Cosentyx Safety Confirmed Through 5 Years

Long-term follow-up has demonstrated a favorable safety profile for secukinumab (Cosentyx) in the treatment of psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), an analysis of data from clinical trials and postmarketing surveillance found.

With up to five years of follow-up for PsO and PsA and up to four years for AS, the exposure-adjusted incidence rates of any serious adverse event were 6.9, 7.9, and 6.3 per 100 patient-years in the PsO, PsA, and AS groups, respectively, according to Atul Deodhar, MD, of the Oregon Health & Science University in Portland, and colleagues.

In addition, the exposure-adjusted incidence rates for serious infections were 1.4, 1.9, and 1.2 per 100 patient-years in the three groups, respectively, the investigators reported online in Arthritis Research & Therapy.

Secukinumab inhibits interleukin (IL)-17A, which plays a central role in the pathogenesis of multiple immune-mediated disorders, and has shown robust efficacy and tolerability in 21 randomized clinical trials for moderate-to-severe PsO, PsA, and AS. Additional follow-up has been provided by postmarketing safety data supplied to regulatory authorities through 2017.

“Secukinumab selectively targets IL-17A, a downstream product of type 17 cells, and leaves the other functions of Th17 cells intact (e.g., the release of IL-22 and tumor necrosis factor) thus limiting the scope for off-target-related effects with secukinumab compared with other biologics,” Deodhar and colleagues wrote.

Treatment for chronic diseases such as PsO, PsA, and AS “is typically intended for long-term use and hence, understanding the long-term efficacy and safety of therapeutic compounds is particularly relevant for clinical decision-making,” they stated.

Accordingly, they reviewed the safety data for patients who participated in the 21 trials, which included 5,181 patients with PsO, 1,380 with PsA, and 794 with AS, and consisted of overall exposure of 16,226.9 patient-years.

Patients enrolled in these clinical trials could have cardiovascular disease, a history of inflammatory bowel disease, basal cell carcinoma, uveitis, or latent tuberculosis, and could previously have been exposed to tumor necrosis factor inhibitors and other biologics. They also could continue treatment with corticosteroids, nonsteroidal anti-inflammatory drugs, and conventional disease-modifying antirheumatic drugs such as methotrexate.

The exposure-adjusted incidence rates of any adverse event were 204.4, 147, and 140.1 per 100 patient-years for the pooled PsO, PsA, and AS groups, respectively. Treatment discontinuations because of adverse events occurred in 6.4%, 7.5%, and 7.3%, respectively.

In the PsO group, nine patients died from causes including pulmonary embolism, arrhythmia, and myocardial infarction. In the PsA cohort, there were 11 deaths from causes such as septic shock, pneumonia, and myocardial infarction, while in the AS group there were five deaths, with causes including respiratory failure and cerebrovascular accident.

Opportunistic infections were reported at rates of 0.13 per 100 patient-years for PsO, 0.21 per 100 for PsA, and 0.1 per 100 for AS. These included herpes zoster, toxoplasmosis, and Mycobacterium avium complex infections.

The investigators also looked at rates of adverse events of special interest. In the PsO, PsA, and AS groups, the incidence rates of cutaneous or mucosal Candida infections were 2.2, 1.5, and 0.7 per 100 patient-years, respectively. All were localized and most were mild or moderate.

For neutropenia, the rates per 100 patient-years were 0.3, 0.2, and 0.5 in the PsO, PsA, and AS groups, with most cases being mild or moderate and associated clinical events most often being viral upper respiratory tract infections, urinary tract infections, and diarrhea.

Inflammatory bowel disease was reported at rates of 0.01, 0.05, and 0.1 per 100 patient-years in the PsO, PsA, and AS cohorts, while major cardiovascular events occurred in 0.3, 0.4, and 0.6, respectively. In addition, malignancies were reported in 0.8, 1.1, and 0.5 per 100.

Suicidality-related events were reported in eight patients with PsO, with one completed suicide, and in three patients with PsA. All were in patients with coexisting disorders such as depression, anxiety, bipolar disorder, or alcoholism.

Analysis of postmarketing data found similar results as in the clinical trials, with incidence rates of infections and serious infections being 4.7 and 1.8 per 100 patient-years, and rates of 0.2 per 100 for malignancies, inflammatory bowel disease, and major cardiovascular events.

“This long-term (up to five years) safety assessment provides a broader understanding of the safety of secukinumab and supports its long-term use in these chronic systemic inflammatory conditions,” Deodhar and colleagues concluded.

A limitation of the analysis is the protocol-specified nature of the clinical trials, which may not fully encompass real-world treatment.

last updated 05.03.2019