Safety and efficacy of tofacitinib for treatment of ulcerative colitis: final analysis of OCTAVE Open, an open-label, long-term extension study with up to 7.0 years of treatment.
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
22
09
2021
received:
31
08
2021
accepted:
11
11
2021
pubmed:
3
12
2021
medline:
2
4
2022
entrez:
2
12
2021
Statut:
ppublish
Résumé
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present final data from OCTAVE Open, an open-label, long-term extension study. The primary objective of OCTAVE Open was to assess the safety and tolerability of long-term tofacitinib in patients with ulcerative colitis; evaluating efficacy was a secondary objective. Eligible patients included OCTAVE Induction 1&2 non-responders and OCTAVE Sustain completers/treatment failures. Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. Incidence rates (unique patients with events/100 patient-years) for adverse events of special interest were calculated; ≤7.0 years of observation. Efficacy endpoints derived from Mayo score were reported ≤36 months (last scheduled endoscopy visit). In OCTAVE Open, 769 of 944 patients (81.5%) initially received tofacitinib 10 mg b.d. Among all patients (2440.8 patient-years of exposure), incidence rates (IRs; 95% confidence intervals) for deaths and adverse events of special interest were: deaths, 0.25 (0.09-0.54); serious infections, 1.61 (1.14-2.20); herpes zoster (non-serious and serious), 3.16 (2.47-3.97); opportunistic infections, 0.87 (0.54-1.33); major adverse cardiovascular events, 0.16 (0.04-0.42); malignancies (excluding non-melanoma skin cancer), 1.03 (0.67-1.52); non-melanoma skin cancer, 0.75 (0.45-1.19); deep vein thrombosis, 0.04 (0.00-0.23); pulmonary embolism, 0.21 (0.07-0.48). At Month 36, 66.9% and 40.3% showed clinical response, 64.6% and 37.1% had endoscopic improvement, and 58.9% and 33.7% maintained or achieved remission, with tofacitinib 5 and 10 mg b.d. respectively. Tofacitinib demonstrated consistent safety up to 7.0 years. Data collected up to Month 36 support long-term efficacy beyond the 52-week maintenance study.
Sections du résumé
BACKGROUND
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present final data from OCTAVE Open, an open-label, long-term extension study.
AIMS
The primary objective of OCTAVE Open was to assess the safety and tolerability of long-term tofacitinib in patients with ulcerative colitis; evaluating efficacy was a secondary objective.
METHODS
Eligible patients included OCTAVE Induction 1&2 non-responders and OCTAVE Sustain completers/treatment failures. Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. Incidence rates (unique patients with events/100 patient-years) for adverse events of special interest were calculated; ≤7.0 years of observation. Efficacy endpoints derived from Mayo score were reported ≤36 months (last scheduled endoscopy visit).
RESULTS
In OCTAVE Open, 769 of 944 patients (81.5%) initially received tofacitinib 10 mg b.d. Among all patients (2440.8 patient-years of exposure), incidence rates (IRs; 95% confidence intervals) for deaths and adverse events of special interest were: deaths, 0.25 (0.09-0.54); serious infections, 1.61 (1.14-2.20); herpes zoster (non-serious and serious), 3.16 (2.47-3.97); opportunistic infections, 0.87 (0.54-1.33); major adverse cardiovascular events, 0.16 (0.04-0.42); malignancies (excluding non-melanoma skin cancer), 1.03 (0.67-1.52); non-melanoma skin cancer, 0.75 (0.45-1.19); deep vein thrombosis, 0.04 (0.00-0.23); pulmonary embolism, 0.21 (0.07-0.48). At Month 36, 66.9% and 40.3% showed clinical response, 64.6% and 37.1% had endoscopic improvement, and 58.9% and 33.7% maintained or achieved remission, with tofacitinib 5 and 10 mg b.d. respectively.
CONCLUSION
Tofacitinib demonstrated consistent safety up to 7.0 years. Data collected up to Month 36 support long-term efficacy beyond the 52-week maintenance study.
Identifiants
pubmed: 34854095
doi: 10.1111/apt.16712
pmc: PMC9300081
doi:
Substances chimiques
Piperidines
0
Pyrimidines
0
Pyrroles
0
tofacitinib
87LA6FU830
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
464-478Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK120515
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
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