Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients: Post Hoc Analysis From 21 Clinical Trials.
Journal
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases
ISSN: 1536-7355
Titre abrégé: J Clin Rheumatol
Pays: United States
ID NLM: 9518034
Informations de publication
Date de publication:
01 Dec 2021
01 Dec 2021
Historique:
pubmed:
23
8
2020
medline:
26
11
2021
entrez:
23
8
2020
Statut:
ppublish
Résumé
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Interstitial lung disease (ILD) is an extra-articular manifestation of RA. We investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD. This post hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 2 phase (P)1, 10 P2, 6 P3, 1 P3b/4, and 2 long-term extension studies. Interstitial lung disease events were adjudicated as "probable" (supportive clinical evidence) or "possible" (no supportive clinical evidence) compatible adverse events. Incidence rates (patients with events per 100 patient-years) were calculated for ILD events. Of 7061 patients (patient-years of exposure = 23,393.7), 42 (0.6%) had an ILD event; median time to ILD event was 1144 days. Incidence rates for ILD with both tofacitinib doses were 0.18 per 100 patient-years. Incidence rates generally remained stable over time. There were 17 of 42 serious adverse events (40.5%) of ILD; for all ILD events (serious and nonserious), 35 of 42 events (83.3%) were mild to moderate in severity. A multivariable Cox regression analysis identified age 65 years or older (hazard ratio 2.43 [95% confidence interval, 1.13-5.21]), current smokers (2.89 [1.33-6.26]), and Disease Activity Score in 28 joints-erythrocyte sedimentation rate score (1.30 [1.04-1.61]) as significant risk factors for ILD events. Across P1/2/3/4/long-term extension studies, incidence rates for ILD events were 0.18 following tofacitinib treatment, and ILD events were associated with known risk factors for ILD in RA.
Sections du résumé
BACKGROUND/OBJECTIVE
OBJECTIVE
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Interstitial lung disease (ILD) is an extra-articular manifestation of RA. We investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD.
METHODS
METHODS
This post hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 2 phase (P)1, 10 P2, 6 P3, 1 P3b/4, and 2 long-term extension studies. Interstitial lung disease events were adjudicated as "probable" (supportive clinical evidence) or "possible" (no supportive clinical evidence) compatible adverse events. Incidence rates (patients with events per 100 patient-years) were calculated for ILD events.
RESULTS
RESULTS
Of 7061 patients (patient-years of exposure = 23,393.7), 42 (0.6%) had an ILD event; median time to ILD event was 1144 days. Incidence rates for ILD with both tofacitinib doses were 0.18 per 100 patient-years. Incidence rates generally remained stable over time. There were 17 of 42 serious adverse events (40.5%) of ILD; for all ILD events (serious and nonserious), 35 of 42 events (83.3%) were mild to moderate in severity. A multivariable Cox regression analysis identified age 65 years or older (hazard ratio 2.43 [95% confidence interval, 1.13-5.21]), current smokers (2.89 [1.33-6.26]), and Disease Activity Score in 28 joints-erythrocyte sedimentation rate score (1.30 [1.04-1.61]) as significant risk factors for ILD events.
CONCLUSIONS
CONCLUSIONS
Across P1/2/3/4/long-term extension studies, incidence rates for ILD events were 0.18 following tofacitinib treatment, and ILD events were associated with known risk factors for ILD in RA.
Identifiants
pubmed: 32826657
pii: 00124743-202112000-00037
doi: 10.1097/RHU.0000000000001552
pmc: PMC8612919
doi:
Substances chimiques
Antirheumatic Agents
0
Piperidines
0
Pyrimidines
0
Pyrroles
0
tofacitinib
87LA6FU830
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e482-e490Informations de copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
This study was sponsored by Pfizer Inc. G.C. has received research grants from Novartis and Pfizer Inc. and is a speaker, advisor and/or consultant to AbbVie, Bristol-Myers Squibb, Eli Lilly, Genzyme, Janssen, Novartis, Pfizer Inc., and Roche. E.M. has received research grants from Eli Lilly, Pfizer Inc., and Roche and is a member of the speakers' bureaus for AbbVie, Bristol-Myers Squibb, Eli Lilly, Pfizer Inc., Roche, and Sanofi. M.H.C. has received research grants from Gilead, Pfizer Inc., and Roche; and is a consultant and member of the speakers' bureaus for Eli Lilly and Pfizer Inc. A.F. has received research grants from Boehringer Ingelheim and Corbus and is a consultant to Boehringer Ingelheim and Roche. A.F. is a former employee of the University of Colorado and is currently employed by Bristol-Myers Squibb. P.R. is a consultant to Pfizer Inc. S.C. is a consultant to AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Novartis, and Pfizer Inc. J.L.R., A.V.T., T.G., K.K., L.W., and D.P.L., are employees and shareholders of Pfizer Inc. S.S. is a former employee of Pfizer Inc., Capelle aan den IJssel, the Netherlands. J.K.P., H.M., and O.C. declare no conflict of interest.
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