Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
BackgroundChronic spontaneous urticaria (CSU) is inadequately controlled in many patients and greatly affects quality of life. Remibrutinib, a highly selective, oral, novel covalent Bruton tyrosine kinase inhibitor, might be effective in CSU.ObjectiveThis first-in-patient trial aimed to evaluate the efficacy and safety of remibrutinib in CSU treatment and characterize the dose–response.MethodsThis randomized, double-blind, placebo-controlled, phase 2b dose-finding trial evaluated remibrutinib (12 weeks) in patients inadequately controlled with second-generation H1-antihistamines, with at least moderately active CSU, with or without prior anti-IgE treatment (NCT03926611). Patients received remibrutinib 10 mg once daily, 35 mg once daily, 100 mg once daily, 10 mg twice daily, 25 mg twice daily, 100 mg twice daily, or placebo (1:1:1:1:1:1:1 ratio). The main end points were weekly Urticaria Activity Score change from baseline at week 4 and safety.ResultsOverall, 311 patients were randomized. Reduced symptom score was observed for all remibrutinib doses from week 1 until week 12, with weekly Urticaria Activity Score change from baseline at week 4: −19.1 (10 mg once daily), −19.1 (35 mg once daily), −14.7 (100 mg once daily), −16.0 (10 mg twice daily), −20.0 (25 mg twice daily), −18.1 (100 mg twice daily), and −5.4 for placebo (nominal P < .0001 for all doses vs placebo). Most adverse events were mild or moderate, with no dose-dependent pattern.ConclusionRemibrutinib was highly effective in the treatment of CSU over the entire dose range, with a rapid onset of action and a favorable safety profile. Chronic spontaneous urticaria (CSU) is inadequately controlled in many patients and greatly affects quality of life. Remibrutinib, a highly selective, oral, novel covalent Bruton tyrosine kinase inhibitor, might be effective in CSU. This first-in-patient trial aimed to evaluate the efficacy and safety of remibrutinib in CSU treatment and characterize the dose–response. This randomized, double-blind, placebo-controlled, phase 2b dose-finding trial evaluated remibrutinib (12 weeks) in patients inadequately controlled with second-generation H1-antihistamines, with at least moderately active CSU, with or without prior anti-IgE treatment (NCT03926611). Patients received remibrutinib 10 mg once daily, 35 mg once daily, 100 mg once daily, 10 mg twice daily, 25 mg twice daily, 100 mg twice daily, or placebo (1:1:1:1:1:1:1 ratio). The main end points were weekly Urticaria Activity Score change from baseline at week 4 and safety. Overall, 311 patients were randomized. Reduced symptom score was observed for all remibrutinib doses from week 1 until week 12, with weekly Urticaria Activity Score change from baseline at week 4: −19.1 (10 mg once daily), −19.1 (35 mg once daily), −14.7 (100 mg once daily), −16.0 (10 mg twice daily), −20.0 (25 mg twice daily), −18.1 (100 mg twice daily), and −5.4 for placebo (nominal P < .0001 for all doses vs placebo). Most adverse events were mild or moderate, with no dose-dependent pattern. Remibrutinib was highly effective in the treatment of CSU over the entire dose range, with a rapid onset of action and a favorable safety profile.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 it