Abstract
Abbreviations and Acronyms:
ACPA (anti–citrullinated protein antibody), ACR (American College of Rheumatology), BeSt (Behandel-Strategieën [trial]), CDAI (Clinical Disease Activity Index), CRP (C-reactive protein), CTLA-4:Ig (cytotoxic T lymphocyte–associated antigen 4:immunoglobulin fusion protein), DAS28 (Disease Activity Score in 28 joints), DMARD (disease-modifying antirheumatic drug), EULAR (European League Against Rheumatism), HCQ (hydroxychloroquine), MTX (methotrexate), SDAI (Simplified Disease Activity Index), SSZ (sulfasalazine), TEAR (Treatment of Early Aggressive Rheumatoid Arthritis [study]), TNF (tumor necrosis factor)Treatment Principles
Goals of Therapy
Early Referral and Diagnosis
Variable | Score |
---|---|
Target population: Who should be tested? | |
Patients who have at least 1 joint with definite clinical synovitis (swelling) b The criteria are for classification of new patients. In addition, patients with erosive disease typical of RA with a history compatible with fulfillment of the 2010 criteria should be classified as having RA. Patients with long-standing disease including those with inactive disease (with or without treatment) who, on the basis of retrospectively available data, have previously fulfilled the 2010 criteria should be classified as having RA. | |
Patients with synovitis not better accounted for by another disease | |
Classification criteria for RA (score-based algorithm: add score of categories A-D. A score ≥6/10 is needed for definite classification) | |
A) Joint involvement e Joint involvement refers to any swollen or tender joint on examination, which may be confirmed by imaging evidence of synovitis. Distal interphalangeal joints, first carpometacarpal joints, and first metatarsophalangeal joints are excluded from assessment. Categories of joint distribution are classified according to location and number of involved joints, with placement in the highest category possible on the basis of pattern of joint involvement. | |
1 large joint | 0 |
2-10 large joints | 1 |
1-3 small joints (with or without involvement of large joints) | 2 |
4-10 small joints (with or without involvement of large joints) | 3 |
>10 joints, including at least 1 small joint | 5 |
B) Serologic findings (at least one test result is needed for classification) i Negative refers to international unit values that are less than or equal to ULN for the laboratory and assay; low positive refers to international unit values that are higher than ULN but 3 times ULN or less for the laboratory and assay; high positive refers to international unit values that are more than 3 times ULN for the laboratory and assay. When RF information is available only as positive or negative, a positive result should be scored as low positive for RF. | |
Negative RF and negative ACPA | 0 |
Low positive RF or low positive ACPA | 2 |
High positive RF or high positive ACPA | 3 |
C) Acute phase reactants (at least one test result is needed for classification) | |
Normal CRP and normal ESR | 0 |
Abnormal CRP or abnormal ESR | 1 |
D) Duration of symptoms (wk) | |
<6 | 0 |
≥6 | 1 |
- Narváez J.
- Sirvent E.
- Narváez J.A.
- et al.
- Szkudlarek M.
- Klarlund M.
- Narvestad E.
- et al.
Assessment of Disease Activity
- Crowson C.S.
- Rahman M.U.
- Matteson E.L.
- Haavardsholm E.A.
- Østergaard M.
- Hammer H.B.
- et al.
- Schipper L.G.
- Vermeer M.
- Kuper H.H.
- et al.
- Wells G.
- Becker J.C.
- Teng J.
- et al.
- Haavardsholm E.A.
- Østergaard M.
- Hammer H.B.
- et al.
Formulas for calculation of recommended composite measures | ||||
SDAI = TJC + SJC + PGA + EGA + CRP | ||||
CDAI = TJC + SJC + PGA + EGA | ||||
Disease activity cutoffs | ||||
---|---|---|---|---|
Absolute disease activity level | ||||
Index | Remission | Low | Moderate | High |
SDAI | ≤3.3 | ≤11 | ≤26 | >26 |
CDAI | ≤2.8 | ≤10 | ≤22 | >22 |
Treat-to-Target Principle
- Verstappen S.M.
- Jacobs J.W.
- van der Veen M.J.
- et al.
Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial).
- Schipper L.G.
- Vermeer M.
- Kuper H.H.
- et al.
- Smolen J.S.
- Han C.
- van der Heijde D.M.
- et al.
Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade [published correction appears in Ann Rheum Dis. 2011;70(8):1519].
- Smolen J.S.
- Han C.
- van der Heijde D.M.
- et al.
Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade [published correction appears in Ann Rheum Dis. 2011;70(8):1519].
Assessment of Disease Severity and Prognosis
- Saevarsdottir S.
- Wedrén S.
- Seddighzadeh M.
- et al.
Nonpharmacologic Principles
Treatment Approach
Initial Treatment Approach
- Visser K.
- Katchamart W.
- Loza E.
- et al.

- Breedveld F.C.
- Weisman M.H.
- Kavanaugh A.F.
- et al.
- St Clair E.W.
- van der Heijde D.M.
- Smolen J.S.
- et al.
Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial.
- Svensson B.
- Boonen A.
- Albertsson K.
- van der Heijde D.
- Keller C.
- Hafström I.
Critical Time Point
- Breedveld F.C.
- Weisman M.H.
- Kavanaugh A.F.
- et al.
- St Clair E.W.
- van der Heijde D.M.
- Smolen J.S.
- et al.
Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial.
- Klareskog L.
- van der Heijde D.
- de Jager J.P.
- et al.
Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial.
Six to 12 Months of Disease
- Rantalaiho V.
- Korpela M.
- Laasonen L.
- et al.
Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial.
- Schiff M.
- Keiserman M.
- Codding C.
- et al.

- Smolen J.S.
- Kay J.
- Doyle M.K.
- et al.
Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial [published correction appears in Lancet. 2009;374(9699):1422].
- Emery P.
- Fleischmann R.
- Filipowicz-Sosnowska A.
- et al.
The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial.
- Cohen S.B.
- Emery P.
- Greenwald M.W.
- et al.
Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks.
- Emery P.
- Keystone E.
- Tony H.P.
- et al.
Beyond the First 6 to 12 Months of Disease

- Grossman J.M.
- Gordon R.
- Ranganath V.K.
- et al.
Potential Pitfalls and Alternative Approaches
- Hetland M.L.
- Stengaard-Pedersen K.
- Junker P.
- et al.
Radiographic progression and remission rates in early rheumatoid arthritis: MRI bone oedema and anti-CCP predicted radiographic progression in the 5-year extension of the double-blind randomised CIMESTRA trial.
Recommendations
Supplemental Online Material
- Supplemental Table
- Video 1
Author Interview Video
References
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Article Info
Footnotes
Potential Competing Interests: Dr Davis is an investigator on studies with Centocor Inc, Malvern, PA; VA Cooperative Studies Program, US Department of Veterans Affairs, Washington, DC; Genentech, Inc, South San Francisco, CA; Novartis Corp, East Hanover, NJ; Rheumatoid Arthritis Investigational Network/University of Nebraska Medical Center, Omaha; and UCB Pharma, Inc, Smyrna, GA. He has received grant support or contracts from the Arthritis Foundation , Indianapolis, IN; Centocor ; Genentech ; Mayo Foundation , Rochester, MN; Myriad RBM, Inc , Austin, TX; National Center for Research Resources and National Institutes of Arthritis and Musculoskeletal and Skin Diseases , National Institutes of Health , Bethesda, MD; Novartis Corp ; UCB Pharma, Inc ; and University of Nebraska Medical Center Cooperative Studies Program .
Dr Matteson is an investigator on studies with the American College of Rheumatology, Atlanta, GA; Amgen Inc, Thousand Oaks, CA; Ardea Biosciences, San Diego, CA; AstraZeneca, London, UK; Biogen Idec, Weston, MA; Centocor Inc, Malvern, PA; Eli Lily and Co, Indianapolis, IN; Genentech, Inc, South San Francisco, CA; Hoffman-LaRoche Inc, Nutley, NJ; Human Genome Sciences, Inc, Rockville, MD; Janssen Biotech, Inc, Horsham, PA; Pfizer Inc, New York, NY; Novartis Corp, East Hanover, NJ; Roche, Indianapolis, IN; Schering-Plough/Merck & Co, Inc, Whitehouse Station, NJ; and UCB Group; UCB, Inc, Atlanta, GA. He has received grant support or contracts from Amgen , Bristol-Myers Squibb , New York, NY; Centocor/Johnson & Johnson ; Genentech ; Mayo Foundation , Rochester, MN; Novartis ; National Institutes of Health , Bethesda, MD; and Veteran's Administration, US Department of Veterans Affairs , Washington, DC. He participates as consultant/scientific advisory board member for Abbott Laboratories, Abbott Park, IL; Amgen, Biogen Idec; Centocor; Crescendo Bioscience, South San Francisco, CA; West Lafayette, IN; Horizon Pharma USA, Inc, Deerfield, IL; and Novartis.