Fig 1.
Base cohorts for MACE and VTE outcomes, inclusion and exclusion criteria, exposure sets, and study cohorts.
Abbreviations: RA Rheumatoid Arthritis; JAKi Janus Kinase inhibitor; TNF-αi Tumor Necrosis Factor α inhibitor; DANBIO Danish Rheumatologic database; MACE major adverse cardiovascular events; VTE venous thromboembolism. TCPS time-conditional propensity score; T0 will be defined as the study cohort entry date for JAKi users (i.e., first start of JAKi treatment) and the corresponding matching date for TNF-αi users.
Fig 2.
Base cohorts for the outcome of serious viral infection, inclusion and exclusion criteria, exposure sets, and study cohorts.
Abbreviations: RA Rheumatoid Arthritis; JAKi Janus Kinase inhibitor; TNF-αi Tumor Necrosis Factor α inhibitor; HIV Human Immunodeficiency Virus; DANBIO Danish Rheumatologic database. TCPS time-conditional propensity score; T0 will be defined as the study cohort entry date for JAKi users (i.e., first start of JAKi treatment) and the corresponding matching date for TNF-αi users.
Fig 3.
Graphical description of the time-dependent exposure set for Janus Kinase inhibitors (JAKis) users.
(A) We depict an example of potential controls (patients A2, A3, A4, A5) to be included in the exposure set for a JAKi user with previous TNF-αi use (patient A1), and three examples (patients A6, A7, and A8) who are not eligible to be controls for that JAKi user based on: (i) calendar time (TNF-αi use within ± 90 days from T0), (ii) type of TNF-αi at T0 (not applicable for JAKis users with no previous use of TNF-αi), (iii) time since the start of the patient’s first TNF-αi drug within a difference of ± 90 calendar days (i.e., look back period from study cohort entry date up to base cohort entry), and (iv) duration (days) of the most recent TNF-αi treatment course, starting looking from T0 and continue backwards in time until a period free of treatment > 90 days. (B) Potential controls (patients B3 and B4) to be included in the exposure set for a JAKi user with no previous TNF-αi use (patient B1), and one example (patient B2) who is not eligible to be a control for that JAKi user based on the requirements above (i), (iii), and (iv). While infliximab and etanercept were used to exemplify patients using different TNF-α drugs, the list of TNF-αis used in the study is not restricted to these two drugs. Abbreviations: NA not applicable; JAKi Janus Kinase inhibitor; TNF-αi tumor necrosis factor α inhibitor; T0 will be defined as the study cohort entry date for JAK inhibitor users and the corresponding matching date for TNF-αi users.
Table 1.
Timeline of the study.