Adverse events due to influenza (flu) among patients with rheumatoid arthritis treated with tofacitinib (XELJANZ) do not differ significantly from rates reported among differently-treated arthritis patients or among those from different age groups, according to new findings.
In late-breaking data presented at the American College of Rheumatology (ACR) Convergence 2020, an international team of investigators sponsored by Pfizer reported little differentiation in adverse events due to the flu among rheumatoid arthritis patients receiving the JAK inhibitor, adalimumab, methotrexate (MTX), or placebo.
The findings are meant to represent the potential risk of severe respiratory RNA viral infection susceptibility among patients with rheumatoid arthritis undergoing care with tofacitinib, given concern for such patients sparked by the coronavirus 2019 (COVID-19) pandemic.
Led by Kevin L. Winthrop, MD, MPH, of the Oregon Health & Science University in Portland, investigators collected and assessed data on influenza adverse events (AEs) in a Pfizer tofacitinib clinical program for the treatment of rheumatoid arthritis.
As they noted, patients with rheumatoid arthritis have increased susceptibility to the flu and complications from it. “The COVID-19 pandemic highlights the need to understand acute respiratory RNA viral infections in pts receiving tofacitinib,” investigators wrote.
Their post hoc analysis included evaluation of patients with rheumatoid arthritis from 21 trials and 2 open-label, long-term extension studies from 2005-2019. The trials ranged from phase 1 through 3b/4.
Winthrop and colleagues analyzed their patient population as 2 cohorts. The first cohort was a phase 2-3b/4 patient population who either received 5 or 10mg twice-daily tofacitinib as monotherapy or with background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), adalimumab, MTX, or placebo in controlled trials.
The second, overall cohort included patients who received ≥1 dose of tofacitinib as monotherapy or with background csDMARDs in phase 1-3b/4 and long-term extension studies.
Investigators summarized data by mean tofacitinib dose per patient. Incidence rates (IRs), as per unique patients with events per 100 patient-years of treatment exposure (censored at day of first worst event or up to last dose plus 28 days), were evaluated for influenza AEs.
Their assessment included 7964 patients, with 496 (6.2%) reported influenza AEs; another 3 occurred outside the observed risk period.
Among the phase 2-3b/4 cohort of 6690 patients, incidence rates for flu AEs were fairly similar across the rheumatoid arthritis treatment arms:
- Tofacitinib 5mg twice-daily: IR, 2.07 (95% CI, 1.55-2.71)
- Tofacitinib 10mg twice-daily: IR, 3.37 (95% CI, 2.61-4.29)
- Adalimumab: IR, 2.00 (95% CI, 1.00-3.58)
- MTX: IR, 1.68 (95% CI, 0.55-3.93)
- Placebo: IR, 3.23 (95% CI, 1.55-5.94)
Influenza-like illness was actually least incidental among rheumatoid arthritis patients treated with twice-daily 5mg tofacitinib (IR, 0.12; 95% CI, 0.02-0.34). Influenza diagnosis, however, was actually most incidental in patients administered twice-daily 10mg tofacitinib (IR, 3.01; 95% CI, 2.29-3.88). Nearly two-thirds (62.7%) of all influenza AEs were deemed mild in severity.
Among the majority of patients with influenza AEs, Winthrop and colleagues observed no change to tofacitinib treatment (60.6%) nor temporary stop of treatment (28.8%) for a mean duration of 11.1 days. Regardless, mean days to influenza resolution was similar regardless of regimen continuation.
Investigators confirmed their post hoc assessment, which spanned 14-15 flu seasons, showed a generally similar rate of influenza AEs among rheumatoid arthritis patients treated with either tofacitinib, adalimumab, MTX, or placebo. Differentiations among tofacitinib doses and patient age groups were also not observed.
The study, “Influenza Adverse Events in Patients with Rheumatoid Arthritis in the Tofacitinib Clinical Program,” was presented at ACR 2020.