An Active Surveillance, Post Authorization Safety Study (PASS) of Serious Infection, Malignancy, Cardiovascular (CV) and Other Safety Events of Interest among Patients Treated with Tofacitinib for Moderately to Severely Active Rheumatoid Arthritis (RA) within the Swedish, Population based, Anti Rheumatic Treatment in Sweden (ARTIS) register. (Safety of tofacitinib in ARTIS)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  XELJANZ
• Study drug International non-proprietary name (INN) or common name:
  TOFACITINIB CITRATE
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AF01) tofacitinib

  tofacitinib
• Medical condition to be studied:
  Rheumatoid arthritis

Population studied

• Short description of the study population:
  Since 1999, ARTIS has conducted a prospective, observational disease-based cohort study safety surveillance programme with the primary aim of studying the safety of new therapies for RA during routine post-marketed clinical use based on SRQ linked to additional registers, and includes all presently available biologics used for the treatment of patients with inflammatory rheumatic diseases. ; It covers around 90% of all biologic initiations in Sweden after 1999. By August 2017, the follow-up within ARTIS included over 40,000 patients (65% women),; and almost 80,000 biologics treatment initializations. Matched general population subjects, and additional health and demographic information are derived from the mandatory, semi-automated data registration within population registers maintained by the National Board of Health and Welfare (Socialstyrelsen) and Statistics; Sweden.
• 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)
• Estimated number of subjects:
  344

Study design details

• Study design:
  This is an active surveillance study of existing nationwide cohorts in Sweden using linkages between drug-based registers, disease-based registers, national death register, cancer register, inpatient register, and outpatient register.
• Main study objective:
  To estimate the rates of serious infections, malignancy, CV and other safety events of interest among patients with RA in Sweden who initiate tofacitinib. Rates will also be estimated among RA patients who initiate biologic DMARDs (bDMARDs), bDMARD and targeted synthetic DMARD (tsDMARD) naïve RA patients, and the general population to provide context for tofacitinib rates.
• Setting:
  Sweden is a Scandinavian country with 10 million inhabitants. The prevalence of RA in Sweden is around 0.7% and the overall incidence 41/100,000 per year.; ; Swedish health-care is tax-funded and offers universal access. Hospital referral is based on geography rather than insurance-status. Patients with RA are typically treated by rheumatologists, the vast majority of whom work in public and hospital-based clinics. Health and demographic information is collected in a series of registers with a high degree of completeness resulting from the mandatory and semi-automated registration of their data.; Based on each Swedish resident’s unique personal identification number, issued to all Swedish residents alive in 1947 or born/immigrated thereafter, linkage of data from different registers is possible.14 The registers are maintained by governmental bodies (the main registers used in this project are held by the National Board of Health and Welfare (Socialstyrelsen) and Statistics Sweden), who may perform data linkages and provide; de-identified data for research purposes.; ; Use of a RA treatment for a particular patient in Sweden has never been subject to a formal approval process (with the exception of a period during 2002-2003, when manufacturing issues led to reduced availability of etanercept), mandatory treatment history, or disease activity indices. Instead, the Swedish Society for Rheumatology has issued guidelines for the use of biologics, which are revised on an annual basis, but the ultimate decision to treat with biologics and which biologic to use have always resided with the treating rheumatologist.
• Comparators:
  Three comparator cohorts will be assembled for risk characterization purposes: (1) RA patients who are treated with bDMARD (2) RA patients who are naïve to bDMARDs and tsDMARDs, and (3) a general population cohort.
• Outcomes:
  1. Hospitalized infections overall.; 2. Opportunistic infections.; 3. Herpes zoster (hospitalized).; 4. Hepatitis.; 5. Fractures.; 6. NMSC.; 7. Malignancies (overall, excluding NMSC).; 8. Lung Cancer.; 9. Lymphoma (overall and independently by subtype, including non-Hodgkin lymphoma, Hodgkin lymphoma, and chronic lymphatic leukemia).; 10. CV events, including deep vein thrombosis/pulmonary embolism (DVT/PE).; 11. Major Adverse Cardiovascular Events (MACE).; 12. Myocardial infarction (MI); 13. Gastrointestinal (GI) perforations.; 14. Progressive multifocal leukoencephalopathy (PML).; 15. Interstitial lung disease, pending feasibility.; 16. All-cause Mortality.
• Data analysis plan:
  Descriptive summaries of baseline variables and crude rates of safety event of interest included in ARTIS. An interim and final analysis of endpoints will describe the rates of events overall with supplemental linked data. ; Pending feasibility, comparative, adjusted analyses that control for sex, age, year of treatment start, treatment history, disease severity, comorbidities, and other potential confounders will be performed for a final report