TY - JOUR
T1 - An Integrated Analysis of the Safety of Tofacitinib in Psoriatic Arthritis across Phase III and Long-Term Extension Studies with Comparison to Real-World Observational Data
AU - Burmester, Gerd R.
AU - Curtis, Jeffrey R.
AU - Yun, Huifeng
AU - FitzGerald, Oliver
AU - Winthrop, Kevin L.
AU - Azevedo, Valderilio F.
AU - Rigby, William F.C.
AU - Kanik, Keith S.
AU - Wang, Cunshan
AU - Biswas, Pinaki
AU - Jones, Thomas
AU - Palmetto, Niki
AU - Hendrikx, Thijs
AU - Menon, Sujatha
AU - Rojo, Ricardo
N1 - Funding Information:
Gerd R. Burmester has received consulting fees from AbbVie, Gilead, Lilly, and Pfizer Inc and lecture fees from AbbVie, Lilly, and Pfizer Inc. Jeffrey R. Curtis has received research grants and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Eli Lilly, Janssen, Myriad, Pfizer Inc, Regeneron, Roche, and UCB. Huifeng Yun has received grant/research support from Pfizer Inc. Oliver FitzGerald has received research grants and honoraria from AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer Inc, and UCB. Kevin L. Winthrop has received consulting fees from AbbVie, Galapagos, Gilead, GSK, Lilly, Pfizer Inc, Roche, and UCB. Valderilio F. Azevedo has received grant/research support and consulting fees from AbbVie, Lilly, Novartis, and Pfizer Inc and lecture fees from AbbVie, Boehringer Ingelheim, Celltrion, Janssen, Lilly, Novartis, and Pfizer Inc. William F.C. Rigby has received consulting fees for work unrelated to this manuscript. Keith S. Kanik, Cunshan Wang, Pinaki Biswas, Thomas Jones, Thijs Hendrikx, and Ricardo Rojo are shareholders and employees of Pfizer Inc. Sujatha Menon is an employee of Pfizer Inc. Niki Palmetto was an employee of Pfizer Inc at the time of the analysis.
Funding Information:
This study was funded by Pfizer Inc. Medical writing support, under the guidance of the authors, was provided by Carole Evans, PhD, and Richard Knight, PhD, CMC Connect, McCann Health Medical Communications Ltd, and was funded by Pfizer Inc, New York, NY, USA, in accordance with good publication practice (GPP3) guidelines (Ann Intern Med 2015;163:461–4).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). Objective: Our objective was to compare the incidence rates (IRs) of adverse events in tofacitinib clinical trials and real-world observational data for alternative treatments. Methods: The tofacitinib “dose-comparison cohort” included months 0–12 of two phase III studies (tofacitinib 5 [n = 238] and 10 [n = 236] mg twice daily [BID]); the “all-tofacitinib comparison cohort” (n = 783) included two phase III and one ongoing long-term extension study (data cutoff May 2016). An “observational comparison cohort” (n = 5799) comprised patients initiating a conventional synthetic disease-modifying antirheumatic drug (DMARD), biologic DMARD, or apremilast in the US Truven MarketScan database from 2010 to 2015. IRs for serious infections (SIEs; requiring hospitalization), herpes zoster (HZ), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, and major adverse cardiovascular events (MACE) across cohorts were qualitatively compared. Results: IRs (patients with events/100 patient-years) for SIEs were similar between the tofacitinib dose-comparison cohort (5 mg BID: 1.3; 10 mg BID: 2.0) and the observational comparison cohort (1.1–7.9; treatment dependent). The tofacitinib dose-comparison cohort had a higher rate of HZ (5 mg BID: 2.0; 10 mg BID: 2.7) than did the observational comparison cohort (0.8–2.0). IRs for NMSC were generally lower in the all-tofacitinib comparison cohort (0.5) than in the observational comparison cohort (0.4–6.0). IRs for MACE, malignancies excluding NMSC, and NMSC were similar between cohorts. Conclusion: In patients with PsA, tofacitinib had a safety profile similar to that of other systemic therapies in real-world settings, except for the risk of HZ, a known risk of tofacitinib. Trial Registration: ClinicalTrials.gov: NCT01877668; NCT01882439; NCT01976364.
AB - Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). Objective: Our objective was to compare the incidence rates (IRs) of adverse events in tofacitinib clinical trials and real-world observational data for alternative treatments. Methods: The tofacitinib “dose-comparison cohort” included months 0–12 of two phase III studies (tofacitinib 5 [n = 238] and 10 [n = 236] mg twice daily [BID]); the “all-tofacitinib comparison cohort” (n = 783) included two phase III and one ongoing long-term extension study (data cutoff May 2016). An “observational comparison cohort” (n = 5799) comprised patients initiating a conventional synthetic disease-modifying antirheumatic drug (DMARD), biologic DMARD, or apremilast in the US Truven MarketScan database from 2010 to 2015. IRs for serious infections (SIEs; requiring hospitalization), herpes zoster (HZ), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, and major adverse cardiovascular events (MACE) across cohorts were qualitatively compared. Results: IRs (patients with events/100 patient-years) for SIEs were similar between the tofacitinib dose-comparison cohort (5 mg BID: 1.3; 10 mg BID: 2.0) and the observational comparison cohort (1.1–7.9; treatment dependent). The tofacitinib dose-comparison cohort had a higher rate of HZ (5 mg BID: 2.0; 10 mg BID: 2.7) than did the observational comparison cohort (0.8–2.0). IRs for NMSC were generally lower in the all-tofacitinib comparison cohort (0.5) than in the observational comparison cohort (0.4–6.0). IRs for MACE, malignancies excluding NMSC, and NMSC were similar between cohorts. Conclusion: In patients with PsA, tofacitinib had a safety profile similar to that of other systemic therapies in real-world settings, except for the risk of HZ, a known risk of tofacitinib. Trial Registration: ClinicalTrials.gov: NCT01877668; NCT01882439; NCT01976364.
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U2 - 10.1007/s40264-020-00904-9
DO - 10.1007/s40264-020-00904-9
M3 - Article
C2 - 32006348
AN - SCOPUS:85078953837
SN - 0114-5916
VL - 43
SP - 379
EP - 392
JO - Drug Safety
JF - Drug Safety
IS - 4
ER -