Etanercept
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
Etanercept: Hypermobility of coccyx
One-Sentence Summary
Etanercept is a TNF-blocking fusion protein, originally used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and juvenile idiopathic arthritis. The TxGNN model (deep learning) predicts it may be effective for hypermobility of coccyx (top-ranked prediction), but the evidence is weak.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Hypermobility of coccyx |
| TxGNN Prediction Score | 0.9963 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Etanercept is, however, a well-known soluble TNF receptor fusion protein that binds TNF and blocks its inflammatory signalling, and it is established in rheumatoid arthritis.
The prediction is also contradicted in part. Several case reports describe etanercept-associated cutaneous vasculitis, nephropathy and accelerated nodulosis, so the drug may trigger rather than treat vasculitis in some patients.
Other Predictions at a Glance
| Predicted Indication | TxGNN Score | Evidence Level | Decision |
|---|---|---|---|
| Hypermobility of coccyx | 0.9963 | L5 | Hold |
| Kummell disease | 0.9955 | L5 | Hold |
| Vertebral disease | 0.9916 | L5 | Hold |
Clinical Trial Evidence
For the top prediction (hypermobility of coccyx):
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT07138898 | Phase 2 | Recruiting | 80 | Perioperative immunosuppressant management in rheumatology patients having shoulder arthroplasty. It does not test etanercept in rheumatoid vasculitis. |
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00421915 | Phase 3 | Completed | 84 | Placebo-controlled etanercept 25 mg twice weekly in ankylosing spondylitis; primary endpoint ASAS 20 at week 12 |
| NCT00434044 | Phase 3 | Completed | 150 | Double-blind placebo-controlled study in Chinese patients with ankylosing spondylitis |
| NCT00421980 | Phase 3 | Completed | 84 | Open-label long-term extension; long-term safety in ankylosing spondylitis |
| NCT00317499 | Phase 3 | Completed | 205 | Double-blind placebo-controlled etanercept in psoriatic arthritis and psoriasis |
| NCT02376790 | Phase 3 | Completed | 851 | Etanercept with or without methotrexate in psoriatic arthritis |
| NCT00247962 | Phase 4 | Completed | 566 | Etanercept versus sulphasalazine in ankylosing spondylitis |
| NCT00873730 | Phase 4 | Completed | 108 | Etanercept 100 mg versus 50 mg weekly in ankylosing spondylitis |
| NCT02509026 | Phase 4 | Completed | 210 | Withdrawal and retreatment in non-radiographic axial spondyloarthritis |
| NCT02486302 | N/A | Completed | 1534 | Real-world effectiveness of Enbrel in RA, PsA, axSpA and psoriasis |
| NCT00544557 | N/A | Completed | 1715 | Observational study of etanercept in routine ankylosing spondylitis care |
For polyarticular and juvenile chronic JIA:
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT02840175 | Phase 3 | Completed | 62 | Biologic tapering in oligoarticular or RF-negative polyarticular JIA with inactive disease |
| NCT03781375 | Phase 3 | Terminated | 25 | Etanercept plus methotrexate versus methotrexate alone in polyarticular JRA; terminated early |
| NCT00443430 | Phase 4 | Completed | 85 | TREAT in JIA: early aggressive therapy regimens including etanercept |
No clinical trials are registered for hypermobility of coccyx, Kummell disease, WHIM syndrome, vertebral disease or rheumatoid nodulosis. No trial lists RF-positive polyarticular JIA specifically.
Literature Evidence
For rheumatoid vasculitis:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33058033 | 2021 | Systematic Review | Clin Rheumatol | Biological drugs in rheumatoid vasculitis; evidence low-quality and mixed |
| 28391344 | 2017 | Review | Nephrol Dial Transplant | Role of TNFα blockade in ANCA-associated vasculitis and glomerulonephritis |
| 28123776 | 2017 | Cohort | RMD Open | Drug-specific risk of lupus-like and vasculitis-like events with TNF inhibitors in RA (BSRBR-RA) |
| 31632872 | 2019 | Case Report | Cureus | Etanercept-associated nephropathy |
| 10955351 | 2000 | Case Report | J Rheumatol | Leukocytoclastic vasculitis due to etanercept |
| 12209493 | 2002 | Case Report | Arthritis Rheum | Accelerated nodulosis and vasculitis after etanercept for RA |
| 15853915 | 2005 | Review | Scand J Immunol | Immunology of cutaneous vasculitis with etanercept and infliximab |
| 25544845 | 2014 | Case Report | Case Rep Med | Large vessel vasculitis in an RA patient on anti-TNF therapy |
For axial spondyloarthritis and ankylosing spondylitis:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40621455 | 2025 | Network Meta-analysis | Front Immunol | Risk of new-onset and recurrent uveitis with different biologics in ankylosing spondylitis |
| 25887212 | 2015 | Systematic Review | Cochrane Database Syst Rev | TNF-alpha inhibitors for ankylosing spondylitis |
| 28682112 | 2017 | Review | Expert Opin Biol Ther | Efficacy and tolerance of etanercept in axial spondyloarthritis |
| 23686218 | 2013 | Meta-analysis | Rheumatol Int | TNF blockers in ankylosing spondylitis |
For polyarticular JIA:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 10717011 | 2000 | Clinical trial | N Engl J Med | Etanercept in children with polyarticular JRA who did not tolerate or responded inadequately to methotrexate |
| 40148850 | 2025 | Meta-analysis | BMC Pediatr | Etanercept versus adalimumab in polyarticular JIA |
| 27135404 | 2016 | Systematic Review / HTA | Health Technol Assess | Clinical and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab in JIA |
| 12528122 | 2003 | Open-label extension | Arthritis Rheum | Long-term efficacy and safety of etanercept in polyarticular-course JRA |
No literature was found for hypermobility of coccyx, Kummell disease or WHIM syndrome.
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 11196G | Brenzys | Injection, 50 mg in 1 mL single-use pre-filled syringes (pack of 4) | Not available in the compiled data |
Safety Considerations
- Drug Interactions: 100 interactions were identified in the interaction database, of which the main ones are listed here.
- Major: corticosteroids (hydrocortisone, prednisone, prednisolone, dexamethasone, betamethasone, budesonide, triamcinolone including ophthalmic), deferiprone, and radiopharmaceuticals/radioimmunotherapies (iobenguane I-131, ibritumomab tiuxetan, tositumomab and tositumomab I-131).
- Moderate: metronidazole, tinidazole, rosuvastatin, simvastatin.
- Minor: zinc salts (sulfate, acetate, gluconate).
- Literature-reported adverse events: vasculitis, nephropathy, accelerated nodulosis, disseminated herpes zoster, uveitis (less effective than monoclonal anti-TNF antibodies) and neurological events with anti-TNF therapy.
Please refer to the TGA-approved Product Information (PI) for warnings and contraindications, which were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold (for the top-ranked prediction, hypermobility of coccyx)
Rationale:
- The high TxGNN score (0.9963) comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence, so it is not supported by clinical evidence.
- Rheumatoid nodulosis, hypermobility of coccyx, Kummell disease, vertebral disease and WHIM syndrome are all Hold, and WHIM syndrome carries added infection risk in an immunodeficient population.
To proceed, the following is needed:
- Mechanism of action data from DrugBank.
- TGA Product Information (warnings, contraindications and approved indications for Brenzys).
- Controlled studies (or a prospective registry) of etanercept in rheumatoid vasculitis that address the vasculitis signal.
- For guardrail candidates: standard TNF-inhibitor monitoring (infection and TB screening, uveitis risk), and paediatric dosing and growth monitoring for JIA.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.