Ustekinumab
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Ustekinumab: From Psoriasis to 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 (mainly atopic dermatitis), with 6 clinical trials (2 directly relevant Phase 2 trials) and 20 publications currently supporting this direction. The direct evidence is limited to small Phase 2 studies that showed only modest and inconsistent benefit.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Psoriatic arthritis, psoriasis, parapsoriasis (the Singapore licence records contain no indication text) |
| Predicted New Indication | Dermatitis |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 5 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Based on known pharmacology, ustekinumab is a human monoclonal antibody that blocks the shared p40 subunit of IL-12 and IL-23. This suppresses Th1 and Th17 signalling, which is the basis of its efficacy in psoriasis.
Atopic dermatitis is driven mainly by Th2 pathways (IL-4/IL-13), although Th1, Th17 and Th22 activity contributes variably. The mechanistic fit is therefore partial. Any benefit is likely limited to subsets, such as Asian or intrinsic phenotypes or chronic lesions. Phase 2 data show only modest, inconsistent benefit.
The other top-ranked predictions (neonatal dermatomyositis, acne keloid, acrodermatitis chronica atrophicans, and others) have no trials or literature and are computational predictions only. The two pityriasis lichenoides predictions (ranks 9 and 10) are biologically plausible through their link to parapsoriasis, but also lack clinical evidence.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01945086 | Phase 2 | Completed | 79 | Randomised, double-blind, placebo-controlled study of two ustekinumab doses in Japanese adults with severe atopic dermatitis. The strongest direct evidence, with modest efficacy |
| NCT01806662 | Phase 2 | Completed | 32 | Randomised pilot of ustekinumab in chronic atopic dermatitis with suboptimal response to prior therapy. Directly relevant but underpowered |
| NCT05535738 | Phase 2/3 | Active, not recruiting | 45 | Contact dermatitis model using biologics (including ustekinumab) to study skin inflammation. Mechanistic and exploratory |
| NCT07352566 | Phase 4 | Not yet recruiting | 10 | Microdevice for testing drugs directly in skin affected by atopic dermatitis and psoriasis. Methodological, no efficacy conclusions |
| NCT02074982 | Phase 3 | Completed | 676 | CLEAR study of secukinumab vs ustekinumab in plaque psoriasis. Ustekinumab was the comparator, so it does not address dermatitis |
| NCT01356758 | N/A | Completed | 126 | Cardiovascular risk assessment in severe psoriasis patients on biologics. Not relevant to dermatitis efficacy |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27304428 | 2017 | RCT | Experimental Dermatology | Phase 2, double-blind, placebo-controlled study in 33 adults with moderate-to-severe atopic dermatitis, assessing efficacy and safety of ustekinumab |
| 28338223 | 2017 | RCT (Phase 2) | British Journal of Dermatology | Randomised, double-blind, placebo-controlled study in Japanese patients with severe atopic dermatitis |
| 29164954 | 2018 | Systematic review | J Dermatol Treat | Evaluated the efficacy and safety of ustekinumab in atopic dermatitis |
| 33074565 | 2021 | Systematic review / meta-analysis | Allergy | Evidence appraisal of systemic treatments for moderate-to-severe atopic dermatitis, supporting EAACI guidelines |
| 29098604 | 2018 | Systematic review / meta-analysis | Am J Clin Dermatol | Examined whether biologics are efficacious in atopic dermatitis |
| 33849369 | 2022 | Real-world evidence analysis | J Dermatol Treat | Evaluated ustekinumab in atopic dermatitis; prior reports were anecdotal with conflicting results |
| 36208443 | 2022 | Review | Dermatologic Therapy | Synthesis of off-label uses of ustekinumab |
| 32347968 | 2020 | Review | Contact Dermatitis | Review of biologics in severe allergic contact dermatitis |
| 32172523 | 2020 | Review | Clin Drug Investig | Reviews atopic dermatitis agents that failed placebo-controlled trials, to identify reasons for failure |
| 31514420 | 2019 | Review | Children (Basel) | Biologic options, including off-label use, for paediatric psoriasis and atopic dermatitis |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13704P | Stelara Solution for Injection 45mg/0.5 ml | Injection, solution | Not recorded in the data compiled for this report |
| SIN15438P | Stelara Concentrate for Solution for Infusion 130mg/26ml | Infusion, solution concentrate | Not recorded in the data compiled for this report |
| SIN17103P | Stelara Solution for Injection in Pre-filled Pen 90mg/1ml | Injection, solution | Not recorded in the data compiled for this report |
| SIN13995P | Stelara Solution for Injection in Pre-filled Syringe 45mg/0.5ml | Injection, solution | Not recorded in the data compiled for this report |
| SIN13996P | Stelara Solution for Injection in Pre-filled Syringe 90mg/1ml | Injection, solution | Not recorded in the data compiled for this report |
All five registrations are valid single-ingredient products from Cilag AG, and none has been cancelled.
Safety Considerations
- Drug Interactions: 100 interactions were identified, with the following examples listed.
- Moderate: corticosteroids (hydrocortisone, triamcinolone, dexamethasone, betamethasone, budesonide, prednisone, prednisolone); anticoagulants (warfarin, apixaban, rivaroxaban, dicoumarol); simvastatin; radiopharmaceuticals and radioimmunotherapies (iobenguane I-131, ibritumomab tiuxetan, tositumomab).
- Minor: zinc salts (sulfate, acetate, gluconate, chloride).
Package insert warnings and contraindications are not available in the compiled data. Please refer to the package insert for these.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence level is L2, based on small Phase 2 randomised trials in atopic dermatitis (n=79 and n=32–33) that showed only modest, inconsistent benefit. The mechanistic fit is partial, because atopic dermatitis is mainly Th2-driven. The package insert safety data are also missing. Newer targeted agents for atopic dermatitis may make this a lower priority.
To proceed, the following is needed:
- Singapore package insert warnings, contraindications and approved indication text
- Detailed mechanism of action data
- Adequately powered Phase 3 evidence, or identification of a responsive atopic dermatitis subgroup (for example, Asian or intrinsic phenotypes)
- A review of how ustekinumab compares with currently approved atopic dermatitis therapies
- A safety assessment covering the interactions listed above, particularly with corticosteroids and anticoagulants
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.