Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry.
Adult
Antibodies, Monoclonal, Humanized
/ therapeutic use
Colitis, Ulcerative
/ drug therapy
Crohn Disease
/ drug therapy
Female
Humans
Male
Middle Aged
Netherlands
/ epidemiology
Piperidines
/ therapeutic use
Prospective Studies
Protein Kinase Inhibitors
/ therapeutic use
Pyrimidines
/ therapeutic use
Pyrroles
/ therapeutic use
Registries
Treatment Outcome
Tumor Necrosis Factor-alpha
/ antagonists & inhibitors
Ustekinumab
/ therapeutic use
real world
tofacitinib
ulcerative colitis
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
28
12
2019
revised:
21
01
2020
accepted:
24
02
2020
pubmed:
3
4
2020
medline:
3
10
2020
entrez:
3
4
2020
Statut:
ppublish
Résumé
Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). To evaluate effectiveness, safety and use of tofacitinib in daily practice. UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation. In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively. Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients.
Sections du résumé
BACKGROUND
Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).
AIM
To evaluate effectiveness, safety and use of tofacitinib in daily practice.
METHODS
UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation.
RESULTS
In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively.
CONCLUSION
Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients.
Identifiants
pubmed: 32237087
doi: 10.1111/apt.15689
pmc: PMC7187329
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Piperidines
0
Protein Kinase Inhibitors
0
Pyrimidines
0
Pyrroles
0
Tumor Necrosis Factor-alpha
0
tofacitinib
87LA6FU830
vedolizumab
9RV78Q2002
Ustekinumab
FU77B4U5Z0
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
880-888Investigateurs
H H Fidder
(HH)
C Y Ponsioen
(CY)
M Duijvestein
(M)
M J L Romberg-Camps
(MJL)
P W J Maljaars
(PWJ)
G Bouma
(G)
S van der Marel
(S)
D J de Jong
(DJ)
J J L Haans
(JJL)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
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