Red Flags
- Acute hot swollen joint with fever — joint aspiration to exclude septic arthritis; do not assume RA flare[1]
- Severe RA flare with constitutional symptoms, vasculitis, scleritis, or interstitial lung disease — same-day rheumatology[1]
- Latent TB or prior TB exposure starting biologic or JAK inhibitor — IGRA/Mantoux + chest X-ray; treat latent TB before starting[1]
- JAK inhibitor signal: increased CV events, malignancy, VTE in patients ≥65 with risk factors — review indication and consider alternatives[1]
First-line treatment
Interventions
- Phase 1: methotrexate + short-term glucocorticoid[1]Start methotrexate at diagnosis (with folic acid); add short-term glucocorticoid bridge (taper within 3 months). Reassess at 3 months and aim remission or low disease activity at 6 months
- Phase 2: add biologic or targeted synthetic DMARD if Phase 1 fails[1]Add anti-TNF, IL-6 inhibitor, or JAK inhibitor (with caution per safety signals) to methotrexate. Consider patient factors (age, comorbidity, infection risk, CV risk) in agent choice
- Phase 3: switch class if Phase 2 fails[1]Switch to a different mechanism of action; rituximab, abatacept, IL-6 inhibitor (if not used), or JAK inhibitor; consider drug levels, anti-drug antibodies
- Treat-to-target with regular reassessment[1]Aim remission or low disease activity (DAS28 <2.6 or <3.2); reassess every 1–3 months early, every 3–6 months once stable; escalate or switch if target not met; consider tapering once sustained remission
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Methotrexate[1] | Conventional synthetic DMARD (anti-folate) | Start 10–15 mg PO/SC weekly with folic acid 5 mg weekly (different day); titrate to 25 mg weekly | — | First-line per EULAR; SC route improves bioavailability; LFT and FBC monitoring; alcohol restriction; teratogen |
| Glucocorticoid (bridge therapy)[1] | Systemic corticosteroid | Prednisolone 30 mg PO daily tapering to 7.5 mg over 8 weeks then off by 3 months | — | Bridge while DMARD takes effect; minimise duration to <3 months; bone protection (calcium, vitamin D, bisphosphonate per fracture risk) |
| Anti-TNF (etanercept, adalimumab, infliximab, certolizumab, golimumab)[1] | TNF-alpha inhibitor (biologic) | Etanercept 50 mg SC weekly; adalimumab 40 mg SC every 2 weeks; infliximab 3 mg/kg IV at 0, 2, 6 weeks then every 8 weeks | — | Add when methotrexate inadequate; latent TB and HBV screen; certolizumab preferred in pregnancy (no placental transfer); biosimilars widely available |
| Tocilizumab or sarilumab[1] | IL-6 receptor inhibitor | Tocilizumab 162 mg SC weekly; sarilumab 200 mg SC every 2 weeks | — | Useful in monotherapy where methotrexate not tolerated; lipid increase, neutropenia, GI perforation risk |
| Rituximab[1] | Anti-CD20 monoclonal antibody | 1 g IV × 2 doses 2 weeks apart, repeat at 6 months | — | Seropositive RA failing TNF; HBV screen and prophylaxis; vaccinate before; long-lasting immunosuppression |
| JAK inhibitor (tofacitinib, baricitinib, upadacitinib)[1] | Janus kinase inhibitor | Tofacitinib 5 mg PO BD; baricitinib 4 mg PO daily; upadacitinib 15 mg PO daily | — | Reserve for second-line; ORAL Surveillance signal — CV events, malignancy, VTE in patients ≥65 with risk factors; latent TB and HBV screen; oral biologic alternative |
Methotrexate[1]
Conventional synthetic DMARD (anti-folate)
- Adult
- Start 10–15 mg PO/SC weekly with folic acid 5 mg weekly (different day); titrate to 25 mg weekly
- Paediatric
- —
First-line per EULAR; SC route improves bioavailability; LFT and FBC monitoring; alcohol restriction; teratogen
Glucocorticoid (bridge therapy)[1]
Systemic corticosteroid
- Adult
- Prednisolone 30 mg PO daily tapering to 7.5 mg over 8 weeks then off by 3 months
- Paediatric
- —
Bridge while DMARD takes effect; minimise duration to <3 months; bone protection (calcium, vitamin D, bisphosphonate per fracture risk)
Anti-TNF (etanercept, adalimumab, infliximab, certolizumab, golimumab)[1]
TNF-alpha inhibitor (biologic)
- Adult
- Etanercept 50 mg SC weekly; adalimumab 40 mg SC every 2 weeks; infliximab 3 mg/kg IV at 0, 2, 6 weeks then every 8 weeks
- Paediatric
- —
Add when methotrexate inadequate; latent TB and HBV screen; certolizumab preferred in pregnancy (no placental transfer); biosimilars widely available
Tocilizumab or sarilumab[1]
IL-6 receptor inhibitor
- Adult
- Tocilizumab 162 mg SC weekly; sarilumab 200 mg SC every 2 weeks
- Paediatric
- —
Useful in monotherapy where methotrexate not tolerated; lipid increase, neutropenia, GI perforation risk
Rituximab[1]
Anti-CD20 monoclonal antibody
- Adult
- 1 g IV × 2 doses 2 weeks apart, repeat at 6 months
- Paediatric
- —
Seropositive RA failing TNF; HBV screen and prophylaxis; vaccinate before; long-lasting immunosuppression
JAK inhibitor (tofacitinib, baricitinib, upadacitinib)[1]
Janus kinase inhibitor
- Adult
- Tofacitinib 5 mg PO BD; baricitinib 4 mg PO daily; upadacitinib 15 mg PO daily
- Paediatric
- —
Reserve for second-line; ORAL Surveillance signal — CV events, malignancy, VTE in patients ≥65 with risk factors; latent TB and HBV screen; oral biologic alternative
Safety-net
- Take methotrexate exactly as prescribed (weekly, never daily) — daily dosing causes life-threatening toxicity[1]
- Any infection (chest, urinary, dental, skin) — same-day medical review while on biologic or JAK inhibitor; pause therapy and seek antibiotic[1]
- Tell every healthcare worker about your DMARD or biologic — affects infection management and surgery planning[1]
Referral criteria
- All suspected new RA (early arthritis with persistent synovitis ≥6 weeks)Rheumatology within 4–6 weeks[1]
- Failure of methotrexate at adequate dose and durationRheumatology for biologic/JAK inhibitor consideration[1]
- Extra-articular RA (vasculitis, scleritis, interstitial lung disease, neurological)Subspecialty co-management[1]
- Pregnancy planning on RA medicationJoint rheumatology and obstetric pre-conception clinic[1]
Clinical summary
EULAR-aligned treat-to-target conventional, biological, and targeted synthetic DMARD pathway for adults with rheumatoid arthritis.