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 German Registry Rheumatoide Arthritis: Beobachtung der Biologika Therapie (RABBIT) (Safety of tofacitinib in RABBIT)

Study type

• Study topic:
  Disease /health condition

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

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  XELJANZ
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AF01) tofacitinib

  tofacitinib
• Medical condition to be studied:
  Rheumatoid arthritis

Population studied

• Short description of the study population:
  The study population will comprise all patients with RA enrolled within RABBIT who receive tofacitinib following European Medicines Agency (EMA) approval and German launch. For contextualization purposes, the study population will also include RABBIT patients treated with bDMARDs and nbDMARDs. As initiation of tofacitinib in ; RABBIT will be from 01 May 2017 onwards, only treatments initiated after this date will be included in the final report.
• 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:
  500

Study design details

• Study design:
  This active surveillance study is using data from RABBIT, an ongoing, prospective observational cohort study started in 2001 with the primary aim of studying the safety of new therapies for RA during routine post-marketed clinical use. RABBIT is being conducted by German Rheumatism Research Center
• Main study objective:
  To evaluate the rates of serious infections, malignancy, CV, and other specified outcomes among patients with RA in a German register who initiate tofacitinib. Rates will also be estimated among existing cohorts of bDMARD and nbDMARD patients to provide context for rates observed on tofacitinib. No a priori hypotheses will be tested in this descriptive study
• Setting:
  The German Biologics Register RABBIT has been active since May 2001 under the auspices of the “Kompetenznetz entzündlich-rheumatische Systemerkrankungen” (“Competence Network Rheumatology”).
• Comparators:
  The bDMARD comparator cohort will be presented in the final report, while the nbDMARD comparator cohort will be included in both interim and final report reports.
• Outcomes:
  Endpoints in RABBIT derive from physician reports of the occurrence of any AE or event of ; interest. The events of interest, based on previously identified risks in the treated and ; untreated RA population, include: ; 1. Serious infections (excluding TB): pneumonia, other infections of the respiratory ; system, infections of the CNS, sepsis, bone or joint infections, OI, other infections. ; 2. TB. ; 3. Herpes Zoster. ; 4. Fractures. ; 5. Cardiac disorders: heart failure, coronary artery disease, myocardial infarction, ; MACE, other cardiac disorders. ; 6. Hematologic disorders: bone marrow depression and hypoplastic anaemia, decreased ; white blood cells, platelet disorders, other blood dyscrasia. ; 7. Disorders of the nervous system (excluding infections): stroke, central demyelination, ; other disorders of the CNS, disorders of the peripheral nervous system, psychiatric ; disorders.; 8. Progressive multifocal leukoencephalopathy. ; 9. Allergic conditions and hypersensitivity. ; 10. Hepatic failure. ; 11. Gastrointestinal (GI) perforations: Lower intestinal perforations, Other GI ; perforations. ; 12. Pregnancy. ; 13. Thromboembolic events: deep vein thrombosis (DVT) and pulmonary embolism ; (PE). ; 14. Operations and hospitalisations: bone and joint surgery and other joint therapeutic ; procedures, other operations and (major) therapeutic procedures that lead to ; hospitalization. ; 15. Other serious diagnoses, symptoms, and syndromes. ; 16. NMSC. ; 17. Malignancies, (overall, excluding NMSC). ; 18. Lymphoma (overall and independently by subtype, including non-Hodgkin ; lymphoma, Hodgkin lymphoma, and chronic lymphatic leukemia). ; 19. Lung cancer. ; 20. All-cause Mortality. ; 21. Leukaemia (excl. B-CLL) ; 22. Other haematopietic neoplasms (malignant and benign) ; 23. Solid malignancies (overall)) ; 24. Glioblastoma ; 25. Benign neoplasms ; 26. Unspecified neoplasms and precanceroses ; 27. Metastases, cancer related and morbidities and associated syndromes ; 28. Interstitial lung disease, pending
• Data analysis plan:
  The initial analyses will consist of descriptive comparisons of baseline status and crude event rates between the different cohorts. The final analysis of endpoints will provide the rates of events overall and in subgroups defined by baseline characteristics. Pending feasibility, rates of malignancy, serious infection, CV and other event rates will be compared between tofacitinib treated RA patients and the comparator cohorts using methods that adjust for sex, age, year of treatment start, treatment history, disease severity, comorbidities, and other potential confounders.