Ustekinumab
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Ustekinumab: Dermatitis
One-Sentence Summary
Ustekinumab is an IL-12/IL-23 antagonist, originally used to treat psoriasis, psoriatic arthritis and related conditions. The TxGNN model predicts it may be effective for dermatitis (in the available evidence, mainly atopic dermatitis), with 6 clinical trials (2 directly testing ustekinumab in atopic dermatitis) and 20 publications identified. However, the clinical results to date have been modest and inconsistent.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Dermatitis |
| TxGNN Prediction Score | 0.9999 |
| Evidence Level | L2 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, ustekinumab blocks the p40 subunit shared by IL-12 and IL-23, which inhibits the Th1 and Th17 pathways. This is well established in psoriasis.
Psoriasis and dermatitis are both chronic inflammatory skin diseases. However, atopic dermatitis is mainly driven by Th2 immunity, with variable Th1/Th17 contributions (for example in chronic, intrinsic, paediatric or Asian-phenotype disease). The mechanistic rationale is therefore plausible but only partial.
Clinical results in atopic dermatitis have been modest and inconsistent. Th2-targeted agents such as dupilumab and tralokinumab are clearly more effective.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT01945086 | Phase 2 | Completed | 79 | Randomised, double-blind, placebo-controlled study of two ustekinumab doses in Japanese adults with severe atopic dermatitis |
| NCT01806662 | Phase 2 | Completed | 32 | Randomised pilot of ustekinumab in chronic atopic dermatitis with sub-optimal response to prior therapy |
| NCT05535738 | Phase 2/3 | Active, not recruiting | 45 | Contact dermatitis model using biologics to study skin inflammation via suction blistering (mechanistic study) |
| NCT02074982 | Phase 3 | Completed | 676 | CLEAR: secukinumab vs ustekinumab in plaque psoriasis (existing indication, not dermatitis) |
| NCT01356758 | N/A | Completed | 126 | Cardiovascular risk assessment in severe psoriasis patients on biologics (not dermatitis efficacy) |
| NCT07352566 | Phase 4 | Not yet recruiting | 10 | Microdevice for testing drugs in situ on atopic dermatitis and psoriasis skin (no efficacy data) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27304428 | 2017 | RCT | Exp Dermatol | Phase 2 placebo-controlled study of ustekinumab in 33 adults with moderate-to-severe atopic dermatitis |
| 28338223 | 2017 | RCT | Br J Dermatol | Phase 2 placebo-controlled study 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 |
| 32927498 | 2020 | Network meta-analysis | Cochrane Database Syst Rev | Compares systemic treatments for eczema |
| 33074565 | 2021 | Systematic review/meta-analysis | Allergy | Evidence appraisal of systemic treatments for moderate-to-severe atopic dermatitis (for the EAACI guideline) |
| 29098604 | 2018 | Systematic review/meta-analysis | Am J Clin Dermatol | Asks whether biologics are efficacious in atopic dermatitis |
| 33849369 | 2022 | Real-world evidence | J Dermatolog Treat | Real-world analysis of ustekinumab in atopic dermatitis; anecdotal reports show conflicting results |
| 36208443 | 2022 | Review | Dermatol Ther | Review of off-label uses of ustekinumab |
| 32172523 | 2020 | Review | Clin Drug Investig | Reviews atopic dermatitis therapies that failed clinical trials |
| 32347968 | 2020 | Review | Contact Dermatitis | Reviews biologics in allergic contact dermatitis |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 10767Q | Stelara | Injection 45 mg in 0.5 mL | Not listed in the data compiled for this report |
Safety Considerations
- Drug Interactions: 100 interactions were identified. The ones listed here are mostly moderate:
- Corticosteroids (hydrocortisone, triamcinolone, dexamethasone, betamethasone, budesonide, prednisone, prednisolone): Moderate
- Anticoagulants (warfarin, apixaban, rivaroxaban, dicoumarol): Moderate
- Simvastatin: Moderate
- Radiopharmaceuticals and radioimmunotherapies (iobenguane I-131, ibritumomab tiuxetan, tositumomab, tositumomab I-131): Moderate
- Zinc salts (sulfate, acetate, gluconate, chloride): Minor
Please refer to the TGA-approved Product Information (PI) for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: Two Phase 2 randomised trials and several systematic reviews have tested ustekinumab in atopic dermatitis, but the results have been modest and inconsistent. The mechanistic fit is only partial, and Th2-targeted agents are clearly more effective. This is better treated as a research question than a repurposing candidate for now. The other nine predictions (for example neonatal dermatomyositis, pityriasis lichenoides) have no supporting trials or literature.
To proceed, the following is needed:
- A critical appraisal of the Phase 2 results (NCT01945086, NCT01806662 and PMIDs 27304428, 28338223) to confirm the magnitude of effect
- Evidence for a defined subgroup (for example chronic, intrinsic, paediatric or Asian-phenotype disease) where Th1/Th17 activity predominates
- Mechanism of action data and TGA Product Information safety details (warnings and contraindications)
- Comparison with approved Th2-targeted therapies in the Australian context
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.