Efficacy and safety of rilzabrutinib in patients with moderate-to-severe atopic dermatitis: 16-week results from a proof-of-concept phase II clinical trial
Bibliographic record
Abstract
BACKGROUND: Atopic dermatitis (AD), the most common inflammatory skin disorder, carries a significant public health burden. Many patients with moderate-to-severe AD are unable to achieve adequate disease control with topical treatment and require treatment with oral immunosuppressants or monoclonal antibody injections. A continued unmet need for a safe, effective and easy-to-use oral drug exists. AD has a complex pathophysiology, including adaptive- and innate-dependent mechanisms, some of which involve Bruton tyrosine kinase (BTK). Rilzabrutinib is an oral, selective and reversible covalent BTK inhibitor. OBJECTIVES: To assess the efficacy and safety of rilzabrutinib in patients with moderate-to-severe AD and inadequate response or intolerance to topical corticosteroids. METHODS: Eligible adults were enrolled in two staggered dose-regimen cohorts: 800 mg daily (400 mg twice daily) or 1200 mg daily (400 mg three times daily) and randomized 3 : 2 to receive rilzabrutinib or placebo for 16 weeks. The primary efficacy endpoint was percentage change in Eczema Area and Severity Index (EASI) score from baseline to week 16. Key secondary endpoints included the proportion of participants at week 16 achieving an Investigator's Global Assessment score of 0 or 1, achieving EASI 75 and with a reduction in the weekly average of the daily Peak Pruritus Numerical Rating Scale (PP-NRS) of ≥ 4 from baseline. Safety was measured by recording adverse events (AEs). RESULTS: The primary endpoint did not reach statistical significance [least squares mean difference vs. placebo: 800 mg -6.3% (P = 0.62); 1200 mg -3.9% (P = 0.67)]. The key secondary endpoints also did not demonstrate significant improvements with rilzabrutinib vs. placebo. However, a rapid improvement in absolute and relative change in weekly average of the daily PP-NRS was demonstrated with rilzabrutinib. Rilzabrutinib was well tolerated. Treatment-emergent AEs (TEAEs) were mostly mild, with a low incidence of serious AEs. TEAEs occurring at a higher frequency with rilzabrutinib than with placebo included nausea and diarrhoea. AEs associated with previous generations of BTK inhibitors were not seen with rilzabrutinib. CONCLUSIONS: This study did not meet its primary endpoint. However, consistent results favouring rilzabrutinib with regard to itch response were observed. These findings also highlight the acceptable safety profile of rilzabrutinib vs. the AEs associated with other BTK inhibitors.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".