Brodalumab Treatment Research Articles

Real-World Data on Brodalumab Treatment in Patients with Moderate-to-Severe Plaque Psoriasis: An Observational Study from the Czech Republic BIOREP Registry.

The aim of this observational, multicenter study was to assess the real-world use of brodalumab for the treatment of moderate-to-severe plaque psoriasis in patients in the Czech Republic, using data from the BIOREP registry. The study included 273 patients aged≥18years with moderate-to-severe psoriasis who received brodalumab. Endpoints were drug survival (time from treatment initiation to discontinuation), effectiveness [Psoriasis Area and Severity Index (PASI)], and health-related quality-of-life [Dermatology Life Quality Index (DLQI)]. Predicted drug survival probability was 92.4% [95% confidence interval (CI): 89.1, 95.7%] at 6months and 84.2% (95% CI 79.5, 89.1%) at 12months; this was maintained at 24months [80.4% (95% CI 74.5, 86.8%)]. Younger age, higher body mass index, and no previous biologic treatment were significantly associated with longer drug survival. Absolute PASI≤3 after 3months was achieved by 89.8% of patients; 92.4%, 77.8%, and 59.1% reached PASI 75, PASI 90, and PASI 100, respectively. After 12months, 96.5% of 141 patients had an absolute PASI≤3. The proportion of patients achieving DLQI 0/1 was 87.3% at 12months. This study demonstrated high and sustained drug survival with high rates of skin clearance and improved quality of life in patients with relatively severe disease treated with brodalumab. Improvements were observed as early as 3months post-treatment initiation and were sustained for up to 24months in a real-life setting.

43795 Effectiveness in real-world practice after one year of Brodalumab treatment for patients with moderate-to-severe psoriasis and effectiveness in obese patients: thirty-three patient cohort

43795 Effectiveness in real-world practice after one year of Brodalumab treatment for patients with moderate-to-severe psoriasis and effectiveness in obese patients: thirty-three patient cohort

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 of Long-Term Treatment with Brodalumab on Anxiety or Depressive Symptoms in Japanese Patients with Psoriasis: The ProLOGUE Study.

Evidence on treatment effectiveness in patients with psoriasis having anxiety or depressive symptoms helps shared decision-making. This single-arm, open-label, prospective study-ProLOGUE-was conducted to assess the effectiveness of brodalumab on self-assessed anxiety and depressive symptoms in Japanese patients with psoriasis. Patients aged ≥ 18years with plaque psoriasis without peripheral arthritis symptoms who had responded inadequately to current therapies were enrolled at 15 Japanese facilities and received brodalumab 210mg subcutaneously. A total of 73 patients were enrolled (male, 82%; median age, 54years). The proportion of patients without anxiety symptoms changed significantly from baseline (72.6%) to weeks 12 (88.9%, p = 0.008) and 48 (87.7%, p = 0.02); the proportion of patients without depressive symptoms did not change significantly. The Generalized Anxiety Disorder-7 score (median [quartile(Q)1-Q3], 1.0 [0.0-5.0] at baseline; 0.0 [0.0-2.0] at week12, p = 0.008; and 0.0 [0.0-1.0] at week 48, p = 0.007) and Patient Health Questionnaire-8 score (median [Q1-Q3], 2.0 [0.0-4.0] at baseline; 1.0 [0.0-4.0] at week12, p = 0.03; and 0.0 [0.0-2.0] at week48, p = 0.004) significantly decreased after treatment. The median Psoriasis Area and Severity Index scores after treatment were < 1, irrespective of the presence of baseline anxiety or depressive symptoms. At week 12, the health-related quality of life was more impaired in patients with versus without baseline depressive symptoms, which largely resolved at week48. Brodalumab treatment resulted in the reduction of the levels of self-assessed anxiety and depressive symptoms in Japanese patients with psoriasis. Unlike anxiety symptoms, depressive symptoms did not resolve completely with brodalumab treatment. Patients with psoriasis having depressive symptoms may require long-term treatment. UMIN Clinical Trials Registry identifier: UMIN000027783, Japan Registry of Clinical Trials identifier: jRCTs031180037.

Effectiveness of brodalumab in improving itching and skin pain in Japanese patients with psoriasis: The ProLOGUE study.

Itching and skin pain are bothersome symptoms of psoriasis, but evidence is limited regarding the treatment effectiveness on these symptoms in daily clinical settings. We assessed the changes in the levels of itching and skin pain after brodalumab treatment in Japanese patients with psoriasis using patient-reported outcomes (PROs). Patients with psoriasis who have inadequate response to existing treatments were enrolled in the single-arm, open-label, multicenter, prospective ProLOGUE study and received brodalumab 210 mg subcutaneously in daily clinical practice. Psoriasis Area and Severity Index (PASI) and PRO assessments were performed at baseline and weeks 12 and 48. Seventy-three patients (men, 82.2%; median age, 54.0 years) were enrolled. The Itch Numeric Rating Scale (NRS; p< 0.0001 at weeks 12 and 48) and Skin Pain NRS (week 12, p= 0.0004; week 48, p< 0.0001) scores significantly decreased from baseline. The Itch NRS score was significantly higher in patients with a Dermatology Life Quality Index (DLQI) score of ≥2 (vs. 0/1; p< 0.0001 at weeks 12 and 48) and in patients with a Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) global satisfaction domain score of ≤70% (vs. >70%; week 12, p= 0.0120; week 48, p= 0.0348). The Itch NRS score cutoff value for achieving a PASI score of ≤2, DLQI score of 0/1, and TSQM-9 global satisfaction domain score of >70% was 1 at week 12 and 0 at week 48. Brodalumab treatment was associated with improvement in itching and skin pain in Japanese patients with psoriasis. An Itch NRS score of 0 can be a long-term treatment goal for psoriasis (Japan Registry of Clinical Trials identifier: jRCTs031180037).

Treatment with brodalumab is not associated with improved sleep problems in real-life patients with plaque psoriasis: Results of the ProLOGUE study.

Psoriasis impacts various aspects of patients' health-related quality of life and is associated with sleep problems. However, research discussing the associations between interleukin-17 blockage therapies and sleep problems in patients with psoriasis is insufficient. We aimed to assess the effectiveness of brodalumab in alleviating sleep problems in real-life patients with plaque psoriasis. This analysis was part of the single-arm, open-label, multicenter, prospective, cohort study, ProLOGUE (study period October 2017-March 2020), which involved Japanese patients with plaque psoriasis. Assessments included correlation of Medical Outcomes Study Sleep Scale-Revised (MOS Sleep-R) scores (Sleep Problems Index-II [SPI-II] and MOS Sleep-R subscale scores) with multiple patient-reported outcome scores and the Psoriasis Area and Severity Index (PASI) at baseline. Additionally, change from baseline in MOS Sleep-R scores was assessed at weeks 12 and 48 of brodalumab treatment. Seventy-three patients were enrolled (male 82.2%, median age 54.0 years). At baseline, the SPI-II score correlated with the Patient Health Questionnaire-8 score (Spearman correlation coefficient [ρ]=-0.474) and weakly correlated with the Itch Numeric Rating Scale (NRS; ρ=-0.366), Skin Pain NRS (ρ=-0.275), and all Treatment Satisfaction Questionnaire for Medication-9 domain scores (ρ=0.270, ρ=0.303, and ρ=0.322 for effectiveness, convenience, and global satisfaction, respectively) but did not correlate with the PASI score. The SPI-II score and MOS Sleep-R subscale scores, except the Snoring score (p=0.0319), did not significantly change from baseline to week 12 of brodalumab treatment. In conclusion, treatment with brodalumab did not improve overall sleep problems in real-life patients with plaque psoriasis, suggesting that sleep problems require attention in daily clinical practice (Japan Registry of Clinical Trials identifier, jRCTs031180037).

Real world experience of brodalumab treatment in patients with moderate-to-severe plaque psoriasis in the Greek population: Results from an interim analysis of the BrIDGE study.

Brodalumab's clinical efficacy and favorable safety profile have been demonstrated during controlled clinical trials, but real-world data remain scarce. BrIDGE, an ongoing 104 week, observational, prospective, multicenter study conducted in Greece, enrolled moderate-to-severe plaque psoriasis patients, with body surface area (BSA) > 10 or psoriasis area severity index score (PASI) > 10 and dermatology life quality index (DLQI) > 10, based on European consensus, initiating brodalumab treatment as per routine clinical practice. This interim analysis includes evaluations 12-16 weeks following treatment initiation. Key efficacy endpoints included proportion of patients achieving static Physician's Global Assessment (sPGA) score of "clear/almost clear" (0/1) and a reduction ≥75%, 90%, 100% from baseline in PASI (PASI75, PASI90, and PASI100) at weeks 12-16. Other endpoints included time to achieve PASI100, changes in self-reported DLQI and psoriasis symptom inventory (PSI) at weeks 12-16. From 200 patients (mean age 51.4 years, 70% male, mean disease duration 13.8 years) enrolled, 72.8% achieved sPGA of 0/1, whereas 70.2%, 47.5%, and 32.0% achieved corresponding PASI75, PASI90, and PASI100 responses following 12-16 weeks of brodalumab treatment, according to the "as-observed" analysis. The mean time to achieve PASI100 was 13.7 ± 1.2 weeks for the 32% who achieved PASI100. Concurrent decreases in mean DLQI and PSI were observed. Furthermore, 90% adherence to brodalumab was noted and nine adverse events were reported. Brodalumab confers substantial clinical improvements short-term as reflected by high levels of skin clearance in moderate-to-severe plaque psoriasis patients within 12-16 weeks of treatment under everyday clinical conditions, followed by improvements in symptoms and quality of life and a favorable safety profile.

Work productivity in real-life employed patients with plaque psoriasis: Results from the ProLOGUE study.

Psoriasis poses a substantial economic burden by reducing the work productivity of affected patients. We aimed to evaluate the negative impact of plaque psoriasis on work productivity and effectiveness of brodalumab in improving work productivity impairment in real-life employed patients. This analysis was conducted in employed patients from ProLOGUE, an open-label, multicenter, prospective cohort study (Japan Registry of Clinical Trials identifier: jRCTs031180037). Outcomes included association of Work Productivity and Activity Impairment-Psoriasis (WPAI-PSO) domain scores with scores from various patient-reported outcome measures or Psoriasis Area and Severity Index (PASI) scores at baseline. Change from baseline in WPAI-PSO domain scores following brodalumab treatment was also evaluated. Of the 73 patients enrolled, 51, 48, and 40 patients were considered employed at baseline, Week 12, and Week 48 of brodalumab treatment, respectively. In the model adjusted by age and sex, the work productivity loss score correlated with the Dermatology Life Quality Index (DLQI), itch Numeric Rating Scale (NRS), Patient Health Questionnaire-8 (PHQ-8), and skin pain NRS scores (partial Spearman correlation coefficient [ρ]=0.608, 0.510, 0.461, and 0.424, respectively); presenteeism score correlated with the DLQI, itch NRS, and skin pain NRS scores (ρ=0.568, 0.500, and 0.403, respectively); and activity impairment score correlated with the DLQI and PHQ-8 scores (ρ=0.530 and 0.414, respectively). None of the WPAI-PSO domain scores correlated with the PASI score. All WPAI-PSO domain scores (except absenteeism) significantly reduced from baseline to Weeks 12 (p < 0.0001) and 48 (p < 0.001) with brodalumab treatment. In conclusion, work productivity impairment in psoriasis was associated with various subjective symptoms that can be captured using patient-reported outcome measures. Brodalumab treatment improved work productivity in real-life employed patients with plaque psoriasis.

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.

Effectiveness of brodalumab in achieving treatment satisfaction for patients with plaque psoriasis: The ProLOGUE study

BackgroundReal-life evidence on the quality of treatment with brodalumab in patients with plaque psoriasis based on patient-reported outcomes remains limited. ObjectiveTo assess the effectiveness of brodalumab in achieving treatment satisfaction for real-life Japanese patients with psoriasis. MethodsAs part of a single-arm, open-label, multicenter, prospective study (ProLOGUE), Psoriasis Area and Severity Index (PASI) scores, body surface area (BSA), and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) domain scores were assessed at baseline and Weeks 12 and 48 of brodalumab treatment. Patient Global Assessment (PtGA) scores were captured at Weeks 12 and 48. ResultsSeventy-five patients were enrolled, of whom 73 received brodalumab. PASI scores and BSA significantly reduced from baseline at Weeks 12 and 48 (all P < 0.0001). Most (90%) patients felt the treatment was effective on the PtGA scale at Weeks 12 and 48. TSQM-9 domain scores significantly improved at Weeks 12 and 48 (all P < 0.0001). A PASI score of ≤ 2 was suggested as a treatment goal for biologic treatment of psoriasis from a receiver operating characteristic curve analysis, although some of the TSQM-9 domain scores did not improve in patients achieving this goal. No new safety signals were observed. ConclusionTreatment with brodalumab was associated with improved objective symptoms and satisfaction in Japanese patients with psoriasis. A PASI score of ≤ 2 as a goal for biologic treatment of psoriasis may be feasible, although achieving this PASI goal alone may be insufficient to clearly improve long-term patient satisfaction (Japan Registry of Clinical Trials identifier: jRCTs031180037).

26580 Efficacy of treatment with brodalumab after treatment failure of previous interleukin 17A inhibitors in patients with psoriasis

Objectives: Studies on switching between IL-17 inhibitors are limited and have primarily been retrospective assessing the efficacy of ixekizumab after switching from secukinumab without addressing the cause of previous treatment discontinuation. We assessed the efficacy of brodalumab treatment in patients with previous treatment failure with IL-17A inhibitors.

Brodalumab treatment in psoriasis patients with severe renal failure.

Brodalumab treatment in psoriasis patients with severe renal failure.

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.

18501 Twenty patients with moderate to severe psoriasis succesfully treated with brodalumab after a failed treatment with secukinumab

Psoriasis is a chronic inflammatory skin disease, associated with a range of co-morbidities, including metabolic and psychological disorders. Brodalumab is a human monoclonal antibody that antagonizes the interleukin (IL) 17 pathway by binding to human IL-17RA. The mechanism of action of brodalumab is unique because it inhibits the IL-17 receptor and not the IL-17A molecule itself like secukinumab and ixekizumab. IL-17RA binds IL-17A, IL-17C, IL17F, and IL-25 and is expressed in multiple tissues like vascular endothelial cells, peripheral T cells, B-cell lineages, fibroblasts, etc. We present 20 patients with moderate to severe psoriasis successfully treated with brodalumab after a failed treatment with secukinumab (16 patients with plaque psoriasis and 4 with palmoplantar pustulosis). Twelve of them had received secukinumab as first line therapy, whereas the rest had undergone of through at least one biologic therapy in the past. All patients had not achieved PASI-75 or PPPGA:0/1 after 12 weeks of therapy, so we switched to brodalumab. Results showed PASI-90, PASI-100, and PPPGA:0 scores in 20% and 80% and 100% of the patients respectively whereas 100% of patients had achieved sPGA 0 or 1 in week 12 of therapy with brodalumab. Brodalumab was more effective than secukinumab in the above patients. Is unknown how patients, who have failed treatment with anti–IL-17 agent respond to brodalumab treatment, but that may relate to the unique mechanism of the drug, that targets IL-17RA. Therefore, brodalumab may be a therapeutic option for psoriasis patients, who have failed other therapies, including other IL-17 antagonists. More data are needed.

Short-term transcriptional response to IL-17 receptor-A antagonism in the treatment of psoriasis

IL-17 antagonists induce impressive clinical benefits in psoriasis, but it is unknown to what extent cellular and molecular psoriasis characteristics are suppressed by a clinically relevant dose/schedule of any IL-17-receptor antagonist. We sought to examine the effects of the IL-17 receptor-A antagonist brodalumab, on clinical and molecular psoriasis features over a 12-week period. A subset of patients (n= 116) enrolled in 3 phase-3 randomized clinical trials (AMAGINE -1 [Efficacy, Safety, and Withdrawal and Retreatment With Brodalumab in Moderate to Severe Plaque Psoriasis Subjects], -2 [P3 Study Brodalumab in Treatment of Moderate to Severe Plaque Psoriasis], and -3 [Efficacy and Safety of Brodalumab Compared With Placebo and Ustekinumab in Moderate to Severe Plaque Psoriasis in Subjects]) participated in a mechanistic substudy where punch biopsies were collected (lesional and nonlesional skin) between baseline and 12 weeks. This cohort included moderate-to-severe psoriasis patients treated with 140 mg (n= 46), 210 mg (n= 41) brodalumab, or placebo (n= 29). Key epidermal psoriatic features, including T-cell and dendritic cell subsets, were examined using immunohistochemistry. Treatment-induced changes in lesional skin gene expression profiles were evaluated using Affymetrix arrays. IL-17 receptor-A antagonism caused extensive improvements in clinical, histologic, and transcriptomic features of psoriasis. Cellular infiltrates (CD3+, CD8+, CD11c+, CD163+), markers of keratinocyte proliferation (Ki67+, KRT16), and inflammatory cytokines (IL-17A/C/F, IL-23A, IL-12B) decreased progressively, reaching close to nonlesional levels, paralleled by decreases in epidermal thickness. Psoriasis transcriptome gene expression improved ∼85% to 95% in responders whose psoriasis area severity index improved by 75% from baseline by week 12 (n= 63), compared with ∼30% to 65% in nonresponders (n= 12), while the residual disease genomic profile was 10% of the psoriasis transcriptome, which is less than for earlier generation drugs. IL-17-dependent gene expression, including keratinocyte genes, improved earlier and more extensively following brodalumab treatment compared with ustekinumab treatment (anti-IL-23/-IL-12). The clinically approved dose and schedule for brodalumab leads to nearly complete resolution of clinical, histologic, and transcriptomic features of psoriasis. Evidently, IL-17-induced release of keratinocyte-derived inflammatory mediators is a key driver of psoriasis pathogenesis.

Improvement in nail psoriasis with brodalumab treatment over 52 weeks: An analysis of two phase 3 studies

Improvement in nail psoriasis with brodalumab treatment over 52 weeks: An analysis of two phase 3 studies

Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials

Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB). To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti-interleukin 17 receptor A monoclonal antibody. Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis. The analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time-adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors. There was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide. Comparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment.

Spotlight on brodalumab in the treatment of moderate-to-severe plaque psoriasis: design, development, and potential place in therapy

Brodalumab is a novel fully human immunoglobulin G2 monoclonal antibody that antagonizes the interleukin (IL)-17 pathway by binding with high affinity to human IL-17RA. The role of IL-17A in the pathogenesis of psoriasis, as well as the remarkable effectiveness of IL-17 inhibitors in the treatment of moderate-to-severe plaque psoriasis, is well established. The mechanism of action of brodalumab is unique in that it inhibits the IL-17 receptor compared to the two other currently FDA-approved IL-17 inhibitors, secukinumab and ixekizumab, which inhibit the IL-17A molecule itself. The efficacy of brodalumab in the treatment of moderate-to-severe plaque psoriasis has been demonstrated in phase 2 and 3 trials, and subsequently the FDA approved this medication in February 2017. Brodalumab was approved in Japan in July 2016 and approval is pending in Europe. The safety and adverse effects of brodalumab were reviewed across several clinical trials, which, similar to other IL-17 inhibitors, demonstrated increased rates of neutropenia and Candida infections. Brodalumab treatment, similar to ixekizumab and secukinumab, showed no improvement in inflammatory bowel disease patients, and on the contrary, more exacerbations were encountered. Suicidal ideation and behavior events have been reported with brodalumab treatment and are of significant concern. Brodalumab provides another highly effective treatment option for moderate-to-severe plaque psoriasis.