Upadacitinib
| Evidence Level: L5 | Predicted Indications: 2 |
Table of Contents
- Upadacitinib
- Upadacitinib: From Rheumatoid Arthritis to Colobomatous Microphthalmia-Rhizomelic Dysplasia Syndrome
Upadacitinib: From Rheumatoid Arthritis to Colobomatous Microphthalmia-Rhizomelic Dysplasia Syndrome
One-Sentence Summary
Upadacitinib is a selective JAK1 inhibitor, originally used to treat rheumatoid arthritis. The TxGNN model predicts it may be effective for colobomatous microphthalmia-rhizomelic dysplasia syndrome, but there are currently 0 clinical trials and 0 publications supporting this direction. The prediction rests on the model score alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Rheumatoid arthritis |
| Predicted New Indication | Colobomatous microphthalmia-rhizomelic dysplasia syndrome |
| TxGNN Prediction Score | 99.61% |
| Evidence Level | L5 |
| US Market Status | Cancelled only |
| Number of NDAs | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, upadacitinib is a selective JAK1 inhibitor, and its efficacy in rheumatoid arthritis is established through suppression of JAK-STAT-mediated cytokine signaling.
The predicted condition is a rare developmental disorder with eye and skeletal malformations. Disorders like this are generally not driven by JAK-STAT-mediated inflammation, so a plausible mechanistic link cannot be established from the available data. The high score (0.996) most likely reflects shared gene or pathway neighbors in the knowledge graph rather than a validated biological rationale. The prediction should be treated as a hypothesis-generating signal only.
A second prediction, brachydactyly-syndactyly syndrome (score 99.58%, also L5, also Hold), is a congenital limb malformation and has the same limitations: no trials, no literature, and no inflammatory component to target.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA211675 | Rinvoq (AbbVie Inc.) | Tablet, extended release | Not available |
| NDA218347 | Rinvoq (AbbVie Inc.) | Solution | Not available |
Both authorizations are listed as cancelled in the data compiled for this report.
Safety Considerations
- Drug Interactions: The interaction screening returned 100 interacting drugs in total; the 20 reviewed here show the following pattern:
- Major: Systemic and other corticosteroids (hydrocortisone, triamcinolone, dexamethasone, beclomethasone dipropionate, betamethasone, budesonide, prednisone, prednisolone, ophthalmic triamcinolone); clarithromycin; cobicistat; deferiprone; iobenguane (I-131).
- Moderate: Aprepitant, cimetidine, miconazole, deferasirox.
- Minor: Zinc sulfate, zinc acetate, zinc gluconate.
- JAK inhibitors as a class carry significant safety warnings (infections, thrombosis, malignancy, major adverse cardiovascular events). Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The only support is a high knowledge-graph score. There are no clinical trials or publications, no plausible mechanistic link to JAK1 signaling, and the product’s US authorizations are cancelled. A benefit-risk case cannot be made for a congenital structural condition given the known JAK inhibitor safety profile.
To proceed, the following is needed:
- Package insert warnings and contraindications (required before any safety screening)
- Mechanism of action data to assess whether any biological link exists
- Evidence of a JAK-STAT or inflammatory component in the predicted condition (e.g., preclinical or genetic studies)
- Clarification of the cancelled US authorization status
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.