Unmet needs in rheumatoid arthritis

Abstract

Until the pathophysiology/etiology of rheumatoid arthritis (RA) is better understood, treatment strategies must focus on disease management. Early diagnosis and treatment with disease-modifying antirheumatic drugs (DMARDs) are necessary to reduce early joint damage, functional loss, and mortality. Several clinical trials have now clearly shown that administering appropriate DMARDs early yields better therapeutic outcomes. However, RA is a heterogeneous disease in which responses to treatment vary considerably for any given patient. Thus, choosing which patients receive combination DMARDs, and which combinations, remains one of our major challenges in treating RA patients. In many well controlled clinical trials methotrexate and other DMARDs, including the tumor necrosis factor-alpha inhibitors, have shown considerable efficacy in controlling the inflammatory process, but many patients continue to have active disease. Optimizing clinical response requires the use of a full spectrum of clinical agents with different therapeutic targets. Newer therapies, such as rituximab, that specifically target B cells have emerged as viable treatment options for patients with RA.

Figure 1

Etanercept in active rheumatoid arthritis (TEMPO trial): ACR responses at 52 weeks. *P < 0.01, ^‡P < 0.0001, versus placebo; ^†P < 0.05, ^§P < 0.0001, versus etanercept. ACR, American College of Rheumatology; MTX, methotrexate; TEMPO, Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes. Reprinted with permission [16].

Figure 2

Adalimumab plus methotrexate in active rheumatoid arthritis: mean change from baseline in total Sharp score. *P < 0.01, ^†P ≤ 0.001, versus placebo. MTX, methotrexate. Reproduced with permission [18]. Copyright ^© 2004 by John Wiley & Sons, Inc.