Malignancy and Cardiovascular Risk Assessment Using the Consortium of Rheumatology Researchers of North America Registry (Corrona) as an External Comparator for Tofacitinib-Exposed Patients within the Rheumatoid Arthritis BID Clinical Trial Program: A Comparative Post-Approval Safety Study (Matched Analysis for Xeljanz with Corrona)

Study identification

• EU PAS number:
  EUPAS23344
• Study ID:
  41400
• Official title and acronym:
  Malignancy and Cardiovascular Risk Assessment Using the Consortium of Rheumatology Researchers of North America Registry (Corrona) as an External Comparator for Tofacitinib-Exposed Patients within the Rheumatoid Arthritis BID Clinical Trial Program: A Comparative Post-Approval Safety Study (Matched Analysis for Xeljanz with Corrona)
• DARWIN EU® study:
  No
• Study countries:
  United States
• Study description:
  Tofacitinib (Xeljanz®) is an oral Janus kinase inhibitor for treatment of RA in patients with inadequate response to methotrexate (MTX-IR). The clinical development program included approximately 4800 patients with 7000 patient-years of exposure at the time of submission to the US Food and Drug Administration in 2011 (Pfizer, 2014). Due to the design of the Phase 3 trials, limited patient numbers and exposure are available for the comparators in these trials. As such, external data sources (ie, published and public-domain literature sources) have been used to provide background rates for qualitative comparison to the clinical program safety events. The proposed study seeks to supplement those data by performing a formal comparison of malignancy and cardiovascular event rates from the tofacitinib clinical trial program with event rates from the Consortium of Rheumatology Researchers of North America (Corrona) registry. The primary analysis will be on a cohort of RA patients within Corrona initiating a biologic that overlap the tofacitinib population characteristics based on prior disease modifying antirheumatic drug use and patient clinical and demographic characteristics. A propensity score will be used to determine patients in the two cohorts with common support (a similar range of scores). Multivariable adjusted hazard ratios will be estimated to compare the risk of malignancy and cardiovascular events in the two populations. A series of secondary Corrona RA cohorts will be compared to the tofacitinib clinical trial population for sensitivity analyses to evaluate the robustness of the estimated effects in the primary analysis. Secondary cohorts include, but are not limited to, direct propensity score matched population, RA initiators restricted to ‘tofa trial eligible’ biologic initiators, and a comparison to rates in the full RA population. A final report (detailing all statistical analyses and conclusions) will be delivered by Corrona.
• Study status:
  Finalised

Study timelines

Date when funding contract was signed

Actual: 12/11/2014

Study start date

Planned: 15/02/2019

Actual: 20/11/2019

Date of final study report

Planned: 31/07/2020

Actual: 08/04/2021

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

Pfizer, Inc.

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Non-EU RMP only