Ruxolitinib

Evidence Level: L5

Predicted Indications: 10

Ruxolitinib

Pharmacist Assessment Report

Ruxolitinib: Uterine corpus perivascular epithelioid cell tumor

One-Sentence Summary

Ruxolitinib is an oral JAK1/2 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 (PEComa), with a very high score. However, this is a model prediction only: no clinical trials and no publications were found for this specific indication.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	Uterine corpus perivascular epithelioid cell tumor
TxGNN Prediction Score	0.9973
Evidence Level	L5
India Market Status	Listed in a compiled Indian medicine price dataset (5 of 5) – CDSCO approval status is not included in this data
Number of Listed Products	5 (valid: 5)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in the data compiled for this report. Ruxolitinib is a JAK1/2 inhibitor, and its efficacy in myeloproliferative neoplasms is established. Mechanistically, it may be applicable to tumours in which JAK-STAT signalling plays a role.

For uterine PEComa, the link is speculative. PEComas are generally driven by mTOR/PI3K pathway activation, and possible crosstalk with JAK-STAT signalling is a hypothesis rather than an established finding. The very high score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence of JAK1/2 biology in this tumour.

The same pattern appears across the related PEComa-family predictions: benign PEComa, lung PEComa, lymphangiomyoma and lymphangioleiomyomatosis. These carry similarly high scores but no supporting studies.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

Currently no related literature available.

India Market Information

Authorization Number	Product Name	Dosage Form
Registration No. 114043	Jakavi 15mg Tablet (Novartis India Ltd)	Strip of 14 tablets
Registration No. 113919	Jakavi 5mg Tablet (Novartis India Ltd)	Strip of 14 tablets
Registration No. 114073	Jakavi 20mg Tablet (Novartis India Ltd)	Strip of 10 tablets
Registration No. 114253	Jakavi 15mg Tablet (Novartis India Ltd)	Strip of 10 tablets
Registration No. 113944	Jakavi 20mg Tablet (Novartis India Ltd)	Strip of 14 tablets

All five registrations are valid single-ingredient oral products. The licence records do not include approved indication text.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (kinase inhibitor), not a conventional cytotoxic agent
Myelosuppression Risk	Medium. Cytopenias such as thrombocytopenia, anaemia and neutropenia are recognised with JAK inhibitors; please refer to the package insert warnings and precautions
Emetogenicity Classification	Low
Monitoring Items	CBC with differential, liver and renal function
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Drug Interactions: 338 interactions were recorded. The most clinically important are those rated Major:
- Clarithromycin
- Cobicistat
- Deferasirox
- Deferiprone
- Ibritumomab tiuxetan
- Tositumomab and Tositumomab (I-131)
- Samarium (153Sm) lexidronam
Moderate interactions include dexamethasone, rosuvastatin, fenfluramine, dexfenfluramine, sibutramine, troglitazone, palifermin and strontium chloride Sr-89.

Please refer to the package insert for warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction for uterine PEComa rests on the model score alone (L5), with no trials, no literature and no established mechanistic rationale. The drug is marketed in India, but not for this indication.

Among the other predicted indications, hemophagocytic lymphohistiocytosis (HLH) is the best supported. It has a mechanistic rationale (JAK/STAT-driven cytokine storm), a response-stratified paediatric study, case series and retrospective cohorts, and is rated L3. It is a more promising repurposing candidate to prioritise. Myxoid liposarcoma has only preclinical JAK-STAT data.

To proceed, the following is needed:

Evidence of JAK-STAT dependence in uterine PEComa (preclinical or case-level data)
Detailed mechanism of action data (MOA)
Package insert warnings and contraindications for the India-marketed products
A decision on whether to re-prioritise the HLH indication, which would require a prospective trial design
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.