Safety Of Brodalumab Research Articles

Efficacy and Safety of Brodalumab, an Anti-interleukin-17 Receptor A Monoclonal Antibody, for Palmoplantar Pustulosis: 16-Week Results of a Randomized Clinical Trial.

Palmoplantar pustulosis (PPP), a refractory skin disease characterized by repeated eruptions of sterile pustules and vesicles on palms and/or soles, involves interleukin-17 pathway activation. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, is being investigated for use in PPP treatment. The aim was to assess the efficacy and safety of brodalumab in Japanese PPP patients with moderate or severe pustules/vesicles. A phase 3, randomized, double-blind, placebo-controlled trial was conducted between July 2019 and August 2022, at 41 centers in Japan. Patients aged 18-70 years with a diagnosis of PPP for ≥24 weeks, a PPP Area Severity Index (PPPASI) score of ≥12, a PPPASI subscore of pustules/vesicles of ≥2, and inadequate response to therapy were included. Participants were randomized 1:1 to receive brodalumab 210 mg or placebo, subcutaneously (SC) at baseline, weeks 1 and 2, and every 2 weeks (Q2W) thereafter until week 16. Changes from baseline to week 16 in the PPPASI total score (primary endpoint) and other secondary skin-related endpoints and safety endpoints were assessed. Of the 126 randomized patients, 50 of 63 in the brodalumab group and 62 of 63 in the placebo group completed the 16-week period. Reasons for discontinuation were adverse event (n = 6), withdrawal by patient/parent/guardian (n = 3), progressive disease (n = 3), and lost to follow-up (n = 1) in the brodalumab group and Good Clinical Practice deviation (n = 1) in the placebo group. Change from baseline in the PPPASI total score at week 16 was significantly higher (p = 0.0049) with brodalumab (least-squares mean [95% confidence interval {CI}] 13.73 [10.91-16.56]) versus placebo (8.45 [5.76-11.13]; difference [95% CI] 5.29 [1.64-8.94]). At week 16, brodalumab showed a trend of rapid improvement versus placebo for PPPASI-50/75/90 response (≥50%/75%/90% improvement from baseline) and Physician's Global Assessment 0/1 score: 54% versus 24.2%, 36.0% versus 8.1%, 16.0% versus 0.0%, and 32.0% versus 9.7%, respectively. Infection was the dominant treatment-emergent adverse event (TEAE); the commonly reported TEAEs were otitis externa (25.4%/1.6%), folliculitis (15.9%/3.2%), nasopharyngitis (14.3%/4.8%), and eczema (14.3%/12.9%) in the brodalumab/placebo groups, respectively. The severity of most TEAEs reported was Grade 1 or 2 and less frequently Grade ≥3. Brodalumab SC 210 mg Q2W demonstrated efficacy in Japanese PPP patients. The most common TEAEs were mild infectious events. NCT04061252 (Date of Trial Registration: August 19, 2019).

Effectiveness of Brodalumab in Patients with Moderate-to-Severe Plaque Psoriasis Located in Difficult-to-Treat Areas.

Recent knowledge of psoriasis pathogenesis has led to the development of selective drugs. Among these, brodalumab is a monoclonal antibody targeting the interleukin (IL)-17A receptor approved for the treatment of moderate-to-severe plaque psoriasis. Biologics may be considered in patients with milder diseases in case of active psoriatic arthritis, severe impact on patient's quality of life, and involvement of sensitive and difficult-to-treat areas. These skin locations commonly require systemic drugs. Recently, psoriasis severity monitoring has also changed. Indeed, the clinical evaluation by means of specific efficacy scores was combined with serological evaluation by means of the assay of specific inflammatory biomarkers. An observational study enrolled patients affected by moderate-to-severe plaque psoriasis involving difficult-to-treat areas, undergoing treatment with brodalumab to evaluate the effectiveness and safety of brodalumab in patients with psoriasis affecting difficult-to-treat areas (scalp and palmoplantar regions). Secondary outcomes were the assessment of the development of serum markers of inflammation during the treatment period as well as the evaluation of the dermoscopic features of the affected sites to quantify disease activity and response to treatment. Twenty-five patients were included in the study. A statistically significant reduction from baseline in PASI, PSSI, ppPASI and DLQI values as early as week 24 was observed, with further improvement up to week 52. Plasma levels of MMP-3, VEGF-A, and hs-PCR decreased during treatment from week 0 to week 52. Our real-life experience suggests brodalumab as a valuable option for the management of psoriasis located in difficult-to-treat areas. Moreover, our study highlights that the use of brodalumab reduces the plasmatic levels of inflammatory biomarkers (MMP-3, VEGF-A and hs-PCR), showing how the drug modulates the skin inflammatory response by reducing systemic inflammation.

Brodalumab in the Treatment of Plaque Psoriasis Localized in Difficult-to-Treat Areas: A Narrative Review.

Psoriasis is a common chronic, immune-mediated, inflammatory skin disease that in certain localization results difficult to treat. Psoriatic lesions in difficult-to-treat areas might be hardly managed as no standardized therapeutic approach and the application of topical treatments might have great limitations. Systemic agents, including biologic therapies, have been proven effective in treating this subgroup of patients. In particular, current evidence has shown beneficial effects with the use of brodalumab, a fully human IgG2 monoclonal antibody antagonizing the IL-17 receptor A subunit (IL-17RA). The aim of this narrative review was to collect published data about efficacy and safety of brodalumab in the treatment of psoriasis occurring in difficult-to-treat areas. Data on brodalumab effectiveness and safety deriving from both trials and real-world setting that had been published in the last 15 years were collected for this review, together with clinical findings issued during international meetings. In phase 3 trials, brodalumab demonstrated to be effective in promoting a rapid response in scalp psoriasis as well as in generalized pustular psoriasis and erythrodermic psoriasis. Nail psoriasis demonstrated marked clinical improvement after treatment with brodalumab. Amelioration of palmoplantar psoriasis was also described in brodalumab-treated patients. Various retrospective real-world studies reported a complete clearance of psoriatic lesions in difficult-to-treat areas, including genitalia, through short-term brodalumab treatment. Brodalumab, combining rapid and sustained efficacy with a favorable safety profile, may be a valid therapeutic option for severe variants of psoriasis as well as for psoriasis localized in difficult-to-treat areas.

Effectiveness and safety of brodalumab in the treatment of plaque, scalp and palmoplantar psoriasis: A multicentre retrospective study in a Spanish population.

The data in clinical practice regarding the effectiveness and safety of brodalumab in psoriasis are scarce, especially at scalp and palmoplantar locations. The main objective was the percentage of patients achieving absolute PASI ≤3/ ≤1/ =0 for plaque psoriasis and the percentage of patients achieving an IGA 0-1/IGA 0 for the special locations at Week 52 of treatment. Observational retrospective multicentre study in 28 Spanish Hospitals that included adult patients with plaque psoriasis treated with brodalumab, from September 2018 until March 2021. A total of 200 patients were included. The mean baseline PASI was 10.97 (±6.28) with a mean basal scalp (n = 58) and palmoplantar (n = 40) IGA of 2.10 (±0.97) and 2.15 (±1.26), respectively. At Week 52, 93.98%/75.90%/68.67% of patients reached an absolute PASI ≤3/ ≤1/ =0 in plaque psoriasis (n = 83), with a percentage of patients achieving scalp (n = 27) and palmoplantar (n = 19) IGA 0-1/IGA 0 of 96.3%/88.9% and 100%/88.9%, respectively. Fifteen per cent of patients reported any adverse events with candidiasis being the most reported (6%), but only 6% of the adverse events required the withdrawal. Brodalumab demonstrated high PASI and IGA responses and was well tolerated in clinical practice in plaque, scalp and palmoplantar psoriasis.

Brodalumab for the treatment of plaque psoriasis in a real-life setting: a 3 years multicenter retrospective study-IL PSO (Italian landscape psoriasis).

Brodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited. The aim of this study was to evaluate the long-term effectiveness and safety of brodalumab in psoriasis. We also assessed the drug survival of brodalumab in a 3 years timespan. We conducted a retrospective multicenter study on 606 patients followed up at 14 Italian dermatology units, all treated with brodalumab according to Italian guidelines. Patients' demographics and disease characteristics were retrieved from electronic databases. At baseline and weeks 12, 24, 52, 104 and 156, we evaluated the psoriasis area and severity index (PASI) score and investigated for adverse events. The proportions of patients reaching 75, 90 and 100% (PASI 75, PASI 90 and PASI 100, respectively) improvement in PASI, compared with baseline, were also recorded. At week 12, 63.53% of the patients reached PASI 90 and 49.17% PASI 100. After 3 years of treatment, 65.22% of patients maintained a complete skin clearance, and 91.30% had an absolute PASI of 2 or less. Patients naïve to biological therapies had better clinical responses at weeks 12, 24 and 52. However, after 2 years of treatment, no significant differences were observed. Body mass index did not interfere with the effectiveness of brodalumab throughout the study. No new safety findings were recorded. After 36 months, 85.64% of our patients were still on treatment with brodalumab. Our data confirm the effectiveness and the safety of brodalumab in the largest real-life cohort to date, up to 156 weeks.

Effectiveness of Brodalumab on Scalp, Palmoplantar, and Genital Psoriasis: A Descriptive Pilot Study

Introduction. Psoriasis of the scalp, genital areas, and palms and soles represents a treatment challenge in clinical practice. Randomized clinical trials and real‐life studies investigating the efficacy of biological drugs in these sites are scarce. The present is a descriptive retrospective real‐life study with the aim to evaluate the efficacy and safety of brodalumab in these difficult‐to‐treat areas. Materials and Methods. 158 psoriatic patients with scalp involvement, 69 with genital involvement, and 54 with palmoplantar involvement being treated with brodalumab were assessed at weeks 16, 28, and 48 using PSSI (Psoriasis Scalp Severity Index), sPGA‐G (Physician Global Assessment of Genitalia), and ppPASI (Palmoplantar Psoriasis Area and Severity Index). Results. The achievement of relative PSSIs (75%, 90%, and 100%) was already observed in week 16. 86% achieved PSSI75, 80% PSSI90, and 75% PSSI100. The sPGA‐g 0/1 was achieved by 83% of patients at week 16 and 100% at week 24 and 48. At week 16 ppPASI75, 90, and 100 were all reached by 76.9% of patients; at week 24, 84.6% of patients reached all relative ppPASI. Conclusions. Brodalumab proved to be effective and safe in the treatment of scalp, genital, and palmoplantar regions.

Ixekizumab and brodalumab indirect comparison in the treatment of moderate to severe psoriasis: Results from an Italian single-center retrospective study in a real-life setting.

Eleven biologic drugs are currently approved for psoriasis management. Real‐life studies are needed to guide clinicians in choosing a tailored‐tail therapy. The aim of our retrospective study is to indirectly compare the efficacy and safety of ixekizumab and brodalumab in psoriasis patients. A single‐centre real‐life retrospective study was performed enrolling moderate‐to‐severe psoriatic patients under biologic treatment with ixekizumab or brodalumab. For each patient, clinical and demographic data were collected and the effectiveness and safety of brodalumab and ixekizumab treatment were evaluated at weeks 4, 12, and 24. Psoriasis Area Severity Index (PASI) and Body Surface Area (BSA) were used for psoriasis severity. A total of 139 patients were included in the study: 98(70.5%) and 41(29.5%) patients received ixekizumab and brodalumab, respectively. Mean PASI and BSA significantly reduced at each follow up for both ixekizumab and brodalumab groups. Even if ixekizumab reached higher rates of PASI90 and PASI100 than brodalumab (PASI90: 43.8% vs. 39.0% PASI100: 20.4% vs. 17.1% at week4 and PASI90: 83.6% vs. 75.6% PASI100: 71.5% vs. 60.9% at week24), these results were not statistically significant. Adverse events, mainly mild, were registered in 25.5% of ixekizumab and 26.8% of brodalumab group, respectively. Discontinuation rate was higher for brodalumab (17.1% vs. 9.1%), without statistical significance. Our study showed comparable efficacy and safety for ixekizumab and brodalumab.

Long-term efficacy and safety of brodalumab in moderate-to-severe plaque psoriasis: a post hoc pooled analysis of AMAGINE-2 and -3.

Brodalumab is a monoclonal antibody that blocks multiple interleukin (IL)-17 family cytokines by binding to the shared A subunit of the IL-17 receptor. In Phase 3 trials, brodalumab provided high levels of skin clearance through 52 weeks in patients with moderate-to-severe psoriasis and was generally well tolerated. To assess efficacy response rates and safety outcomes through 120 weeks for patients with moderate-to-severe psoriasis who received brodalumab. Safety and efficacy data were pooled for patients from AMAGINE-2 and -3 who received continuous brodalumab 210 mg every 2 weeks, or brodalumab 210 mg every 2 weeks after receiving either brodalumab 140 mg or placebo through Week 12. Efficacy data are presented using observed data, non-responder imputation (NRI) and a combination of NRI and missing at random assumption to account for missing data. Absolute PASI scores are presented using mixed-effect model repeated measure modelling and multiple imputation. Based on observed data at Week 120, 86% of the continuous brodalumab 210 mg group achieved PASI 90 and 74% achieved PASI 100. At Week 12, 58% of this group achieved absolute PASI ≤1; this proportion increased to approximately 80% at Week 52 and persisted through Week 120. Among patients receiving continuous brodalumab 210 mg, median duration of brodalumab exposure was 747 days and the overall exposure-adjusted event rate of treatment emergent adverse events per 100 patient-years was 329. Safety through 120 weeks was comparable to the results of the primary AMAGINE-2 and -3 studies. Patients who switched to brodalumab 210 mg after receiving either brodalumab 140 mg or placebo through Week 12 showed similar skin clearance and safety profiles. Brodalumab treatment was well tolerated and resulted in high levels of skin clearance that were rapidly achieved and maintained through Week 120, supporting its long-term efficacy and safety profile.

Safety of Brodalumab in Plaque Psoriasis: Integrated Pooled Data from Five Clinical Trials.

Brodalumab is approved for treatment of moderate-to-severe plaque psoriasis. Here, we assess the safety profile of brodalumab using pooled safety data from 5 phase II/III trials of brodalumab 140 mg or 210 mg. In total, 4,464 patients received brodalumab, representing 8,891.6 patient-years of exposure. During the placebo-controlled 12-week induction period, rates of serious adverse events per 100 patient-years were 10.8 and 9.6 (brodalumab 140 mg and 210 mg, respectively) vs 4.3 and 6.5 (ustekinumab and placebo, respectively); infections were the most frequent serious adverse event. Rates of serious adverse events during the comparator-controlled 52-week period were 14.4, 10.2 and 8.3 per 100 patient-years for brodalumab 210 mg, brodalumab 140 mg, and ustekinumab, respectively. Brodalumab was not associated with increased risks of malignancy, major adverse cardiac events, suici dal ideation and behaviour, or fatal events. Overall, brodalumab demonstrated an acceptable safety profile in short- and long-term treatment.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

Efficacy and safety of brodalumab, an anti-IL17RA monoclonal antibody, in patients with axial spondyloarthritis: 16-week results from a randomised, placebo-controlled, phase 3 trial

ObjectiveTo investigate the efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with axial spondyloarthritis (axSpA).MethodsIn a multicentre, placebo-controlled phase 3 study (NCT02985983) conducted...

Brodalumab in psoriatic arthritis: results from the randomised phase III AMVISION-1 and AMVISION-2 trials

ObjectiveTo compare the efficacy and safety of brodalumab, an interleukin-17 receptor subunit A inhibitor, with placebo, in patients with psoriatic arthritis (PsA).MethodsAdult patients with active PsA and inadequate response to,...

Efficacy and safety of brodalumab in the Korean population for the treatment of moderate to severe plaque psoriasis: A randomized, phase III, double-blind, placebo-controlled study.

Psoriasis, a chronic inflammatory skin disease, negatively impacts patients’ quality of life (QoL). This randomized, phase III, double‐blind, placebo‐controlled, multicenter study evaluated the efficacy and safety of brodalumab, a human anti‐interleukin‐17 receptor A monoclonal antibody, in Korean patients with moderate to severe plaque psoriasis. Coprimary end‐points were the percentage of patients with 75% or more improvement in Psoriasis Area and Severity Index (PASI 75) and static Physician’s Global Assessment (sPGA) success (score 0/1) at week 12. Secondary end‐points included the percentage improvement from baseline in PASI score and proportion of patients with PASI 50/75/90/100 responses. QoL was assessed with the Dermatology Life Quality Index (DLQI). Eligible patients were randomized to receive brodalumab 210 mg (N = 40) or placebo (N = 22) every 2 weeks (Q2W) at a 2:1 ratio for 12 weeks. Subsequently, all patients entered an open‐label extension phase and received brodalumab 210 mg Q2W until week 62. At week 12, the proportion of patients who achieved the coprimary end‐points, PASI 75 and sPGA success, was significantly higher in the brodalumab 210 mg Q2W group compared with the placebo group (92.5% vs 0%). At week 12, the mean ± SD percentage improvement in the PASI score was 96.87 ± 6.01% in the brodalumab 210 mg Q2W group, which was maintained until study end (week 64). PASI 50/75/90 responses were achieved by 100% of patients receiving brodalumab 210 mg Q2W at weeks 6, 13, and 24, respectively; PASI 100 was achieved by 82.8% of patients at week 64. Brodalumab treatment rapidly improved DLQI scores. The most common treatment‐emergent adverse events were nasopharyngitis, upper respiratory tract infections, tinea pedis, and urticaria. Overall, treatment with brodalumab 210 mg Q2W resulted in a rapid and significant clinical benefit and was well tolerated in patients with moderate to severe plaque psoriasis in Korea.

15908 Long-term efficacy and safety of brodalumab in patients with or without metabolic syndrome

Background: We assessed 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, stratified by baseline metabolic syndrome (MetSyn) status.

16525 Long-term efficacy and safety in clinical trials of brodalumab by prior response to adalimumab

Background: We assessed the long-term efficacy and safety of brodalumab in patients with moderate to severe plaque psoriasis stratified by prior adalimumab response status at baseline.

Brodalumab for the treatment of moderate-to-severe plaque-type psoriasis: a real-life, retrospective 24-week experience.

Brodalumab was efficacious and safe in moderate-to-severe plaque-type psoriasis in the AMAGINE trials; published reports under real-life conditions are limited. To evaluate the effectiveness and safety of brodalumab in patients with moderate-to-severe plaque-type psoriasis in a real-world setting. This observational, retrospective study enrolled adult patients (≥18years) with moderate-to-severe plaque-type psoriasis who underwent 24weeks of treatment with brodalumab at 17 Italian dermatological centres. Baseline data included demographics, comorbidities, age of onset and duration of psoriasis and previous treatments. Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), static PGA of Genitalia, Dermatology Life Quality Index and patient satisfaction were assessed at weeks 0, 4, 12 and 24; adverse events were recorded. Seventy-eight patients (mean age 47.9years, 71.8% male, average disease duration 16.8years) were enrolled. A rapid and significant reduction in mean PASI score was observed after 4weeks of treatment, decreasing further at weeks 12 and 24 (all P<0.0001 vs. baseline). A higher number of cardiometabolic comorbidities and previous therapies were negatively associated with the achievement of PASI 90 at all assessments. Brodalumab was effective in bio-experienced patients, including those who had failed on anti-interleukin (IL)-17 therapies. Quality of life and patient satisfaction increased significantly during treatment (P<0.0001 and P<0.01 vs. baseline, respectively). Treatment was interrupted in 9 (11.5%) patients due to adverse events (n=4), lack of efficacy (n=3), lost to follow-up (n=1) and surgical procedure (n=1). Brodalumab is effective and safe in the treatment of moderate-to-severe psoriasis in a real-world setting, including in patients with failure to anti-IL17 therapies.

Brodalumab to the Rescue: Efficacy and Safety of Brodalumab in Patients with Psoriasis and Prior Exposure or Inadequate Response to Biologics.

While biologic therapies for psoriasis are effective for many patients, some patients may lose response, have inadequate control of disease, or develop intolerance to certain biologic agents. It may therefore be beneficial for patients whose psoriasis fails to respond to one biologic to switch to a different biologic therapy, in particular one with a different mechanism of action. However, it remains unclear how prior biologic exposure or lack of response affects the efficacy and safety of subsequent biologics in patients with moderate-to-severe psoriasis. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has previously been shown to be efficacious in treating moderate-to-severe psoriasis in three large phase 3 trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3). In this review, we summarize the efficacy and safety of brodalumab in patients with moderate-to-severe psoriasis and a history of biologic exposure. Further, we describe improvements in skin clearance and quality of life measures as well as safety in patients who had inadequate response to ustekinumab and who were rescued with brodalumab therapy. Lastly, we discuss improvements in skin clearance following rescue with brodalumab in patients whose disease failed to respond to secukinumab and ixekizumab. The findings of our review suggest that brodalumab is a safe and efficacious treatment regardless of past biologic use or lack of response to prior biologic therapy.

Recapture Rate of Brodalumab in Patients With a Lapse in Treatment.

The National Psoriasis Foundation has emphasized the importance of achieving skin clearance targets throughout the course of treatment. However, patients with psoriasis often stop and restart treatment for reasons such as psychological distress, dissatisfaction with treatment, inconvenience, cost, or comorbidities. Brodalumab is a fully human anti-interleukin-17 receptor A monoclonal antibody efficacious for the treatment of moderate-to-severe plaque psoriasis. This review discusses the efficacy and safety of brodalumab and other biologic therapies in patients with psoriasis who stop and restart treatment. These clinically relevant and important findings can help inform real-world treatment decisions. J Drugs Dermatol. 2020;19(4):384-387. doi:10.36849/JDD.2020.5026.

Long-term Efficacy and Safety of Brodalumab in Patients With or Without History of Psoriatic Arthritis: Analysis of Two Phase 3 Psoriasis Studies

Abstract not available.

Long-term Efficacy and Safety of Brodalumab in Patients With Psoriasis Disease Duration &lt;10 and ≥10 Years: Analysis of Two Phase 3 Studies

Abstract not available.