There is a need for postmarketing evidence generation for novel biologics and biosimilars. The objective was to assess the feasibility, strengths, and limitations of the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) Distributed Research Network (DRN) to examine the utilization and comparative safety of immune-modulating agents among patients with autoimmune diseases. We conducted a retrospective cohort study among patients enrolled in health insurance plans participating in the BBCIC DRN between January 1, 2006, and September 30, 2015. Eligible patients were adult (≥18 years) new users of a disease-modifying nonbiologic and/or biologic agent with a prior diagnosis of rheumatoid arthritis (RA), other inflammatory conditions (psoriasis, psoriatic arthritis, ankylosing spondylitis), or inflammatory bowel disease (IBD). Follow-up started at treatment initiation and ended at the earliest outcome occurrence (serious infection); treatment discontinuation; switching, death, disenrollment, or end of the study period. The study leveraged the FDA Sentinel System infrastructure for data management and analysis; descriptive statistics of patient characteristics and unadjusted incidence rates of study outcomes during follow-up were calculated.