Seven-Year US Safety Data Confirms Brodalumab's Stable Risk Profile in Psoriasis Treatment
核心洞察
A comprehensive seven-year US pharmacovigilance analysis of brodalumab covering 5,449 patients and 7,845 patient-years of exposure shows no completed suicides and only one suicide attempt in year 3.
The study confirms brodalumab's consistent safety profile with arthralgia (搜索) remaining the most common adverse event (140 cases) and low rates of serious infections (2.17/100 patients) compared to other biologic therapies.
Adverse event rates for major safety concerns including cardiovascular events (0.24/100 patients), malignancy (搜索) (1.01/100 patients), and inflammatory bowel disease (搜索) (0.06/100 patients) remained lower than comparative registry data.
A comprehensive seven-year pharmacovigilance analysis of brodalumab (Siliq) has reinforced the IL-17 receptor A (搜索) antagonist's established safety profile in treating moderate-to-severe plaque psoriasis (搜索), with no completed suicides reported and consistently low rates of serious adverse events compared to other biologic therapies.
The analysis, covering data from August 15, 2017, through August 14, 2024, examined safety reports from 5,449 US patients representing approximately 7,845 patient-years of exposure. Despite brodalumab carrying a boxed warning regarding suicidal ideation and behavior in its US prescribing information, the extended surveillance period documented no completed suicides and only one suicide attempt, which occurred in year 3.
Adverse Event Profile Remains Consistent
Throughout the seven-year monitoring period, 2,719 patients (49.9%) reported at least one adverse event, with 24.3% of reports originating from healthcare providers. Arthralgia (搜索) remained the most frequently reported adverse event with 140 total cases, maintaining similar reporting rates compared to the previous year (2.57/100 patients in year 7 versus 2.63 in year 6).
Other commonly reported adverse events included headache in 58 patients, fatigue in 54, injection-site reactions in 43, and myalgia in 40 patients. The analysis documented five new cases of arthralgia (搜索), five new cases of headache, four new cases of fatigue, and two new cases each of myalgia, injection-site reactions, and diarrhea during year 7.
Low Infection and Cardiovascular Risk Rates
Serious infections occurred in 118 cases (2.17/100 patients) throughout the seven-year period, with only four events determined to be related to brodalumab. This rate remained comparable to the six-year report (2.20/100 patients) and was notably lower than rates calculated from the Psoriasis (搜索) Longitudinal Assessment and Registry (PSOLAR), which reported 3.95/100 patients across 12,095 patients receiving biologic or systemic therapy.
The fungal infection rate remained low at 0.17 per 100 patients, with two new Candida infections reported in year 7 and no new invasive fungal infections since year 6. One case of Tinea infection occurred in year 7 that was deemed possibly related to brodalumab.
Cardiovascular safety data showed no new adjudicated major adverse cardiovascular events (MACEs) in year 7. Across the entire surveillance period, 13 adjudicated MACEs were reported, yielding a crude reporting rate of 0.24/100 patients—significantly lower than PSOLAR's rate of 1.55/100 patients. Notably, 92.3% of patients experiencing MACEs had documented cardiovascular risk factors, preexisting conditions, or relevant concurrent medications, and 53.8% continued brodalumab treatment after the event.
Psychiatric Safety and Depression Monitoring
Depression (搜索) was documented in 60 patients throughout the seven years, with a crude adverse event reporting rate comparable to the six-year report (1.10 versus 1.13/100 patients). Only four cases (6.7%) were deemed related to brodalumab, all occurring before the four-year pharmacovigilance report. Two new cases of depression were reported in year 7, though reporters did not provide causality assessments.
The single suicide attempt reported in year 3 occurred in a patient with a history of depression (搜索), and the reporting physician indicated no suspected causal relationship between brodalumab and the depressed mood or self-harm attempt.
Malignancy and Inflammatory Bowel Disease Rates
Malignancy (搜索) events were reported in 55 patients, totaling 64 cases, yielding a crude reporting rate of 1.01/100 patients in year 7—lower than PSOLAR's rate of 1.78/100 patients (excluding nonmelanoma skin cancer). New malignancy cases included neoplasm of the right ovary, colorectal cancer, nonmelanoma skin cancers (two basal cell, one squamous cell), renal cancer, and prostate cancer. Four of the reported malignancies throughout the seven years were deemed possibly related to brodalumab.
Inflammatory bowel disease (搜索) remained infrequent, with only three cases reported over the entire seven-year period (0.06/100 patients) and no additional cases in year 7. This rate was lower than those reported in a 20-year Danish study of 235,038 patients with psoriasis (搜索), which found IBD rates of 0.32 events/100 patients across all therapies and 0.14 events/100 patients for biologic therapies.
Comparative Safety Profile
The analysis compared brodalumab's safety profile to PSOLAR registry data, consistently showing lower rates across major adverse event categories. Crude reporting rates remained lower for adjudicated MACEs (0.24 versus 1.55/100 patients), serious infections (2.17 versus 3.95/100 patients), and malignancy (搜索) (1.01 versus 1.78/100 patients excluding nonmelanoma skin cancer in PSOLAR).
Data from the CorEvitas Psoriasis (搜索) Patient Registry revealed comparable depression (搜索) history rates across participants initiating biologics: 22.8% for brodalumab, 25.7% for IL-12 (搜索)/23 or IL-23 (搜索) inhibitors, and 26.7% for other IL-17A inhibitors, suggesting that despite REMS requirements, the pharmacovigilance findings are likely representative of the US population.
Clinical Implications
The seven-year analysis reinforces brodalumab's distinctive mechanism of blocking multiple IL-17 isoforms (IL-17A, IL-17C (搜索), and IL-17F (搜索)) while simultaneously reducing IL-23 (搜索) and IL-12 (搜索) subunit gene expression, suggesting broader immunomodulatory effects beyond direct IL-17 receptor antagonism. The consistent safety profile supports its continued use in moderate-to-severe plaque psoriasis (搜索) management, particularly given psoriasis (搜索) typically requires long-term treatment.
The physician authors suggest that available pharmacovigilance evidence indicates no clear indication that brodalumab poses a unique or elevated suicide risk compared to similar biologic therapies. Worldwide postmarketing surveillance data support that brodalumab's suicide risk profile aligns with that of other biologics for psoriasis (搜索) treatment.