Daily Literature Update
Deucravacitinib in patients with inflammatory bowel disease: 12-week efficacy and safety results from 3 randomized phase 2 studies in Crohn’s disease and ulcerative colitis
D’Haens G, Danese S, Panaccione R, et al. Deucravacitinib in patients with inflammatory bowel disease: 12-week efficacy and safety results from 3 randomized phase 2 studies in Crohn’s disease and ulcerative colitis. J Crohns Colitis. 2025 Jun 4;19(6):jjaf080. PMID: 40355364.
Introduction
TYK2 mediates IL-23 signaling important in IBD pathogenesis; deucravacitinib is a selective oral TYK2 inhibitor studied for efficacy and safety in Crohn’s disease and ulcerative colitis.
Study Overview
Study Type: 3 randomized, double-blind, placebo-controlled Phase 2 trials
Population: 239 Crohn’s disease; 169 ulcerative colitis patients
Intervention: Deucravacitinib at 3, 6, or 12 mg twice daily
Outcomes: Clinical remission/response and endoscopic endpoints at 12 weeks
Key Findings
- Primary efficacy endpoints not met in any study
- High placebo effect complicated efficacy evaluation
- Significant endoscopic response at 3 mg BID dose in Crohn’s disease (LATTICE-CD)
- Deucravacitinib was well tolerated with no new safety concerns
- LATTICE-CD and IM011-127 trials terminated early due to lack of efficacy
Context & Related Research
- D’Haens et al., 2025: Deucravacitinib failed to achieve primary endpoints versus placebo in Crohn’s and UC; safety profile consistent (PMID:40355364).
- Sandborn et al., 2025: VTX958, another TYK2 inhibitor in Crohn’s disease, showed numeric but not statistically significant improvements; safety acceptable (PMID:37366120).
- Sandborn et al., 2022: The LATTICE-UC phase 2 study showed no significant remission difference with deucravacitinib 6 mg BID in UC; good tolerability (PMID:36291677).
Clinical Implications
- Deucravacitinib does not currently demonstrate meaningful induction efficacy in moderate to severe IBD.
- Safety remains favorable with no new safety signals, supporting ongoing research.
- High placebo responses in trials highlight the need for optimized study designs.
Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Randomized, placebo-controlled design across 3 phase 2 studies | High placebo response rates affecting efficacy signals |
| Dosing variation allowed preliminary dose-response assessment | Early termination limited long-term data, smaller sample in IM011-127 |
| Consistent safety monitoring aligned with psoriasis data | 12-week induction period may be too short to detect full effects |
Future Directions
Further research should evaluate longer treatment durations, optimized dosing, biomarker-driven patient selection, and trial design improvements to clarify the role of deucravacitinib in IBD.
Conclusion
Deucravacitinib was safe and well tolerated but did not demonstrate significant clinical benefit over placebo in moderate to severe Crohn’s disease or ulcerative colitis after 12 weeks of treatment.
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Citations
- D’Haens G, Danese S, Panaccione R, et al. Deucravacitinib in patients with inflammatory bowel disease: 12-week efficacy and safety results from 3 randomized phase 2 studies in Crohn’s disease and ulcerative colitis. J Crohns Colitis. 2025 Jun 4;19(6):jjaf080. PMID: 40355364.
- Sandborn WJ, et al. VTX958 in Crohn’s disease: phase 2 trial results. 2025. PMID: 37366120.
- Sandborn WJ, et al. LATTICE-UC phase 2 study: deucravacitinib 6 mg BID in UC. 2022. PMID: 36291677.
