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Rheumatology · ACR

Rheumatoid arthritis

ACR
A
Source:American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis (2021)EULAR 2022/2023APLAR 2018
Verified Apr 2026
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Red Flags

  • Acute hot swollen joint with fever — joint aspiration to exclude septic arthritis; do not assume RA flare; empirical antibiotic[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]
  • Pregnancy or planning pregnancy on methotrexate, leflunomide, or JAK inhibitor — switch to safer agent (sulfasalazine, hydroxychloroquine, certolizumab) ≥3 months pre-conception[1]

First-line treatment

Interventions

  • 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
  • Comprehensive cardiovascular and bone health[1]
    RA confers ≈50% increased CV risk; manage hypertension, lipids, diabetes; smoking cessation. Bone protection on glucocorticoid: calcium, vitamin D, bisphosphonate per fracture risk
  • Vaccination before immunosuppression[1]
    Pneumococcal, influenza annual, COVID-19, recombinant zoster vaccine ≥18 years on immunosuppression, hepatitis B; defer live vaccines once on biologic/JAK inhibitor

First-line drug therapy

DrugClassAdultPaediatricNotes
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—First-line for moderate-severe RA; SC route improves bioavailability; LFT and FBC every 2 weeks initially then 8–12 weekly; alcohol restriction; teratogen — contraception
Hydroxychloroquine[1]Antimalarial / immunomodulator200–400 mg PO daily (maximum 5 mg/kg actual body weight)—Mild RA monotherapy or combination; baseline retinal exam and annual screening from year 5; safe in pregnancy
Sulfasalazine[1]5-aminosalicylateStart 500 mg PO BD, titrate to 1 g BD-TDS—First-line alternative or in pregnancy; FBC and LFT monitoring; sulfa allergy; safe with hydroxychloroquine in 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, 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 weeksPer local protocolAdd when conventional DMARD inadequate; latent TB and HBV screen; certolizumab preferred in pregnancy (no placental transfer); biosimilars widely available
Tocilizumab or sarilumab[1]IL-6 receptor inhibitorTocilizumab 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 antibody1 g IV × 2 doses 2 weeks apart, repeat at 6 months—Seropositive RA failing TNF inhibitor; HBV screen and prophylaxis; vaccinate before; long-lasting immunosuppression
JAK inhibitor (tofacitinib, baricitinib, upadacitinib)[1]Janus kinase inhibitorTofacitinib 5 mg PO BD; baricitinib 4 mg PO daily; upadacitinib 15 mg PO daily—Oral biologic alternative; ORAL Surveillance signal — increased CV events, malignancy, VTE in some patients ≥50; reserve for second-line; latent TB and HBV screen
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
—
First-line for moderate-severe RA; SC route improves bioavailability; LFT and FBC every 2 weeks initially then 8–12 weekly; alcohol restriction; teratogen — contraception
Hydroxychloroquine[1]
Antimalarial / immunomodulator
Adult
200–400 mg PO daily (maximum 5 mg/kg actual body weight)
Paediatric
—
Mild RA monotherapy or combination; 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; safe with hydroxychloroquine in 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, 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
Per local protocol
Add when conventional DMARD 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 inhibitor; 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
—
Oral biologic alternative; ORAL Surveillance signal — increased CV events, malignancy, VTE in some patients ≥50; reserve for second-line; latent TB and HBV screen

Safety-net

  1. Take methotrexate exactly as prescribed (weekly, never daily) — daily dosing causes life-threatening toxicity[1]
  2. Any infection (chest, urinary, dental, skin) — same-day medical review while on biologic or JAK inhibitor; pause therapy and seek antibiotic[1]
  3. Tell every healthcare worker (dentist, surgeon, A&E) 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, positive serology, raised inflammatory markers)Rheumatology within 4–6 weeks[1]
  • Failure of two conventional DMARDs 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

Treat-to-target conventional synthetic, biological, and targeted synthetic DMARD pathway for adults with rheumatoid arthritis.

References

  1. 1.American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis (2021); EULAR 2022/2023; APLAR 2018 (2021)

On this page

  • Red flags
  • First-line treatment
  • Safety-net
  • Referral
  • References