Circulating Brodalumab Levels and Therapy Outcomes in Patients With Psoriasis Treated With Brodalumab: A Case Series

TY - JOUR

T1 - Circulating Brodalumab Levels and Therapy Outcomes in Patients With Psoriasis Treated With Brodalumab

T2 - A Case Series

AU - Enevold, Christian

AU - Loft, Nikolai

AU - Bregnhøj, Anne

AU - Zachariae, Claus

AU - Iversen, Lars

AU - Skov, Lone

AU - Nielsen, Claus Henrik

PY - 2022/7

Y1 - 2022/7

N2 - Importance: Given the possible treatment modalities in psoriasis management, little is known about whether drug monitoring is associated with response rate.Objective: To determine whether drug monitoring is associated with response to brodalumab therapy.Design: A 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.Exposure: Treatment with brodalumab, 210 mg, at weeks 0, 1, 2, then every 2 weeks.Main Outcomes and Measures: Outcome measures were PASI reductions vs brodalumab levels and antibrodalumab antibodies.Results: Twenty 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 Relevance: Results 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.

AB - Importance: Given the possible treatment modalities in psoriasis management, little is known about whether drug monitoring is associated with response rate.Objective: To determine whether drug monitoring is associated with response to brodalumab therapy.Design: A 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.Exposure: Treatment with brodalumab, 210 mg, at weeks 0, 1, 2, then every 2 weeks.Main Outcomes and Measures: Outcome measures were PASI reductions vs brodalumab levels and antibrodalumab antibodies.Results: Twenty 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 Relevance: Results 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.

KW - Antibodies, Monoclonal

KW - Antibodies, Monoclonal, Humanized

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Psoriasis/complications

KW - Severity of Illness Index

KW - Treatment Outcome

U2 - 10.1001/jamadermatol.2022.1863

DO - 10.1001/jamadermatol.2022.1863

M3 - Journal article

C2 - 35648430

SN - 0003-987X

VL - 158

SP - 762

EP - 769

JO - JAMA Dermatology

JF - JAMA Dermatology

IS - 7

ER -