Tofacitinib Treatment Safety in Moderate to Severe Ulcerative Colitis: Comparison of Observational Population Cohort Data From the IBM MarketScan® Administrative Claims Database With Tofacitinib Trial Data.
indirect comparison
safety
ulcerative colitis
Journal
Inflammatory bowel diseases
ISSN: 1536-4844
Titre abrégé: Inflamm Bowel Dis
Pays: England
ID NLM: 9508162
Informations de publication
Date de publication:
19 08 2021
19 08 2021
Historique:
received:
17
06
2020
pubmed:
17
12
2020
medline:
10
2
2022
entrez:
16
12
2020
Statut:
ppublish
Résumé
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We aimed to estimate the overall incidence of safety events in patients with UC in a real-life population cohort for comparison with the tofacitinib UC clinical trial program. Clinical trial-like criteria were applied to an IBM MarketScan® claims database population-based cohort (n = 22,967) of patients with UC (October 2010 to September 2015) to identify a UC trial-like cohort treated with tumor necrosis factor inhibitors (TNFi; n = 6366) to compare with the tofacitinib UC clinical trial cohort (n = 1157). Incidence rates (events per 100 patient-years; [95% confidence interval]) in the UC trial-like cohort were as follows: serious infections, 3.33 (2.73-4.02); opportunistic infections (OIs; excluding herpes zoster [HZ]), 1.45 (1.06-1.93); HZ, 1.77 (1.34-2.29); malignancies (excluding nonmelanoma skin cancer [NMSC]), 0.63 (0.43-0.90); NMSC, 1.69 (1.35-2.10); major adverse cardiovascular events (MACE), 0.51 (0.31-0.79); pulmonary embolism (PE), 0.54 (0.30-0.89); deep vein thrombosis (DVT), 1.41 (1.00-1.93); and gastrointestinal perforations, 0.31 (0.16-0.54). Compared with the UC trial-like cohort, tofacitinib-treated patients had numerically lower incidence rates for serious infections (1.75 [1.27-2.36]), OIs (excluding HZ; 0.16 [0.04-0.42]), NMSC (0.78 [0.47-1.22]), PE (0.16 [0.04-0.41]), and DVT (0.04 [0.00-0.23]), and a higher rate for HZ (3.57 [2.84-4.43]); rates for malignancies (excluding NMSC), MACE, and gastrointestinal perforations were similar. When acknowledging limitations of comparing claims data with controlled clinical trial data, incidence rates for HZ among TNFi-treated patients in the UC trial-like cohort were lower than in the tofacitinib UC clinical trial cohort; rates for serious infections, OIs, NMSC, PE, and DVT were numerically higher. NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612.
Sections du résumé
BACKGROUND
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We aimed to estimate the overall incidence of safety events in patients with UC in a real-life population cohort for comparison with the tofacitinib UC clinical trial program.
METHODS
Clinical trial-like criteria were applied to an IBM MarketScan® claims database population-based cohort (n = 22,967) of patients with UC (October 2010 to September 2015) to identify a UC trial-like cohort treated with tumor necrosis factor inhibitors (TNFi; n = 6366) to compare with the tofacitinib UC clinical trial cohort (n = 1157).
RESULTS
Incidence rates (events per 100 patient-years; [95% confidence interval]) in the UC trial-like cohort were as follows: serious infections, 3.33 (2.73-4.02); opportunistic infections (OIs; excluding herpes zoster [HZ]), 1.45 (1.06-1.93); HZ, 1.77 (1.34-2.29); malignancies (excluding nonmelanoma skin cancer [NMSC]), 0.63 (0.43-0.90); NMSC, 1.69 (1.35-2.10); major adverse cardiovascular events (MACE), 0.51 (0.31-0.79); pulmonary embolism (PE), 0.54 (0.30-0.89); deep vein thrombosis (DVT), 1.41 (1.00-1.93); and gastrointestinal perforations, 0.31 (0.16-0.54). Compared with the UC trial-like cohort, tofacitinib-treated patients had numerically lower incidence rates for serious infections (1.75 [1.27-2.36]), OIs (excluding HZ; 0.16 [0.04-0.42]), NMSC (0.78 [0.47-1.22]), PE (0.16 [0.04-0.41]), and DVT (0.04 [0.00-0.23]), and a higher rate for HZ (3.57 [2.84-4.43]); rates for malignancies (excluding NMSC), MACE, and gastrointestinal perforations were similar.
CONCLUSIONS
When acknowledging limitations of comparing claims data with controlled clinical trial data, incidence rates for HZ among TNFi-treated patients in the UC trial-like cohort were lower than in the tofacitinib UC clinical trial cohort; rates for serious infections, OIs, NMSC, PE, and DVT were numerically higher.
CLINICALTRIALS.GOV
NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612.
Identifiants
pubmed: 33324993
pii: 6039005
doi: 10.1093/ibd/izaa289
pmc: PMC8376127
doi:
Substances chimiques
Piperidines
0
Pyrimidines
0
tofacitinib
87LA6FU830
Banques de données
ClinicalTrials.gov
['NCT01458574', 'NCT01465763', 'NCT01470612', 'NCT01458951']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1394-1408Informations de copyright
© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.
Références
Aliment Pharmacol Ther. 2019 Nov;50(10):1068-1076
pubmed: 31599001
Curr Med Res Opin. 2015;31(9):1655-64
pubmed: 26135040
Contemp Clin Trials Commun. 2018 Nov 10;12:154-160
pubmed: 30480162
Gut. 2017 May;66(5):839-851
pubmed: 26893500
Am J Gastroenterol. 2015 Nov;110(11):1582-7
pubmed: 26346865
Inflamm Bowel Dis. 2017 Oct;23(10):1689-1701
pubmed: 28906290
Clin Transl Gastroenterol. 2016 Apr 28;7:e168
pubmed: 27124701
Inflamm Bowel Dis. 2012 Feb;18(2):201-11
pubmed: 21484965
Gastroenterology. 2012 Feb;142(2):257-65.e1-3
pubmed: 22062358
Aliment Pharmacol Ther. 2018 Jan;47(2):219-228
pubmed: 29159817
Gastroenterology. 2014 Jan;146(1):85-95; quiz e14-5
pubmed: 23735746
Clin Gastroenterol Hepatol. 2012 Oct;10(10):1079-87; quiz e85-6
pubmed: 22813440
Pharmacoepidemiol Drug Saf. 2018 Apr;27(4):398-404
pubmed: 29446185
Gastroenterology. 2014 Jan;146(1):96-109.e1
pubmed: 23770005
Comput Biol Med. 1992 Sep;22(5):351-61
pubmed: 1424580
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
Inflamm Bowel Dis. 2019 Jul 17;25(8):1417-1427
pubmed: 30839057
BMJ Open Gastroenterol. 2017 Jul 3;4(1):e000155
pubmed: 28944071
Pharmacoepidemiol Drug Saf. 2013 Jan;22(1):40-54
pubmed: 22745038
Clin Gastroenterol Hepatol. 2019 Jul;17(8):1541-1550
pubmed: 30476584
J Crohns Colitis. 2014 Jun;8(6):443-68
pubmed: 24613021
Inflamm Bowel Dis. 2015 Mar;21(3):674-98
pubmed: 25545375
Clin Colon Rectal Surg. 2019 Jan;32(1):54-60
pubmed: 30647546
Inflamm Bowel Dis. 2018 Sep 15;24(10):2173-2182
pubmed: 29788127
N Engl J Med. 2005 Dec 8;353(23):2462-76
pubmed: 16339095
World J Gastroenterol. 2016 May 28;22(20):4794-801
pubmed: 27239106
Am J Manag Care. 2018 Dec 1;24(12):e374-e379
pubmed: 30586485