Immunogenicity and skin clearance recapture in clinical studies of brodalumab - 09/01/20
, Mark Lebwohl, MD b, Robert J. Israel, MD c, Abby Jacobson, PA-C dAbstract |
Background |
Antidrug antibodies (ADAs) may change pharmacokinetic or pharmacodynamic profiles of biologic therapies, potentially decreasing efficacy.
Objective |
To evaluate the potential effects of brodalumab immunogenicity on safety, efficacy, and retreatment.
Methods |
Data from 1 phase 2 and 3 phase 3 studies of brodalumab in psoriasis were analyzed.
Results |
Overall, 2.7% of patients had positive test results for binding ADAs after receiving brodalumab; ADAs were transient in 1.4% of patients, and there were no neutralizing ADAs. Among ADA-positive patients, 60.0% (3/5) achieved a static physician's global assessment score of 0 or 1 at week 12 in the group receiving the brodalumab 210 mg every 2 weeks, compared with 79.1% (1131/1429) of ADA-negative patients. All patients (100%) who experienced return of disease and were retreated with brodalumab 210 mg every 2 weeks (none were ADA positive) achieved at least a 75% improvement in Psoriasis Area And Severity Index, ≥90% of whom regained response by week 8 of retreatment. Hypersensitivity reactions were less frequent with brodalumab than with placebo. Injection site reactions occurred in 1.8% of patients treated with brodalumab versus 2% of patients treated with ustekinumab.
Limitations |
Retreatment could be assessed in only 1 phase 3 brodalumab study.
Conclusion |
Brodalumab compares favorably with other biologics in terms of immunogenicity and high rates of efficacy recapture upon retreatment.
Le texte complet de cet article est disponible en PDF.Key words : antidrug antibody, brodalumab, immunogenicity, psoriasis
Abbreviations used : ADA, AE, IL, mAb, PASI, PASI 75, PASI 90, PASI 100, sPGA
Plan
| Funding sources: Supported by Ortho Dermatologics. |
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| Disclosure: Dr Bagel is a speaker and investigator for AbbVie, Celgene, Eli Lilly, Janssen, Novartis, and Ortho Dermatologics and an investigator for Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, and LEO Pharma. Dr Lebwohl is an employee of Mount Sinai, which receives research funds from AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Incyte, Janssen/Johnson & Johnson, LEO Pharma, MedImmune/AstraZeneca, Novartis, Pfizer, SCIderm, UCB, Valeant, and Vidac Pharma and is also a consultant for Allergan, Aqua, Arcutis, Boehringer Ingelheim, LEO Pharma, Menlo, Promius, and Verrica. Dr Israel is an employee of Bausch Health and holds stock and/or stock options in the company. Dr Jacobson is an employee of Ortho Dermatologics and holds stock and/or stock options in Bausch Health. |
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| Reprints not available from the authors. |
Vol 82 - N° 2
P. 344-351 - février 2020 Retour au numéro
Article précédent
- A randomized phase 3b/4 study to evaluate concomitant use of topical ivermectin 1% cream and doxycycline 40-mg modified-release capsules, versus topical ivermectin 1% cream and placebo in the treatment of severe rosacea
- Martin Schaller, Lajos Kemény, Blanka Havlickova, J. Mark Jackson, Marcin Ambroziak, Charles Lynde, Melinda Gooderham, Eva Remenyik, James Del Rosso, Jolanta Weglowska, Rajeev Chavda, Nabil Kerrouche, Thomas Dirschka, Sandra Johnson
- Long-term efficacy and safety of brodalumab in the treatment of psoriasis: 120-week results from the randomized, double-blind, placebo- and active comparator–controlled phase 3 AMAGINE-2 trial
- Luis Puig, Mark Lebwohl, Hervé Bachelez, Jeffrey Sobell, Abby A. Jacobson
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