Background: Randomized controlled trials have shown the efficacy and safety of brodalumab in patients with moderate to severe plaque psoriasis.Objective: To evaluate the efficacy and safety of brodalumab through 120 weeks of treatment in the AMAGINE-2 trial.Methods: Patients received ustekinumab through week 52 followed by brodalumab 210 mg every 2 weeks, continuous brodalumab 210 mg every 2 weeks, or any dose of brodalumab. Efficacy data were reported through 120 weeks by using observed data, last observation carried forward, and nonresponder imputation analyses.Results: Of patients who received brodalumab 210 mg every 2 weeks, 84.4%, 75.6%, and 61.1% achieved 75%, 90%, and 100% improvement from baseline in Psoriasis Area and Severity Index at 120 weeks (observed data analysis), respectively. Patients who received brodalumab 210 mg every 2 weeks after receiving ustekinumab through 52 weeks achieved a similar skin clearance response as patients who received continuous brodalumab 210 mg every 2 weeks. Safety through 120 weeks was comparable to that of the blinded study periods.

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Summary Background Brodalumab is efficacious for the treatment of moderate‐to‐severe plaque psoriasis through 52 weeks. Objectives To evaluate the efficacy and safety of brodalumab through 120 weeks, including following withdrawal and retreatment. Methods At baseline, patients were randomized to brodalumab (n = 222) or placebo (n = 220). At week 12, patients achieving a static Physician's Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1) with brodalumab were rerandomized to brodalumab (n = 83) or placebo (n = 84; later re‐treated with brodalumab if sPGA ≥ 3 occurred), and patients receiving placebo switched to brodalumab (n = 208). Safety was assessed by exposure‐adjusted rates of treatment‐emergent adverse events. Results Among those who achieved sPGA 0/1 at week 12 and were rerandomized to brodalumab, 96% and 80% using observed data, respectively, and 74% and 61% using nonresponder imputation, respectively, achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) and PASI 100 at week 120. Following withdrawal from brodalumab, return of disease occurred after a mean ± SD duration of 74·7 ± 50·5 days. Among those who switched from brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55% and 51% at week 20, respectively and 94% and 75% at week 120, respectively; PASI 100 rates at week 120 were 75% and 60%, respectively. Efficacy was maintained through week 120 in those receiving brodalumab after placebo. No new safety signals were observed. Conclusions These findings indicate that brodalumab is efficacious and safe for continuous long‐term treatment of psoriasis, and support the potential for response after discontinuation and retreatment.

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.

BackgroundChronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment.ObjectiveThe aim of the study was to assess the long-term efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis.MethodsPatients who completed a 12-week, phase II, dose-ranging clinical trial received brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated.ResultsOverall, 181 patients received brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to < 100 or PASI 100 at weeks 12, 240, and 264 was associated with greater likelihood for DLQI 0 or 1 compared with achieving PASI 75 to < 90. Over 5 years, one adverse event of suicidal ideation was reported, no suicides occurred, and no new safety signals emerged.ConclusionsBrodalumab demonstrated skin clearance and improved quality of life, with an acceptable safety profile, throughout 5 years of treatment.ClinicalTrials.gov IdentifierNCT01101100.Electronic supplementary materialThe online version of this article (10.1007/s40257-019-00466-2) contains supplementary material, which is available to authorized users.

Background: Antidrug antibodies (ADAs) may change pharmacokinetic or pharmacodynamic profiles of biologic therapies, potentially decreasing efficacy.Objective: To evaluate the potential effects of brodalumab immunogenicity on safety, efficacy, and retreatment.Methods: Data from 1 phase 2 and 3 phase 3 studies of brodalumab in psoriasis were analyzed.Results: Overall, 2.7% of patients had positive test results for binding ADAs after receiving brodalumab; ADAs were transient in 1.4% of patients, and there were no neutralizing ADAs. Among ADA-positive patients, 60.0% (3/5) achieved a static physician's global assessment score of 0 or 1 at week 12 in the group receiving the brodalumab 210 mg every 2 weeks, compared with 79.1% (1131/1429) of ADA-negative patients. All patients (100%) who experienced return of disease and were retreated with brodalumab 210 mg every 2 weeks (none were ADA positive) achieved at least a 75% improvement in Psoriasis Area And Severity Index, $90% of whom regained response by week 8 of retreatment. Hypersensitivity reactions were less frequent with brodalumab than with placebo. Injection site reactions occurred in 1.8% of patients treated with brodalumab versus 2% of patients treated with ustekinumab.Limitations: Retreatment could be assessed in only 1 phase 3 brodalumab study.Conclusion: Brodalumab compares favorably with other biologics in terms of immunogenicity and high rates of efficacy recapture upon retreatment. ( J Am Acad Dermatol 2020;82:344-51.)

Background The topical corticosteroid halobetasol propionate (HP) and the retinoid tazarotene (TAZ) are effective in psoriasis treatment. To mitigate adverse cutaneous reactions observed with monotherapy, a fixedcombination HP 0.01%/TAZ 0.045% lotion has been developed for the treatment of plaque psoriasis in adults.Objectives To investigate the long-term safety, efficacy and maintenance of response with HP/TAZ lotion. Methods This was a 1-year, multicentre, open-label study in 555 adults with psoriasis [Investigator's Global Assessment (IGA) score of 3 ('moderate') or 4 ('severe') and body surface area (BSA) of 3-12% at baseline]. HP/TAZ was administered once daily for 8 weeks and then intermittently as needed in 4-week intervals for up to 1 year based on achievement of treatment success [IGA score of 0 ('clear') or 1 ('almost clear')]. Maximum continuous exposure was 24 weeks.Results Of 550 participants with postbaseline safety data, 318 (57.8%) achieved treatment success during the study.Of those, 54.4% achieved treatment success within the first 8 weeks; retreatment was not required for >4 weeks in over half (55.3%), and 6.6% did not require any retreatment. Among participants enrolled for the full 52 weeks, 77.5% maintained BSA ≤5% on treatment. There were marked improvements in severity of itching, dryness and burning/stinging over the study course. The most common treatment-related adverse events were application site reactions of dermatitis, pruritus, pain and irritation. Conclusions Fixed-combination HP/TAZ lotion provided maintained efficacy with a favourable tolerability and safety profile, supporting its use for the long-term treatment and management of moderate-to-severe plaque psoriasis.

Summary Background Obesity is associated with psoriasis and negatively affects response to therapy. Objectives To evaluate the efficacy and safety of brodalumab in nonobese vs. obese patients with psoriasis. Methods This is a post hoc analysis of the prospective, phase III, multicentre, randomized, placebo‐ and active‐comparator‐controlled AMAGINE‐2 and AMAGINE‐3 trials, in which patients were randomized to treatment with brodalumab 210 mg every 2 weeks, ustekinumab or placebo for a 12‐week induction phase. At week 12, patients who received brodalumab 210 mg every 2 weeks continued brodalumab, those treated with ustekinumab continued ustekinumab, and those who received placebo switched to brodalumab 210 mg every 2 weeks. Patients were categorized by body mass index (BMI) category (< 30 or ≥ 30 kg m−2) and efficacy was evaluated using the physician‐rated Psoriasis Area and Severity Index and static Physician's Global Assessment instruments. Results In total, 281 of 687 patients (40·9%) were obese. Skin clearance was comparable across BMI subgroups in brodalumab‐treated patients. Psoriasis Area and Severity Index 100% improvement rates in nonobese and obese patients at week 12 were 54·1% and 49·5%, respectively, and at week 52 they were 72·6% and 64·8%, respectively. Week 12 ustekinumab responses were lower than brodalumab responses and were 6–17% lower in obese than in nonobese patients. No appreciable differences in overall safety were observed between nonobese and obese patients. Conclusions The efficacy and safety of brodalumab did not differ between patients with moderate‐to‐severe psoriasis who had a BMI < 30 kg m−2 or a BMI ≥ 30 kg m−2.