Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Infection Rates from the Ulcerative Colitis Clinical Programme.
Adult
Colitis, Ulcerative
/ drug therapy
Dose-Response Relationship, Drug
Female
Herpes Zoster
/ diagnosis
Humans
Immunocompromised Host
/ drug effects
Incidence
Infections
/ diagnosis
Janus Kinase Inhibitors
/ administration & dosage
Male
Medication Therapy Management
/ statistics & numerical data
Opportunistic Infections
/ diagnosis
Piperidines
/ administration & dosage
Pyrimidines
/ administration & dosage
Risk Assessment
/ statistics & numerical data
Severity of Illness Index
Infections
tofacitinib
ulcerative colitis
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
22 Jun 2021
22 Jun 2021
Historique:
pubmed:
28
11
2020
medline:
15
12
2021
entrez:
27
11
2020
Statut:
ppublish
Résumé
Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We report integrated analyses of infections in the Phase [P]2 and P3 OCTAVE programmes. Three cohorts were analysed: Induction [P2/3 induction studies]; Maintenance [P3 maintenance study]; and Overall [all tofacitinib-treated patients in induction, maintenance, or ongoing, open-label, long-term extension studies; as of May 2019]. Proportions and incidence rates [IRs; unique patients with events/100 patient-years] of serious infections [SIs], herpes zoster [HZ] [non-serious and serious], and opportunistic infections [OIs] are reported [censored at time of event]. In the Induction Cohort [N = 1220], no patients receiving placebo and eight [0.9%] receiving tofacitinib 10 mg twice daily [BID] developed SIs. Maintenance Cohort [N = 592] SI IRs (95% confidence interval [CI]) were 1.94 [0.23-7.00] for placebo and 1.35 [0.16-4.87] and 0.64 [0.02-3.54] for tofacitinib 5 and 10 mg BID, respectively; HZ IRs were 0.97 [0.02-5.42], 2.05 [0.42-6.00], and 6.64 [3.19-12.22], respectively. In the Overall Cohort [N = 1157; 82.9% predominantly received tofacitinib 10 mg BID], SI, HZ, and non-HZ OI IRs were 1.70 [1.24-2.27], 3.48 [2.79-4.30], and 0.15 [0.04-0.38], respectively. No SIs resulted in death. During induction, SIs were more frequent with tofacitinib versus placebo. SIs were generally infrequent in the Maintenance and Overall Cohorts, with rates comparable between treatment groups. Maintenance Cohort HZ IR was numerically higher with tofacitinib 10 mg BID versus 5 mg BID. Overall Cohort HZ IRs remained stable over time. Non-HZ OIs and viral infections were rare.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We report integrated analyses of infections in the Phase [P]2 and P3 OCTAVE programmes.
METHODS
METHODS
Three cohorts were analysed: Induction [P2/3 induction studies]; Maintenance [P3 maintenance study]; and Overall [all tofacitinib-treated patients in induction, maintenance, or ongoing, open-label, long-term extension studies; as of May 2019]. Proportions and incidence rates [IRs; unique patients with events/100 patient-years] of serious infections [SIs], herpes zoster [HZ] [non-serious and serious], and opportunistic infections [OIs] are reported [censored at time of event].
RESULTS
RESULTS
In the Induction Cohort [N = 1220], no patients receiving placebo and eight [0.9%] receiving tofacitinib 10 mg twice daily [BID] developed SIs. Maintenance Cohort [N = 592] SI IRs (95% confidence interval [CI]) were 1.94 [0.23-7.00] for placebo and 1.35 [0.16-4.87] and 0.64 [0.02-3.54] for tofacitinib 5 and 10 mg BID, respectively; HZ IRs were 0.97 [0.02-5.42], 2.05 [0.42-6.00], and 6.64 [3.19-12.22], respectively. In the Overall Cohort [N = 1157; 82.9% predominantly received tofacitinib 10 mg BID], SI, HZ, and non-HZ OI IRs were 1.70 [1.24-2.27], 3.48 [2.79-4.30], and 0.15 [0.04-0.38], respectively. No SIs resulted in death.
CONCLUSIONS
CONCLUSIONS
During induction, SIs were more frequent with tofacitinib versus placebo. SIs were generally infrequent in the Maintenance and Overall Cohorts, with rates comparable between treatment groups. Maintenance Cohort HZ IR was numerically higher with tofacitinib 10 mg BID versus 5 mg BID. Overall Cohort HZ IRs remained stable over time. Non-HZ OIs and viral infections were rare.
Identifiants
pubmed: 33245746
pii: 6007683
doi: 10.1093/ecco-jcc/jjaa233
pmc: PMC8218715
doi:
Substances chimiques
Janus Kinase Inhibitors
0
Piperidines
0
Pyrimidines
0
tofacitinib
87LA6FU830
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
914-929Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.
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