Background/Purpose: Patients (pts) with RA have increased susceptibility to seasonal influenza and its complications.¹ The COVID-19 pandemic highlights the need to understand acute respiratory RNA viral infections in pts receiving tofacitinib. We present data on influenza adverse events (AEs) in the tofacitinib RA clinical program.

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 analyzed as two cohorts: P2–3b/4 cohort (pts who received tofacitinib 5 or 10 mg twice daily [BID] as monotherapy or with background conventional synthetic [cs]DMARDs, adalimumab [ADA], MTX, or placebo in P2–3b/4 controlled studies) and Overall cohort (pts who received ≥ 1 dose of tofacitinib, as monotherapy or with background csDMARDs, in P1–3b/4 and LTE studies; data were summarized 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 worst event or up to last dose +28 days) were evaluated for influenza AEs (a composite of several MedDRA preferred terms). In the Overall cohort, the time to resolution of influenza AEs by action taken was summarized descriptively.

Results: In total, 7,964 pts were included; 496 (6.2%) reported influenza AEs, three of which occurred outside the risk period. In the P2–3b/4 cohort (N=6,690), IRs for influenza AEs generally appeared similar across treatment arms (Table 1). In the Overall cohort, IRs for influenza AEs were also similar across average tofacitinib doses and pt age groups (Table 2). Mild, moderate, and severe influenza AEs were reported in 311 (62.7%), 170 (34.3%), and 15 (3.0%) pts, respectively. Nine (1.8%) pts had serious influenza AEs (average tofacitinib 5 mg BID, n=6; average tofacitinib 10 mg BID, n=3); eight (1.6%) of these were hospitalized (average tofacitinib 5 mg BID, n=6; average tofacitinib 10 mg BID, n=2), and two (0.4%) died (at time of death, one pt each was receiving tofacitinib 5 and 10 mg BID; both had H1N1 and risk factors for mortality due to influenza). In the majority of pts with influenza AEs, no change to tofacitinib treatment was made (69.6%, n=345) or tofacitinib was stopped temporarily (28.8%, n=143) for a mean duration of 11.1 days; the mean number of days to resolution of influenza AEs was numerically similar irrespective of these actions (Table 3).

Conclusion: This post hoc analysis of influenza AEs across the RA clinical program, over 14–15 seasons, showed generally similar rates between tofacitinib, ADA, MTX, and placebo, and between tofacitinib doses and pt age groups. Limitations include varying exposure across treatment arms in the P2–3b/4 cohort. The majority of pts reported mild to moderate influenza AEs.

1. Blumentals WA et al. BMC Musculoskelet Disord 2012; 13: 158.

Acknowledgments: Study sponsored by Pfizer Inc. Medical writing support was provided by Kirsten Woollcott, CMC Connect, and funded by Pfizer Inc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/influenza-adverse-events-in-patients-with-rheumatoid-arthritis-in-the-tofacitinib-clinical-program/