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 type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  XELJANZ
• Medical condition to be studied:
  Rheumatoid arthritis

Population studied

• Short description of the study population:
  Patients diagnosed with Rheumatoid arthritis.; ; Inclusion Criteria; To maximize comparability of the tofacitinib and Corrona patients, Corrona patients must meet the following criteria of tofacitinib studies at the index date:; 1. Aged 18 years or older at index date;; 2. Diagnosis of RA (per American College of Rheumatology [ACR criteria]);; 3. ACR functional class of I, II or III;; 4. No Serious infections, defined as any infection (viral, bacterial, or fungal) requiring parenteral antimicrobial therapy or hospitalization for treatment, or meeting other criteria that require the infection to be classified as a serious adverse event, in the past year;; 5. No current or past malignancies with the exception of non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ;; 6. No current uncontrolled clinically significant hepatic events or liver disorder, gastrointestinal (GI/bowel perforation), pulmonary, cardiac, or neurological disease; (demyelinating disorder/other neurologic); and; 7. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.; Additionally, to ensure completeness of Corrona patient data, Corrona patients must also meet the following criteria:; 1. Initiation and follow-up captured in the Corrona registry during anytime between January 1, 2006 – May 10, 2016 for malignancy, and during February 1, 2009 –; May 10, 2016 for CV analyses; and; 2. At least 1 follow-up visit after biologic initiation during follow-up in the registry.; ; Exclusion Criteria; 1. Any Corrona patient that does not meet one or more of the inclusion criteria will be excluded.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Immunocompromised
• Estimated number of subjects:
  21000

Study design details

• Main study objective:
  The objective of this study is to estimate the incidence rates and corresponding hazard rate ratios of malignancy and cardiovascular endpoints comparing patients from the tofacitinib RA BID clinical program to patients initiating a biologic DMARD and never exposed to tofacitinib (unexposed) in the Corrona registry.
• Outcomes:
  The proposed study will evaluate incidence rates and corresponding hazard rate ratios of the following outcomes among persons exposed to tofacitinib versus comparator. All outcomes described in this section are primary: 1. All malignancies (excluding NMSC), 2. Major adverse cardiovascular events (MACE), 3. Non-fatal MI, and 4. Non-fatal stroke.
• Data analysis plan:
  The primary analysis cohort will be a cohort of patients initiating a biologic within Corrona with no prior tofacitinib exposure that overlaps with the tofacitinib population characteristics based on prior DMARD and TNF use, and patient characteristics. Overlap will be defined as the “common support” for the propensity score distribution, i.e. the range of propensity score values that both populations have in common. A propensity score for use of tofacitinib will be derived and only patients with common support (i.e. overlapping propensity distributions between tofacitinib population and Corrona populations, distributions will be trimmed where there is no overlap) will be used in a multivariable analysis. The cohort from which this population will be derived will be active RA patients initiating a bDMARD with at least one follow-up and no prior tofacitinib exposure. The propensity model will include DMARD history, eligibility criteria and other relevant factors.