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Abstract
Methotrexate (MTX) is well-established as the "anchor drug" for patients with rheumatoid arthritis (RA), to be used early and aggressively, with higher long-term effectiveness, tolerability, and safety than any other disease-modifying antirheumatic drug (DMARD). However, about 20% to 40% of patients experience incomplete responses to MTX and require further therapy, with options including other nonbiologic DMARDs, low dose glucocorticoids, and biologic agents. Non-biologic DMARDs in combination with MTX may provide similar efficacy to a biologic agent in clinical trials, with fewer adverse events and lower costs. This review presents a summary of 21 clinical trials documenting the efficacy and safety of MTX in combination with other non-biologic DMARDs.
Treatment of patients with rheumatoid arthritis (RA) has been advanced considerably over the last two decades through earlier treatment with methotrexate (MTX), low dose glucocorticoids, other disease-modifying antirheumatic drugs (DMARDs), and new biologic agents, targeted to low disease activity or remission.12 Methotrexate is the most commonly prescribed DMARD3 and is considered the "anchor drug" in RA.4 Nonetheless, about 20% to 40% of patients experience incomplete responses with MTX as monotherapy. Methotrexate in combination with other DMARDs has been shown to be efficacious in many of these patients to achieve acceptable low disease activity.
In DMARD-naive patients, the balance between efficacy and toxicity favors MTX over other conventional DMARDs. Methotrexate should be considered as the anchor drug not only for monotherapy but also for combination therapy when MTX monotherapy does not result in disease control.5 Combinations with conventional DMARDs offer a possible alternative to adding a biologic agent to MTX, often with similar efficacy and possibly greater safety, at lower cost.6 This review summarizes available reports concerning efficacy ficacy and safety of MTX in combination with other nonbiologic biologic DMARDs.
Methods
A PubMed search was performed to search for studies that included at least one ann of treatment involving MTX in combination with other non-biologic DMARDs. We used the following search tenus: rheumatoid arthritis, randomized trial, MTX, DMARDs, triple therapy rheumatoid, and combination therapy to retrieve clinical trials, including combination therapy of MTX with other DMARDs. We also perfonned a hand search of references from the included reports. The search yielded 21 clinical trials, but the review was not exhaustive. It was not possible to...