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When initial therapy proves insufficient, treatment escalation includes: Biologic DMARDs targeting specific inflammatory pathways (TNF inhibitors, IL-6 inhibitors, T-cell costimulation blockers, B-cell depleting agents) Targeted synthetic DMARDs such as JAK inhibitors (tofacitinib, baricitinib, upadacitinib), which carry FDA boxed warnings for serious cardiovascular events, malignancy, and thrombosis [24] [25] Combination DMARD therapy Short-term glucocorticoids for symptom control during treatment initiation Before starting biologic or targeted synthetic DMARDs, screening for tuberculosis and hepatitis B is recommended, along with appropriate vaccinations according to ACR guidelines

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