Ruxolitinib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Ruxolitinib
- Ruxolitinib: From Myelofibrosis to Uterine Corpus Perivascular Epithelioid Cell Tumor (PEComa)
Ruxolitinib: From Myelofibrosis to Uterine Corpus Perivascular Epithelioid Cell Tumor (PEComa)
One-Sentence Summary
Ruxolitinib is an oral JAK inhibitor, originally used for myeloproliferative neoplasms such as myelofibrosis and polycythemia vera. The TxGNN model predicts it may be effective for uterine corpus perivascular epithelioid cell tumor, but this is a prediction only, with 0 clinical trials and 0 publications supporting it. Other predicted indications have more support, notably hemophagocytic lymphohistiocytosis (HLH), and are summarised under "Conclusion and Next Steps".
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Myelofibrosis, polycythemia vera and related myeloproliferative neoplasms (from the knowledge graph; the Singapore registry entries contain no indication text) |
| Predicted New Indication | Uterine corpus perivascular epithelioid cell tumor |
| TxGNN Prediction Score | 99.73% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 4 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled data. Based on known information, ruxolitinib is a JAK1/2 inhibitor. Its efficacy in myeloproliferative neoplasms is established, and these diseases are driven by overactive JAK-STAT signalling.
The link to the predicted indication is weak. PEComas are typically driven by activation of the mTOR pathway (loss of TSC1 or TSC2), and the data compiled for this report do not establish any connection between this pathway and JAK1/2 inhibition. The high score most likely reflects network similarity to related diseases in the knowledge graph rather than direct biological or clinical evidence.
The same pattern holds for the other PEComa-family predictions (benign PEComa, lung PEComa, lymphangiomyoma, lymphangioleiomyomatosis). All are prediction-only with no trials or publications. Lymphangioleiomyomatosis is mTOR-driven and already has an established therapy, sirolimus.
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 |
|---|---|---|
| SIN14927P | JAKAVI TABLET 10MG | Tablet |
| SIN14398P | JAKAVI TABLET 20MG | Tablet |
| SIN14397P | JAKAVI TABLET 15MG | Tablet |
| SIN14396P | JAKAVI TABLET 5MG | Tablet |
All four registrations are valid single-ingredient oral products from Novartis Pharma Stein AG. No indication text is recorded for them in the registry data.
Safety Considerations
- Drug Interactions: 100 interactions were found in the DDInter database. The 20 reviewed include the following.
- Major: clarithromycin, cobicistat, deferasirox, deferiprone, ibritumomab tiuxetan, tositumomab, tositumomab (I-131), samarium (153Sm) lexidronam
- Moderate: dexamethasone, rosuvastatin, fenfluramine, dexfenfluramine, sibutramine, troglitazone, palifermin, strontium chloride Sr-89
- Minor: aprepitant, cimetidine, miconazole, clotrimazole
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on model score alone (L5). There are no trials or publications, and the known biology of PEComa (mTOR-driven) does not point to a role for JAK inhibition.
Other predicted indications with more support:
- Hemophagocytic lymphohistiocytosis (HLH), including infection-associated forms (L3): This has the strongest evidence of the predictions reviewed. It includes a prospective pediatric response-stratified study, case series, compassionate-use reports and murine mechanistic work. Most evidence is retrospective or case-based, and no registered trials were identified, so a prospective controlled trial is still needed.
- Liposarcoma (L4): Two preclinical papers describe JAK-STAT signalling in myxoid liposarcoma. There is no clinical evidence with ruxolitinib.
- HLH associated with malignancy (L4): The two supporting papers are indirect, so this would have to be extrapolated from the broader secondary HLH literature.
To proceed, the following is needed:
- A mechanistic rationale linking JAK/STAT inhibition to PEComa biology, plus any preclinical or clinical data in PEComa
- The mechanism of action and the package insert warnings and contraindications, which are missing from the compiled data and are needed for safety screening
- Singapore-approved indication text for the four registrations
- For HLH, a prospective controlled trial design and a route and dosing assessment
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.