Ustekinumab
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Ustekinumab: From Psoriasis to Dermatitis
One-Sentence Summary
Ustekinumab is an IL-12/23 antagonist originally used for psoriasis, psoriatic arthritis and parapsoriasis. The TxGNN model predicts it may be effective for dermatitis, a broad term that in the available trials mostly means atopic dermatitis. Currently 6 clinical trials (3 directly relevant) and 20 publications are linked to this direction, but the controlled data suggest limited efficacy.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Psoriatic arthritis, psoriasis, parapsoriasis |
| Predicted New Indication | Dermatitis |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L2 |
| US Market Status | Cancelled only (all 11 listed licenses are marked cancelled) |
| Number of NDAs | 11 (BLA) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Ustekinumab blocks the shared p40 subunit of IL-12 and IL-23, which suppresses Th1 and Th17 signaling. This is the basis for its use in psoriasis, a Th1/Th17-driven skin disease.
Some chronic inflammatory skin disease, including a subset of atopic dermatitis, involves these pathways, so the prediction has a biological basis. However, atopic dermatitis is predominantly Th2-driven, so the mechanistic fit is only partial. The Phase 2 data also appear to show limited efficacy.
The very high TxGNN score should be read with caution. “Dermatitis” covers heterogeneous conditions (atopic, contact and others), so the score alone does not establish a specific indication. Detailed mechanism-of-action data from DrugBank were not available for this report; the description above is based on known pharmacology.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01945086 | Phase 2 | Completed | 79 | Randomized, double-blind, placebo-controlled study of two ustekinumab doses in Japanese adults with severe atopic dermatitis; the strongest controlled evidence available |
| NCT01806662 | Phase 2 | Completed | 32 | Randomized pilot of ustekinumab in chronic atopic dermatitis with sub-optimal response to prior therapy; small sample |
| NCT05535738 | Phase 2/3 | Active, not recruiting | 45 | Contact dermatitis model using biologics to study skin inflammation by suction blistering; mechanistic, not an efficacy trial |
| NCT02074982 | Phase 3 | Completed | 676 | CLEAR: secukinumab vs ustekinumab in plaque psoriasis; not evidence for dermatitis |
| NCT01356758 | N/A | Completed | 126 | Cardiovascular risk in severe psoriasis patients on biologics; not relevant to dermatitis efficacy |
| NCT07352566 | Phase 4 | Not yet recruiting | 10 | Skin microdevice for testing approved drugs in situ; a methodology study |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27304428 | 2017 | RCT (Phase 2) | Exp Dermatol | Double-blind, placebo-controlled study of ustekinumab in 33 adults with moderate-to-severe atopic dermatitis |
| 28338223 | 2017 | RCT (Phase 2) | Br J Dermatol | Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis |
| 29164954 | 2018 | Systematic review | J Dermatolog Treat | Evaluates efficacy and safety of ustekinumab in atopic dermatitis |
| 33849369 | 2022 | Real-world analysis | J Dermatolog Treat | Real-world effectiveness of ustekinumab in atopic dermatitis; prior reports are anecdotal with conflicting results |
| 33074565 | 2021 | Systematic review/Meta-analysis | Allergy | Evidence appraisal of systemic treatments for moderate-to-severe atopic dermatitis |
| 29098604 | 2018 | Systematic review/Meta-analysis | Am J Clin Dermatol | Efficacy of biologics in atopic dermatitis |
| 36208443 | 2022 | Review | Dermatol Ther | Review of off-label uses of ustekinumab |
| 32347968 | 2020 | Review | Contact Dermatitis | Biologics in allergic contact dermatitis |
| 32172523 | 2020 | Review | Clin Drug Investig | Reviews atopic dermatitis agents that failed clinical trials |
| 31514420 | 2019 | Review | Children (Basel) | Biologic options for pediatric psoriasis and atopic dermatitis |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| BLA125261 | STELARA | Injection, solution | Not available in compiled data (status: cancelled) |
| BLA761331 | WEZLANA | Injection, solution | Not available in compiled data (status: cancelled) |
| BLA761338 | STEQEYMA | Injection, solution | Not available in compiled data (status: cancelled) |
| BLA761343 | Selarsdi | Injection, solution | Not available in compiled data (status: cancelled) |
| BLA761406 | YESINTEK | Solution | Not available in compiled data (status: cancelled) |
The data list 11 BLAs in total (including the Stelara originator and several biosimilars), all with cancelled status. This should be verified against current FDA records.
Safety Considerations
- Drug Interactions: 100 interactions were found in the DDI query. The ones listed here are mostly Moderate:
- Corticosteroids (hydrocortisone, prednisone, prednisolone, dexamethasone, betamethasone, triamcinolone, budesonide)
- Anticoagulants (warfarin, apixaban, rivaroxaban, dicoumarol)
- Simvastatin
- Radiopharmaceuticals/radioimmunotherapies (iobenguane I-131, ibritumomab tiuxetan, tositumomab)
- Zinc salts (Minor)
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: Two Phase 2 randomized, placebo-controlled studies exist in atopic dermatitis (evidence level L2), but the mechanism fits only partially because atopic dermatitis is mainly Th2-driven, and efficacy in these studies appears limited. “Dermatitis” is also too broad to define a specific indication. All US licenses are listed as cancelled, and the package-insert safety data are missing.
To proceed, the following is needed:
- Full results (primary endpoints, effect size) of NCT01945086 and NCT01806662, plus confirmation of the study populations
- A narrower target indication (e.g., a specific dermatitis subtype or Th1/Th17-high patient subset)
- FDA package insert warnings and contraindications
- Verification of current US market and licensing status
- Detailed mechanism-of-action data from DrugBank
- Consideration of the parapsoriasis-related predictions (pityriasis lichenoides, acute lichenoid pityriasis) as better mechanistic fits, although they currently have no clinical evidence
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.