Serious Infection More Likely in Older Rheumatoid Arthritis Patients

June 7, 2020
Samara Rosenfeld

A team investigated data from trials of tofacitinib, adalimumab, and placebo.

Kevin Winthrop, MD, MPH

A post hoc analysis suggests the risk of serious infection events or overall infections is similar for tofacitinib and adalimumab in older patients with rheumatoid arthritis.

The findings came from research published as part of the European E-Congress of Rheumatology 2020 (EULAR 2020) meeting due to the cancellation of the in-person meeting.

Kevin Winthrop, MD, MPH, from Oregon Health & Science University, and a team of investigators assessed the incidence rates of overall infection events and serious infection events in patients from phase 2, 3, and 3b/4 tofacitinib rheumatoid arthritis trials which had a tumor necrosis factor inhibitor (adalimumab) active control or comparator arm. The team used pooled data from months 0-12.

They included and assessed patients randomized to receive tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, adalimumab 40 mg subcutaneously every other week, and placebo. The team assessed the patients overall and by age (<65 or >65 years old).

Winthrop and the investigators defined serious infection events as those requiring hospitalization or parenteral antimicrobial therapy or meeting other criteria for a serious adverse event. They calculated incidence rates and 95% confidence intervals for all infection events and serious infection events. Only first infection events that happened <28 days after the last dose or to the data cut-off date were used.

There were 2180 patients included in the studies—tofacitinib 5 mg twice daily (n=1064; 943.4 patient-years); tofacitinib 10 mg twice daily (n=306; 236.6 patient-years); adalimumab (n=643; 554.3 patient-years); placebo (n=167; 108.1 patient-years). A majority of the patients (84%) were <65 years old, while 15.6% were >65 years old.

The incidence rates for all infection events and serious infection events were higher with tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, and adalimumab in patients >65 years old compared to those <65 years old. When the investigators stratified by age, incidence rates for all events were similar across the active treatment groups. With placebo, incidence rates were lower versus the active treatment groups overall, and in patients <65 years old. In the placebo group, incidence rates were also numerically lower versus the active treatment groups in patients >65 years old.

Incidence rates for serious infection were similar across active treatment groups in patients <65 years old. For patients >65 years old, incidence rates were numerically higher for tofacitinib 10 mg twice daily versus adalimumab and were similar for tofacitinib 5 mg twice daily and adalimumab. Winthrop and the team noted tofacitinib twice daily is not an approved dose for the treatment of rheumatoid arthritis.

The investigators said the comparison was limited due to variation in sample size and patient-years of exposure between treatment and age groups and a small number of cases in the >65-year age group, which led to wide 95% confidence intervals. The findings were consistent with increasing age being a known factor for infections.

The study, “Age-Based (<65 Vs >65 Years) Incidence of Infections and Serious Infections in Tofacitinib-, Adalimumab-, and Placebo-Treated Patients With Rheumatoid Arthritis: A Post Hoc Analysis of Phase 2, Phase 3, and Phase 3B/4 Tofacitinib Studies,” was published online on the EULAR 2020 website.


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