Cyclosporine
| Evidence Level: L3 | Predicted Indications: 7 |
Table of Contents
Cyclosporine: From Transplant Immunosuppression to Chronic Granulomatous Disease
One-Sentence Summary
Cyclosporine is a calcineurin-inhibiting immunosuppressant most widely used to prevent transplant rejection and graft-versus-host disease (GvHD); no UK marketing authorisation record is present in this evidence pack. The TxGNN model predicts a possible link to Chronic Granulomatous Disease (autosomal recessive), with 1 clinical trial and 1 publication currently identified in support, both describing cyclosporine’s established role as GvHD prophylaxis during stem cell transplantation rather than a direct novel effect on the disease itself.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not on record in this evidence pack — no UK marketing authorisation or original-indication data supplied (see UK Market Information below) |
| Predicted New Indication | Chronic Granulomatous Disease (autosomal recessive) |
| TxGNN Prediction Score | 99.68% |
| Evidence Level | L3 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for Cyclosporine is flagged as a data gap in this evidence pack (DrugBank query pending, DG002). Based on established pharmacology, Cyclosporine is a calcineurin inhibitor that blocks T-cell activation and cytokine production, and is used clinically to prevent solid-organ transplant rejection and to prevent/treat graft-versus-host disease (GvHD) after allogeneic haematopoietic stem cell transplantation (HSCT).
Chronic Granulomatous Disease (CGD) is a primary immunodeficiency caused by defective NADPH oxidase in phagocytes; its established curative treatment is allogeneic HSCT. The clinical trial and literature identified for this candidate do not describe Cyclosporine treating the underlying NADPH oxidase defect. Instead, they describe Cyclosporine’s conventional role as post-transplant immunosuppression/GvHD prophylaxis in children undergoing HSCT for non-malignant diseases, of which CGD is one example.
This means the TxGNN association is most plausibly explained by Cyclosporine’s supportive role within the standard-of-care transplant pathway for CGD, rather than a direct disease-modifying mechanism against CGD itself. This distinction is important and should be clarified before further evaluation.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT01917708 | Phase 1 | Completed | 10 | Single-arm study of abatacept combined with cyclosporine and mycophenolate mofetil as GvHD prophylaxis in children/adolescents undergoing unrelated allogeneic HSCT for serious non-malignant diseases; assessed tolerability and immunological effects over 2 years’ follow-up. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22078471 | 2012 | Retrospective case series | The Journal of Allergy and Clinical Immunology | Reports excellent survival following sibling or unrelated-donor HSCT for CGD, supporting HSCT (with Cyclosporine used as standard GvHD prophylaxis) as an effective curative approach. |
UK Market Information
Cyclosporine is currently not marketed in the UK according to this evidence pack, with 0 marketing authorisations on record and no license entries supplied. No product name, dosage form, or approved-indication text is therefore available to tabulate.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
(Note: this evidence pack flags a Blocking data gap — TFDA/MHRA label warnings and contraindications are not yet available — which prevents a full S1 safety pre-assessment.)
Conclusion and Next Steps
Decision: Hold
Rationale: The identified trial and literature support Cyclosporine’s established use as GvHD prophylaxis during HSCT — the actual curative therapy for CGD — rather than demonstrating a direct disease-modifying effect of Cyclosporine on CGD. Combined with a Blocking data gap on regulatory safety labelling and the absence of any current UK marketing authorisation, the evidence does not yet support progressing beyond a holding position.
To proceed, the following is needed:
- TFDA/MHRA SmPC warnings, contraindications and drug-interaction data (Blocking gap, DG001)
- Confirmed mechanism-of-action data from DrugBank (High-priority gap, DG002)
- Clarification of whether the CGD association reflects a genuine disease-modifying role or solely Cyclosporine’s supportive use as GvHD prophylaxis during HSCT
- Confirmation of a UK supply/licensing route, since 0 marketing authorisations are currently on record
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.