Dataset Information

Malignancy Rates in Brodalumab Clinical Studies for Psoriasis.

ABSTRACT: BACKGROUND:Brodalumab is a fully human anti-interleukin-17 receptor A monoclonal antibody efficacious for the treatment of adults with moderate-to-severe plaque psoriasis. OBJECTIVE:This study summarizes malignancy rates in psoriasis clinical studies of brodalumab. METHODS:Data were pooled from one phase II study and three large, multicenter, phase III randomized studies of brodalumab for the treatment of psoriasis, including two studies with randomization to brodalumab, ustekinumab, or placebo. Data from the 52-week (brodalumab and ustekinumab) and long-term (brodalumab) pools were summarized as exposure-adjusted or follow-up time-adjusted event rates per 100 patient-years (PY). RESULTS:Exposure-adjusted event rates per 100 PY at 52 weeks were lower with brodalumab (n = 4019; 3446 total PY of exposure) than with ustekinumab (n = 613; 495 total PY of exposure), including adjudicated malignancies (0.9 vs 2.6) and Surveillance, Epidemiology, and End Results (SEER)-adjudicated malignancies (0.3 vs 0.4). The exposure-adjusted event rate of adjudicated malignancies in the brodalumab group remained stable in the long-term analysis (0.9 [82 events]). CONCLUSIONS:Rates of malignancy among brodalumab-treated patients with psoriasis were generally low. TRIAL REGISTRY:ClinicalTrials.gov identifier NCT00975637; NCT01101100; NCT01708590 (AMAGINE-1); NCT01708603 (AMAGINE-2); NCT01708629 (AMAGINE-3).

SUBMITTER: Gottlieb A

PROVIDER: S-EPMC7275023 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Malignancy Rates in Brodalumab Clinical Studies for Psoriasis.

Gottlieb Alice A Lebwohl Mark M Liu Clive C Israel Robert J RJ Jacobson Abby A

American journal of clinical dermatology 20200601 3

<h4>Background</h4>Brodalumab is a fully human anti-interleukin-17 receptor A monoclonal antibody efficacious for the treatment of adults with moderate-to-severe plaque psoriasis.<h4>Objective</h4>This study summarizes malignancy rates in psoriasis clinical studies of brodalumab.<h4>Methods</h4>Data were pooled from one phase II study and three large, multicenter, phase III randomized studies of brodalumab for the treatment of psoriasis, including two studies with randomization to brodalumab, us ...[more]

PMID: 32207067

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Project description:ImportanceGiven the possible treatment modalities in psoriasis management, little is known about whether drug monitoring is associated with response rate.ObjectiveTo determine whether drug monitoring is associated with response to brodalumab therapy.DesignA multicenter case series study of patients with psoriasis treated with brodalumab whose treatment with previous IL-17A inhibitor therapy failed. Patients were recruited from the Departments of Dermatology at Gentofte and Aarhus University Hospitals, Denmark, between 2018 and 2020. Patient visits were conducted after 4 and 12 weeks of therapy. Patients not achieving Psoriasis Area and Severity Index 75% improvement from baseline (PASI 75) after 12 weeks were discontinued and considered nonresponders. Patients maintaining PASI 75 response were followed up for up to 52 weeks.ExposureTreatment with brodalumab, 210 mg, at weeks 0, 1, 2, then every 2 weeks.Main outcomes and measuresOutcome measures were PASI reductions vs brodalumab levels and antibrodalumab antibodies.ResultsTwenty patients with psoriasis (13 [65%] were male; median age, 50 years [range, 19-66 years]) were included. After 12 weeks of therapy, patients with quantifiable levels of brodalumab (≥0.05 μg/mL) experienced significantly higher PASI reductions than those without (median, 93%; range, 61%-100% vs median, -3; range, -49% to 94%, respectively; P = .006). After 12 weeks of therapy, 4 of 5 patients (80%) not achieving PASI 75 had subquantifiable drug levels (<0.05 μg/mL), although this finding was seen for only 3 of 14 PASI 75 responders (21%). None of 7 patients (35%) with subquantifiable drug levels after 12 weeks of therapy maintained response. No antibrodalumab antibodies were detected in any of the tested samples.Conclusions and relevanceResults of this case series study suggest that circulating brodalumab level is a factor associated with clinical treatment response. Monitoring patient levels of circulating brodalumab may aid clinical decision-making and help prevent ineffective therapy.

Project description:Brodalumab, an interleukin-17 receptor A inhibitor, demonstrated rapid and robust efficacy with a favorable safety profile in patients with moderate to severe plaque psoriasis. Here, we present data from a multicenter, open-label extension study in patients with plaque psoriasis with/without psoriatic arthritis who completed 64 weeks of treatment with brodalumab (140 or 210 mg, every 2 weeks [Q2W]). Patients were enrolled to evaluate the long-term safety and efficacy of a modified dose of brodalumab. Eligible patients were switched to a reduced dose of brodalumab (140 mg every 4 weeks on day 1) in the extension study; the dose and dosing interval were modified sequentially at the physician's discretion (minimum 140 mg every 8 weeks and maximum 210 mg Q2W) until drug approval, after which all patients were switched to 210 mg Q2W for postmarketing surveillance. Of the 129 patients enrolled, 107 (82.9%) completed the 108-week or more extension study. All patients had psoriasis that was well controlled with brodalumab treatment on day 1. Improvement in psoriasis-related symptoms, evaluated with the Psoriasis Area and Severity Index, Psoriasis Scalp Severity Index, Dermatology Life Quality Index, Nail Psoriasis Severity Index, and American College of Rheumatology 20, 50 and 70, was maintained during the 108-week extension study. Brodalumab treatment was well tolerated throughout, and no new safety signals were identified. The most commonly reported treatment-related adverse event was nasopharyngitis, followed by influenza and oral candidiasis. No cases of serious candida infection or Crohn's disease were observed in this study. Serious treatment-related adverse events, such as appendicitis, brain abscess, bacterial meningitis, colon cancer, immunoglobulin A nephropathy and tubulointerstitial nephritis, were reported in one patient each. No anti-brodalumab-binding antibodies or brodalumab-neutralizing antibodies were detected in any patient throughout the extension study. Overall, the long-term efficacy and safety of brodalumab were demonstrated over 108 weeks.

Dataset Information

Malignancy Rates in Brodalumab Clinical Studies for Psoriasis.

Publications

Malignancy Rates in Brodalumab Clinical Studies for Psoriasis.

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