Pirfenidone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Pirfenidone: From Idiopathic Pulmonary Fibrosis to Extracutaneous Mastocytoma
One-Sentence Summary
Pirfenidone is an oral anti-fibrotic drug, originally used to treat idiopathic pulmonary fibrosis and related interstitial pneumonias. The TxGNN model predicts it may be effective for extracutaneous mastocytoma (score 99.7%), but no clinical trials and no publications currently support this specific prediction. This is a computational prediction only (Evidence Level L5).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Idiopathic pulmonary fibrosis (also acute interstitial pneumonia and idiopathic interstitial pneumonia, per the knowledge graph; the Singapore licences carry no indication text) |
| Predicted New Indication | Extracutaneous mastocytoma |
| TxGNN Prediction Score | 99.71% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available. Based on known information, pirfenidone is an anti-fibrotic agent whose efficacy in idiopathic pulmonary fibrosis is established. It is generally understood to dampen TGF-β and TNF-α signalling and fibroblast activity, and mechanistically it may be applicable to mast-cell-driven tissue remodelling.
The link between the original and predicted indications is weak. Pulmonary fibrosis is a non-malignant scarring disease, while mastocytoma is a mast cell neoplasm. The only plausible connection is pirfenidone's anti-inflammatory and anti-fibrotic effect on the tissue environment around mast cells. No direct evidence supports efficacy in mast cell neoplasms. This is a hypothesis, not a demonstrated effect.
Other top-ranked predictions are also mostly tumours of fibroblast or mast cell origin (dermatofibrosarcoma protuberans, aggressive systemic mastocytosis, fibrosarcomas), and none has trial or literature support. The one with some indirect evidence is fibroblastic neoplasm (rank 9, L4), which is summarised below for context.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
No literature was found for extracutaneous mastocytoma. For context, the table below shows the literature found for the related prediction fibroblastic neoplasm (rank 9), in descending order of evidence strength.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12907346 | 2003 | Pilot clinical study | Am J Gastroenterol | Pilot project testing pirfenidone, a non-cytotoxic oral anti-fibrotic, in desmoid tumours of familial adenomatous polyposis |
| 27835939 | 2016 | In vitro | BMC Musculoskelet Disord | Pirfenidone inhibited TGF-β1-driven activity in Dupuytren's disease-derived fibroblasts |
| 30927912 | 2019 | In vitro | BMC Musculoskelet Disord | Studied pirfenidone's effect on TGF-β1-stimulated non-SMAD signalling in Dupuytren's fibroblasts |
| 35129055 | 2022 | Preclinical | Pharm Dev Technol | Explored pirfenidone as a locally injectable anti-fibrotic for Dupuytren's disease |
| 29702057 | 2018 | Case report | Perm J | Undifferentiated pleomorphic sarcoma reported after pirfenidone use (possible safety signal; causality not established) |
| 32572469 | 2020 | Case report | Rheumatology (Oxford) | Multiple eruptive dermatofibromas aggravated by mycophenolate mofetil and pirfenidone in a patient with systemic sclerosis |
This evidence is mostly preclinical, focused on benign disease, and partly contradictory. Two case reports raise a possible tumour-promoting signal.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15601P | ESBRIET FILM COATED TABLET 801MG | Tablet, film coated | Not stated in the data compiled |
| SIN15600P | ESBRIET FILM COATED TABLET 267MG | Tablet, film coated | Not stated in the data compiled |
Both licences are valid single-ingredient products (oral), manufactured by Delpharm Milano S.r.l.
Safety Considerations
- Drug Interactions: 100 interactions were identified, and the 20 listed in the data compiled for this report are all rated Moderate. They include bupropion, omeprazole, esomeprazole, lansoprazole, cimetidine, eliglustat, obeticholic acid, oxandrolone, naltrexone, miconazole, nitisinone, glycerol phenylbutyrate, rolapitant, deferasirox, ticlopidine, lumefantrine, disulfiram, primaquine, thiabendazole and ivacaftor.
- Other signals from the literature: Two case reports (undifferentiated pleomorphic sarcoma; aggravated dermatofibromas) raise a possible tumour-related signal that needs further investigation. Pirfenidone's known hepatotoxicity is also relevant for any repurposing involving liver disease.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The high TxGNN score (99.7%) is a computational prediction only. There are no trials or publications for extracutaneous mastocytoma, and the plausible mechanism (anti-fibrotic effect) does not address the disease's actual drivers. Neighbouring predictions also show no supporting evidence, and the literature on related fibroblastic tumours includes possible safety signals.
To proceed, the following is needed:
- Singapore package insert warnings and contraindications (currently blocking safety screening)
- Mechanism of action data for pirfenidone, to support mechanistic analysis
- Preclinical studies (e.g. mast cell lines or models) testing pirfenidone's effect on mast cell neoplasms
- Evaluation of the tumour-related safety signals reported in case reports
- Route compatibility and similarity-to-original-indication assessments, which are still pending
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.