Efficacy and safety of tofacitinib dose de-escalation and dose escalation for patients with ulcerative colitis: results from OCTAVE Open.
Adult
Colitis, Ulcerative
/ drug therapy
Dose-Response Relationship, Drug
Drug-Related Side Effects and Adverse Reactions
/ epidemiology
Female
Humans
Maintenance Chemotherapy
Male
Middle Aged
Piperidines
/ administration & dosage
Pyrimidines
/ administration & dosage
Pyrroles
/ administration & dosage
Remission Induction
Treatment Outcome
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
28
06
2019
revised:
15
07
2019
accepted:
02
10
2019
pubmed:
30
10
2019
medline:
28
7
2020
entrez:
30
10
2019
Statut:
ppublish
Résumé
For patients with UC, flexible maintenance dosing therapy may confer advantages for safety, efficacy, costs and patient preference. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. To assess the efficacy and safety of tofacitinib dose de-escalation and escalation in patients with UC. We evaluated data (November 2017 data cut-off) from OCTAVE Open, an ongoing, open-label, long-term extension study. The dose de-escalation group comprised 66 tofacitinib induction responders in remission following 52 weeks' tofacitinib 10 mg b.d. maintenance therapy, subsequently de-escalated to 5 mg b.d. in OCTAVE Open. The dose escalation group comprised 57 tofacitinib induction responders who experienced treatment failure while receiving 5 mg b.d. maintenance therapy, subsequently escalated to 10 mg b.d. in OCTAVE Open. After tofacitinib de-escalation, 92.4% (61/66) and 84.1% (53/63) of patients maintained clinical response and 80.3% (53/66) and 74.6% (47/63) maintained remission, at months 2 and 12, respectively. After dose escalation, 57.9% (33/57) and 64.9% (37/57) of patients recaptured clinical response and 35.1% (20/57) and 49.1% (28/57) were in remission, at months 2 and 12, respectively. The incidence rate of herpes zoster with dose escalation (7.6 patients with events/100 patient-years) was numerically higher than in the overall tofacitinib UC programme. Following tofacitinib de-escalation in patients already in remission on 10 mg b.d., most maintained remission, although 25.4% lost remission, at month 12. For induction responders who dose-escalated following treatment failure on 5 mg b.d. maintenance therapy, 49.1% achieved remission by month 12. (ClinicalTrials.gov number: NCT01470612).
Sections du résumé
BACKGROUND
For patients with UC, flexible maintenance dosing therapy may confer advantages for safety, efficacy, costs and patient preference. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC.
AIM
To assess the efficacy and safety of tofacitinib dose de-escalation and escalation in patients with UC.
METHODS
We evaluated data (November 2017 data cut-off) from OCTAVE Open, an ongoing, open-label, long-term extension study. The dose de-escalation group comprised 66 tofacitinib induction responders in remission following 52 weeks' tofacitinib 10 mg b.d. maintenance therapy, subsequently de-escalated to 5 mg b.d. in OCTAVE Open. The dose escalation group comprised 57 tofacitinib induction responders who experienced treatment failure while receiving 5 mg b.d. maintenance therapy, subsequently escalated to 10 mg b.d. in OCTAVE Open.
RESULTS
After tofacitinib de-escalation, 92.4% (61/66) and 84.1% (53/63) of patients maintained clinical response and 80.3% (53/66) and 74.6% (47/63) maintained remission, at months 2 and 12, respectively. After dose escalation, 57.9% (33/57) and 64.9% (37/57) of patients recaptured clinical response and 35.1% (20/57) and 49.1% (28/57) were in remission, at months 2 and 12, respectively. The incidence rate of herpes zoster with dose escalation (7.6 patients with events/100 patient-years) was numerically higher than in the overall tofacitinib UC programme.
CONCLUSIONS
Following tofacitinib de-escalation in patients already in remission on 10 mg b.d., most maintained remission, although 25.4% lost remission, at month 12. For induction responders who dose-escalated following treatment failure on 5 mg b.d. maintenance therapy, 49.1% achieved remission by month 12. (ClinicalTrials.gov number: NCT01470612).
Identifiants
pubmed: 31660640
doi: 10.1111/apt.15555
pmc: PMC9328429
doi:
Substances chimiques
Piperidines
0
Pyrimidines
0
Pyrroles
0
tofacitinib
87LA6FU830
Banques de données
ClinicalTrials.gov
['NCT01470612']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
271-280Subventions
Organisme : Pfizer Inc
Pays : International
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2019 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
Références
Gastroenterology. 2014 Jan;146(1):85-95; quiz e14-5
pubmed: 23735746
Am J Gastroenterol. 2014 Feb;109(2):163-9
pubmed: 24419479
Inflamm Bowel Dis. 2017 Aug;23(8):1394-1402
pubmed: 28671873
J Crohns Colitis. 2017 Jul 1;11(7):769-784
pubmed: 28513805
Gastroenterology. 2015 Dec;149(7):1716-30
pubmed: 26381892
Am J Gastroenterol. 2019 Mar;114(3):384-413
pubmed: 30840605
Am J Gastroenterol. 2011 Apr;106(4):685-98
pubmed: 21427713
Clin Gastroenterol Hepatol. 2015 May;13(5):847-58.e4; quiz e48-50
pubmed: 24879926
Aliment Pharmacol Ther. 2020 Jan;51(2):271-280
pubmed: 31660640
Gut. 2011 Jun;60(6):780-7
pubmed: 21209123
Br J Clin Pharmacol. 2018 Jun;84(6):1136-1145
pubmed: 29377257
Gastroenterology. 2014 Jan;146(1):96-109.e1
pubmed: 23770005
Dig Liver Dis. 2019 Mar;51(3):327-334
pubmed: 30555013
Inflamm Bowel Dis. 2018 Sep 15;24(10):2258-2265
pubmed: 29850873
N Engl J Med. 2017 May 4;376(18):1723-1736
pubmed: 28467869
Am J Gastroenterol. 2010 Mar;105(3):501-23; quiz 524
pubmed: 20068560
Clin Gastroenterol Hepatol. 2019 Jul;17(8):1541-1550
pubmed: 30476584
Inflamm Bowel Dis. 2018 Sep 15;24(10):2173-2182
pubmed: 29788127
Aliment Pharmacol Ther. 2014 Aug;40(4):338-53
pubmed: 24957164
N Engl J Med. 2005 Dec 8;353(23):2462-76
pubmed: 16339095