Real-world Evidence of Brodalumab Safety for the Treatment of Psoriasis

Abstract

Plaque psoriasis is a chronic skin disorder involving dysregulated inflammation. While numerous biologic therapies targeting inflammatory mediators have been approved for moderate-to-severe psoriasis, their safety profiles may include an increased risk of adverse events (AEs), such as infections, cardiovascular diseases, and malignancies. Because patients with psoriasis also have increased incidence of comorbidities, long-term real-world AE monitoring is critical to further evaluate the safety of biologic therapies postapproval. Brodalumab is a recombinant, fully human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. The safety profile of brodalumab has been established in clinical trials and industry-sponsored US pharmacovigilance reports. Herein, we summarize AEs reported in nonsponsored open-label and real-world studies of brodalumab. Across all studies, most common AEs were similar to those listed in the brodalumab package insert. While AEs of special interest were not reported comprehensively, their rates were generally low, with 3 cases of major adverse cardiac events, 2 cases of malignancy, 11 cases of depression, and no completed suicides in the overall safety population (N = 1701). There were 6 cases of serious infection and no serious fungal infections. Studies evaluating AEs of interest for brodalumab showed no causal link to suicide and no increase in risk of cardiac events or serious infection compared with other biologics. Together, these studies support a consistent safety profile of brodalumab in real-world use.

Plain language summary

Psoriasis is a lifelong disease that occurs when immune defenses and inflammation become overactive, causing skin cells to grow rapidly and develop into itchy, painful plaques. For patients with moderate-to-severe psoriasis, injectable therapies called biologics promote disease control by suppressing different parts of the immune system. However, this may also increase the risk of undesired effects (called adverse events [AEs]) like infections, heart conditions, and cancers. Because patients are frequently diagnosed with other medical conditions that coexist alongside their psoriasis, long-term monitoring of AEs is necessary to evaluate the safety of biologics in real-world settings. Brodalumab is a biologic approved for moderate-to-severe plaque psoriasis in adults who lack response to previous treatments. In the United States, brodalumab is only available under a Risk Evaluation and Mitigation Strategy for an observed risk of suicidality; however, findings from real-world safety data show a lack of association. This review summarizes AEs reported in nonsponsored clinical and real-world, observational studies of brodalumab from multiple countries. Across all studies, 1701 patients were evaluated. Rates of common AEs such as headache and joint pain were similar to those listed in the brodalumab package insert. Few special events were reported, including 3 cases of major cardiac events, 2 cases of cancer, 11 cases of depression, and 6 serious infections. Studies found no association between brodalumab and risk of suicide, cardiac events, or serious infection compared with other biologics. Overall, these studies show consistent safety data for brodalumab and support its use for the treatment of moderate-to-severe psoriasis.