Remission in rheumatoid arthritis: Wishful thinking or clinical reality?

OBJECTIVES: To review the concept of remission in rheumatoid arthritis (RA), as defined by the Food and Drug Administration (FDA), the American College of Rheumatology (ACR), and the European League Against Rheumatism (EULAR). To delineate differences between significant clinical improvements, very low disease activity, and the achievement of true remission. To evaluate the prevalence of these outcomes with biologic therapy and traditional disease-modifying antirheumatic drugs (DMARD) regimens. METHODS: The MEDLINE database was searched for the key words "remission" and "rheumatoid arthritis." Efficacy data of RA clinical trials from 1985 to 2004 are based on a literature review of medical journals and abstracts from rheumatology meetings. We review 3 well-defined sets of criteria established by the ACR, EULAR, and the FDA for measuring remission. RESULTS: Defining remissions in clinical trials and clinical practice requires appropriate standardized and objective outcome measures, such as the ACR and EULAR remission criteria. Traditional DMARDs often provide symptom relief, improvements in physical function, and the slowing of radiographic progression in patients with RA, but rarely lead to the complete cessation of RA activity. Remission, as defined by the ACR criteria, has been observed in 7 to 22% of patients treated with traditional DMARD monotherapy (ie, gold, penicillamine, methotrexate [MTX], cyclosporine A, or sulfasalazine), but these remissions have often been short-lived. Treatments with DMARD combinations, biologic monotherapy, and biologic combination therapy with MTX offer greater hope and may facilitate the higher rates of remission. Clinical trial results have shown that newer DMARDs such as leflunomide or the combination of multiple DMARDs can generally elicit greater EULAR remission rates (ranging from 13 to 42%) than monotherapies. Biologic combinations with MTX have also been shown to induce significant remission (as defined by the EULAR criteria) in RA patients, with a 31% rate observed with infliximab plus MTX at 54 weeks, a 50% rate observed for adalimumab plus MTX after 2 years of therapy, and a 41% rate observed for etanercept plus MTX after 2 years of therapy. CONCLUSIONS: In the era of biologics and combination therapy, identifying remission or at least very low disease activity as the ultimate goal in RA therapy should become the new standard for the outcome of all RA trials. The criteria established by the FDA, the ACR, and the EULAR represent an important step toward achieving this goal.