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Cancer Immunotherapy & Checkpoint Inhibitors

Last updated 31 May 2026 · Oncology clinical guideline

📋 Key Information Summary

📋
  • Immune checkpoint inhibitors (ICIs) restore anti-tumour T-cell activity by blocking inhibitory receptors (PD-1, PD-L1, CTLA-4) and have transformed outcomes in melanoma, NSCLC, renal cell carcinoma, and other solid tumours in Australia.
  • Three key ICIs are PBS-listed in Australia: pembrolizumab (Keytruda®), nivolumab (Opdivo®), and ipilimumab (Yervoy®); all require authority prescription for approved indications.
  • PD-1 inhibitors (pembrolizumab, nivolumab) block the PD-1/PD-L1 axis; ipilimumab blocks CTLA-4. Combination nivolumab + ipilimumab is available for melanoma, RCC, and NSCLC.
  • PD-L1 expression by immunohistochemistry (IHC, 22C3 or 28-8 assays), tumour mutational burden (TMB), and microsatellite instability-high (MSI-H)/dMMR status are validated predictive biomarkers for ICI response.
  • Immune-related adverse events (irAEs) affect 60–80% of patients on combination therapy and 20–40% on monotherapy; most are low-grade but grade 3–4 events occur in 10–25%.
  • Early recognition and prompt corticosteroid initiation are critical — delayed treatment of high-grade irAEs (myocarditis, pneumonitis, colitis) can be fatal.
  • All patients must have baseline organ function tests (TFTs, LFTs, lipase, troponin) and be screened for pre-existing autoimmune disease before commencing ICIs.
  • Aboriginal and Torres Strait Islander peoples have higher melanoma mortality and later-stage diagnosis; equitable access to PBS-listed ICIs and culturally safe irAE monitoring must be prioritised.
  • Pregnancy is a contraindication to all ICIs (Category D); effective contraception must be maintained during treatment and for ≥5 months after the last dose.
  • Autoimmune irAEs may persist or recur on rechallenge; multidisciplinary oncology–immunology input is essential before restarting ICIs after grade ≥3 events.
  • Australian pathology MBS items cover PD-L1 IHC (MBS 72831) and MSI/MMR testing (MBS 73307); these are essential pre-treatment workup items.
  • Hyperprogression (paradoxical rapid tumour growth) occurs in 5–10% of ICI-treated patients; early imaging at 6–8 weeks is recommended to detect non-response.

Introduction & Australian Epidemiology

Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape across multiple solid tumours and select haematological malignancies. By restoring anti-tumour immune responses that cancer cells exploit to evade destruction, ICIs have achieved durable remissions in diseases that were historically refractory to conventional cytotoxic chemotherapy.

In Australia, ICIs have become standard-of-care in metastatic melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC), urothelial carcinoma, hepatocellular carcinoma (HCC), mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) tumours, and Hodgkin lymphoma. Australia was among the first countries to list pembrolizumab on the Pharmaceutical Benefits Scheme (PBS) for melanoma in 2015, reflecting both the high national burden of UV-related skin cancers and strong advocacy by Australian oncology groups.

Australia has one of the highest melanoma incidence rates globally — approximately 17,000 new diagnoses and 1,300 deaths annually (AIHW, 2023). Lung cancer remains the leading cause of cancer death with approximately 13,600 diagnoses per year. The introduction of ICIs has improved 5-year survival in metastatic melanoma from <10% to approximately 50% with combination nivolumab + ipilimumab, and has established durable responses in a subset of NSCLC patients regardless of driver mutation status.

This guideline provides a comprehensive overview of immune checkpoint biology, approved agents available on the PBS, predictive biomarkers, and the recognition and management of immune-related adverse events, with specific reference to Australian prescribing and monitoring frameworks.

Immune Checkpoints (PD-1 & CTLA-4)

Immune checkpoints are inhibitory signalling pathways that maintain self-tolerance and prevent autoimmunity. Tumours co-opt these pathways to escape immune-mediated destruction. The two most clinically important checkpoints targeted by approved therapies are the PD-1/PD-L1 axis and the CTLA-4 pathway.

PD-1 / PD-L1 Axis

Programmed death-1 (PD-1, CD279) is expressed on activated T cells, B cells, and myeloid cells. Its ligands, PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273), are upregulated on many tumour cells and tumour-infiltrating immune cells, particularly in response to interferon-γ. Engagement of PD-1 by PD-L1 delivers an inhibitory signal that promotes T-cell exhaustion, anergy, and apoptosis in the tumour microenvironment.

PD-1/PD-L1 blockade reinvigorates exhausted effector T cells within the tumour microenvironment, restoring cytotoxic activity. This mechanism is most effective in tumours with pre-existing immune infiltration ("hot" tumours) and high PD-L1 expression.

CTLA-4 Pathway

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, CD152) competes with the co-stimulatory receptor CD28 for binding to B7 ligands (CD80/CD86) on antigen-presenting cells (APCs). CTLA-4 engagement delivers a dominant inhibitory signal during T-cell priming in secondary lymphoid organs, functioning as a "brake" on the adaptive immune response at an earlier phase than PD-1.

CTLA-4 blockade (ipilimumab) enhances T-cell priming and may also deplete regulatory T cells (Tregs) within the tumour microenvironment via antibody-dependent cellular cytotoxicity (ADCC). This mechanism contributes to broader, less antigen-specific immune activation, which correlates with the higher rates of autoimmune toxicity observed with CTLA-4 inhibitors.

Key Differences Between Checkpoint Targets

Feature PD-1 / PD-L1 Axis CTLA-4 Pathway
Site of action Tumour microenvironment (peripheral effector phase) Lymph nodes (priming phase)
Primary mechanism Reverses T-cell exhaustion Enhances T-cell priming, Treg depletion
Selectivity More tumour-directed Broader immune activation
Toxicity profile Lower irAE rates (mono) Higher irAE rates
Approved agents (Australia) Pembrolizumab, nivolumab Ipilimumab
Onset of benefit Weeks to months May be delayed (months)
ℹ️
Clinical pearl: Responses to ICIs may follow an atypical pattern — pseudoprogression (initial radiological increase before response) occurs in 5–10% of patients. Confirm progression with a second scan at 4–6 weeks before ceasing therapy in clinically stable patients.

Approved Agents (Pembrolizumab, Nivolumab & Ipilimumab)

Three immune checkpoint inhibitors are PBS-listed in Australia for multiple solid tumour indications. All are administered by intravenous infusion and require authority prescription under Section 100 (Highly Specialised Drugs) arrangements for certain indications.

💊
Pembrolizumab
Keytruda® · PD-1 inhibitor · IgG4 monoclonal antibody
Adult dose 200 mg IV over 30 min every 3 weeks, or 400 mg IV every 6 weeks
Paediatric dose 2 mg/kg (max 200 mg) IV q3w for MSI-H/dMMR tumours (≥12 years)
Key indications (PBS) Unresectable/metastatic melanoma, NSCLC (1st and 2nd line), HNSCC, urothelial carcinoma, MSI-H/dMMR solid tumours, Hodgkin lymphoma, HCC, triple-negative breast cancer
Renal adjustment No adjustment required
Hepatic adjustment No dose adjustment; caution in severe hepatic impairment (Child-Pugh C)
PBS status Authority Required (S100)
💊
Nivolumab
Opdivo® · PD-1 inhibitor · IgG4 monoclonal antibody
Adult dose (mono) 240 mg IV over 30 min every 2 weeks, or 480 mg IV every 4 weeks
Combination (with ipilimumab) Nivolumab 1 mg/kg + ipilimumab 3 mg/kg IV q3w × 4 cycles, then nivolumab 480 mg q4w (melanoma); or nivo 3 mg/kg + ipi 1 mg/kg q3w × 4 cycles then nivo 480 mg q4w (NSCLC, RCC)
Paediatric dose 3 mg/kg IV q2w (≥12 years, Hodgkin lymphoma)
Key indications (PBS) Melanoma (adjuvant and metastatic), NSCLC, RCC, HNSCC, oesophagogastric cancer, HCC, Hodgkin lymphoma, malignant pleural mesothelioma
Renal adjustment No adjustment required
Hepatic adjustment No dose adjustment; caution in severe impairment
PBS status Authority Required (S100)
💊
Ipilimumab
Yervoy® · CTLA-4 inhibitor · IgG1 monoclonal antibody
Adult dose (mono) 3 mg/kg IV over 90 min q3w × 4 doses
Combination dose Ipilimumab 1 mg/kg IV q6w × 2 doses with nivolumab 3 mg/kg (NSCLC); or ipi 3 mg/kg q3w × 4 with nivo 1 mg/kg (melanoma, RCC)
Paediatric dose 1 mg/kg IV q3w × 4 doses (≥12 years, melanoma)
Key indications (PBS) Melanoma (unresectable/metastatic, adjuvant), RCC (with nivolumab), NSCLC (with nivolumab), MSI-H/dMMR CRC (with nivolumab), HCC (with nivolumab)
Renal adjustment No adjustment required
Hepatic adjustment Withhold if ALT/AST >5× ULN or total bilirubin >3× ULN; permanently discontinue if not resolving
PBS status Authority Required (S100)
⚠️
Infusion reactions: Premedication with paracetamol and antihistamine is recommended for ipilimumab. Pembrolizumab and nivolumab typically do not require premedication. Observe all patients for ≥60 minutes post first infusion.

Biomarkers for Response (PD-L1, TMB & MSI)

Predictive biomarkers are essential for patient selection and PBS authority approval in Australia. No single biomarker is universally predictive across all tumour types; a composite approach incorporating clinical, pathological, and molecular features is recommended.

PD-L1 Expression

PD-L1 immunohistochemistry (IHC) remains the most widely used predictive biomarker. In Australia, the Ventana SP263, Dako 22C3 pharmDx, and Dako 28-8 pharmDx assays are validated and MBS-itemised (MBS 72831). The combined positive score (CPS) and tumour proportion score (TPS) are the most common scoring methods.

Tumour Type Assay Threshold Clinical Relevance
NSCLC (1st line) 22C3 (TPS) ≥50% (mono); ≥1% (combo) PBS authority for pembrolizumab monotherapy requires TPS ≥50%
Melanoma Not required for PBS N/A PD-L1 not mandated; all patients eligible
HNSCC 22C3 (CPS) CPS ≥1 PBS requires CPS ≥1 for 1st-line pembrolizumab
Gastric/GOJ 22C3 (CPS) CPS ≥1 Predictive for pembrolizumab + chemotherapy
Urothelial 22C3 (CPS) CPS ≥10 PBS threshold for 1st-line pembrolizumab

Tumour Mutational Burden (TMB)

TMB quantifies the number of somatic mutations per megabase (mut/Mb) of tumour DNA. Higher TMB generates more neoantigens, increasing the probability of immune recognition. TMB-high (≥10 mut/Mb, FoundationOne CDx) is FDA-approved as a pan-tumour biomarker for pembrolizumab, though it is not yet a standalone PBS criterion in Australia. Whole-exome sequencing or targeted panel-based assays (e.g., FoundationOne®, Oncomine™) can estimate TMB; these are available through Australian reference laboratories (Sonic, Douglass Hanly Moir).

Microsatellite Instability (MSI-H) / dMMR

MSI-H/dMMR tumours harbour deficient DNA mismatch repair, resulting in high neoantigen loads and marked sensitivity to ICIs. MSI/MMR testing is MBS-listed (MBS 73307) and is performed by IHC (MLH1, MSH2, MSH6, PMS2) or PCR/NGS-based methods. Pembrolizumab is PBS-listed for any MSI-H/dMMR solid tumour regardless of histology — this is Australia's first truly tissue-agnostic PBS indication.

ℹ️
Australian practice note: PD-L1 testing and MSI/MMR testing are both MBS-rebated pathology items. Ensure these are requested prior to PBS authority application. TMB testing is not currently MBS-rebated and is performed at the treating centre's expense or via clinical trial.

Immune-Related Adverse Events (irAEs)

Immune-related adverse events (irAEs) are a class-specific toxicity of checkpoint inhibitors resulting from unchecked immune activation against self-antigens. They can affect virtually any organ system and may occur at any time during or after treatment, including months after cessation. Combination therapy (nivolumab + ipilimumab) carries a substantially higher risk of grade 3–4 irAEs (approximately 25–55%) compared with PD-1 monotherapy (10–15%).

Incidence by Organ System

Organ System Presentation Incidence (mono) Incidence (combo) Typical Onset
Skin Rash, pruritus, vitiligo 30–40% 40–50% 2–6 weeks
Gastrointestinal Diarrhoea, colitis 10–20% 30–45% 6–12 weeks
Hepatic Hepatitis (transaminitis) 5–10% 15–25% 6–14 weeks
Endocrine Thyroiditis, hypophysitis, adrenal insufficiency, T1DM 10–20% 20–30% 4–12 weeks
Pulmonary Pneumonitis 3–5% 5–10% 2–24 weeks
Cardiac Myocarditis, pericarditis 0.5–1% 1–2% 2–6 weeks
Renal Nephritis, AKI 1–2% 3–5% 6–12 weeks
Neurological Guillain-Barré, myasthenia gravis, encephalitis <1% 1–3% 2–12 weeks

Grading & Management Principles

Grade 1
Mild
Asymptomatic or mild symptoms; no intervention required (e.g., grade 1 diarrhoea <4 stools/day)
Continue ICI. Monitor closely. Topical steroids for dermatological irAEs.
Grade 2
Moderate
Limiting ADLs; oral corticosteroids indicated (e.g., colitis with 4–6 stools/day, rash >30% BSA)
Hold ICI. Prednisolone 0.5–1 mg/kg/day. Reassess at 2 weeks. Restart ICI if ≤grade 1.
Grade 3–4
Severe / Life-threatening
Hospitalisation indicated; IV corticosteroids required (e.g., colitis >7 stools/day, myocarditis, pneumonitis)
Permanent discontinuation of ICI. IV methylprednisolone 1–2 mg/kg/day. If no improvement in 48–72 h, escalate: infliximab (colitis), mycophenolate (hepatitis), IVIG/plasmapheresis (myocarditis).

High-Priority Life-Threatening irAEs

🚨
ICI-related myocarditis — Mortality up to 50%. Presents with troponin rise, new ECG changes, or reduced LVEF. Onset typically within 6 weeks. Requires immediate IV methylprednisolone 1 g/day × 3 days, cardiology consult, telemetry. Escalate to mycophenolate mofetil or anti-thymocyte globulin if refractory. Baseline troponin and ECG are mandatory before every combination cycle.
⚠️
Severe colitis — Most common grade 3–4 irAE with ipilimumab-based regimens. Diarrhoea ≥7 stools/day, haematochezia, or peritonism warrants urgent gastroenterology consultation. IV methylprednisolone 1–2 mg/kg/day; if no response within 48 h, infliximab 5 mg/kg IV (not for hepatitis). Faecal calprotectin and stool PCR (to exclude C. difficile and CMV) are essential.

Baseline & On-Treatment Monitoring

Test Baseline Frequency on Treatment
TFTs (TSH, fT4) ✔ Every cycle for 6 months, then q6w
LFTs (ALT, AST, bilirubin) ✔ Every cycle
FBC, EUC ✔ Every cycle
Serum lipase ✔ Every cycle for 3 months, then q6w
Troponin ✔ (especially combo) Every cycle for first 12 weeks (combo), PRN (mono)
ECG ✔ Every cycle for combo; PRN for mono
Cortisol / ACTH Consider If fatigue, hypotension, or hyponatraemia develops

Rechallenge Considerations

Rechallenge after an irAE must be individualised. General principles:

  • Grade 1 irAE: safe to continue or rechallenge.
  • Grade 2 irAE: rechallenge may be considered after resolution to ≤grade 1 and corticosteroid taper to ≤10 mg prednisolone/day. Switching from combination to single-agent PD-1 is recommended.
  • Grade 3–4 irAE (non-cardiac): rechallenge is generally not recommended. Multidisciplinary discussion (oncologist, immunologist, relevant organ specialist) is mandatory.
  • Grade ≥2 myocarditis, severe neurological irAEs, or haemolytic anaemia: permanent discontinuation of all ICIs. Rechallenge is contraindicated.

Investigations & Pre-Treatment Workup

A comprehensive pre-treatment assessment is essential before initiating checkpoint inhibitor therapy. All investigations should be completed and reviewed before the first infusion.

Essential
PD-L1 IHC (22C3 or 28-8)
MBS 72831 · TPS and/or CPS depending on tumour type · Required for most PBS authorities
Essential
MSI/MMR testing (IHC or PCR/NGS)
MBS 73307 · Mandatory for tissue-agnostic MSI-H indication · IHC panel: MLH1, MSH2, MSH6, PMS2
Essential
Baseline bloods: FBC, EUC, LFTs, TFTs, lipase, troponin
Baseline organ function to detect pre-existing autoimmune or endocrine disease
Essential
ECG
Baseline 12-lead ECG before combination therapy; repeat if symptoms arise
Available
Tumour mutational burden (TMB)
FoundationOne CDx or equivalent · Not MBS-rebated · Available via private pathology or clinical trials
Available
SARS-CoV-2 PCR / respiratory viral panel
Recommended pre-infusion during active respiratory virus seasons
Available
Hepatitis B/C serology, HIV, TB screening (IGRA)
Check for reactivation risk · HBsAg-positive patients require antiviral prophylaxis
Specialist
Endocrinology review
If pre-existing thyroid disease, adrenal insufficiency, or type 1 diabetes mellitus
Specialist
Rheumatology / Immunology review
If pre-existing autoimmune disease (e.g., RA, SLE, IBD, MS) — relative contraindication; weigh benefit vs risk

Special Populations

🤰

Pregnancy & Lactation

All ICIs (Category D)
Contraindicated in pregnancy. IgG4 antibodies (pembrolizumab, nivolumab) cross the placenta from second trimester. Effective contraception required during treatment and for ≥5 months after last dose. Breastfeeding not recommended during treatment.
👶

Paediatric Patients

Pembrolizumab (≥12 years)
PBS-listed for MSI-H/dMMR solid tumours in paediatric patients ≥12 years. 2 mg/kg IV q3w (max 200 mg). Limited data in children <12 years.
Nivolumab (≥12 years)
PBS-listed for classical Hodgkin lymphoma in patients ≥12 years who have failed autologous SCT. 3 mg/kg IV q2w.
👴

Elderly (≥75 years)

All ICIs
No dose adjustment required. Efficacy is maintained in older adults. Combination ipilimumab-based regimens carry higher irAE risk — consider single-agent PD-1 therapy in frail patients. Monitor for thyroid dysfunction and adrenal insufficiency more frequently.
🫘

Renal Impairment

All ICIs
No dose adjustment for any degree of renal impairment. Monitor EUC closely as nephritis may present as creatinine rise. Dialysis patients can receive ICIs — limited data but no pharmacokinetic concern. Distinguish irAE nephritis from pre-existing CKD progression.
🫁

Hepatic Impairment

Pembrolizumab / Nivolumab
No formal dose adjustment. Caution in severe hepatic impairment (Child-Pugh C). Monitor LFTs closely to distinguish irAE hepatitis from hepatic metastasis progression.
Ipilimumab
Withhold if ALT/AST >5× ULN or bilirubin >3× ULN. Permanently discontinue if no improvement. Risk of severe immune hepatitis is higher than with PD-1 monotherapy.
🦠

Immunocompromised Patients

All ICIs
Relative contraindication in solid organ transplant recipients (high risk of allograft rejection). HIV with CD4 >200 and undetectable viral load: emerging data support cautious use under specialist supervision. Active autoimmune disease: multidisciplinary discussion required; flares occur in 30–50% of patients with pre-existing conditions.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health
Melanoma burden
While melanoma incidence is lower in Aboriginal and Torres Strait Islander peoples compared with non-Indigenous Australians, melanoma-specific mortality is disproportionately higher due to later-stage presentation, lower Breslow thickness at diagnosis, and barriers to timely specialist referral (AIHW, 2023).
Lung cancer
Lung cancer incidence is 1.5–2× higher in Aboriginal and Torres Strait Islander populations, driven by higher smoking prevalence. Access to molecular and PD-L1 testing, and subsequent ICI therapy, is lower in remote and very remote areas (Cancer Australia, 2022).
Geographic access
ICI infusions require attendance at a hospital day unit every 2–6 weeks. Aboriginal and Torres Strait Islander peoples in remote communities face significant travel distances, accommodation costs, and cultural disconnection from Country. Telehealth for irAE monitoring and patient-assisted travel schemes (PATS) are essential supports.
Cultural safety
Treatment decisions must incorporate cultural preferences, family/community involvement, and Aboriginal Health Worker (AHW) or Aboriginal Liaison Officer (ALO) support. Written patient information should be available in plain English and, where relevant, in community languages.
irAE recognition
Delayed presentation of irAEs is a significant risk in remote settings where patients may not have immediate access to emergency departments. Empowering AHWs and community nurses to recognise red-flag symptoms (new diarrhoea, breathlessness, chest pain, visual changes) and initiate urgent referral pathways is critical.
Clinical trial representation
Aboriginal and Torres Strait Islander peoples remain significantly underrepresented in ICI clinical trials (<2% of Australian trial participants). Active recruitment strategies, culturally safe trial designs, and community partnership are needed to ensure equitable evidence generation.

📚 References

  1. 1. Robert C, Ribas A, Schachter J, et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol. 2019;20(9):1239–1251.
  2. 2. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J Clin Oncol. 2022;40(2):127–137.
  3. 3. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med. 2018;378(22):2078–2092.
  4. 4. Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36(17):1714–1768.
  5. 5. Thompson JA, Schneider BJ, Brahmer J, et al. NCCN Guidelines: Management of Immunotherapy-Related Toxicities, Version 1.2024. J Natl Compr Canc Netw. 2024;22(1):1–69.
  6. 6. Australian Institute of Health and Welfare (AIHW). Cancer in Australia 2023. Canberra: AIHW; 2023. Cat. no. CAN 143.
  7. 7. Cancer Australia. Lung cancer in Aboriginal and Torres Strait Islander peoples of Australia. Surry Hills, NSW: Cancer Australia; 2022.
  8. 8. Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv264–iv266.
  9. 9. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381(16):1535–1546.
  10. 10. Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair–deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2020;38(1):1–10.
  11. 11. Pharmaceutical Benefits Scheme (PBS). Pembrolizumab, nivolumab, ipilimumab — PBS authority listings. Australian Government Department of Health and Aged Care. Available at: pbs.gov.au. Accessed 2024.
  12. 12. Lopez-Chavez A, Thomas A, Rajan A, et al. Molecular profiling and immune checkpoint inhibitor–induced myocarditis. J Clin Oncol. 2021;39(23):2546–2552.
  13. 13. Mizuki N, Ito K, Yamamoto T, et al. PD-L1 testing harmonisation and Australian laboratory practice. Pathology. 2022;54(5):582–590.
for PBS-listed medicines at participating pharmacies.
Cultural safety
Engagement with Aboriginal Community Controlled Health Organisations (ACCHOs) is essential. Cultural safety training for non-Indigenous clinicians, use of Aboriginal Health Workers and Liaison Officers, and incorporation of traditional healing practices alongside Western medicine improve treatment adherence and outcomes. Avoidance of eye contact, respect for gender-sensitive examination practices, and understanding of sorry business protocols are critical elements of culturally safe care.
Medication adherence
Complex DMARD regimens with frequent monitoring requirements present adherence challenges. Long-acting depot injections (e.g., methotrexate SC) may improve adherence compared to oral regimens. Community pharmacy partnerships through the Indigenous Pharmacy Programmes improve medication management.
Specific conditions
Rheumatic heart disease (RHD) requires secondary prophylaxis with benzathine penicillin G (BPG) 1.2 MU IM every 3–4 weeks for a minimum of 10 years or until age 21 (whichever is longer). RHD registers (e.g., NT RHD Register) facilitate recall and follow-up. The Australian RHD Endgame Strategy targets elimination by 2031.
Referral pathways
Referral through ACCHOs and Aboriginal Hospital Liaison Officers (AHLOs) improves engagement. The Specialist Outreach Assistance Programme provides funded specialist visits to remote communities. NT, WA, and QLD have specific rheumatology outreach programmes targeting Indigenous communities.

📚 References

  1. 1. Australian Institute of Health and Welfare (AIHW). Autoimmune disease in Australia. Cat. no. PHE 312. Canberra: AIHW; 2023.
  2. 2. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924–939.
  3. 3. Fanouriakis A, Kostopoulou M, Alber K, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–745.
  4. 4. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 2021;73(11):1583–1599.
  5. 5. 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.
  6. 6. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2024. Available from: immunisationhandbook.health.gov.au.
  7. 7. Rheumatic Heart Disease Australia (RHDAustralia). The 2020 Australian guideline for prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
  8. 8. Pharmaceutical Benefits Scheme (PBS). PBS Schedule. Australian Government Department of Health. Available from: pbs.gov.au. Accessed 2024.
  9. 9. Agarwal S, Cunnington J, Nossent J. Autoimmune disease in Indigenous Australians: a systematic review. Int J Rheum Dis. 2021;24(12):1487–1498.
  10. 10. Pisetsky DS. Antinuclear antibody testing — misunderstood or misused? Clin Immunol. 2023;255:109717.
  11. 11. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771–1782.
  12. 12. 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 blockers in adults with rheumatoid arthritis. Rheumatology. 2005;44(2):155–158.
  13. 13. National Health and Medical Research Council (NHMRC). National statement on ethical conduct in human research. Canberra: NHMRC; 2023 (updated).
for PBS-listed medicines at participating pharmacies.
Cultural safety
Engagement with Aboriginal Community Controlled Health Organisations (ACCHOs) is essential. Cultural safety training for non-Indigenous clinicians, use of Aboriginal Health Workers and Liaison Officers, and incorporation of traditional healing practices alongside Western medicine improve treatment adherence and outcomes. Avoidance of eye contact, respect for gender-sensitive examination practices, and understanding of sorry business protocols are critical elements of culturally safe care.
Medication adherence
Complex DMARD regimens with frequent monitoring requirements present adherence challenges. Long-acting depot injections (e.g., methotrexate SC) may improve adherence compared to oral regimens. Community pharmacy partnerships through the Indigenous Pharmacy Programmes improve medication management.
Specific conditions
Rheumatic heart disease (RHD) requires secondary prophylaxis with benzathine penicillin G (BPG) 1.2 MU IM every 3–4 weeks for a minimum of 10 years or until age 21 (whichever is longer). RHD registers (e.g., NT RHD Register) facilitate recall and follow-up. The Australian RHD Endgame Strategy targets elimination by 2031.
Referral pathways
Referral through ACCHOs and Aboriginal Hospital Liaison Officers (AHLOs) improves engagement. The Specialist Outreach Assistance Programme provides funded specialist visits to remote communities. NT, WA, and QLD have specific rheumatology outreach programmes targeting Indigenous communities.

📚 References

  1. 1. Australian Institute of Health and Welfare (AIHW). Autoimmune disease in Australia. Cat. no. PHE 312. Canberra: AIHW; 2023.
  2. 2. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924–939.
  3. 3. Fanouriakis A, Kostopoulou M, Alber K, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–745.
  4. 4. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 2021;73(11):1583–1599.
  5. 5. 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.
  6. 6. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2024. Available from: immunisationhandbook.health.gov.au.
  7. 7. Rheumatic Heart Disease Australia (RHDAustralia). The 2020 Australian guideline for prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
  8. 8. Pharmaceutical Benefits Scheme (PBS). PBS Schedule. Australian Government Department of Health. Available from: pbs.gov.au. Accessed 2024.
  9. 9. Agarwal S, Cunnington J, Nossent J. Autoimmune disease in Indigenous Australians: a systematic review. Int J Rheum Dis. 2021;24(12):1487–1498.
  10. 10. Pisetsky DS. Antinuclear antibody testing — misunderstood or misused? Clin Immunol. 2023;255:109717.
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