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

Enevold, Christian; Loft, Nikolai; Bregnhøj, Anne; Zachariae, Claus; Iversen, Lars; Skov, Lone; Nielsen, Claus Henrik

doi:10.1001/jamadermatol.2022.1863

Cited by 10 publications

(9 citation statements)

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“…The systemic exposure of brodalumab has been shown to be lower in patients with a higher body weight [ 43 ]. Additionally, an association between body weight, brodalumab serum levels and clinical response has been reported [ 44 , 45 ]. A phase II trial reported declining PASI response rates with increasing body weight [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Single-Centre Real-World Study on Drug Survival and Effectiveness of Brodalumab for Treatment of Psoriasis and Psoriatic Arthritis

2023

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Background Clinical trials have established the efficacy of brodalumab in treatment of psoriasis and psoriatic arthritis. Real-world evidence is needed to fully evaluate the drug. Objective Here we investigate drug survival and clinical effectiveness of brodalumab in patients with psoriasis and psoriatic arthritis in a real-world setting. Methods This was a retrospective single-centre study enrolling patients receiving brodalumab for psoriasis at the Department of Dermatology, Aarhus University Hospital, Denmark. The primary endpoints were drug survival, reasons for discontinuation, percentage of patients achieving a Psoriasis Area and Severity Index (PASI) ≤ 2 and clinical effectiveness against psoriatic arthritis. Results Eighty-three patients were included (mean age 49.2 ± 17.4 years, 59.0% male, 9.6% bio-naïve, mean baseline PASI 10.9 ± 6.9). Twenty-seven patients discontinued treatment primarily due to ineffectiveness and adverse events (AEs). Kaplan–Meier-estimated 1-year drug survival was 65.7%. An absolute Psoriasis Area and Severity Index (PASI) ≤ 2 was achieved by 68.2% of patients at end of follow-up, by 70.0% at weeks 12–17 and by 76.2% after 40–60 weeks of treatment. Neither drug survival nor PASI ≤ 2 was associated with baseline PASI ≥ 10, body mass index ≥ 30, previous treatment with > 2 biologics or other IL-17 inhibitors in particular ( P > 0.05). Psoriatic arthritis remission or partial remission was achieved by 10 out of 18 patients with psoriatic arthritis; treatment failure was reported in 5 patients. Conclusions Brodalumab was effective against psoriasis and psoriatic arthritis in a real-world setting. The drug survival was lower than reported in other real-world settings.

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Section: Discussionmentioning

confidence: 99%

Single-Centre Real-World Study on Drug Survival and Effectiveness of Brodalumab for Treatment of Psoriasis and Psoriatic Arthritis

2023

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“…Ixekizumab, another human monoclonal antibody, inhibits the inflammatory response mediated by IL-17A binding to the IL-17A receptor (IL-17AR), whereas brodalumab can specifically block the IL-17 receptor. Extensive clinical studies have shown that ixekizumab and brodalumab are beneficial and used by the FDA in adults with moderate to severe plaque psoriasis (114,124). Emerging evidence hints that the therapeutic interventions on IL-17A may be a promising treatment strategy in ND patients.…”

Section: Targeting the Il-17a/il-17ar Axismentioning

confidence: 99%

Th17 cells and inflammation in neurological disorders: Possible mechanisms of action

et al. 2022

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Neurological disorders (NDs) are one of the leading causes of global death. A sustained neuroinflammatory response has been reported to be associated with the pathogenesis of multiple NDs, including Parkinson’s disease (PD), multiple sclerosis (MS), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and major depressive disorder (MDD). Accumulating evidence shows that the recruitment of abundant lymphocytes in the central nervous system may contribute to promoting the development and progress of inflammation in neurological disorders. As one subset of T lymphocytes, CD4+ T cells have a critical impact on the inflammation of neurological disorders. T helper (Th) 17 is one of the most studied CD4+ Th subpopulations that produces cytokines (e.g., IL-17A, IL-23, IL-21, IL-6, and IFN-γ), leading to the abnormal neuroinflammatory response including the excessive activation of microglia and the recruitment of other immune cell types. All these factors are involved in several neurological disorders. However, the possible mechanisms of Th17 cells and their associated cytokines in the immunopathology of the abovementioned neurological disorders have not been clarified completely. This review will summarize the mechanisms by which encephalitogenic inflammatory Th17 cells and their related cytokines strongly contribute to chronic neuroinflammation, thus perpetuating neurodegenerative processes in NDs. Finally, the potential therapeutic prospects of Th17 cells and their cytokines in NDs will also be discussed.

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“…For SEC, our group found a minimal effective C t of 33.2 μg/ml and proposed a target C t of 39.1 μg/ml corresponding with 92.7% probability of achieving an absolute PASI ≤2 or reduction in PASI of ≥90% 24 . For the other biologics, data suggest either the presence of an exposure‐response association or show conflicting results; or data are lacking 25–38 …”

Section: Introductionmentioning

confidence: 99%

“…24 For the other biologics, data suggest either the presence of an exposure-response association or show conflicting results; or data are lacking. [25][26][27][28][29][30][31][32][33][34][35][36][37][38] Here, we present a cohort of IL-17i-treated Pso patients, followed up in a monocentric, academic, Pso-dedicated, integrated care setting, named PsoPlus. 39 Our objectives were to (1) present IL-17i effectiveness, (2) report on treatment modifications and (3) describe the utility of C t measurements during clinical practice.…”

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confidence: 99%

Blocking interleukin‐17 in psoriasis: Real‐world experience from the PsoPlus cohort

Schots

Soenen

Blanquart

et al. 2023

Acad Dermatol Venereol

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Background Real‐world studies on the use of biologics in psoriasis (Pso) are increasing, but still scarce. Trough concentrations (Cts) of interleukin‐17 inhibitors (IL‐17i) seem promising for clinical decision‐making, but their value in daily practice has yet to be proven. Objectives To report on IL‐17i effectiveness, treatment modifications and Ct use in our clinic. Methods Data were collected from IL‐17i‐treated Pso patients followed up in the PsoPlus clinic at the Dermatology department, Ghent University Hospital, Belgium. Descriptive statistics and Kaplan–Meier analysis were performed. Results A total of 111 patients were included, counting for 134 IL‐17i courses (secukinumab, ixekizumab, and brodalumab). Fifty‐five per cent of the patients were bio‐naive prior to IL‐17i initiation. During maintenance, merely 97.0% and 77% achieved near‐complete and complete skin clearance, respectively. Major reasons for treatment modification were suboptimal response (63.0%) and safety issues (9.3%). Reported modifications were switch (25.4%), dose escalation (11.9%), dose de‐escalation (6.7%), treatment association (6.0%) and IL‐17i stop (3.0%). Overall drug survival was 69.0 months, without difference between the different IL‐17i (p = 0.078). Ixekizumab tended to have the highest survival. Drug survival was higher in bio‐naive subjects compared to bio‐experienced subjects (p = 0.011). Ct was measured in 20 patients and interpreted post hoc. In 85%, the clinical decision was in accordance with the Ct (e.g. substantiated need for dose escalation). For the other cases, the Ct would have led to another clinical decision if known at that time. Conclusions This real‐world study showed that IL‐17i are very effective drugs for Pso, with ixekizumab as leading biologic. Prior bio‐experience seemed to impact IL‐17i drug survival. Treatment modifications were mainly performed in case of insufficient response, primarily via switch and dose escalation, and least frequently in ixekizumab patients. Ct might rationalize clinical decision‐making; however, there is need for standardized algorithms to corroborate its use.

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

Cited by 10 publications

References 37 publications

Single-Centre Real-World Study on Drug Survival and Effectiveness of Brodalumab for Treatment of Psoriasis and Psoriatic Arthritis

Single-Centre Real-World Study on Drug Survival and Effectiveness of Brodalumab for Treatment of Psoriasis and Psoriatic Arthritis

Th17 cells and inflammation in neurological disorders: Possible mechanisms of action

Blocking interleukin‐17 in psoriasis: Real‐world experience from the PsoPlus cohort

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