Addition of the nonbiologic disease-modifying antirheumatic drug (DMARD) leflunomide is indicated for this patient. She has chronic moderate to severe rheumatoid arthritis with one or more poor prognostic markers, which may include young age, involvement of more than three joints, seropositivity, elevated inflammatory markers, and radiographic changes. She has continued to have active disease despite treatment with sulfasalazine and the biologic agent etanercept as suggested by continued synovitis of four joints and elevated inflammatory markers. A “treat to target” approach has been found to improve the outcomes in patients such as in this case, and additional therapy is needed to achieve a low disease activity or remission. A combination of a biologic agent (preferably a tumor factor necrosis α inhibitor) and a nonbiologic DMARD is thought to be the best option to achieve this goal. Because of her side-effect history with methotrexate, the addition of the alternative nonbiologic DMARD leflunomide at this point would be the next best strategy.

Biologic agents are frequently used in combination with a nonbiologic DMARD. However, concurrent use of two or more biologic agents is not recommended because infection rates are significantly increased with minimal, if any, added efficacy. Therefore, the addition of abatacept, anakinra, or rituximab is inappropriate.