The long-term safety and tolerability is consistent with the known safety profile of ixekizumab in multiple chronic inflammatory diseases, including psoriasis, psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA), according to study results published in Rheumatology.
Ixekizumab is a monoclonal antibody that targets interleukin-17A and is used for the treatment of several inflammatory diseases. In an integrated analysis of 21 clinical trials, the investigators aimed to characterize the long-term safety and tolerability of ixekizumab in patients with psoriasis, PsA, and axSpA.
Using data from randomized controlled trials, the researchers examined the rates of adverse events (AEs) and treatment-emergent adverse events (TEAEs), summarized by exposure-adjusted incidence rates, associated with ixekizumab use.
The pooled population included 8228 patients, of whom 5898 had psoriasis, 1401 had PsA, and 929 had axSpA. The percentage of men ranged from 48.5% to 69.9% in the analysis, with all groups including predominantly white patients (74%-91.3%). The cumulative exposure time was 20,895.9 person-years (PYs), with up to 5, 3 and 2 years of exposure for patients treated for psoriasis, PsA, and axSpA, respectively.
The overall incidence rates of patients with ≥1 TEAE were 29.5 per 100 PYs in the psoriasis group (86.6% of patients), 50.6 per 100 PYs in the PsA group (80.5% of patients), and 55.9 per 100 PYs in the axSpA group (80.4% of patients). Severe TEAEs were reported by 8.1% to 16.7% of patients across all groups. The most frequently reported events among all groups were nasopharyngitis (14.4%-25.7%), upper respiratory tract infections (10.5%-15.6%), and injection site reactions (9.7%-11.1%). The most commonly reported TEAEs of special interest were infections, including nasopharyngitis, upper respiratory tract infections, and bronchitis. Infections were most common during the first year, with incidence rates ranging from 49.5 to 56.6 per 100 PYs, and decreased over time to ≤40.1 per 100 PYs across all groups.
Major cardiovascular events, malignancies, and inflammatory bowel disease were rare, with incidence rates of <1 per 100 PYs across all groups. Serious adverse events were reported at an incidence rate of 5.4 to 6.0 per 100 PYs and remained stable over time. Discontinuation from the study due to adverse events was reported in <10% of patients in all groups.
Among the pooled population, 43 deaths were reported, including 35, 6, and 2 in the psoriasis, PsA, and axSpA groups, respectively. The predominant cause of death was major cardiovascular events in the psoriasis and PsA groups, though ixekizumab was not associated with individual causes of death.
The most significant limitation of the analysis included the survival bias that occurs in long-term study extensions, since only patients who continue to respond to treatment are enrolled in such studies.
“Chronic diseases such as [psoriasis], PsA and axSpA require long-term treatment management. Therefore, long-term assessment of safety is needed to evaluate the benefit-risk of treatment,” the researchers concluded. “This long-term analysis on the safety of ixekizumab was consistent with previously published reports and did not show any new safety signals.”
Disclosures: The clinical trial was supported by Eli Lilly and Company. Several authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.
Genovese MC, Mysler E, Tomita T, Papp KA, Salvarani C, Schwartzman S, et al. Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials [published online May 25, 2020]. Rheumatology (Oxford). doi:10.1093/rheumatology/keaa189