Brodalumab for the Treatment of Psoriasis: A Review of Phase III Trials

Farahnik, Benjamin; Beroukhim, Kourosh; Abrouk, Michael; Nakamura, Mio; Zhu, Tian Hao; Singh, Rasnik; Lee, Kristina; Bhutani, Tina; Koo, John

doi:10.1007/s13555-016-0121-x

Cited by 91 publications

(51 citation statements)

References 38 publications

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“…Three agents targeting the IL‐17 cytokine pathway are available; secukinumab and ixekizumab are specific to IL‐17A, whereas brodalumab is directed against the IL‐17 receptor. IL‐17 inhibitors have shown generally favourable safety profiles in patients with psoriasis . However, increased risk of Candida infections, worsening of pre‐existing inflammatory bowel disease and, rarely, new‐onset ulcerative colitis and Crohn's disease have been reported during treatment .…”

Section: Introductionmentioning

confidence: 99%

“…IL‐17 inhibitors have shown generally favourable safety profiles in patients with psoriasis . However, increased risk of Candida infections, worsening of pre‐existing inflammatory bowel disease and, rarely, new‐onset ulcerative colitis and Crohn's disease have been reported during treatment . The observed increase in Candida infections is not unexpected, as IL‐17 is known to play a key role in the host defence against yeast and fungi .…”

Section: Introductionmentioning

confidence: 99%

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Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

Crowley

Warren

Cather³

2019

Acad Dermatol Venereol

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Psoriasis is a chronic disease that requires long‐term treatment. Consequently, understanding the safety and tolerability of any potential treatment over time is critical to effective prescribing. The biologic agents currently available for the treatment of psoriasis target a number of different inflammatory cytokines involved in psoriasis disease pathogenesis. The monoclonal antibodies tildrakizumab, guselkumab and risankizumab target the p19 subunit that is specific to interleukin (IL)‐23. This article reviews published data on the safety of these IL‐23p19 inhibitors in patients with psoriasis compared with other currently available biologic therapies. Data from randomized, placebo‐ and active‐controlled phase 3 clinical trials show tildrakizumab, guselkumab and risankizumab to have a favourable risk–benefit profile in patients with moderate to severe psoriasis. No significant safety concerns have been observed for any of these IL‐23p19 inhibitors in the data published to date. The most commonly reported adverse events (AEs) associated with these agents in phase 3 studies were upper respiratory tract infections. No increase was seen in rates of serious infections, malignancies or major adverse cardiovascular events, with no signals suggestive of an elevated risk of opportunistic infections, active tuberculosis or reactivation of latent tuberculosis infection, mucocutaneous Candida infections, triggering or worsening of inflammatory bowel disease, demyelinating disorders or suicidal ideation. Selectively targeting IL‐23p19 may help avoid AEs that have been associated with biologic agents with other mechanisms of action. Data from long‐term extension studies and patient registries will further establish the safety profile of IL‐23p19 inhibitors for the treatment of moderate to severe psoriasis in routine practice.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

Crowley

Warren

Cather³

2019

Acad Dermatol Venereol

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“…Among the three phase III trials comparing brodalumab 210 mg to placebo, the pooled proportion of patients achieving PASI 75 and sPGA 0-1 at 12 weeks were 85.3% and 78.6%, respectively 20,21. The pooled proportion experiencing adverse events was 57.6%, with nasopharyngitis, upper respiratory infection (URI), headache, and arthralgia as the most commonly cited adverse events.…”

Section: Resultsmentioning

confidence: 99%

Emerging targeted therapies for plaque psoriasis – impact of ixekizumab

Kazemi

Farahnik

Koo

et al. 2017

CCID

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BackgroundRecent studies into the pathogenesis of psoriasis have identified the importance of interleukin 17 (IL-17) in disease activity and have thus provided a new target for biologic therapy. Ixekizumab, the most recent US Food and Drug Administration (FDA)-approved anti-IL-17 biologic agent, appears to be a promising medication for patients suffering from moderate-to-severe plaque psoriasis.MethodsWe reviewed the results of phase III trials for ixekizumab in order to assess the efficacy, safety, and impact on quality of life of this agent in the treatment of plaque psoriasis. Additionally, we compared these results to phase II and phase III trials for other biologic psoriasis medications including the anti-IL-23 agents tildrakizumab and guselkumab, the combined anti-IL-12 and anti-IL-23 agent ustekinumab, and the anti-IL-17 agents brodalumab and secukinumab.ResultsPooled results from individual studies demonstrate that among the most efficacious dosing regimens of these anti-interleukin therapies, ixekizumab achieves higher Psoriasis Area and Severity Index 75 rates and similar or higher static Physician Global Assessment 0-1 rates than the other anti-IL-17 and anti-IL-23 agents. The safety profile of ixekizumab is similar to these agents, with nasopharyngitis, upper respiratory infection, headache, arthralgia, and injection-site erythema as the most commonly reported adverse events.ConclusionIxekizumab is a highly efficacious, newly FDA-approved treatment for moderate-to-severe plaque psoriasis that demonstrates a robust clinical response, significant improvement in patient quality of life, and a favorable safety profile.

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“…In der Induktionsphase der UNCOVER-Studien wurden bei 9% der alle zwei Wochen mit Ixekizumab behandelten Patienten Antikörper gegen Ixekizumab nachgewiesen. Nur bei etwa 1% der Patienten wurden neutralisierende Antikörper gefunden [22] [33]. Nach lediglich 2,1 Wochen unter Therapie wiesen 25% der Patienten bereits ein PASI 75-Ansprechen auf, wie eine gepoolte Analyse der AMAGINE-2-und AMAGINE-3-Studie ergab [30,34].…”

Section: Il-17-blockadeunclassified

IL-17-Blockade in der Psoriasis-Therapie

Sondermann¹,

Körber²

2018

Kompass Dermatol

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Die Psoriasis vulgaris ist eine immun-mediierte chronisch-inflammatorische Erkrankung, von der in Deutschland rund 2 Millionen Menschen betroffen sind. Die zugrunde liegende Inflammation bei der Psoriasis kommt durch ein komplexes Zusammenspiel von Genen, Umweltfaktoren und dem angeborenen sowie erworbenen Immunsystem zustande. Bei der Psoriasis handelt es sich nicht um eine reine Hauterkrankung, sondern um eine chronisch-inflammatorische Systemerkrankung, die Schweregrad-adaptiert mit einer Reihe von Komorbiditäten assoziiert sein kann. Wie in den letzten Jahren immer mehr herausgearbeitet werden konnte, stellt Interleukin(IL)-17A ein proinflammatorisches Schlüsselzytokin bei der Pathogenese der psoriatischen Inflammation dar und ist somit ein potentes Ziel für die Psoriasis-Therapie. Zum jetzigen Zeitpunkt stehen in Deutschland zwei IL-17A-Antagonisten (Secukinumab und Ixekizumab) und seit dem 1.9.2017 auch Brodalumab, der erste IL-17-Rezeptor-Blocker (IL-17RA) zur Verfügung. Alle genannten Substanzen haben in Deutschland eine First-Line-Zulassung zur Behandlung der mittelschweren bis schweren Psoriasis erhalten. Ein Charakteristikum der IL-17-Blockade ist ein exzellentes Therapieansprechen, das sehr schnell erreicht wird. Über 70% der Patienten erreichen in Phase-3-Studien unter einer IL-17-Blockade eine Psoriasis Area and Severity Index(PASI)-Verbesserung von 90, über 40% der Patienten können sogar eine komplette Erscheinungsfreiheit (PASI 100) erlangen. Die Sicherheit und Verträglichkeit der IL-17A-Inhibitoren ist bislang weitestgehend vergleichbar mit den bisher zugelassenen Biologika. Eine klassenabhängige Nebenwirkung ist jedoch das vermehrte Auftreten von Candidosen, da IL-17A bei der Abwehr der entsprechenden Erreger unter physiologischen Bedingungen beteiligt ist. Unter Brodalumab wurde im Studienprogramm eine erhöhte Rate von Suizidgedanken und suizidalem Verhalten einschließlich vollendeter Suizide beobachtet. Letztlich konnte jedoch keine kausale Verbindung des suizidalen Verhaltens zur Behandlung mit Brodalumab hergestellt werden. Dennoch ist beim Einsatz von Brodalumab bei Patienten mit psychischen Problemen wie z.B. Depressionen in der Anamnese Vorsicht geboten. Die Therapielandschaft der Psoriasis-Behandlung hat sich durch die Etablierung der IL-17-Inhibitoren stark zum Positiven verändert. Eine «Schwierigkeit» besteht nun darin, aus der Fülle der zur Verfügung stehenden konventionellen Systemtherapeutika und Biologika das individuell zum jeweiligen Patienten passende Präparat auszuwählen. Der zunehmende Erfahrungsgewinn mit den neuen Substanzen sowie die gerade erschienene, neu überarbeitete S3-Leitlinie zur Psoriasis-Behandlung werden bei den Entscheidungsprozessen unterstützend wirken.

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Brodalumab for the Treatment of Psoriasis: A Review of Phase III Trials

Cited by 91 publications

References 38 publications

Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

Emerging targeted therapies for plaque psoriasis – impact of ixekizumab

IL-17-Blockade in der Psoriasis-Therapie

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Brodalumab for the Treatment of Psoriasis: A Review of Phase III Trials

Cited by 91 publications

References 38 publications

Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

Emerging targeted therapies for plaque psoriasis &ndash; impact of ixekizumab

IL-17-Blockade in der Psoriasis-Therapie

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Product

Resources

About

Emerging targeted therapies for plaque psoriasis – impact of ixekizumab