Azathioprine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Azathioprine
- Azathioprine: From Rheumatoid Arthritis to Colobomatous Microphthalmia-Rhizomelic Dysplasia Syndrome
Azathioprine: From Rheumatoid Arthritis to Colobomatous Microphthalmia-Rhizomelic Dysplasia Syndrome
One-Sentence Summary
Azathioprine is an immunosuppressant, listed in the knowledge graph for rheumatoid arthritis. The TxGNN model predicts it may be effective for colobomatous microphthalmia-rhizomelic dysplasia syndrome, a rare developmental malformation syndrome. Currently there are no clinical trials and no publications supporting this prediction, so it rests on the model score alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Rheumatoid arthritis (from knowledge graph; the Singapore licence records contain no indication text) |
| Predicted New Indication | Colobomatous microphthalmia-rhizomelic dysplasia syndrome |
| TxGNN Prediction Score | 99.9994% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available for this report. Azathioprine is known as a purine-antimetabolite immunosuppressant. It suppresses the proliferation of immune cells, which is why it is used in immune-mediated conditions such as rheumatoid arthritis.
The predicted condition is a rare developmental syndrome affecting the eye and skeleton. It has no known inflammatory or immune-mediated driver that azathioprine would plausibly address. No mechanistic link could be identified between the original indication and this new one.
The very high score is a graph-based prediction only. It should not be read as evidence of clinical benefit.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form |
|---|---|---|
| SIN11000P | AZAFRINE TABS. 50 mg | Tablet |
| SIN10165P | AZATHIOPRINE PCH TABLET 50 mg | Tablet |
| SIN02082P | IMURAN TABLET 50 mg | Tablet, film coated |
All three are valid single-ingredient oral products, and none has been cancelled.
Safety Considerations
- Contraindication signals (knowledge graph, not package-insert text): pancreatitis, thrombocytopenia, anaemia (including macrocytic anaemia), impaired renal function, infectious disease (including fungal infection and dermatophytosis), lymphoma (including primary CNS lymphoma, lymphosarcoma and hepatosplenic T-cell lymphoma), hepatic vein thrombosis and Budd-Chiari syndrome.
- Drug Interactions: the interaction screening returned 100 entries. The main ones are:
- Moderate: mesalazine, balsalazide, olsalazine and sulfasalazine (the aminosalicylates).
- Minor: zinc acetate, zinc gluconate and zinc sulfate.
- Further entries, such as aspirin, metformin and omeprazole, have an unclassified severity level.
Please refer to the package insert for the official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction has no trials or literature behind it, and no plausible immune-mediated mechanism. Azathioprine's myelosuppressive and immunosuppressive profile adds safety concerns without any expected benefit.
To proceed, the following is needed:
- Evidence that the condition has an immune or inflammatory component that azathioprine could target
- Any clinical or preclinical study supporting this use
- Package-insert warnings and contraindications from the HSA
- Detailed mechanism-of-action data
Note on other predictions for this drug: Lower-ranked predictions for inflammatory bowel disease and ulcerative colitis are supported by many trials and systematic reviews and reach evidence level L1. These are established clinical uses rather than new repurposing findings. They would warrant "Proceed with Guardrails": TPMT/NUDT15 testing, blood count and liver monitoring, and malignancy and infection surveillance.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.