Combination therapy with multiple disease-modifying antirheumatic drugs inrheumatoid arthritis: A preventive strategy

The traditional "pyramid" or sequential approach to treatment of patients w ith rheumatoid arthritis involved use of a nonsteroidal anti-inflammatory d rug for months to years while seeking to avoid use of second-line antirheum atic drugs until evidence of joint damage was seen. This approach led to sh ort-term reduction of inflammation and a few remissions. However, long-term remissions were rare, and most patients experienced poor long-term outcome s, including joint destruction, severe functional declines, considerable ec onomic losses, work disability, and premature mortality. At this time, a "p reventive" strategy is evolving in which early aggressive treatment with di sease-modifying antirheumatic drugs is used, seeking to minimize long-term joint damage. When residual inflammation remains after maximum doses of sin gle agents, as is usually the case, combinations of disease-modifying antir heumatic drugs appear to be a reasonable consideration for many patients. M ethotrexate is the most commonly used "anchor drug" in combination therapy. Evidence from randomized, controlled clinical trials and observational stu dies have indicated increased efficacy and acceptable land often lower) tox icity for combinations of methotrexate plus cyclosporine, hydroxychloroquin e, sulfasalazine, leflunomide, etanercept, and infliximab. Further studies lasting 5 years or more are needed to determine the long-term effectiveness , toxicities, and optimal clinical use of disease-modifying antirheumatic d rug combinations. At this time, such combinations are taken by at least som e patients under care of almost all rheumatologists, and it appears likely that they will be used increasingly in the coming decades.