An Active Surveillance, Post Authorization Safety Study (PASS) to Investigate Relevant Safety Outcomes among Patients Treated with Flixabi for Rheumatoid Arthritis (RA) within the German Registry Rheumatoide Arthritis: Beobachtung der Biologika-Therapie (RABBIT)

Study type

• Study topic:
  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:
  FLIXABI
• Study drug International non-proprietary name (INN) or common name:
  INFLIXIMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AB02) infliximab

  infliximab
• Medical condition to be studied:
  Rheumatoid arthritis

Population studied

• Short description of the study population:
  Patients with rheumatoid arthritis enrolled in the RABBIT register who initiated treatment with Flixabi (index drug group) or other infliximab products including Remicade, Zessly, Remsima, and Inflectra (comparator group) after at least one prior csDMARD failure. Patients must have a rheumatologist-confirmed diagnosis of RA and be at least 18 years of age at initiation of treatment.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)

Study design details

• Study design:
  Non-interventional prospective observational cohort study
• Main study objective:
  The objectives were to compare patients exposed to Flixabi (index group) and patients treated with any other; infliximab except Flixabi (comparator group). The pre-defined outcomes comprised tuberculosis, serious; infections (excluding tuberculosis) / sepsis, congestive heart failure, myocardial infarction, central; demyelination / demyelinating disorders, serious hematologic disorders, neoplasms / malignancies, death,; serious systemic hypersensitivity reactions / serious infusion reactions, hepatic failure, serious gastrointestinal; ulcer / perforation, stroke, venous thromboembolism, pregnancy and pregnancy outcomes, and immunogenicity.; Events are classified as serious or non-serious by the reporting physician.
• Setting:
  Patients with RA enrolled and observed in RABBIT between 01 January 2017 and 30 June 2025 were analysed; according to their exposure groups and described both at the time of enrolment and at each start of therapy using; summary measures.
• Comparators:
  Any other infliximab except Flixabi
• Outcomes:
  Events of interest were defined in the RABBIT study protocol and comprise outcomes of tuberculosis (incident and reactivated), other serious infections, myocardial infarction, heart failure, stroke, venous thromboembolism, central demyelination, hepatic failure, serious systemic hypersensitivity reactions/serious infusion reactions, serious gastrointestinal ulcer/perforation, serious hematologic disorders, malignancies and deaths. In case of an event of interest or in case of an SAE which had been assigned to be possibly related to a DMARD, the treating physician is asked to complete a query for additional information. For all events of interest, as well as for pregnancies and pregnancy-related outcomes, additional event-specific queries are used. For SAEs with a possible relation to DMARD use, a general additional query is used without event-specific questions. All additional queries comprise details for greater specification of the event, related diagnostic and therapeutic procedures, as well as ; the course of DMARD therapy. In addition, all other medications the patient had been treated with at the time of the event are reported.
• Summary results:
  A total of 215 treatment episodes were eligible for the analyses, including 32 episodes based on 32 patients for; Flixabi and 183 episodes based on 174 patients for the comparator group. Mean age at index date was 56.7 years; in the Flixabi versus 57.0 years in the comparator group. Most patient characteristics were comparable for both; groups.No events occurred in the Flixabi group for several pre-defined safety outcomes where events were; observed in the comparator group, including serious infections/sepsis, myocardial infarction,; neoplasms/malignancies, serious hematologic disorders, demyelinating disorders, serious gastrointestinal; ulcer/perforation, stroke, and death.One case of venous thromboembolism (VTE) was observed in the Flixabi; treatment group. No VTE events were recorded in the comparator group. The unadjusted IR of VTE in the; Flixabi group was 34.75 (95% CI: 0.44–97.63). For immunogenicity, five events were observed in the Flixabi; group, corresponding to an unadjusted IR of 96.65 (95% CI: 31.38–225.54). In the comparator group, 14 events; were observed, resulting in an unadjusted IR of 57.9 (95% CI: 31.65–97.14).The fully adjusted Cox regression; model for immunogenicity shows a numerically increased, but statistically not significant risk in the Flixabi; group compared with the comparator group (HR: 2.16, 95% CI: 0.59–7.87).