Additional common AEs listed in the brodalumab package insert include headache, myalgia, influenza, diarrhea, oropharyngeal pain, nausea, injection-site reactions, fatigue, neutropenia, and Tinea infections.1 Among the 45 cases of headache (0.99 events/100 PYs), 29 (64%) occurred among women, and the 2 cases reported during the fourth year had other potential contributing causes. Since the 3-year pharmacovigilance report, 3 new cases of myalgia were reported (0.68 events/100 PYs), with 2 patients continuing treatment. Of 1 new case of influenza, brodalumab was discontinued as the patient also reported COVID-19 and strep pharyngitis; it is unknown if therapy was resumed. One new case of diarrhea was reported in year 4 (0.72 events/100 PYs). Of 1 new case of oropharyngeal pain (0.46 events/100 PYs), which was described as pain in the back of the throat, dosage was maintained. Of 29 cases of nausea (0.64 events/100 PYs), most occurred among patients aged between 40 and 69 years and 17 (59%) occurred among women. In year 4, there were no new reports of injection-site reactions, fatigue, or neutropenia; no Tinea infections were reported throughout the 4 years.
Clinical Events of Special Interest
Clinical events such as serious infections, fungal infections, inflammatory bowel disease, malignancies, depression, and suicide have been deemed of special interest by the reporter or company (Figure 1).
Infections
All cases of infection, including duplicate diagnoses, such as COVID-19 and pneumonia on the same report, were counted separately. Overall, there were 102 serious infections reported, 3 of which were determined to be related to brodalumab (as previously reported4). The rate of serious infections (2.24 events/100 PYs) decreased compared with previously reported data (3.0 events/100 PYs).4 Although no serious fungal infections were reported, 1 new fungal infection, onychomycosis, led to the patient discontinuing brodalumab. There were no new reports of oral candidiasis.
There were 24 cases of confirmed COVID-19 and 2 cases of suspected COVID-19. For most of these cases (21/26; 81%), patients had underlying comorbid conditions, and 12 (46%) cases were deemed serious by the company. There were 3 deaths due to COVID-19 (1 of which occurred before vaccine availability, 1 of which the patient was not vaccinated, and 1 with unknown vaccination status). All 3 COVID-19–related deaths were in patients aged ≥65 years with comorbid conditions.
One case of tuberculosis (TB) was reported. The patient began treatment with brodalumab in November 2019. After a positive test for TB on an unknown date in 2020, the patient discontinued brodalumab while receiving TB treatment and then tested negative for TB in July 2020. History of travel exposure, prior therapies, or concomitant therapies was not reported.
Inflammatory Bowel Disease
No new cases of Crohn’s disease were reported since the 3-year pharmacovigilance report. One case of Crohn’s disease was previously reported in a patient who had symptomatic history before brodalumab initiation, which led to discontinuation.5
One new case of ulcerative colitis was reported in a patient who started brodalumab in July 2018 after failing to respond to tumor
necrosis factor α and interleukin-17A inhibitors. In October 2020, the patient was officially diagnosed with ulcerative colitis, which was not suspected to be related to brodalumab, and brodalumab therapy was not discontinued.
The event rate for inflammatory bowel disease in this analysis (0.04 events/100 PYs) is similar to the previously reported rate in the 3-year analysis.4
Malignancies
Malignancy rates from a long-term clinical trial and 1-, 2-, and 3-year US pharmacovigilance studies were 0.9, 1.0, 0.8, and 1.1 events/100 PYs, respectively.4 In this 4-year analysis, 37 malignancies were reported in 32 cases (0.81 events/100 PYs), reducing the event rate previously reported in the 3-year analysis (1.1 events/100 PYs).4 Types of reported malignancies included hepatic, lung, ovarian, endometrial, prostate, renal, and gallbladder cancers; 1 case of plasma cell myeloma; 3 other neoplasms (neck tumor, carcinoma removed from the leg, and malignancy removed from the arm); and other unspecified neoplasms. Dermatologic malignancies included 1 keratoacanthoma-type squamous cell carcinoma, 8 other squamous cell carcinomas, 7 basal cell carcinomas, and 1 malignant melanoma. None of the reported malignancies were deemed related to brodalumab. Of the 32 cases with malignancies, 10 continued and 18 discontinued brodalumab. Treatment status was unknown for the remaining 4 cases.
Depression and Reported Case of Suicide Attempt
There were 52 reported cases of depression (1.14 events/100 PYs), with 4 cases previously determined to be related to brodalumab. There were 4 new cases of depression, with no causality assessments provided by the reporter. As previously described, a physician reported a case involving a suicide attempt, with no indicated causal relationship between brodalumab and the reported adverse events (depressed mood and attempted self-harm).4 No new suicide attempts were reported in year 4, and no completed suicides were reported throughout the 4 years.
DISCUSSION
This pharmacovigilance report summarizes 4 years of the most common AEs from the brodalumab package insert and additional AEs of special interest reported from August 15, 2017, through August 14, 2021, in the United States. Consistent with clinical trials and previous pharmacovigilance reports, arthralgia was the most frequently reported AE (115 events). No new cases of suicide attempts were reported since the 3-year report, and no completed suicides were reported. Depression was documented in 52 cases, with 4 cases previously reported to be related to brodalumab.4 Serious infections, none of which were fungal, were reported in 102 cases, and 3 cases were previously reported to be related to brodalumab.4 There were 26 COVID-19 cases, with 3 COVID-19–related deaths occurring during year 4 (all in patients aged ≥65 years with comorbid conditions). No trends were established from reported infections.
Brodalumab has demonstrated a consistent safety profile during long-term clinical trials and throughout 4 years of pharmacovigilance monitoring. There were no new reports of injection-site reactions, fatigue, or neutropenia since the 3-year report; overall, no Tinea infections have been reported. Although 1 case of suicide attempt was previously reported, no causal relationship with brodalumab was established.4
Several limitations of this 4-year report should be considered. There are no groups included for comparison (eg, patients not receiving brodalumab), and only AEs reported to Ortho Dermatologics were documented. Additionally, exact brodalumab administration dates were not available, resulting in the use of patient-exposure estimates based on prescription-dispensing authorization dates. Lastly, contextual information is absent in pharmacovigilance reporting, limiting the interpretation of the relationship between the drug and AEs.
DISCLOSURES
ML is an employee of Mount Sinai; receives research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc.; and is a consultant for Aditum Bio, Almirall, AltruBi Inc., AnaptysBio, Arcutis, Inc., Arena Pharmaceuticals, Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Brickell Biotech, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corevitas, Dermavant Sciences, Dr. Reddy’s Laboratories, Evelo Biosciences, Evommune, Inc., Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd., LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verric. JK has been a consultant or speaker for AbbVie, Amgen, Eli Lilly, EPI, Janssen, LEO Pharma, Novartis, Ortho Dermatologics (a division of Bausch Health US, LLC), Pfizer, Regeneron Pharmaceuticals, Sanofi, and Sun Pharmaceutical. CL has been a consultant, investigator, or speaker for AbbVie, Actavis, Allergan, Amgen, Boehringer Ingelheim, Celgene, Cellceutix, Coherus, Corrona, Dermira, Eli Lilly, Galderma, Glenmark, Janssen, LEO Pharma, Merck, Novartis, Novella, Pfizer, Sandoz, Sienna, Stiefel, Sun Pharmaceutical, UCB, Vitae, and Wyeth. AA has served as a research investigator for and/or scientific advisor to AbbVie, BMS, Dermavant, Dermira, Incyte, Janssen, LEO Pharma, Lilly, Modmed, Novartis, Ortho Dermatologics (a division of Bausch Health US, LLC), Pfizer, Regeneron Pharmaceuticals, Sanofi, Sun Pharmaceutical, and UCB. NR and AJ are employees of Ortho Dermatologics (a division of Bausch Health US, LLC). EG is an employee of Bausch Health.
Funding: This study was supported by Ortho Dermatologics (a division of Bausch Health US, LCC).
Funding: This study was supported by Ortho Dermatologics (a division of Bausch Health US, LCC).
ACKNOWLEDGMENT
Writing and editorial assistance was provided under the direction of the authors by Jenny Johnson PhD ELS and Jenna Lewis MA ELS of MedThink SciCom and funded by Ortho Dermatologics. Ortho Dermatologics is a division of Bausch Health US, LLC. Additional assistance in data analysis and manuscript preparation was provided by Binu Alexander.
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- Lebwohl M, Strober B, Menter A, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373:1318- 1328.
- Lebwohl MG, Papp KA, Marangell LB, et al. Psychiatric adverse events during treatment with brodalumab: analysis of psoriasis clinical trials. J Am Acad Dermatol. 2018;78:81-89.
AUTHOR CORRESPONDENCE
Mark Lebwohl MD lebwohl@aol.com
