Rheumatoid Arthritis

📋 Key Information Summary

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Diagnosis: Based on 2010 ACR/EULAR criteria (score ≥6/10): joint involvement, serology (RF/anti-CCP), acute-phase reactants (CRP/ESR), symptom duration.
First-line DMARD: Methotrexate (MTX) 7.5–25 mg weekly (oral or subcutaneous) with folic acid 5 mg weekly (not on MTX day).
Combination csDMARDs: MTX + sulfasalazine + hydroxychloroquine (triple therapy) for inadequate response to MTX monotherapy.
Biologic/tsDMARD escalation: After failure of ≥2 csDMARDs. Options include TNFi (adalimumab, etanercept), IL-6R (tocilizumab), JAKi (tofacitinib, baricitinib).
Treat-to-target: Aim for remission (DAS28 <2.6) or low disease activity (DAS28 ≤3.2) every 3–6 months.
DAS28 calculation: Based on 28 tender/swollen joint counts, ESR or CRP, patient global assessment (0–100 mm VAS).
Monitoring: FBC, LFTs, creatinine every 2–4 weeks initially for MTX, then every 2–3 months. Annual eye exam for hydroxychloroquine.
Safety: Screen for TB (QuantiFERON) and hepatitis B/C before biologics/JAKi. Live vaccines contraindicated.
Extra-articular: Rheumatoid nodules, interstitial lung disease, vasculitis, episcleritis. Require specialist co-management.
ATSI consideration: Higher prevalence, younger onset, more aggressive disease. Ensure culturally safe care and access to DMARDs.

Introduction & Australian Epidemiology

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory arthritis primarily affecting synovial joints. In Australia, prevalence is ~0.5–1% of adults, with higher rates in Aboriginal and Torres Strait Islander communities. Onset is typically between 35–60 years, with a female:male ratio of 3:1. Early diagnosis and aggressive treat-to-target therapy within 3–6 months of symptom onset ('window of opportunity') significantly improves long-term structural and functional outcomes.

Pathophysiology

Autoimmune-driven synovitis (pannus) leads to cartilage destruction and bone erosion. Key cytokines include TNF-α, IL-6, and IL-1. Genetic predisposition (HLA-DRB1 shared epitope) interacts with environmental triggers (smoking, periodontitis, silica exposure).

Diagnosis & 2010 ACR/EULAR Criteria

No single pathognomonic test. Diagnosis is clinical, supported by serology and imaging. The 2010 ACR/EULAR classification criteria (score ≥6/10 definite RA) are used for early identification.

Domain	Score	Criteria
Joint Involvement	0–5	1 large (0), 2–10 large (1), 1–3 small (2), 4–10 small (3), >10 (at least 1 small) (5)
Serology	0–3	Negative RF & negative ACPA (0), low-positive RF or ACPA (2), high-positive RF or ACPA (3)
Acute Phase Reactants	0–1	Normal CRP and normal ESR (0), abnormal CRP or abnormal ESR (1)
Duration of Symptoms	0–1	<6 weeks (0), ≥6 weeks (1)

Key investigations (MBS items):

Essential

Rheumatoid Factor (RF) & Anti-CCP antibodies

MBS 69480. Anti-CCP more specific (>95%). High titres predict erosive disease.

Available

ESR, CRP, FBC

Baseline for activity and monitoring.

Available

X-rays hands & feet

Baseline for erosion assessment. Repeat annually if active disease.

Referral

Musculoskeletal Ultrasound or MRI

Specialist use for early synovitis detection (not routine primary care).

Disease Activity Scoring (DAS28)

DAS28 is the standard Australian tool for treat-to-target. Calculated using 28 tender/swollen joint counts, ESR (or CRP), and patient global health VAS (0–100).

Remission

DAS28 <2.6

Target state. No active synovitis on exam ideal.

Consider cautious DMARD tapering

Low Activity

DAS28 ≤3.2

Alternative target if remission not achievable.

Optimise current therapy

High Activity

DAS28 >5.1

Active disease requiring therapy escalation.

Intensify DMARD or escalate to biologic

⚠️

Limitation: DAS28 does not assess feet, ankles, or spine. Complement with clinical judgement and patient-reported outcomes.

Methotrexate & Conventional DMARDs

Methotrexate (MTX) is the anchor drug. Start early, escalate dose every 4 weeks to target (usually 15–25 mg/week).

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Methotrexate

Various brands · Antifolate DMARD

Adult dose7.5–25 mg PO/SC weekly. Start 7.5–10 mg, increase by 2.5 mg every 4 weeks.

Paediatric dose0.3–0.6 mg/kg/week (JIA).

Key monitoringFBC, LFTs, creatinine every 2–4 weeks initially, then every 2–3 months. Folic acid 5 mg weekly (not on MTX day).

PBS status✔ PBS General Benefit

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Sulfasalazine

Salazopyrin® · Pyrimidine DMARD

Adult dose500 mg daily, increase by 500 mg weekly to 1–2 g/day in divided doses.

PBS status✔ PBS General Benefit

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Hydroxychloroquine

Plaquenil® · Antimalarial DMARD

Adult dose200–400 mg daily (≤5 mg/kg actual body weight).

Key monitoringBaseline and annual eye exam (maculopathy risk).

PBS status✔ PBS General Benefit

Triple therapy: MTX + sulfasalazine + hydroxychloroquine is an effective and affordable alternative to biologics for moderate disease activity.

Biologics & Targeted Synthetic DMARDs

Indicated after failure of ≥2 csDMARDs (including MTX) or with poor prognostic factors. Require PBS Authority approval.

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Mandatory screening: Tuberculosis (QuantiFERON Gold), hepatitis B/C, HIV status, and varicella immunity before initiation. Live vaccines contraindicated.

Class	Examples	Key Considerations
TNF inhibitors (TNFi)	Adalimumab (Humira®), Etanercept (Enbrel®)	First-line biologic. SC injection. Risk of infection, demyelination.
IL-6 receptor inhibitors	Tocilizumab (Actemra®)	Can mask CRP rise. Monitor lipids and neutrophils. IV or SC.
JAK inhibitors (JAKi)	Tofacitinib (Xeljanz®), Baricitinib (Olumiant®)	Oral. Increased VTE, MACE, malignancy risk in >50y with CV risk factors (FDA warning).

PBS Authority Required: For patients with severe active RA (DAS28 >5.1) despite adequate trial of csDMARDs.

Extra-articular Disease

Occurs in ~20% of patients, often with high-titre RF/anti-CCP. Indicates severe systemic disease.

Rheumatoid nodules

Most common. Usually pressure points. Monitor for infection/ulceration.

Interstitial Lung Disease (ILD)

Screen with HRCT if symptomatic. Avoid MTX if present.

Vasculitis

Rare but serious. Requires high-dose corticosteroids + cyclophosphamide/rituximab.

Scleritis/Episcleritis

Urgent ophthalmology referral.

Treat-to-Target Strategy

1

Set Target

Remission (DAS28 <2.6) or low disease activity (DAS28 ≤3.2) as the primary goal.

2

Measure Activity

Use DAS28 (or CDAI/SDAI) every 3–6 months until target achieved, then every 6 months.

3

Adjust Therapy

If target not met: (1) Optimize MTX dose to 25 mg/week. (2) Add or switch csDMARD (triple therapy). (3) Escalate to biologic/tsDMARD.

4

Sustained Remission

After >6 months remission, cautiously taper glucocorticoids first, then consider DMARD dose reduction (never abrupt cessation).

✅

Australian Standard: Aligns with RACGP/ARA guidelines. Multidisciplinary team (GP, rheumatologist, physiotherapist, podiatrist) essential.

Special Populations

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Pregnancy

Teratogens: Stop MTX, leflunomide, and JAKi ≥3 months pre-conception.

Compatible: Hydroxychloroquine, sulfasalazine, low-dose prednisolone, certolizumab (TNFi without Fc region).

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Renal Impairment

MTX: Contraindicated if eGFR <30 mL/min. Use with caution if eGFR 30–50.

NSAIDs: Avoid if eGFR <60.

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Immunocompromised

Screen and treat latent infections (TB, hepatitis B). Pneumococcal and influenza vaccination pre-biologic.

ATSI Health Considerations

Aboriginal and Torres Strait Islander Health

Epidemiology

Higher prevalence, earlier onset, and more aggressive erosive disease compared to non-Indigenous Australians.

Access & Barriers

Geographic isolation, limited specialist/rheumatology access in remote areas. Cultural safety and trust in health system crucial.

Management

PBS co-payments can be a barrier. Use Closing the Gap PBS scripts (no co-payment for eligible patients). Telehealth rheumatology vital for remote monitoring.

📚 References

1. Aletaha D, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-81.
2. Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3-18.
3. Royal Australian College of General Practitioners (RACGP). Rheumatoid arthritis: early diagnosis and disease management. East Melbourne: RACGP; 2020.
4. Australian Rheumatology Association (ARA). Biologics and targeted synthetic DMARDs: information for prescribers. 2023. Available from: https://www.rheumatology.org.au
5. Australian Government Department of Health. Pharmaceutical Benefits Scheme (PBS). Available from: www.pbs.gov.au
6. National Health and Medical Research Council (NHMRC). Australian guidelines for the prevention and control of infection in healthcare. Canberra: NHMRC; 2019.
7. Aboriginal and Torres Strait Islander Health Team. Cultural safety in healthcare. Australian Institute of Health and Welfare (AIHW). 2022.
8. Fraenkel L, et al. American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924-39.
9. Ytterberg SR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316-26.
10. Buch MH, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75(1):3-15.