Background/Purpose: In 2021, the FDA concluded that there is an increased risk of serious heart-related events with the Janus Kinase (JAK) inhibitor tofacitinib, which is currently indicated for rheumatoid arthritis (RA), psoriatic arthritis (PsA), ulcerative colitis (UC), ankylosing spondylitis (AS) and polyarticular course juvenile idiopathic arthritis (pcJIA). Accordingly, a black box warning was applied to the JAK class for drugs that are indicated for the treatment of arthritis and other inflammatory conditions. Tumor necrosis factor α inhibitors (TNFi) do not carry a black box warning for these adverse events. It is unknown if prescribing patterns or patient behavior was impacted in response to the new black box warning.

Methods: This is a retrospective cohort study of RA patients receiving a JAK inhibitor or TNFi. Patients were included if they received at least 3 fills for a JAK inhibitor or TNFi between 4/1/2021 and 8/31/2022 and maintained coverage until 8/31/2022. Three periods were assessed: pre-black box warning (4/1/2021 – 8/31/2021), washout (9/1/2021-12/1/2021), and post-black box warning period (12/2/2021-8/31/2022). Propensity score matching was conducted utilizing the patient’s demographic profile, including age, gender, socioeconomic status (SES), location, and comorbid conditions. Adherence was measured using proportion of days covered (PDC) and was evaluated overall and during each period. Discontinuation was determined if the last fill occurred greater than 30 days from the end of the study. Discontinuation rates were calculated for each period; p-values < 0.05 were significant.

Results: A total of 815 patients were included in the unmatched analysis, with 215 (26.4%) receiving JAK inhibitors. Differences in age and gender were found between JAK inhibitor and TNFi patients (mean age (SD): 54.8 [8.9] vs 52.4 [11.4] years in JAK inhibitor vs TNFi, p = 0.002; 36 (16.7%) vs 149 (24.8%) males in JAK inhibitor vs TNFi, p=0.02). No differences in SES or comorbidity were found. Patients prescribed JAK inhibitors had higher median PDC (5.6%; p=0.022) during the study compared to TNFi patients and higher median PDC (7.1%; p = 0.014) during the post-black box warning period. No difference in discontinuation rates were found overall and stratified by study period. After matching, 408 patients were evaluated with 50% receiving JAK inhibitors; no differences in underlying demographics or comorbidities were found. Adherence metrics were similar between matched cohorts. There were no significant differences in median PDC (1.8%; p=0.235) or discontinuation rates (28.9% vs 27.9%), in JAK inhibitor and TNFi groups, respectively, p = 0.529.

Conclusion: Adherence and persistence to JAK inhibitors were not significantly impacted by the addition of the black box warning.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/adherence-patterns-in-rheumatoid-arthritis-patients-receiving-a-janus-kinase-jak-inhibitor-or-a-tumor-necrosis-factor-%ce%b1-inhibitor-tnfi-after-the-addition-of-a-black-box-warning-to-jak-inhibit/