RHEUMATOID ARTHRITIS (RA)





















ACR 2010 Rheumatoid Arthritis Diagnostic Criteria
RA diagnosis is made if score ≥ 6 based on the following 4 criteria (Patient receives one score for each criteria)
Joint involvement
  • Joint must be swollen or tender. May be confirmed on imaging.
  • Joints excluded from assessment - DIP joints, 1st carpometacarpal joints (involved in OA), and 1st metatarsophalangeal joints (involved in gout)
Finding Score
1 large joint
  • Large joint - shoulders, elbows, hips, knees, and ankles
0
2 - 10 large joints 1
1 - 3 small joints
  • Small joint - metacarpophalangeal joints, PIP joints, 2nd through 5th metatarsophalangeal joints, thumb interphalangeal joints, and wrists
2
4 - 10 small joints 3
> 10 joints with at least 1 small joint
  • may also include TMJ, AC joint, etc.
5
Serology
  • Either RF or ACPA (Anti-CCP antibodies) is needed for classification
  • Low positive - low-positive refers to IU values that are higher than the upper limits of normal (ULN) but ≤ 3 times the ULN for the laboratory and assay
  • High positive - refers to IU values that are > 3 times the ULN for the laboratory and assay
  • Where rheumatoid factor (RF) information is only available as positive or negative, a positive result should be scored as low-positive for RF
Finding Score
Negative RF and negative ACPA 0
Low-positive RF or low-positive ACPA 2
High-positive RF or high-positive ACPA 3
Acute-phase Reactants
Finding Score
Normal CRP and normal ESR 0
Abnormal CRP or abnormal ESR 1
Duration of symptoms
  • Refers to patient self-report of the duration of signs or symptoms of synovitis (e.g., pain, swelling, tenderness) of joints that are clinically involved at the time of assessment, regardless of treatment status
Finding Score
< 6 weeks 0
≥ 6 weeks 1







  • Reference [24]
DMARD Classes
Conventional synthetic DMARDs (csDMARDs)
  • Methotrexate (Trexall®)
  • Leflunomide (Arava®)
  • Sulfasalazine (Azulfidine®)
  • Hydroxychloroquine (Plaquenil®)
Biologic DMARDs (bDMARDs)
  • Tumor Necrosis Factor inhibitors - adalimumab (Humira®), certolizumab (Cimzia®), etanercept (Enbrel®), golimumab (Simponi®), infliximab (Remicade®)
  • T-cell agents - abatacept (Orencia®)
  • Interleukin-6 inhibitors - tocilizumab (Actemra®), sarilumab (Kevzara®)
  • B-cell agents - rituximab (Rituxan®)
Targeted synthetic DMARDs (tsDMARDs)
  • Tofacitinib (Xeljanz®)
  • Baricitinib (Olumiant®)


  • Reference [25]
EULAR 2016 Recommendations for the treatment of RA
Phase I - Initial therapy
  • First-line: Methotrexate + short-term corticosteroids
    • Methotrexate should be rapidly escalated to a target dose of 25 mg/week. Asian patients may need lower doses (15 - 20 mg/week). Folic acid (at least 5 mg/week) should be taken with methotrexate.
    • Oral corticosteroids may be started at a dose of up to 30 mg/day and tapered as rapidly as tolerated over the course of 3 months. Courses up to 6 months may be used, but only in exceptional cases. Other options for steroids include methylprednisolone 120 mg IM one-time dose or methylprednisolone 250 mg IV one-time dose.
  • Second-line (methotrexate contraindicated): leflunomide or sulfasalazine + short-term corticosteroids
    • Leflunomide should be dosed at 20 mg/day without a loading dose
    • Sulfasalazine should be escalated to 3 grams/day
    • Oral corticosteroids may be started at a dose of up to 30 mg/day and tapered as rapidly as tolerated over the course of 3 months. Courses up to 6 months may be used, but only in exceptional cases. Other options for steroids include methylprednisolone 120 mg IM one-time dose or methylprednisolone 250 mg IV one-time dose.

  • If there is no improvement after 3 months, or target is not achieved at 6 months, then Phase II
Phase II - Adjust therapy for non/incomplete responders
  • Prognostically unfavorable factors present: add a bDMARD or tsDMARD
    • Prognostically unfavorable factors - high levels of RF or ACPA; very high disease activity; early joint damage; failure of 2 csDMARDs
    • bDMARD (Biologic agents)
      • Tumor Necrosis Factor inhibitors - adalimumab, certolizumab, etanercept, golimumab, infliximab
      • T-cell agents - abatacept
      • Interleukin-6 inhibitors - tocilizumab, sarilumab
      • B-cell agents - rituximab
    • tsDMARD (JAK-inhibitors)
      • Tofacitinib (Xeljanz®)
      • Baricitinib (Olumiant®)
    • For patients who cannot take a concomitant csDMARD, IL-6 inhibitors and tsDMARDs have some advantages
  • Prognostically unfavorable factors NOT present: change to or add second csDMARD
    • Leflunomide, sulfasalazine, methotrexate alone or in combination
    • Ideally, concomitant short-term corticosteroids should also be used as in Phase I
    • If there is no improvement after 3 months, or target is not achieved at 6 months, then add bDMARD or tsDMARD as above

  • If there is no improvement after 3 months, or target is not achieved at 6 months, then Phase III
Phase III - Adjust therapy for non/incomplete responders to Phase II
  • Change bDMARD or use tsDMARD
    • Replace any first bDMARD with any other bDMARD or change to tsDMARD
    • TNF inhibitors may be replaced with another TNF inhibitor
    • Continue csDMARD


  • Response defined as 70% improvement in the DAS28 score
  • *Response rate for switching from one TNF inhibitor to another or from TNF inhibitor to other bDMARD class
  • Reference [24]
Response rates for RA therapies
Treatment Response rate (% of treated patients)
Methotrexate (MTX) 20 - 40%
Leflunomide (Arava®) 10%
Sulfasalazine (Azulfidine®) 8% at 2g/daily
Hydroxychloroquine (Plaquenil®) N/A
bDMARDs MTX-insufficient responders: 20 - 22%
*TNF inhibitor-insufficient responders: 10 - 12%
tsDMARDs MTX-insufficient responders: 20 - 24%
TNF inhibitor-insufficient responders: 14 - 17%

Reference [24]
Condition Treatment recommendation
Tuberculosis (TB) Before starting biologic or tofacitinib therapy:
  • Screen all patients for TB
  • Latent TB - treat TB for at least 1 month before starting therapy
  • Active TB - patients should complete TB treatment before starting therapy
Congestive Heart Failure
  • Use csDMARDs or non-TNF biologic or tofacitinib over TNF inhibitors
  • If CHF worsens on TNF inhibitor, switch to one of these other therapies
Hepatitis B
  • Untreated patients should be referred for treatment before starting immunosuppressive therapy
  • If patient is receiving or has received effective treatment, then recommendations are the same as those in patients without Hepatitis B
Hepatitis C
  • If patient is receiving or has received effective treatment, then recommendations are the same as those in patients without Hepatitis C
  • In patients who have not been treated effectively, use csDMARDs over TNF inhibitors
Melanoma
(current or past)
  • Use csDMARDs over biologicals or tofacitinib
Non-melanoma skin cancer
(current or past)
  • Use csDMARDs over biologicals or tofacitinib
Lymphoproliferative disorder
(previously-treated)
  • Rituximab is preferred over TNF inhibitors
  • Use csDMARDs or abatacept or tocilizumab over TNF inhibitors
Solid organ tumor
(previously-treated)
  • Recommendations are the same as those in patients without a history of solid organ tumor
Previous serious infection
  • Use csDMARDs over TNF inhibitors
  • Use abatacept over TNF inhibitors



Component Measurement
Number of tender joints 28 joints are measured
(10 MCP joints; 10 PIP joints; 2 wrists, 2 elbow; 2 shoulder; 2 knee)
Number of swollen joints 28 joints are measured
(10 MCP joints; 10 PIP joints; 2 wrists, 2 elbow; 2 shoulder; 2 knee)
ESR or C-reactive protein Either one can be used
Global assessment of health Patients makes a mark on a 10 cm line
with 1 being "very bad" and 10 being "very good"

DAS28 score Disease activity
< 2.6 Remission
2.6 - 3.2 Low disease activity
3.2 - 5.1 Moderate disease activity
> 5.1 High disease activity