis
  • Patients with multiple sclerosis and psoriasis may want to try dimethyl fumarate to treat both
  • Dimethyl fumarate has a generic but is still very expensive
Azathioprine
  • The AAD/NPF guidelines list azathioprine as a possible treatment for psoriasis. They recommend a starting dose of 0.5 mg/kg and state that the usual dose in psoriasis is 75 - 150 mg/day.
  • Azathioprine inhibits ribonucleotide synthesis which either directly or indirectly leads to T-cell suppression
  • Azathioprine has a generic and is cheap
Leflunomide
  • The AAD/NPF guidelines list leflunomide as a possible treatment for psoriasis, and the ACR/NPF guidelines list it as a possible treatment for psoriatic arthritis
  • Leflunomide is an isoxazole immunomodulatory agent which inhibits dihydroorotate dehydrogenase, an enzyme involved in de novo pyrimidine synthesis
  • Leflunomide was compared to placebo for the treatment of psoriasis and psoriatic arthritis in this trial - PMID 15188371
  • Leflunomide has a generic and is cheap
Sulfasalazine
  • The ACR/NPF guidelines list sulfasalazine as a possible treatment for psoriatic arthritis
  • Sulfasalazine was compared to placebo for the treatment of psoriatic arthritis in these trials - PMID 8670601, PMID 8587078, PMID 8961906
  • Sulfasalazine has a generic and is cheap
Hydroxyurea
  • The AAD/NPF guidelines list hydroxyurea as a possible treatment for psoriasis
  • Hydroxyurea is an antineoplastic agent that inhibits ribonucleotide reductase. Hydroxyurea is primarily used to treat sickle cell disease.
  • The AAD/NPF recommend an initial dose of 500 mg twice daily with titration to 1500 mg/day as tolerated
  • Hydroxyurea has a generic and is cheap