New users of infliximab and adalimumab who had moderate to severe psoriasis exhibited an increased risk of hospitalization due to serious infection compared with etanercept users, with use of ustekinumab conversely linked with a decreased risk.
Use of the biologics infliximab and adalimumab may increase the risk of serious infection in patients with psoriasis, according to study findings published today in JAMA Dermatology.
In the treatment landscape of moderate to severe psoriasis, systemic nonbiologic therapies, targeted therapies, and biologics are all commonly used to manage the condition. Although higher efficacy has been observed for biologic than nonbiologic agents, researchers note that long-term comparative safety in a real-world setting is warranted due to the potential risk of serious infection, defined as any infection leading to hospitalization in patients with psoriasis, which may vary based on the biologic agent used.
“Prior observational studies have provided conflicting results on the risk of infection related to use of biologics and mostly used conventional systemic immunosuppressive treatment as a comparator,” said the study authors.
Seeking to assess and compare the risk of serious infection among several biologics, including infliximab, adalimumab, and ustekinumab, as well as targeted synthetic antipsoriatic agents such as etanercept and apremilast, they conducted a nationwide cohort study of adult patients with moderate to severe psoriasis.
Using etanercept as the reference comparator to avoid risk of immortal time bias, participant data on those who were new users of biologic agents or apremilast were derived from the National Health Data System between January 1, 2008, and May 31, 2019 (N = 44,239; mean [SD] age, 48.4 [13.8] years; 22,866 [51.7%] men; median [interquartile range] follow-up, 12 [7-24] months).
“The primary end point was a serious infection in a time-to-event analysis using propensity score–weighted Cox proportional hazards regression models, estimating weighted hazard ratios (wHRs) and 95% CIs," the authors wrote
Among the study cohort, 29,618 (66.9%) patients were indicated to have been prescribed a tumor necrosis factor inhibitor first; 6658 (15.0%), an interleukin (IL)-12/23 inhibitor; 4093, (9.3%) an IL-17 inhibitor; 526 (1.2%), an IL-23 inhibitor; and 3344 (7.6%), apremilast.
A total of 1656 serious infections were identified, with an overall crude incidence rate of 25.0 (95% CI, 23.8-26.2) per 1000 person-years. Gastrointestinal infections served as the most frequent serious infection in the study cohort (n = 645 [38.9%]).
After adjusting for time-dependent covariables, risk of serious infections was found to be higher for new users of adalimumab (wHR, 1.22; 95% CI, 1.07-1.38) or infliximab (wHR, 1.79; 95% CI 1.49-2.16) compared with etanercept.
“In the subgroup that excluded patients with psoriatic arthritis or inflammatory bowel disease, adalimumab was no longer associated with increased risk of serious infection. Thus, a differential risk of serious infections for adalimumab depending on the underlying diseases cannot be excluded,” noted the researchers.
Conversely, ustekinumab was associated with a lower risk of having a serious infection (wHR, 0.79; 95% CI, 0.67-0.94) than etanercept, with no increase in risk observed for new users of guselkumab, apremilast, secukinumab, ixekizumab, or brodalumab vs etanercept.
Notably, risk of serious infection was indicated to be increased with use of concomitant nonsteroidal anti-inflammatory drugs (wHR, 1.47; 95% CI, 1.25-1.73) or systemic corticosteroids (wHR, 2.32; 95% CI, 1.95-2.76).
“Other observational studies are needed to confirm results for the most recent drugs,” concluded the study authors.
Penso L, Dray-Spira R, Weill A, Vegas LP, Zureik M, Sbidian E. Association between biologics use and risk of serious infection in patients with psoriasis. JAMA Dermatol. Published online July 21, 2021. doi:10.1001/jamadermatol.2021.2599