📋 Key Information Summary
- DMARDs (Disease-Modifying Antirheumatic Drugs) are the cornerstone of therapy for inflammatory rheumatic diseases like rheumatoid arthritis (RA), aiming to prevent joint damage and disability.
- Methotrexate remains the anchor drug for RA; standard dose is 15–25 mg once weekly orally or subcutaneously, always co-prescribed with folic acid 5 mg weekly (not on the same day).
- Pre-treatment screening is mandatory before starting any biologic or targeted synthetic DMARD. Essential tests include latent TB screening (IGRA ± CXR), hepatitis B/C serology, and strongyloides serology in at-risk patients.
- Conventional synthetic DMARDs (csDMARDs) include methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine. Choice depends on disease, comorbidities, and pregnancy plans.
- TNF inhibitors (e.g., adalimumab, etanercept) are first-line biologic DMARDs (bDMARDs) after csDMARD failure. They increase infection risk, particularly reactivation of latent TB.
- IL-6 inhibitors (tocilizumab, sarilumab) are effective for RA but can mask infection by suppressing CRP and fever; monitor lipids and for GI perforation.
- JAK inhibitors (tofacitinib, baricitinib, upadacitinib) are oral targeted synthetic DMARDs (tsDMARDs). They carry a higher risk of VTE, herpes zoster, and MACE in high-risk patients over 50 with CV risk factors.
- Routine monitoring for all DMARDs includes FBC, LFTs, and eGFR. Frequency is higher during initiation (e.g., every 2–4 weeks) then every 2–3 months when stable.
- Live vaccines (e.g., MMR, varicella, yellow fever) are contraindicated in patients on biologic/JAK inhibitor therapy.
- For Aboriginal and Torres Strait Islander patients, consider higher rates of comorbid infections (TB, strongyloides), remote access challenges for monitoring, and culturally safe care.
Introduction & Australian Epidemiology
Inflammatory rheumatic diseases like rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis are chronic autoimmune conditions leading to progressive joint damage, disability, and reduced quality of life. Disease-Modifying Antirheumatic Drugs (DMARDs) are fundamental to management, targeting underlying inflammatory pathways to achieve remission or low disease activity.
In Australia, RA affects approximately 2% of the population, with a higher prevalence and earlier onset observed in Aboriginal and Torres Strait Islander communities. The economic and personal burden is significant, making effective, early, and targeted DMARD therapy a priority within the Australian healthcare system.
Australian Context: Access to biologic and targeted DMARDs is primarily through the Pharmaceutical Benefits Scheme (PBS), which requires specific authority and evidence of failure or intolerance to conventional DMARDs. This influences treatment sequencing.
Pre-treatment Screening (TB, HBV, Strongyloides)
Mandatory screening is required before initiating any biologic (bDMARD) or targeted synthetic (tsDMARD) therapy to prevent severe, opportunistic infections.
| Infection | Screening Test | Action if Positive | Australian Notes |
|---|---|---|---|
| Tuberculosis (TB) | Interferon-Gamma Release Assay (IGRA) (e.g., QuantiFERON-TB Gold). TST not preferred on biologics. | Chest X-ray to exclude active TB. If latent TB diagnosed, commence TB prophylaxis (e.g., isoniazid for 6–9 months) BEFORE starting DMARD. | Higher prevalence in ATSI communities and migrants from high-burden countries. Refer to state/territory TB services. |
| Hepatitis B (HBV) | HBsAg, anti-HBs, anti-HBc. | If HBsAg positive: refer hepatology, consider antiviral prophylaxis (e.g., entecavir). If anti-HBc positive only: monitor HBV DNA. | Important in patients from high-prevalence regions (e.g., Asia-Pacific). |
| Hepatitis C | Anti-HCV antibody, HCV RNA if positive. | Treat HCV with DAA therapy if active. DMARDs can be used post-cure. | PBS-listed DAA therapy available. |
| Strongyloides | Strongyloides serology. | Treat with ivermectin (200 mcg/kg daily for 2 days) before immunosuppression. | Critical for patients who have lived in endemic areas (tropical QLD, NT, Pacific Islands, Southeast Asia). Risk of fatal hyperinfection syndrome. |
Safety First: Do NOT initiate biologic/JAK inhibitor therapy until latent TB prophylaxis is commenced or active infections are treated and cleared.
Methotrexate (Dosing, Monitoring, Folate)
Methotrexate (MTX) is the first-line anchor DMARD for rheumatoid arthritis and is used in many other inflammatory conditions. It is a folate antagonist with immunomodulatory effects.
Methotrexate
Various generics · Methoblastin® · Antimetabolite DMARD
Adult dose
Start 7.5–10 mg ONCE WEEKLY. Titrate by 2.5–5 mg every 2–4 weeks to target 15–25 mg/week. Oral or subcutaneous (SC).
Paediatric dose
0.3–0.5 mg/kg/week (JIA). Max 25 mg/week.
Route
Oral or Subcutaneous injection. SC has better bioavailability and less GI side effects.
Folic acid
5 mg orally ONCE weekly, NOT on the same day as MTX. Reduces mucositis, cytopenias, LFT abnormalities.
Key monitoring
FBC, LFTs, eGFR: every 2–4 weeks until dose stable, then every 2–3 months.
PBS status
✔ PBS General Benefit
Critical Safety: Methotrexate is taken ONCE WEEKLY. Daily dosing is a potentially fatal error. Ensure clear patient education and dispensing.
Managing Common Issues
- Nausea/GI intolerance: Consider switching to subcutaneous injection, dose splitting (e.g., 2.5 mg every 12 hours x 3 doses weekly), or antiemetics.
- Elevated LFTs: Hold if transaminases >3x ULN. Re-check after 2–4 weeks. Consider dose reduction or cessation if persistent.
- Cytopenias: Hold for significant leucopenia or thrombocytopenia. Check for concurrent trimethoprim use (avoid).
- Pneumonitis: Rare. Suspect if new dry cough or dyspnoea. Stop MTX and investigate urgently.
Conventional Synthetic DMARDs (csDMARDs)
These are oral agents used as monotherapy or in combination (e.g., triple therapy: MTX + sulfasalazine + hydroxychloroquine).
Sulfasalazine
Salazopyrin® · Pyralin® · Sulfasalazine
Adult dose
Start 500 mg daily, increase by 500 mg weekly to 1–2 g/day in divided doses. Max 3 g/day.
Key monitoring
FBC, LFTs every 2–4 weeks initially, then 3-monthly. Ensure adequate fluid intake.
PBS status
✔ PBS General Benefit
Leflunomide
Arava® · Leflunomide
Adult dose
Loading: 100 mg daily for 3 days (often omitted due to GI side effects). Maintenance: 10–20 mg daily.
Key monitoring
FBC, LFTs, BP. Teratogenic (Category X). Washout with cholestyramine if needed.
PBS status
✔ PBS Restricted Benefit (RA only)
Hydroxychloroquine
Plaquenil® · Hydroxychloroquine
Adult dose
≤5 mg/kg actual body weight daily (typically 200–400 mg daily).
Key monitoring
Baseline & annual eye exam (after 5 years) for retinal toxicity. Renal impairment increases risk.
PBS status
✔ PBS General Benefit
TNF Inhibitors
Tumour Necrosis Factor (TNF) inhibitors were the first class of biologic DMARDs. They are first-line biologics for RA, psoriatic arthritis, and ankylosing spondylitis after csDMARD failure.
Adalimumab
Humira® · Hadlima® · Hyrimoz®
Dose
40 mg SC every 2 weeks.
PBS status
Authority Required
Etanercept
Enbrel® · Brenzys® · Erelzi®
Dose
50 mg SC weekly.
PBS status
Authority Required
Infliximab
Remicade® · Inflectra® · Renflexis®
Dose
3–10 mg/kg IV at 0, 2, 6 weeks then every 8 weeks.
PBS status
Authority Required
Infection Risk: TNF inhibitors significantly increase the risk of serious bacterial infections and reactivation of latent TB. Avoid in patients with active infections or severe heart failure (NYHA III/IV).
IL-6, IL-17, IL-23 Inhibitors
IL-6 Receptor Inhibitors (RA, GCA, JIA)
Tocilizumab
Actemra®
Dose (RA)
8 mg/kg IV every 4 weeks OR 162 mg SC weekly (weight <100 kg) or 162 mg SC twice weekly (>100 kg).
Key Issue
Masks infection signs (CRP suppression). Monitor lipids and for GI perforation.
PBS status
Authority Required
Sarilumab
Kevzara®
Dose (RA)
200 mg SC every 2 weeks.
PBS status
Authority Required
IL-17 Inhibitors (PsA, AS)
Secukinumab
Cosentyx®
Dose
150 mg SC every 4 weeks (after loading). Can increase to 300 mg.
PBS status
Authority Required
Ixekizumab
Taltz®
Dose
80 mg SC every 4 weeks (after loading).
PBS status
Authority Required
IL-23 Inhibitors (PsA)
Guselkumab
Tremfya®
Dose
100 mg SC every 8 weeks (after loading).
PBS status
Authority Required
Risankizumab
Skyrizi®
Dose
150 mg SC every 12 weeks (after loading).
PBS status
Authority Required
JAK Inhibitors
Janus Kinase (JAK) inhibitors are oral targeted synthetic DMARDs that block intracellular signalling of multiple cytokines. They are used in RA, PsA, and AS.
Tofacitinib
Xeljanz®
Adult dose
5 mg orally twice daily. Extended-release 11 mg once daily.
Renal impairment
eGFR 30–50: 5 mg once daily. eGFR <30: avoid.
PBS status
Authority Required
Baricitinib
Olumiant®
Adult dose
2 mg or 4 mg orally once daily (preferred 4 mg for RA).
Renal impairment
eGFR 30–60: 2 mg once daily. eGFR <30: avoid.
PBS status
Authority Required
Upadacitinib
Rinvoq®
Adult dose
15 mg orally once daily.
PBS status
Authority Required
Boxed Warning: JAK inhibitors are associated with increased risk of major adverse cardiovascular events (MACE), malignancy, VTE, and serious infections compared to TNF inhibitors in patients >50 years with ≥1 CV risk factor. Use only after failure of a TNF inhibitor in this population.
Herpes Zoster: Risk is significantly increased. Consider recombinant zoster vaccine (Shingrix®, 2 doses) BEFORE starting therapy if age ≥50.
Routine Monitoring on DMARDs
Consistent monitoring is essential for safety. Frequency is higher during initiation and dose changes.
| Test | Frequency (Stable) | Applies To | Action Thresholds |
|---|---|---|---|
| FBC (Full Blood Count) | Every 3 months | MTX, LEF, SSZ, JAKi | Hold for WCC <3.5 or Platelets <100. Review if Hb drops. |
| LFTs (ALT/AST) | Every 3 months | MTX, LEF, SSZ | Hold if >3x ULN. Recheck in 2–4 weeks. |
| eGFR/Creatinine | Every 3–6 months | All (dose adjustments needed) | Dose adjust per SPC. |
| Lipids | Baseline, 3 months, then annually | IL-6 inhibitors, JAK inhibitors | Manage per CV risk. |
| Blood Pressure | Every visit | JAK inhibitors | Manage hypertension. |
Special Populations
Pregnancy & Breastfeeding
Methotrexate: Teratogenic (Category X). Must cease ≥3 months before conception. Effective contraception mandatory.
Leflunomide: Teratogenic (Category X). Requires washout with cholestyramine.
Hydroxychloroquine: Safe in pregnancy. Continue to prevent flare.
Sulfasalazine: Safe, but ensure male partners stop sulfasalazine 3 months pre-conception (reversible oligospermia).
TNF inhibitors: Certolizumab pegol preferred (minimal placental transfer). Others stop by 20 weeks if disease allows.
JAK/IL-6 inhibitors: Limited data. Avoid unless benefits clearly outweigh risks.
Renal Impairment
Methotrexate: Avoid if eGFR <30. Use with caution and dose reduction if eGFR 30–50.
NSAIDs: Avoid with eGFR <30.
JAK inhibitors: Dose reduce (see specific drugs). Avoid baricitinib/tofacitinib if eGFR <30.
Biologics: Generally no dose adjustment but monitor for infections.
Hepatic Impairment
Methotrexate: Avoid in significant liver disease or alcohol use disorder.
Leflunomide: Avoid in active liver disease or ALT >2x ULN.
TNF inhibitors: Use with caution; rare reports of hepatotoxicity.
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
Rheumatic diseases, including rheumatic fever and rheumatic heart disease, have a higher prevalence and greater severity in Aboriginal and Torres Strait Islander communities, particularly in remote areas. Management with DMARDs requires a culturally safe, patient-centred approach.
Practice Point: Partner with local Aboriginal Community Controlled Health Organisations (ACCHOs) for holistic, continuous care. DMARD information sheets in language may be available through state Rheumatology departments.
📚 References
- 1. Ledingham J, Deighton C; British Society for Rheumatology Standards, Audit and Guidelines Working Group. Update on the British Society for Rheumatology guidelines for prescribing TNFα inhibitors in adults with rheumatoid arthritis (update of previous guidelines of April 2001). Rheumatology (Oxford). 2005;44(8):1018-1027.
- 2. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26.
- 3. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924-939.
- 4. Smolen JS, Landewé RBM, Bijlsma JWJ, 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.
- 5. Australian Institute of Health and Welfare (AIHW). Rheumatoid arthritis. Cat. no. PHE 248. Canberra: AIHW; 2021.
- 6. Pharmaceutical Benefits Scheme (PBS). Australian Government Department of Health. PBS Schedule. Available at: https://www.pbs.gov.au.
- 7. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med. 2022;386(4):316-326.
- 8. Buch MH, Landewé R, Rubbert-Roth A, et al. Safety of JAK inhibitors in patients with rheumatoid arthritis and other inflammatory diseases. RMD Open. 2023;9(2):e003073.
- 9. The Royal Australian College of General Practitioners (RACGP). National guide to a preventive health assessment for Aboriginal and Torres Strait Islander people. 3rd edn. East Melbourne, Vic: RACGP; 2018.
- 10. RHDAustralia (Australian Government Department of Health). The Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease. 3rd edition. 2020.
- 11. Australasian Society of Clinical Immunology and Allergy (ASCIA). Guidelines for vaccination of patients on immunosuppressive therapy. 2023.
- 12. Beglinger C, Dudler J, Lottaz D, et al. Strongyloides stercoralis hyperinfection in a patient with rheumatoid arthritis. Ann Rheum Dis. 2005;64(8):1223-1224.