Rheumatoid arthritis
Treatment of Early Rheumatoid Arthritis: Concepts in Management

https://doi.org/10.1016/j.semarthrit.2010.10.004Get rights and content

Objectives

The early diagnosis and treatment of rheumatoid arthritis (RA) are important goals for rheumatologists. This article provides a review of the literature describing evolving concepts in the treatment of early RA, studies that evaluate treatment strategies using a predefined target, and methods to identify patients who are at higher risk for progressive joint damage.

Methods

We conducted a PubMed search for randomized trials using the terms “early rheumatoid arthritis” and subsequently “tight control” to compare the outcomes of studies using early intervention with biologics and disease-modifying antirheumatic drugs (DMARDs) in early RA and also to compare outcomes of strategies of treatment using a predefined target.

Results

The study designs and outcomes of clinical trials of DMARDs and biologic agents in early RA are presented. Early, prompt therapy with combination DMARDs or biologics combined with methotrexate leads to improved outcomes for patients with early RA. In studies where treatment was targeted to a specific outcome, such as remission, the target was achieved more often with targeted treatment than when patients received routine care. Patients who are more likely to experience a rapid disease course that is associated with joint destruction can be identified based on clinical and laboratory variables shown to be predictors of rapid progression.

Conclusions

Early assessment and close monitoring of patients with early RA, targeting remission where possible, are important to optimize long-term outcomes. Specific treatment can be selected from among the many proven therapies to obtain the best results for the individual patient.

Section snippets

Methods

We conducted a PubMed search for randomized trials using the terms “early rheumatoid arthritis” and subsequently “tight control.” References were then limited to include only randomized, controlled trials, English language articles, and human studies. Studies investigating the use of infrequently used or investigational agents were also excluded. The reference lists from the identified publications were scanned to identify further relevant studies, and additional trials were included. The

Literature Search

The PubMed search identified 148 records relevant to this review, and this was supplemented with an additional 7 records identified (Fig. 1). Sixty-six publications were excluded at the screening stage: 5 were not randomized, controlled trials; 14 included nonclinical and/or non-RA endpoints; 30 investigated infrequently used agents (azathioprine, gold, hydroxychloroquine, and penicillamine) or investigational agents; and 17 were nondrug interventions. The remaining 82 articles were obtained

Discussion

Studies on the treatment of patients with early RA have provided important information that can help guide the treatment of these patients. From the earliest studies of traditional DMARDs we learned that early initiation of therapy, particularly DMARD therapy, can lead to less radiographic progression later on in the course of the disease. As more clinical trial data accumulated, we learned that combination DMARD therapy was superior to DMARD monotherapy, and that triple DMARD therapy is even

Conclusion

In early RA, early prompt therapy with methotrexate in combination with other DMARDs or biologics leads to improved outcomes, especially when combined with a tight control strategy aimed at achieving remission or, at least, low disease activity; when the target is rapidly achieved, long-term outcomes are improved. It appears that multidrug treatment is more effective than monotherapy, and that intervening as early as possible with effective treatment yields less damage in the long term.

Acknowledgment

The authors thank Janet Manfre of inScience Communications, a Wolters Kluwer business, for editorial assistance in the preparation of this manuscript.

References (57)

  • R. Landewe et al.

    Disconnect between inflammation and joint destruction after treatment with etanercept plus methotrexate: results from the trial of etanercept and methotrexate with radiographic and patient outcomes

    Arthritis Rheum

    (2006)
  • S.M. van der Kooij et al.

    Clinical and radiological efficacy of initial vs delayed treatment with infliximab plus methotrexate in patients with early rheumatoid arthritis

    Ann Rheum Dis

    (2009)
  • M.J. Plant et al.

    Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis

    Arthritis Rheum

    (2000)
  • D.M. van der Heijde et al.

    Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp's method (van der Heijde modification)

    J Rheumatol

    (1995)
  • H.A. Fuchs et al.

    Evidence of significant radiographic damage in rheumatoid arthritis within the first 2 years of disease

    J Rheumatol

    (1989)
  • F.M. McQueen et al.

    Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset

    Ann Rheum Dis

    (1998)
  • V.P. Nell et al.

    Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis

    Rheumatology (Oxford)

    (2004)
  • T. Mottonen et al.

    Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis

    Arthritis Rheum

    (2002)
  • J. van Aken et al.

    Radiological outcome after four years of early versus delayed treatment strategy in patients with recent onset rheumatoid arthritis

    Ann Rheum Dis

    (2004)
  • H. Makinen et al.

    Sustained remission and reduced radiographic progression with combination disease modifying antirheumatic drugs in early rheumatoid arthritis

    J Rheumatol

    (2007)
  • Y.P. Goekoop-Ruiterman 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)
  • S.M. van der Kooij et al.

    Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis

    Ann Rheum Dis

    (2009)
  • S.M. Verstappen et al.

    Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remissionComputer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial)

    Ann Rheum Dis

    (2007)
  • J. Fransen et al.

    Effectiveness of systematic monitoring of rheumatoid arthritis disease activity in daily practice: a multicentre, cluster randomised controlled trial

    Ann Rheum Dis

    (2005)
  • A randomized trial of hydroxychloroquine in early rheumatoid arthritis: the HERA Study

    Am J Med

    (1995)
  • R.B. Landewe et al.

    COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention

    Arthritis Rheum

    (2002)
  • J.R. O'Dell et al.

    Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial

    Arthritis Rheum

    (2002)
  • M. Calguneri et al.

    Combination therapy versus monotherapy for the treatment of patients with rheumatoid arthritis

    Clin Exp Rheumatol

    (1999)
  • Cited by (0)

    Support for this manuscript was provided by Bristol-Myers Squibb Canada Co.

    Dr. Haraoui has served on advisory boards for and received research grants from Abbott Laboratories, Amgen/Wyeth (Pfizer), Bristol-Myers Squibb, Roche, Schering-Plough (Merck), and UCB. Dr. Pope has consulted for or received research grants from Abbott Laboratories, Actelion, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Pfizer, Roche, Schering-Plough, UCB, United Therapeutics, and Wyeth. The agency that helped coordinate the literature search and draft of the article was commissioned by BMS Canada. The content and opinions are purely those of the authors and not of BMS.

    View full text