Influenza adverse events in patients with rheumatoid arthritis in the tofacitinib clinical programme

ABSTRACT

Background: Patients (pts) with rheumatoid arthritis (RA) have an increased susceptibility to seasonal influenza and its complications.1 In light of the COVID-19 pandemic, there is a need to better understand acute respiratory viral RNA infections, such as influenza, in pts with RA. Objectives: To present a comprehensive summary of data on influenza adverse events (AEs) occurring in the tofacitinib RA clinical programme. Methods: Influenza AEs were evaluated in pts with RA from 21 Phase (P)1-3b/4 trials and two open-label, long-term extension (LTE) studies from 2005-2019. These were analysed as two cohorts P2-3b/4 cohort (pts who received tofacitinib 5 or 10 mg twice daily [BID] as monotherapy or with conventional synthetic [cs]DMARDs, adalimumab, methotrexate or placebo, in P2-3b/4 controlled studies) and Overall cohort (pts who received ≥1 tofacitinib dose, as monotherapy or with csDMARDs, in P1-3b/4 and LTE studies;data were summarised by average tofacitinib dose [average tofacitinib 5 or 10 mg BID based on average total daily dose of <15 or ≥15 mg, respectively]). Incidence rates (IRs;unique pts with events/100 pt-years of exposure;censored at day of first event or up to last dose +28 days) were evaluated for influenza AEs, influenza complication AEs, influenza-like illness (all composites of several MedDRA preferred/verbatim terms) and overall influenza AEs (composite of all preferred/verbatim terms included under influenza AEs, influenza complication AEs and influenza-like illness). In the Overall cohort, the incidence of serious non-influenza AEs within 28 days of the start of an overall influenza AE and time taken to resolution of overall influenza AEs by action taken were summarised descriptively. Results: In total, 7964 pts were included;517 (6.5%) pts reported overall influenza AEs, three of which occurred outside the risk period. In the P2-3b/4 cohort (N=6690), IRs for influenza AEs, influenza-like illness and overall influenza AEs generally appeared similar across treatment arms (Figure 1a). In the Overall cohort, IRs for influenza AEs and influenza-like illness were similar between tofacitinib doses (Figure 1b), and IRs for overall influenza AEs were similar between tofacitinib doses and pt age groups (Figure 1c). No influenza complication AEs (eg pneumonia/encephalitis influenzal) were reported in either cohort. Among pts with overall influenza AEs, nine (1.7%) had serious overall influenza AEs (average tofacitinib 5 mg BID, n=6;average tofacitinib 10 mg BID, n=3). Of these pts, eight (1.5%) were hospitalised (average tofacitinib 5 mg BID, n=6;average tofacitinib 10 mg BID, n=2) and two (0.4%) died (average tofacitinib 5 mg BID, n=1;average tofacitinib 10 mg BID, n=1). Both deaths occurred in pts with H1N1 Influenza A. Twelve (2.3%) pts had a serious non-influenza AE within 28 days of the start of the overall influenza AE (average tofacitinib 5 mg BID, n=6;average tofacitinib 10 mg BID, n=6). The most common serious non-influenza AEs (one event each in average tofacitinib 5 and 10 mg BID groups) were acute respiratory distress syndrome and pneumonia. In most pts with overall influenza AEs, no change to tofacitinib treatment was made (70.2%, n=363) or treatment was stopped temporarily (28.2%, n=146) for a mean duration of 11.0 days. The mean number of days to resolution of overall influenza AEs was numerically similar, ranging from 10.4-11.8 days across tofacitinib doses, irrespective of these actions. Conclusion: This post hoc analysis of influenza AEs across the tofacitinib RA clinical programme, over 14-15 influenza seasons, showed generally similar rates between treatment groups, and between tofacitinib doses and pt age groups. Limitations include varying exposure across treatment arms in the P2-3b/4 cohort. Most influenza AEs were non-serious (98.3%), and were not associated with changes to tofacitinib treatment.