Initial treatment of mildly active rheumatoid arthritis in adults
- Peter H Schur, MD
Peter H Schur, MD
- Editor-in-Chief — Rheumatology
- Section Editor — Basic Science
- Professor of Medicine
- Harvard Medical School
- Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
- Section Editor — Rheumatoid Arthritis
- Emeritus Professor of Rheumatology, Imperial College London
- Visiting Professor, Oxford University
- Stanley Cohen, MD
Stanley Cohen, MD
- Clinical Professor of Medicine
- University of Texas Southwestern Medical School
The treatment of rheumatoid arthritis (RA) is directed toward the control of synovitis and the prevention of joint damage. Joint damage, which may ultimately result in disability, begins early in the course of disease, and patients are less likely to completely respond to therapy the longer active disease persists . Improved outcomes have resulted from the availability and use of potent and well-tolerated disease-modifying antirheumatic drugs (DMARDs) used alone and in combination to aggressively induce and maintain tight control of disease [2-10]. These DMARDs can control synovitis and slow, or even stop, radiographic progression [2,9,11,12]. (See "Clinical manifestations of rheumatoid arthritis" and "Pathogenesis of rheumatoid arthritis" and "General principles of management of rheumatoid arthritis in adults", section on 'Tight control'.)
These observations regarding the course of disease and the efficacy of newer therapeutic approaches, coupled with limits in the ability to accurately identify individuals with a poor prognosis, support our view that every patient with established active RA should be treated with DMARDs at the earliest stage of disease, ideally within less than three months of symptom onset. (See "General principles of management of rheumatoid arthritis in adults", section on 'Prognosis' and "General principles of management of rheumatoid arthritis in adults", section on 'Early use of DMARDs'.)
The choice of therapeutic agents, including both antiinflammatories and DMARDs, is influenced by the degree of disease activity, the risk of a particular medication for a given patient, and patient preferences. The initial treatment of patients with mildly active RA will be reviewed here. The diagnosis and differential diagnosis of RA, the general principles of management, an overview of the therapy of RA, the initial treatment of moderately to severely active RA, and the treatment of disease resistant to initial therapy are presented separately. (See "Diagnosis and differential diagnosis of rheumatoid arthritis" and "General principles of management of rheumatoid arthritis in adults" and "Initial treatment of moderately to severely active rheumatoid arthritis in adults" and "Treatment of rheumatoid arthritis resistant to initial DMARD therapy in adults".)
DEFINITION OF MILDLY ACTIVE RA
Patients with mildly active rheumatoid arthritis (RA) typically meet American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for RA and have all of the following (see "Diagnosis and differential diagnosis of rheumatoid arthritis"):
●Fewer than five inflamed joints
- Anderson JJ, Wells G, Verhoeven AC, Felson DT. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum 2000; 43:22.
- Schoels M, Knevel R, Aletaha D, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search. Ann Rheum Dis 2010; 69:638.
- Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 2005; 52:3381.
- Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med 2007; 146:406.
- de Vries-Bouwstra JK, Goekoop-Ruiterman YP, Verpoort KN, et al. Progression of joint damage in early rheumatoid arthritis: association with HLA-DRB1, rheumatoid factor, and anti-citrullinated protein antibodies in relation to different treatment strategies. Arthritis Rheum 2008; 58:1293.
- Möttönen T, Hannonen P, Leirisalo-Repo M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet 1999; 353:1568.
- Puolakka K, Kautiainen H, Möttönen T, et al. Impact of initial aggressive drug treatment with a combination of disease-modifying antirheumatic drugs on the development of work disability in early rheumatoid arthritis: a five-year randomized followup trial. Arthritis Rheum 2004; 50:55.
- Rantalaiho V, Korpela M, Hannonen P, et al. The good initial response to therapy with a combination of traditional disease-modifying antirheumatic drugs is sustained over time: the eleven-year results of the Finnish rheumatoid arthritis combination therapy trial. Arthritis Rheum 2009; 60:1222.
- Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 2004; 364:263.
- Verstappen SM, Jacobs JW, van der Veen MJ, 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). Ann Rheum Dis 2007; 66:1443.
- Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet 2001; 358:903.
- Sokka T, Kautiainen H, Häkkinen A, Hannonen P. Radiographic progression is getting milder in patients with early rheumatoid arthritis. Results of 3 cohorts over 5 years. J Rheumatol 2004; 31:1073.
- Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008; 59:762.
- Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010; 69:964.
- Huizinga TW, Pincus T. In the clinic. Rheumatoid arthritis. Ann Intern Med 2010; 153:ITC1.
- Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012; 64:625.
- Davis MJ, Dawes PT, Fowler PD, et al. Should disease-modifying agents be used in mild rheumatoid arthritis? Br J Rheumatol 1991; 30:451.
- Wasko MC, Hubert HB, Lingala VB, et al. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA 2007; 298:187.
- Tam LS, Gladman DD, Hallett DC, et al. Effect of antimalarial agents on the fasting lipid profile in systemic lupus erythematosus. J Rheumatol 2000; 27:2142.
- Clark P, Casas E, Tugwell P, et al. Hydroxychloroquine compared with placebo in rheumatoid arthritis. A randomized controlled trial. Ann Intern Med 1993; 119:1067.
- A randomized trial of hydroxychloroquine in early rheumatoid arthritis: the HERA Study. Am J Med 1995; 98:156.
- Das SK, Pareek A, Mathur DS, et al. Efficacy and safety of hydroxychloroquine sulphate in rheumatoid arthritis: a randomized, double-blind, placebo controlled clinical trial--an Indian experience. Curr Med Res Opin 2007; 23:2227.
- Suarez-Almazor ME, Belseck E, Shea B, et al. Antimalarials for treating rheumatoid arthritis. Cochrane Database Syst Rev 2000; :CD000959.
- American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum 2002; 46:328.
- van der Heijde DM, van Riel PL, Nuver-Zwart IH, et al. Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet 1989; 1:1036.
- Weinblatt ME, Reda D, Henderson W, et al. Sulfasalazine treatment for rheumatoid arthritis: a metaanalysis of 15 randomized trials. J Rheumatol 1999; 26:2123.
- Pullar T, Hunter JA, Capell HA. Effect of sulphasalazine on the radiological progression of rheumatoid arthritis. Ann Rheum Dis 1987; 46:398.
- van der Heijde DM, van Riel PL, Nuver-Zwart IH, van de Putte LB. Sulphasalazine versus hydroxychloroquine in rheumatoid arthritis: 3-year follow-up. Lancet 1990; 335:539.
- Dougados M. Sulfasalazine. In: Therapy of Systemic Rheumatic Disorders, van de Putte LBA, Furst DE, Williams HJ, van Riel PLCM (Eds), Marcel Dekker, New York 1998. p.165.
- Box SA, Pullar T. Sulphasalazine in the treatment of rheumatoid arthritis. Br J Rheumatol 1997; 36:382.
- O'Dell JR, Haire CE, Palmer W, et al. Treatment of early rheumatoid arthritis with minocycline or placebo: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 1997; 40:842.
- Kloppenburg M, Breedveld FC, Terwiel JP, et al. Minocycline in active rheumatoid arthritis. A double-blind, placebo-controlled trial. Arthritis Rheum 1994; 37:629.
- Tilley BC, Alarcón GS, Heyse SP, et al. Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group. Ann Intern Med 1995; 122:81.
- O'Dell JR, Paulsen G, Haire CE, et al. Treatment of early seropositive rheumatoid arthritis with minocycline: four-year followup of a double-blind, placebo-controlled trial. Arthritis Rheum 1999; 42:1691.
- O'Dell JR, Blakely KW, Mallek JA, et al. Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine. Arthritis Rheum 2001; 44:2235.
- Corkill MM, Kirkham BW, Chikanza IC, et al. Intramuscular depot methylprednisolone induction of chrysotherapy in rheumatoid arthritis: a 24-week randomized controlled trial. Br J Rheumatol 1990; 29:274.
- Jain R, Lipsky PE. Treatment of rheumatoid arthritis. Med Clin North Am 1997; 81:57.
- Guidelines for monitoring drug therapy in rheumatoid arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum 1996; 39:723.
- DEFINITION OF MILDLY ACTIVE RA
- GENERAL PRINCIPLES
- NONPHARMACOLOGIC AND PREVENTIVE THERAPIES
- PHARMACOLOGIC THERAPY
- Use of DMARDs
- - Patients who lack poor prognostic features
- - Patients with mild activity and poor prognostic signs
- - Other therapies
- - Patients resistant to initial DMARD therapy
- Symptomatic treatment
- - Antiinflammatory agents
- Initial symptomatic therapy
- Inadequate response to NSAIDs
- - Analgesics
- MONITORING AND REEVALUATION
- DRUG THERAPY FOR FLARES
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS