A 52-year-old woman with a 3-year history of seropositive rheumatoid arthritis (RF+ and anti-CCP+) presents with persistent joint pain and swelling despite adequate doses of methotrexate monotherapy for 6 months. She has no contraindications to biologics. What is the drug of choice to add to her current regimen?

Explanation

## First-Line Biologic Therapy in RA **Key Point:** TNF-α inhibitors (TNFi) are the preferred first-line biologic agents for RA patients with inadequate response to conventional synthetic DMARDs (csDMARDs) like methotrexate. **High-Yield:** The treat-to-target strategy in RA recommends adding a biologic (preferably a TNFi) when a patient fails to achieve low disease activity on csDMARD monotherapy within 3–6 months. ### Why Infliximab? | Feature | Infliximab | Adalimumab | Etanercept | |---------|-----------|-----------|----------| | **Type** | Chimeric monoclonal Ab | Fully human monoclonal Ab | TNF receptor fusion protein | | **Administration** | IV infusion | SC injection | SC injection | | **Onset** | Rapid (2–4 weeks) | 2–4 weeks | 2–4 weeks | | **Efficacy in RA** | Excellent | Excellent | Excellent | | **First-line status** | Yes (ACR, EULAR) | Yes (ACR, EULAR) | Yes (ACR, EULAR) | **Clinical Pearl:** Infliximab is typically given as IV induction (3 mg/kg at weeks 0, 2, 6) followed by maintenance every 8 weeks. It must be combined with methotrexate to reduce immunogenicity and improve efficacy. **Mnemonic: TNFi First** — When csDMARD fails, add TNF inhibitor first (infliximab, adalimumab, etanercept, golimumab, certolizumab). ### Why Not the Others? - **Sulfasalazine & Hydroxychloroquine:** These are csDMARDs, not biologics. They are less effective than TNFi for inadequate responders and should not be used as monotherapy add-ons in this scenario. - **Leflunomide:** Also a csDMARD. While it can be combined with methotrexate, TNFi is preferred first-line biologic therapy per ACR/EULAR guidelines. **Warning:** Do NOT confuse TNFi with other biologic classes (IL-6 inhibitors, JAK inhibitors, B-cell depletors). TNFi remains the gold standard initial biologic choice in RA.