PMID- 34376340
OWN - NLM
STAT- MEDLINE
DCOM- 20220221
LR  - 20220221
IS  - 1873-569X (Electronic)
IS  - 0923-1811 (Linking)
VI  - 103
IP  - 3
DP  - 2021 Sep
TI  - A multicenter, open-label, uncontrolled, single-arm phase 2 study of 
      tirabrutinib, an oral Bruton's tyrosine kinase inhibitor, in pemphigus.
PG  - 135-142
LID - S0923-1811(21)00148-1 [pii]
LID - 10.1016/j.jdermsci.2021.07.002 [doi]
AB  - BACKGROUND: The treatment of pemphigus is based on systemic corticosteroid use 
      and adjuvant therapies, but some patients are resistant to conventional therapy. 
      Tirabrutinib is a highly selective oral Bruton's tyrosine kinase inhibitor that 
      may be clinically effective in treating pemphigus by suppressing B-cell 
      signaling. OBJECTIVE: We investigated the efficacy and safety of tirabrutinib in 
      patients with refractory pemphigus. METHODS: This was a multicenter, open-label, 
      single-arm phase 2 study of Japanese patients with refractory pemphigus receiving 
      appropriate treatment with an oral corticosteroid and adjuvant therapies. 
      Patients received postprandial oral tirabrutinib 80 mg once daily for 52 weeks. 
      After 16 weeks of tirabrutinib treatment, the corticosteroid dose was tapered to 
      </=10 mg/day of prednisolone equivalent. RESULTS: In total, 16 patients were 
      evaluated (mean age, 52.5 years; 50 % male). The complete remission rate after 24 
      weeks of treatment (primary endpoint) was 18.8 % (3/16; 95 % confidence interval, 
      6.6 %-43.0 %). By Week 52, eight patients (50.0 %) achieved complete remission 
      and 10 patients (62.5 %) achieved remission. Over 52 weeks of treatment, the mean 
      prednisolone dose decreased from 17.03 to 7.65 mg/day. Incidences of adverse 
      events (AEs) and adverse drug reactions were 87.5 % and 43.8 %, respectively. A 
      relationship with tirabrutinib was ruled out for all serious AEs and Grade >/=3 
      AEs. CONCLUSION: Treatment with tirabrutinib enabled remission and reduced oral 
      corticosteroid exposure over time and did not result in any major safety concerns 
      in patients with refractory pemphigus. Thus, oral tirabrutinib may be a new 
      treatment option for patients with refractory pemphigus.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Yamagami, Jun
AU  - Yamagami J
AD  - Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
FAU - Ujiie, Hideyuki
AU  - Ujiie H
AD  - Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, 
      Hokkaido University, Sapporo, Japan.
FAU - Aoyama, Yumi
AU  - Aoyama Y
AD  - Department of Dermatology, Kawasaki Medical School, Okayama, Japan.
FAU - Ishii, Norito
AU  - Ishii N
AD  - Department of Dermatology, Kurume University School of Medicine, Kurume, Japan.
FAU - Tateishi, Chiharu
AU  - Tateishi C
AD  - Department of Dermatology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Ishiko, Akira
AU  - Ishiko A
AD  - Department of Dermatology, School of Medicine, Faculty of Medicine, Toho 
      University, Tokyo, Japan.
FAU - Ichijima, Tomoki
AU  - Ichijima T
AD  - Clinical Development Planning, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Hagihara, Shunsuke
AU  - Hagihara S
AD  - Department of Statistical Analysis, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Hashimoto, Koji
AU  - Hashimoto K
AD  - Ehime University Graduate School of Medicine, Ehime, Japan.
FAU - Amagai, Masayuki
AU  - Amagai M
AD  - Department of Dermatology, Keio University School of Medicine, Tokyo, Japan. 
      Electronic address: amagai@keio.jp.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20210706
PL  - Netherlands
TA  - J Dermatol Sci
JT  - Journal of dermatological science
JID - 9011485
RN  - 0 (Imidazoles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 9PHQ9Y1OLM (Prednisolone)
RN  - EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase)
RN  - EC 2.7.10.2 (BTK protein, human)
RN  - LXG44NDL2T (tirabrutinib)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Agammaglobulinaemia Tyrosine Kinase/*antagonists & inhibitors
MH  - Dose-Response Relationship, Drug
MH  - Drug Resistance/drug effects
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Imidazoles/*administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Pemphigus/diagnosis/*drug therapy
MH  - Prednisolone/*administration & dosage/adverse effects
MH  - Protein Kinase Inhibitors/*administration & dosage/adverse effects
MH  - Pyrimidines/*administration & dosage/adverse effects
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Efficacy
OT  - Japan
OT  - Phase 2 study
OT  - Refractory pemphigus
OT  - Safety
OT  - Tirabrutinib
EDAT- 2021/08/12 06:00
MHDA- 2022/02/22 06:00
CRDT- 2021/08/11 05:42
PHST- 2021/04/29 00:00 [received]
PHST- 2021/07/02 00:00 [revised]
PHST- 2021/07/04 00:00 [accepted]
PHST- 2021/08/12 06:00 [pubmed]
PHST- 2022/02/22 06:00 [medline]
PHST- 2021/08/11 05:42 [entrez]
AID - S0923-1811(21)00148-1 [pii]
AID - 10.1016/j.jdermsci.2021.07.002 [doi]
PST - ppublish
SO  - J Dermatol Sci. 2021 Sep;103(3):135-142. doi: 10.1016/j.jdermsci.2021.07.002. 
      Epub 2021 Jul 6.