Immunogenicity and skin clearance recapture in clinical studies of brodalumab

Bagel, Jerry; Lebwohl, Mark; Israel, Robert J.; Jacobson, Abby

doi:10.1016/j.jaad.2019.05.094

Cited by 22 publications

(20 citation statements)

References 22 publications

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“…Although treatment discontinuation due to lack of efficacy was reported in two patients, we did not observe any anti‐brodalumab‐binding antibodies and anti‐brodalumab‐neutralizing antibodies in this patient population on long‐term brodalumab treatment at any assessment point. This observed low immunogenicity profile of brodalumab was consistent with that reported in previous clinical trials 22,23 …”

Section: Discussionsupporting

confidence: 91%

Long‐term safety of brodalumab in Japanese patients with plaque psoriasis: An open‐label extension study

Yamaguchi

Takatsu

Ootaki

et al. 2020

The Journal of Dermatology

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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 longterm 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 108week 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.

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Section: Discussionsupporting

confidence: 91%

Long‐term safety of brodalumab in Japanese patients with plaque psoriasis: An open‐label extension study

Yamaguchi

Takatsu

Ootaki

et al. 2020

The Journal of Dermatology

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“…9,25 Immunogenicity is one of several factors that may contribute to a loss of clinical response with biological therapies. 21 Prior studies of biological therapies for psoriasis have shown decreasing response rates over time, which may be related to the emergence of neutralizing antidrug antibodies. 1 In this analysis, two patients rerandomized to placebo had brodalumab-binding antibodies at week 24, whereas none had brodalumab-neutralizing antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…The methods used to quantify the presence of brodalumab-binding antibodies were previously specified. 21…”

Section: Safety and Immunogenicitymentioning

confidence: 99%

Long-term efficacy and safety of brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomized phase III trial (AMAGINE-1)

Papp

Menter

Soung³

et al. 2020

British Journal of Dermatology

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Summary Background Brodalumab is efficacious for the treatment of moderate‐to‐severe plaque psoriasis through 52 weeks. Objectives To evaluate the efficacy and safety of brodalumab through 120 weeks, including following withdrawal and retreatment. Methods At baseline, patients were randomized to brodalumab (n = 222) or placebo (n = 220). At week 12, patients achieving a static Physician's Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1) with brodalumab were rerandomized to brodalumab (n = 83) or placebo (n = 84; later re‐treated with brodalumab if sPGA ≥ 3 occurred), and patients receiving placebo switched to brodalumab (n = 208). Safety was assessed by exposure‐adjusted rates of treatment‐emergent adverse events. Results Among those who achieved sPGA 0/1 at week 12 and were rerandomized to brodalumab, 96% and 80% using observed data, respectively, and 74% and 61% using nonresponder imputation, respectively, achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) and PASI 100 at week 120. Following withdrawal from brodalumab, return of disease occurred after a mean ± SD duration of 74·7 ± 50·5 days. Among those who switched from brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55% and 51% at week 20, respectively and 94% and 75% at week 120, respectively; PASI 100 rates at week 120 were 75% and 60%, respectively. Efficacy was maintained through week 120 in those receiving brodalumab after placebo. No new safety signals were observed. Conclusions These findings indicate that brodalumab is efficacious and safe for continuous long‐term treatment of psoriasis, and support the potential for response after discontinuation and retreatment.

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“…Measurable serum brodalumab levels were only detected in responders. A previous analysis of the current/ 18 preceding 26 study data demonstrated an absence of neutralizing anti‐brodalumab antibodies. Therefore, the lack of efficacy in non‐responders could be related to poor adherence, given that adherence to biologics is reported to be suboptimal 27 .…”

Section: Discussionmentioning

confidence: 84%

Relationship between serum trough levels and efficacy of brodalumab from a post hoc exploratory analysis of a Japanese study in patients with plaque psoriasis

Yamaguchi

Kanai

Kitabayashi

et al. 2020

The Journal of Dermatology

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Previous clinical studies have shown that efficacy and serum brodalumab levels are dose dependent in patients with psoriasis receiving the same dose of brodalumab during the study. This study aimed to investigate the association between dosage, serum levels, and efficacy of brodalumab in Japanese patients with plaque psoriasis with dosage variations during the study. This was a post hoc exploratory analysis of a 108‐week, multicenter, open‐label extension study, which changed into a post‐marketing surveillance study following brodalumab approval in Japan. Eligible patients with plaque psoriasis (n = 129) received brodalumab 140 mg every 4 weeks on Day 1; dosage change at physician’s discretion from 140 mg every 8 weeks to 210 mg every 2 weeks was permitted; patients switched to 210 mg every 2 weeks during the post‐marketing surveillance study. Exploratory endpoints included serum brodalumab levels at Weeks 28 and 108, its association with Psoriasis Area and Severity Index score, and Psoriasis Area and Severity Index score in patients receiving brodalumab 210 mg every 2 weeks at end of study. Median brodalumab trough levels were significantly higher (P < 0.05) at higher vs. lower dosages at Weeks 28 (n = 126) and 108 (n = 111) except for 140 mg every 2 weeks vs. 210 mg every 2 weeks at Week 108 and higher in patients with lower Psoriasis Area and Severity Index scores—significantly different only for Psoriasis Area and Severity Index score 0 vs. >2 at Week 28 (P = 0.0153). Of 100 patients receiving 210 mg every 2 weeks at end of study, 89% had a Psoriasis Area and Severity Index score ≤2. In patients with plaque psoriasis, brodalumab efficacy may depend upon sustained serum trough levels and can be restored by using the approved dose.

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Immunogenicity and skin clearance recapture in clinical studies of brodalumab

Cited by 22 publications

References 22 publications

Long‐term safety of brodalumab in Japanese patients with plaque psoriasis: An open‐label extension study

Long‐term safety of brodalumab in Japanese patients with plaque psoriasis: An open‐label extension study

Long-term efficacy and safety of brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomized phase III trial (AMAGINE-1)

Relationship between serum trough levels and efficacy of brodalumab from a post hoc exploratory analysis of a Japanese study in patients with plaque psoriasis

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