Efficacy and Safety of Rilzabrutinib in Pemphigus : PEGASUS Phase 3 Randomized Study
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
TRIAL DESIGN: Pemphigus is a rare but life-threatening autoimmune disease requiring long-term treatment that minimizes corticosteroid (CS) exposure while providing consistent disease control. The phase 2 pemphigus study of oral, reversible, covalent Bruton tyrosine kinase inhibitor rilzabrutinib demonstrated rapid and sustained efficacy with well-tolerated safety.
METHODS: Adults (aged 18-80 years) were randomized 1:1 to 400 mg rilzabrutinib (n = 65) or placebo (n = 66) twice daily (with CS ≤ 0.5 mg/kg/d) for 37 weeks in the phase 3 PEGASUS study in moderate-to-severe pemphigus vulgaris/pemphigus foliaceus.
RESULTS: The primary endpoint of complete remission from week 29 to week 37 with the amended endpoint CS dose ≤10 mg/d was not significant for 13 of 54 (24%) rilzabrutinib versus 10 of 55 (18%) placebo patients with PV (P = .45). Secondary endpoints showed numerical but nonsignificant improvements with rilzabrutinib (vs placebo) in reduced CS use, prolonged complete remission duration, and faster time to first complete remission.
CONCLUSIONS: Overall, rilzabrutinib was well-tolerated, with similar adverse events reported in both groups. Using minimal CS dose ≤10 mg/d and excluding remote observations, the primary efficacy endpoint was not met. However, results from a prespecified sensitivity analysis using CS dose ≤5 mg/d, considering all observations, and including all patients support Bruton tyrosine kinase inhibition as a viable therapeutic approach for pemphigus.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
The Journal of investigative dermatology - (2024) vom: 16. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Murrell, Dedee F [VerfasserIn] |
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| Links: |
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| Themen: |
BTK or Bruton tyrosine kinase |
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| Anmerkungen: |
Date Revised 28.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.jid.2024.02.023 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a TRIAL DESIGN: Pemphigus is a rare but life-threatening autoimmune disease requiring long-term treatment that minimizes corticosteroid (CS) exposure while providing consistent disease control. The phase 2 pemphigus study of oral, reversible, covalent Bruton tyrosine kinase inhibitor rilzabrutinib demonstrated rapid and sustained efficacy with well-tolerated safety | ||
| 520 | |a METHODS: Adults (aged 18-80 years) were randomized 1:1 to 400 mg rilzabrutinib (n = 65) or placebo (n = 66) twice daily (with CS ≤ 0.5 mg/kg/d) for 37 weeks in the phase 3 PEGASUS study in moderate-to-severe pemphigus vulgaris/pemphigus foliaceus | ||
| 520 | |a RESULTS: The primary endpoint of complete remission from week 29 to week 37 with the amended endpoint CS dose ≤10 mg/d was not significant for 13 of 54 (24%) rilzabrutinib versus 10 of 55 (18%) placebo patients with PV (P = .45). Secondary endpoints showed numerical but nonsignificant improvements with rilzabrutinib (vs placebo) in reduced CS use, prolonged complete remission duration, and faster time to first complete remission | ||
| 520 | |a CONCLUSIONS: Overall, rilzabrutinib was well-tolerated, with similar adverse events reported in both groups. Using minimal CS dose ≤10 mg/d and excluding remote observations, the primary efficacy endpoint was not met. However, results from a prespecified sensitivity analysis using CS dose ≤5 mg/d, considering all observations, and including all patients support Bruton tyrosine kinase inhibition as a viable therapeutic approach for pemphigus | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BTK or Bruton tyrosine kinase | |
| 650 | 4 | |a CDA or control of disease activity | |
| 650 | 4 | |a Desmoglein | |
| 650 | 4 | |a Pemphigus | |
| 650 | 4 | |a Rilzabrutinib | |
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| 700 | 1 | |a Patsatsi, Aikaterini |e verfasserin |4 aut | |
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| 700 | 1 | |a Rudnicka, Lidia |e verfasserin |4 aut | |
| 700 | 1 | |a Vassileva, Snejina |e verfasserin |4 aut | |
| 700 | 1 | |a Uzun, Soner |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Jenny |e verfasserin |4 aut | |
| 700 | 1 | |a Yen, Karl |e verfasserin |4 aut | |
| 700 | 1 | |a Arora, Puneet |e verfasserin |4 aut | |
| 700 | 1 | |a Gourlay, Steven G |e verfasserin |4 aut | |
| 700 | 1 | |a Joly, Pascal |e verfasserin |4 aut | |
| 700 | 1 | |a Werth, Victoria P |e verfasserin |4 aut | |
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