A 55-year-old woman with seropositive RA on methotrexate (MTX) 20 mg/week and sulfasalazine has persistent active disease (DAS28 >3.2). Which is the MOST evidence-based next step per ACR/EULAR treat-to-target guidelines?

• A Add hydroxychloroquine to form triple therapy (MTX + SSZ + HCQ)
• B Switch to leflunomide as methotrexate substitute
• C Add a biologic DMARD (TNF inhibitor) or JAK inhibitor to methotrexate ✓
• D Add low-dose prednisolone 5 mg daily indefinitely

Explanation

ACR 2021 guidelines recommend adding a biologic DMARD (TNF inhibitor, IL-6 inhibitor, abatacept) or a JAK inhibitor (tofacitinib, baricitinib) to methotrexate when disease remains active despite csDMARD combination therapy. Triple therapy (MTX+SSZ+HCQ) is an alternative, particularly in resource-limited settings, but adding a biologic to MTX is the standard escalation. Glucocorticoids are used as bridging therapy, not long-term disease control.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.