Cyclosporine
| Evidence Level: L4 | Predicted Indications: 7 |
Table of Contents
- Cyclosporine
- Cyclosporine: From Rheumatoid Arthritis and Dry Eye to Chronic Granulomatous Disease (Autosomal Recessive)
Cyclosporine: From Rheumatoid Arthritis and Dry Eye to Chronic Granulomatous Disease (Autosomal Recessive)
One-Sentence Summary
Cyclosporine is a calcineurin-inhibiting immunosuppressant, originally used for rheumatoid arthritis, dry eye syndrome, xerophthalmia and Sjogren syndrome. The TxGNN model predicts it may be effective for autosomal recessive chronic granulomatous disease, but there are 0 clinical trials and only 1 publication (a stem cell transplantation cohort study that does not test cyclosporine as a treatment), so the prediction is not supported by independent clinical evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Rheumatoid arthritis, dry eye syndrome, xerophthalmia, Sjogren syndrome (the Medsafe licence records contain no indication text, so these come from the knowledge graph) |
| Predicted New Indication | Granulomatous disease, chronic, autosomal recessive |
| TxGNN Prediction Score | 99.68% |
| Evidence Level | L4 |
| New Zealand Market Status | Cancelled only (no currently valid licences) |
| Number of Authorizations | 4 (all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Cyclosporine is known as a calcineurin inhibitor that suppresses T-cell activation, and its efficacy in immune-mediated conditions such as rheumatoid arthritis and ocular surface inflammation is established.
For chronic granulomatous disease (CGD), the link is weak. CGD is caused by a defect in phagocyte NADPH oxidase, not by overactive T-cells, so calcineurin inhibition has no direct mechanistic rationale. The only publication concerns stem cell transplantation outcomes, where cyclosporine would at most appear as graft-versus-host disease prophylaxis, not as treatment of the disease itself. The very high model score is therefore not backed by independent evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22078471 | 2012 | Cohort | J Allergy Clin Immunol | Survival after matched sibling or unrelated donor stem cell transplantation in CGD; the study addresses transplantation, not cyclosporine as a therapy |
New Zealand Market Information
All four licences are cancelled; none is currently valid. The data compiled for this report contain no approved indication text for these products.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 455598 | Neoral | Cap 100 mg | Not available |
| 455571 | Neoral | Cap 25 mg | Not available |
| 2011344 | Neoral | Cap 50 mg | Not available |
| 455563 | Neoral | Oral liq 100 mg per ml | Not available |
Safety Considerations
- Disease associations flagged in the knowledge graph (drug-disease contraindication links, not package insert text): hypertension, epilepsy, kidney disease, liver disease, gallbladder disease, infectious disease (including eye infections and conjunctivitis), hyperuricaemia, hypertriglyceridaemia, hyperbilirubinaemia (including Gilbert syndrome), thrombocytopenic purpura, pseudotumor cerebri / intracranial hypertension, and cancer or neoplasms (including lymphoma and primary central nervous system lymphoma).
- Drug interactions and transporter/target interactions (7 recorded, from pharmacology data without severity grading): FPR1, ABCG2, SLC10A1 (sodium/bile acid cotransporter), OATP1B1, OATP1B3, peptidylprolyl isomerase A (cyclophilin A) and peptidylprolyl isomerase D. The transporter interactions suggest possible effects on co-administered drugs that depend on these transporters.
Package insert warnings and contraindications were not available. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction has no registered trials, a single transplantation-focused publication, and no plausible mechanistic link between calcineurin inhibition and the NADPH oxidase defect in CGD. In addition, all New Zealand licences for cyclosporine are cancelled.
To proceed, the following is needed:
- Medsafe package insert warnings and contraindications (currently blocking for safety screening)
- Mechanism of action data from DrugBank
- Any preclinical or clinical evidence that cyclosporine itself treats CGD, rather than serving as GVHD prophylaxis in transplantation
- Clarification of the regulatory status in New Zealand, given that all licences are cancelled
- Review of other predicted indications; among the seven predictions, only brain aneurysm has some clinical literature (small 1990s studies of cyclosporine for vasospasm after subarachnoid haemorrhage), and that evidence concerns a downstream complication rather than aneurysm formation
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.