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Background

Methotrexate is considered the preferred disease‐modifying anti‐rheumatic drug (DMARD) for the treatment of rheumatoid arthritis, but controversy exists on the additional benefits and harms of combining methotrexate with other DMARDs.

Objectives

To compare methotrexate and methotrexate‐based DMARD combinations for rheumatoid arthritis in patients naïve to or with an inadequate response (IR) to methotrexate.

Methods

We systematically identified all randomised controlled trials with methotrexate monotherapy or in combination with any currently used conventional synthetic DMARD, biologic DMARDs, or tofacitinib. Three major outcomes (ACR50 response, radiographic progression and withdrawals due to adverse events) and multiple minor outcomes were evaluated. Treatment effects were summarized using Bayesian random‐effects network meta‐analyses, separately for methotrexate‐naïve …