Rheumatoid arthritis (RA) resistant to monotherapy with methotrexate^*

ABW: actual body weight; CDAI: Clinical Disease Activity Index; CRP: c-reactive protein; csDMARD: conventional synthetic disease-modifying antirheumatic drug; DMARD: disease-modifying antirheumatic drug; TNFi: tumor necrosis factor inhibitor.

* Treatment resistance is defined as 1 of the following: Failure to achieve remission/low disease activity after 3 to 4 months of therapy; a need for chronic glucocorticoids; multiple relapses (ie, ≥2 annually); or progressive erosive disease despite therapy. Refer to UpToDate content for additional discussion.

¶ Adverse prognostic features include any of the following: High titer rheumatoid factor or anti-citrullinated peptide antibody, elevated CRP, baseline erosive disease, and prior inadequate response to "triple therapy." High disease activity is defined as a CDAI ≥22 (calculator available). Refer to UpToDate content for discussion of disease activity assessment.

Δ We usually use subcutaneous etanercept or adalimumab as the initial TNFi in combination with continued methotrexate after appropriate pretreatment assessments.

◊ Contraindications to TNF inhibitor therapy include active infection, multiple sclerosis, and decompensated congestive heart failure. Refer to relevant topics for discussion.

§ Other biologic and targeted synthetic DMARDs or leflunomide may also be appropriate. Refer to UpToDate content for discussion.

¥ Recent guidelines^[1] favor the addition of TNFi inhibitors for patients who fail to have an adequate response to methotrexate monotherapy. However, choosing between these options often depends on multiple factors (eg, disease activity, patient preference), and must be individualized. In addition, other biologic agents may be appropriate. Refer to relevant topics for discussion.

‡ Additional adjustments of dosage and administration may be necessary for some patients. Refer to UpToDate content for discussion and appropriate pretreatment assessments for TNFi therapy.