Real-World Evidence to Contextualize Clinical Trial Results and Inform Regulatory Decisions: Tofacitinib Modified-Releas

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ORIGINAL RESEARCH

Real-World Evidence to Contextualize Clinical Trial Results and Inform Regulatory Decisions: Tofacitinib Modified-Release Once-Daily vs Immediate-Release Twice-Daily for Rheumatoid Arthritis Stanley B. Cohen . Jeffrey D. Greenberg . James Harnett

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Ann Madsen . Timothy W. Smith . David Gruben . Richard Zhang . Tatjana Lukic . John Woolcott . Kimberly J. Dandreo . Heather J. Litman . Taylor Blachley . Anne Lenihan . Connie Chen . Jose L. Rivas . Maxime Dougados Received: July 28, 2020 / Accepted: September 5, 2020 Ó The Author(s) 2020

ABSTRACT Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib

James Harnett and Timothy W. Smith were employees of Pfizer Inc at the time of the analysis.

Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12325020-01501-z) contains supplementary material, which is available to authorized users.

formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation. Methods: Two noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBMÒ MarketScanÒ Commercial and Medicare Supplemental US insurance claims databases (March 2016–October 2018). Second, using data collected in the Corrona US RA Registry (February 2016–August 2019), two Clinical Disease Activity Index (CDAI)-based measures of

S. B. Cohen Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, TX, USA J. D. Greenberg  K. J. Dandreo  H. J. Litman  T. Blachley Corrona, LLC, Waltham, MA, USA J. Harnett (&)  A. Madsen  T. W. Smith  R. Zhang  T. Lukic  C. Chen Pfizer Inc, New York, NY, USA e-mail: [email protected] D. Gruben Pfizer Inc, Groton, CT, USA

J. Woolcott Pfizer Inc, Collegeville, PA, USA A. Lenihan Pfizer Inc, London, UK J. L. Rivas Pfizer SLU, Madrid, Spain M. Dougados Department of Rheumatology, Universite´ de Paris, ˆ pital Cochin, Assistance Publique-Ho ˆ pitaux de Ho Paris, Paris, France

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effectiveness were compared between tofacitinib MR 11 mg QD and IR 5 mg BID, and against noninferiority criteria derived from placebo-controlled clinical trials of the tofacitinib IR formulation. Multiple sensitivity analyses of the registry data were conducted to reassure regulators of consistent results across different assumptions. Results: In each study, approximately twothirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority