Ustekinumab
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Ustekinumab: From Psoriasis to Dermatitis
One-Sentence Summary
Ustekinumab was originally used to treat psoriasis, psoriatic arthritis and related skin conditions. The TxGNN model predicts it may be effective for dermatitis (mainly atopic dermatitis), supported by 6 registered clinical trials (2 directly relevant Phase 2 trials) and 20 publications. The evidence is early-stage and shows modest, inconsistent efficacy.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Psoriatic arthritis, psoriasis, parapsoriasis (the Canadian licence records contain no indication text) |
| Predicted New Indication | Dermatitis |
| TxGNN Prediction Score | 0.9999 |
| Evidence Level | L2 (no completed Phase 3 trial in dermatitis; the strongest data are two completed Phase 2 randomized trials) |
| Canada Market Status | Marketed (marketed DINs on record: at least 20) |
| Number of DINs | at least 20 |
| 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 is a human monoclonal antibody that blocks the p40 subunit shared by interleukin-12 (IL-12) and interleukin-23 (IL-23). This inhibits Th1 and Th17/Th22 immune pathways.
These pathways drive inflammation in psoriasis, where ustekinumab’s efficacy is established. They are also implicated in the chronic phase of atopic dermatitis, especially the Th22/IL-23 axis. This is the basis for the prediction.
The rationale is only partial, however. Atopic dermatitis is predominantly driven by Th2 immunity, which ustekinumab does not target directly. Published Phase 2 data show modest and inconsistent efficacy, so the link is plausible but not confirmed.
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. This is the strongest trial in the set. |
| NCT01806662 | Phase 2 | Completed | 32 | Randomized pilot of ustekinumab in chronic atopic dermatitis with sub-optimal response to prior therapy. The small sample limits its strength. |
| NCT05535738 | Phase 2/3 | Active, not recruiting | 45 | Contact dermatitis model using biologics and suction blistering to study skin inflammation. It is mechanistic and exploratory, so relevance is indirect. |
| NCT02074982 | Phase 3 | Completed | 676 | CLEAR study of secukinumab versus ustekinumab in plaque psoriasis. Ustekinumab is only the comparator, so it gives no evidence for dermatitis. |
| NCT01356758 | N/A | Completed | 126 | Cardiovascular risk assessment in severe psoriasis patients on biologics. Not relevant to dermatitis efficacy. |
| NCT07352566 | Phase 4 | Not yet recruiting | 10 | Microdevice for testing drugs directly in skin in atopic dermatitis and psoriasis. It is a methodology study with no efficacy evidence. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27304428 | 2017 | RCT | Experimental Dermatology | Phase 2 double-blind, placebo-controlled study in 33 patients with moderate-to-severe atopic dermatitis assessing efficacy and safety of ustekinumab. |
| 28338223 | 2017 | RCT (Phase 2) | British Journal of Dermatology | Randomized, placebo-controlled Phase 2 study of ustekinumab in Japanese patients with severe atopic dermatitis. |
| 29164954 | 2018 | Systematic review | Journal of Dermatological Treatment | Evaluated efficacy and safety of ustekinumab in atopic dermatitis. |
| 33849369 | 2022 | Real-world evidence analysis | Journal of Dermatological Treatment | Assessed 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, supporting the EAACI guideline. |
| 29098604 | 2018 | Systematic review / meta-analysis | American Journal of Clinical Dermatology | Examined whether biologics are efficacious in atopic dermatitis. |
| 36208443 | 2022 | Review | Dermatologic Therapy | Synthesized the off-label uses of ustekinumab. |
| 32347968 | 2020 | Review | Contact Dermatitis | Reviewed available data on biologics in allergic contact dermatitis. |
| 32172523 | 2020 | Review | Clinical Drug Investigation | Examined atopic dermatitis therapies that failed clinical trials, to understand reasons for failure. |
| 33282108 | 2020 | Review | Journal of Clinical and Aesthetic Dermatology | Reviewed biologic options for pediatric psoriasis and atopic dermatitis, including off-label use. |
Canada Market Information
Ustekinumab products have 20 valid licences in Canada, all single-ingredient. Dosage form and approved indication text were not available for them. The main authorizations are:
| DIN | Product Name |
|---|---|
| 02320673 | STELARA |
| 02320681 | STELARA |
| 02459671 | STELARA I.V. |
| 02544199 | WEZLANA |
| 02550245 | STEQEYMA |
Other biosimilar brands also hold licences: YESINTEK, JAMTEKI, OTULFI and FINLIUS.
Safety Considerations
- Drug Interactions: 100 interactions were identified in total; the main ones listed are:
- Moderate: corticosteroids (hydrocortisone, triamcinolone, dexamethasone, betamethasone, budesonide, prednisone, prednisolone), simvastatin, anticoagulants (apixaban, warfarin, rivaroxaban, dicoumarol), and radiopharmaceuticals/radioimmunotherapies (iobenguane I-131, ibritumomab tiuxetan, tositumomab).
- Minor: zinc salts (sulfate, acetate, gluconate, chloride).
For warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: Two completed Phase 2 randomized trials exist in atopic dermatitis, but published efficacy is modest and inconsistent. The mechanistic rationale is only partial because the disease is mainly Th2-driven. No Phase 3 evidence exists, and package insert safety information has not yet been reviewed, which blocks safety screening.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications, to enable safety screening
- Detailed mechanism of action data
- Critical review of the Phase 2 trial results (NCT01945086 and NCT01806662) for effect size and responder subgroups
- Evidence that a subgroup (e.g., chronic-phase or Th22/IL-23-high disease) benefits, ideally from a larger controlled trial
- Review of interaction management, 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.