RA damages joints irreversibly — every week untreated matters. ACR guidelines: hydroxychloroquine first-line for low disease activity, methotrexate WEEKLY (never daily) for moderate-high RA. This 2026 complete guide covers the autoimmune mechanism, all DMARD classes with an 8-drug table, triple therapy vs biologics, JAK inhibitor black box warning, HCQ retinal screening rule, and treat-to-target explained.