Ustekinumab
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Ustekinumab: From Psoriasis/Crohn’s Disease to Dermatitis (Atopic Dermatitis)
One-Sentence Summary
Ustekinumab (Stelara) is a human monoclonal antibody originally developed for plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis. The TxGNN model predicts it may also be effective for dermatitis, most concretely atopic dermatitis, with 7 clinical trials and 20 publications currently identified in this evidence pack. The drug is not currently marketed in Denmark, and key safety documentation (SmPC warnings/contraindications) is still missing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in Danish licensing data (no marketing authorisations on file); internationally approved for plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis (per literature, PMID 36208443) |
| Predicted New Indication | Dermatitis (evidence concentrated on atopic dermatitis) |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L2 |
| Denmark Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available from the Danish regulatory record or DrugBank extract used to build this pack (flagged as a High-severity data gap). Based on literature evidence in this pack (PMID 27304428), ustekinumab is a fully human IgG1 monoclonal antibody that binds the shared p40 subunit of interleukin-12 (IL-12) and interleukin-23 (IL-23), blocking downstream Th1, Th17 and Th22 pathway activation. This mechanism underlies its approved efficacy in psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis — all conditions with a strong Th17-driven inflammatory component.
Atopic dermatitis and psoriasis are both chronic inflammatory skin diseases, and there is biological plausibility for cross-over efficacy: several publications in this pack (PMID 29164954, PMID 29098604) note that Th17/Th22 activity contributes to atopic dermatitis pathology alongside the classically dominant Th2 axis, providing a rationale for IL-12/23 blockade.
However, this rationale is not as strong as for the approved indications. Real-world and systematic-review evidence in this pack (PMID 33849369, PMID 33074565) reports inconsistent results for ustekinumab in atopic dermatitis, reflecting that AD is more heterogeneous and Th2-dominant than psoriasis. The mechanistic link should therefore be regarded as plausible but not yet firmly established.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01945086 | Phase 2 | Completed | 79 | Randomized, double-blind, placebo-controlled trial of ustekinumab in Japanese adults with severe atopic dermatitis |
| NCT01806662 | Phase 2 | Completed | 32 | Pilot RCT of ustekinumab in chronic atopic dermatitis with sub-optimal response to prior therapy |
| NCT05535738 | Phase 2/3 | Recruiting | 45 | Suction-blistering model comparing biologic anti-inflammatory therapies in skin inflammation |
| NCT02074982 | Phase 3 | Completed | 676 | CLEAR trial: secukinumab vs. ustekinumab in moderate-to-severe plaque psoriasis (not atopic dermatitis; included under broader “dermatitis” tag) |
| NCT07352566 | Phase 4 | Not yet recruiting | 10 | Microdevice testing FDA-approved atopic dermatitis/psoriasis drugs directly in skin |
| NCT07041112 | N/A | Completed | 1000 | Pharmacogenetic observational study of 10-year survival of biologic therapies in cutaneous psoriasis |
| NCT01356758 | N/A | Completed | 126 | Cardiovascular risk assessment in severe psoriasis patients treated with biologic agents |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27304428 | 2017 | RCT (Phase 2) | Experimental Dermatology | Ustekinumab (IL-12/IL-23p40 antagonist) assessed for efficacy/safety in moderate-to-severe atopic dermatitis, n=33 |
| 28338223 | 2017 | RCT (Phase 2) | British Journal of Dermatology | Randomized, double-blind, placebo-controlled study of ustekinumab in Japanese patients with severe atopic dermatitis |
| 33074565 | 2021 | Systematic Review/Meta-analysis | Allergy | EAACI evidence appraisal of systemic treatments (including ustekinumab) for moderate-to-severe atopic dermatitis |
| 29098604 | 2018 | Systematic Review/Meta-analysis | American Journal of Clinical Dermatology | Evaluates whether biologics, including ustekinumab, are efficacious in atopic dermatitis |
| 29164954 | 2018 | Systematic Review | Journal of Dermatological Treatment | Systematic review of ustekinumab specifically in atopic dermatitis treatment |
| 36208443 | 2022 | Review | Dermatologic Therapy | Synthesizes off-label uses of ustekinumab beyond its approved indications |
| 33849369 | 2022 | Observational (Real-world) | Journal of Dermatological Treatment | Real-world evidence on effectiveness of ustekinumab in atopic dermatitis; reports mixed/conflicting results |
| 39987634 | 2025 | Observational (Pharmacovigilance) | International Immunopharmacology | FAERS-based real-world safety analysis of ustekinumab in psoriasis/psoriatic arthritis |
| 39201826 | 2024 | Narrative Review | Children (Basel) | Reviews biologics/small molecules, including ustekinumab, for pediatric AD, psoriasis, alopecia areata and HS |
| 35130397 | 2021 | Review | Dermatology Online Journal | Reviews off-label uses of TNF-α and IL-12/23 inhibitors (including ustekinumab) in dermatology |
Denmark Market Information
Ustekinumab currently has no recorded marketing authorisation in the Danish regulatory dataset used for this evaluation (0 licenses, market status: Not marketed). No national (Laegemiddelstyrelsen) or centralised (EMA) authorisation details are available in this evidence pack.
Safety Considerations
Please refer to the approved Summary of Product Characteristics (SmPC) for safety information. Key warnings, contraindications, and drug-drug interaction data are not currently available in this evidence pack — this is flagged as a Blocking data gap (DG001), meaning a formal safety pre-assessment cannot proceed until the SmPC/label is obtained from the source regulatory agency.
Conclusion and Next Steps
Decision: Hold
Rationale:
- Efficacy evidence for the dermatitis/atopic dermatitis indication is limited to two completed Phase 2 RCTs with mixed real-world results (L2), not yet at the strength typically required to offset the current safety data gap.
- A Blocking-severity data gap (DG001: missing warnings/contraindications) prevents safety pre-assessment, and the drug has no existing marketing authorisation in Denmark to anchor a regulatory pathway.
To proceed, the following is needed:
- Danish/EU-approved SmPC (warnings, contraindications, DDI) to resolve DG001
- Confirmed mechanism-of-action documentation from DrugBank/regulatory source to resolve DG002
- Additional Phase 3 RCT data specific to atopic dermatitis (or a defined dermatitis subtype) to raise evidence level beyond L2
- Clarification of which specific “dermatitis” subtype is intended, given TxGNN’s score covers a broad disease label while most direct trial evidence pertains specifically to atopic dermatitis
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.