Red Flags
- Acute hot swollen joint with fever — joint aspiration to exclude septic arthritis[1]
- Latent or active TB starting biologic — IGRA/Mantoux + chest X-ray; treat latent TB before starting; particular vigilance in TB-endemic settings[1]
- Hepatotoxicity on methotrexate (LFTs >3× ULN) — pause methotrexate, investigate other causes; restart at lower dose if recovers[1]
- Pregnancy planning on methotrexate, leflunomide, or JAK inhibitor — switch ≥3 months pre-conception to safer agent (sulfasalazine, hydroxychloroquine, certolizumab)[1]
First-line treatment
Interventions
- Early DMARD initiation within 3 months of symptom onset[1]Window of opportunity — earlier treatment improves long-term outcomes; do not delay for full investigations once diagnosis is reasonably likely
- Treat-to-target[1]Aim remission (DAS28 <2.6) or low disease activity (DAS28 <3.2); reassess every 1–3 months early disease, every 3–6 months once stable; escalate or switch if target not met
- Triple therapy if methotrexate monotherapy insufficient[1]Methotrexate + hydroxychloroquine + sulfasalazine — affordable and effective; consider before biologic where cost or access limits biologic
- Pre-biologic TB screen — mandatory in TB-endemic regions[1]IGRA preferred + chest X-ray; treat latent TB ≥1 month before biologic; reassess annually during therapy
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 20–25 mg weekly | — | Anchor first-line per IRA; SC route improves bioavailability; LFT and FBC every 4–8 weeks; alcohol restriction; teratogen — contraception |
| Hydroxychloroquine[1] | Antimalarial / immunomodulator | 200–400 mg PO daily (max 5 mg/kg actual body weight) | — | Mild RA monotherapy or combination component; baseline retinal exam and annual screening from year 5; safe in pregnancy |
| Sulfasalazine[1] | 5-aminosalicylate | Start 500 mg PO BD, titrate to 1 g BD-TDS | — | First-line alternative or in pregnancy; FBC and LFT monitoring; sulfa allergy warning; component of triple therapy |
| Leflunomide[1] | Conventional synthetic DMARD (DHODH inhibitor) | 20 mg PO daily (loading 100 mg × 3 days then 20 mg) | — | Alternative to methotrexate; LFT and BP monitoring; long half-life — colestyramine washout for stopping; teratogen |
| Anti-TNF (etanercept, adalimumab, infliximab)[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 conventional DMARD inadequate; latent TB and HBV screen; biosimilars widely available improving access |
| Tocilizumab[1] | IL-6 receptor inhibitor | 162 mg SC weekly | — | 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 |
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 20–25 mg weekly
- Paediatric
- —
Anchor first-line per IRA; SC route improves bioavailability; LFT and FBC every 4–8 weeks; alcohol restriction; teratogen — contraception
Hydroxychloroquine[1]
Antimalarial / immunomodulator
- Adult
- 200–400 mg PO daily (max 5 mg/kg actual body weight)
- Paediatric
- —
Mild RA monotherapy or combination component; baseline retinal exam and annual screening from year 5; safe in pregnancy
Sulfasalazine[1]
5-aminosalicylate
- Adult
- Start 500 mg PO BD, titrate to 1 g BD-TDS
- Paediatric
- —
First-line alternative or in pregnancy; FBC and LFT monitoring; sulfa allergy warning; component of triple therapy
Leflunomide[1]
Conventional synthetic DMARD (DHODH inhibitor)
- Adult
- 20 mg PO daily (loading 100 mg × 3 days then 20 mg)
- Paediatric
- —
Alternative to methotrexate; LFT and BP monitoring; long half-life — colestyramine washout for stopping; teratogen
Anti-TNF (etanercept, adalimumab, infliximab)[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 conventional DMARD inadequate; latent TB and HBV screen; biosimilars widely available improving access
Tocilizumab[1]
IL-6 receptor inhibitor
- Adult
- 162 mg SC weekly
- 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
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; 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 two conventional DMARDs at adequate dose and durationRheumatology for biologic consideration with TB clearance[1]
- Extra-articular RA (vasculitis, scleritis, interstitial lung disease)Subspecialty co-management[1]
- Pregnancy planning on RA medicationJoint rheumatology and obstetric pre-conception clinic[1]
Clinical summary
Treat-to-target methotrexate-anchored DMARD pathway with biologic add-on for adults with rheumatoid arthritis per IRA guidance.