The risk for hospitalization due to infection doubled during the first year of treatment with secukinumab compared with other tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA) or psoriatic arthritis (PsA); however, confounding factors may have influenced this result, according to study findings published in Rheumatology (Oxford).

Researchers conducted a prospective, observational study in which they obtained data via rheumatology registers in Denmark, Sweden, Norway, and Finland from 2010 to 2018. They identified 13,468 patients with SpA (n=7708) and PsA (n=5760) who received 18,177 treatment courses (10,393 for SpA and 7784 for PsA) with either secukinumab or 5 other tumor necrosis factor inhibitors (TNFis), including adalimumab, infliximab, etanercept, certolizumab pegol, and golimumab.

Study patients had initiated treatment with secukinumab or another TNFi between 2015 through 2018. Follow-up lasted for either 12 months or 90 days following treatment discontinuation to account for infections that occurred during treatment washout periods.


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The researchers analyzed whether patients who received secukinumab demonstrated increased likelihood of infection during treatment compared with other TNFi, and which types of infections predominated.

During the first year of treatment, patients who received secukinumab demonstrated increased risk for infection resulting in hospitalization compared with patients who received adalimumab (3.5% vs 1.7%). Rates of infection during treatment with other 4 TNFi fell in between these 2 rates. Patients with PsA had higher infection rates compared with patients who had SpA, but both groups exhibited similar trends for increased risk for infection.

Patients treated with secukinumab and a subcutaneous TNFi were less likely to contract pneumonia, urinary tract infection (UTI), and fungal infection, while those who received infliximab had a higher likelihood of contracting pneumonia (adjusted hazard ratio [aHR], 3.37; 95% CI, 1.69-6.72) and risk for fungal infection remained low (aHR, 0.42; 95% CI, 0.20-0.88). Other infections such as herpes zoster, tuberculosis, and erysipelas occurred so infrequently that meaningful comparisons were not possible.

Sensitivity analysis resulted in a loss of statistical significance and attenuation of hazard ratios, indicating that the increased risk while taking secukinumab may occur due to its differential use in patients previously exposed often to multiple biological disease-modifying antirheumatic drugs (bDMARDs).

Limitations of the study included risk for confounding by indication, a lack of power to detect rare outcomes, exclusion of milder cases of infection that did not require hospitalization or specialized outpatient care, and a lack of available data regarding antibiotic prescriptions or smoking status.

The study authors concluded, “[T]here is a low frequency of hospitalized infections during treatment with secukinumab or TNFi in SpA and PsA. In clinical practice, secukinumab was mainly used in [biologic disease-modifying antirheumatic drug] experienced patients, and the doubled absolute risk in patients treated with secukinumab, compared with adalimumab, (with the other TNFi falling in between) seemed to be partly or entirely explained by confounding factors.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Glintborg B, Di Giuseppe D, Wallman JK, et al. Is the risk of infection higher during treatment with secukinumab than with TNF-inhibitors? An observational study from the Nordic countries. Rheumatology (Oxford). Published online June 20, 2022:keac358. doi:10.1093/rheumatology/keac358