The anchor: methotrexate & conventional DMARDs

The drugs that actually change RA's course are DMARDs — disease-modifying antirheumatic drugs. The first and most important is methotrexate, a cheap, decades-proven drug that's the backbone of nearly every RA regimen. Get this one right and most people do very well.

Methotrexate: the anchor

First-line, weekly: Methotrexate is the anchor first-line DMARD: cheap, effective, and the drug everything else is built around. It's taken once a week (never daily), always with folic acid on a different day to cut side effects, and it takes 6–12 weeks to work. It calms inflammation, slows joint erosion, and by controlling RA it even lowers the disease's raised heart risk. Side effects (nausea, mouth ulcers, liver, blood counts) are mostly manageable with folic acid and monitoring bloods; it's not for use in pregnancy. Evidence ●●●●●

The other conventional DMARDs

Alternatives & partners: When methotrexate isn't tolerated or isn't enough: leflunomide (similar strength, but a very long half-life that lingers for months), sulfasalazine (one of the few DMARDs safe in pregnancy), and hydroxychloroquine (the mildest — used in low-activity disease or in combinations, and needing periodic eye checks). Each is a genuine disease-modifier, not just a painkiller. Evidence ●●●●○

Triple therapy — the underrated bargain

Three cheap generics: Combining methotrexate + sulfasalazine + hydroxychloroquine ('triple therapy') can rival a biologic: two major trials (RACAT, TEAR) found it non-inferior to methotrexate plus a TNF biologic — at a fraction of the cost, all as cheap oral generics. The trade-off is more pills and slower onset, so guidelines often reach for a biologic first for speed — but triple therapy is a genuinely effective, underused option. Evidence ●●●●○

Methotrexate is a WEEKLY drug

Taking methotrexate daily by mistake causes severe, sometimes fatal toxicity — it's a well-documented medication error. Always confirm the once-a-week schedule (many people fix it to a specific day), keep it clearly separate from daily medicines, and always take your folic acid.

The RA Guide