Brodalumab: 5-Year US Pharmacovigilance Report.

INTRODUCTION: Brodalumab is a 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. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. METHODS: Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. RESULTS: Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. CONCLUSION: Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals.

Brodalumab is an injectable treatment approved for moderate-to-severe plaque psoriasis in adults who lacked response to previous treatments. In the USA, brodalumab is only available under a Risk Evaluation and Mitigation Strategy for increased suicidality risks; however, findings from 5 years of real-world safety data have demonstrated a lack of association. In this report, we discuss safety findings reported by US patients and healthcare providers for 4744 patients treated with brodalumab over 5 years. Joint pain (known as arthralgia) was the most common safety finding, with 122 cases reported over 5 years. Other safety findings of interest across 5 years included 106 serious infections (defined as prolonged infections or infections requiring treatment), 54 cases of depression, 49 cases of cancer (in 42 patients), 40 confirmed cases of COVID-19, and 11 cases of major cardiovascular events (such as stroke or heart attack). No completed suicides occurred throughout 5 years, and no new suicidal attempts were reported in year 5. In indirect comparisons with safety data from patients with psoriasis receiving or eligible to receive similar treatments, brodalumab was not associated with an increased risk of serious infection, cancer, major cardiovascular events, or inflammatory bowel disease. Taken together, these data are consistent with safety findings from long-term clinical trials and previous safety reports of brodalumab.

Brodalumab: 4-Year US Pharmacovigilance Report.

Brodalumab is an interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe psoriasis in adults without response or with loss of response to other systemic therapies. Brodalumab carries a boxed warning in the United States regarding suicidal ideation and behavior, though no causal relationship has been established. Here, we summarize 4 years of pharmacovigilance data, from August 15, 2017, through August 14, 2021, reported to Ortho Dermatologics by US patients and healthcare providers. The most common AEs listed in the brodalumab package insert (incidence ≥1%) and AEs of special interest are described. Brodalumab exposure estimates were calculated using the time between the first prescription-dispensing authorization date and last prescription-dispensing authorization date. Data were collected from 4019 patients with an estimated brodalumab exposure of 4563 patient-years. The most common AE was arthralgia (115 events; 2.52 events per 100 patient-years). No completed suicides and no new suicidal attempts were reported. There were 102 cases with serious infections; however, no serious fungal infections (including no new cases of oral candidiasis) were reported. There were 26 COVID-19 cases, and 3 of the cases with comorbid conditions were fatal. There were no new cases of Crohn’s disease. Of 37 reported malignancies among 32 cases, none were deemed related to brodalumab. Four-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and 3-year pharmacovigilance data. J Drugs Dermatol. 2023;22(4) doi:10.36849/JDD.7344 Citation: Lebwohl M, Koo J, Leonardi C, et al. Brodalumab: 4-Year US pharmacovigilance report. J Drugs Dermatol. 2023;22(4):419-422. doi:10.36849/JDD.7344.

Three-year U.S. pharmacovigilance report of brodalumab.

Brodalumab, an interleukin-17 receptor A antagonist, is approved for treatment of moderate-to-severe plaque psoriasis in adults without response or with loss of response to other systemic therapies. In the United States, there is a boxed warning for brodalumab regarding suicidal ideation and behavior; however, no causal relationship between brodalumab and suicidality was established during pivotal trials. In the 2-year pharmacovigilance data, no completed suicides or suicide attempts were reported. The most frequent adverse event (AE) was arthralgia. The safety profile of brodalumab is now being updated after 3 years of pharmacovigilance data. Here, we outline pharmacovigilance data reported to Ortho Dermatologics by patients and healthcare professionals in the United States from August 15, 2017, to August 14, 2020. Brodalumab exposure estimates were obtained by calculating the time between first and last prescription-dispensing authorization dates. Data from 1854 patients were collected, and brodalumab exposure was estimated to be 2736 patient-years. The most frequent AE was arthralgia (111 events; 0.04 events per patient-year). One episode of suicide attempt was reported in a patient with a history of depression. No completed suicides were reported. There were 81 serious infections reported, none of which were fungal. Over the 3-year period, 30 malignancies occurred in 25 patients, none of which were determined to be related to brodalumab. Three-year pharmacovigilance data are consistent with the safety profile of brodalumab previously reported in long-term analyses of clinical trials and the 2-year pharmacovigilance data.

Two-Year US Pharmacovigilance Report on Brodalumab.

INTRODUCTION: Brodalumab is a 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. In the United States, brodalumab carries a boxed warning about suicidal ideation and behavior; however, no causal association was established between brodalumab and suicides reported during pivotal trials. We have previously reported results from an analysis of 1-year pharmacovigilance data in patients in the United States who took brodalumab, in which the most commonly reported adverse event was psoriasis flare. There were no completed suicides, suicide attempts, or serious fungal infections. Here, we provide a 2-year US pharmacovigilance report. METHODS: This analysis summarizes pharmacovigilance data reported to Ortho Dermatologics by US patients and healthcare providers from August 15, 2017, through August 14, 2019. The most common adverse events listed in the brodalumab package insert (incidence ≥ 1%; arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection-site reactions, influenza, neutropenia, and tinea infections) and adverse events of special interest are reported. RESULTS: Data were collected from 2677 patients in the United States who took brodalumab, with an estimated exposure of 1656 patient-years. Arthralgia was the most commonly reported adverse event (73 events; 0.04 events per patient-year). No suicide attempts or completed suicides were reported; there were 25 reports of depression. There were 46 serious infections and no serious fungal infections. One event of Crohn's disease was reported, which led to discontinuation. There were 13 malignancies, with none deemed related to brodalumab. CONCLUSIONS: This pharmacovigilance report supports the safety profile of brodalumab previously reported from long-term analyses of clinical trials and 1-year pharmacovigilance data.