Efalizumab retreatment in patients with moderate to severe chronic plaque psoriasis

doi:10.1016/j.jaad.2005.10.032

Journal of the American Academy of Dermatology

Volume 54, Issue 4, Supplement, April 2006, Pages S164-S170

https://doi.org/10.1016/j.jaad.2005.10.032 Get rights and content

Background

Efalizumab targets T cell–mediated steps important in psoriasis immunopathogenesis.

Objective

We sought to evaluate the efficacy and safety of efalizumab retreatment in patients with moderate to severe plaque psoriasis.

Methods

In this open-label, phase III study, 365 patients who received efalizumab therapy during an earlier clinical trial were retreated with 12 weeks of subcutaneous efalizumab (1 mg/kg/wk) 35 days or more after their last dose of efalizumab.

Results

After 12 weeks of efalizumab retreatment, 56.9% of patients achieved 50% or more improvement from baseline Psoriasis Area and Severity Index (PASI) and 25.3% achieved at least 75% reduction in PASI score. The mean percentage PASI improvement from baseline was 51.2%. Overall, 76.1% of patients surveyed were “very satisfied” or “satisfied” with the efficacy of efalizumab. The safety profile of efalizumab retreatment was similar to that observed in patients receiving efalizumab for the first time.

Limitations

Not all patients received sufficient exposure to efalizumab during their previous efalizumab clinical trial to allow for determination of their initial response to efalizumab. Of 365 patients enrolled in the study, 282 received at least 12 weeks of prior efalizumab therapy; of these patients, 208 (73.8%) achieved a PASI-50 response from their previous therapy.

Conclusion

These results suggest that retreatment with efalizumab therapy is an efficacious option for patients who have previously discontinued treatment.

Section snippets

Study design

This was an open-label, multidose, multicenter, phase III study. Patients with plaque psoriasis were enrolled at up to 50 centers in the United States and Canada. Eligible patients had completed a protocol-defined course of treatment and follow-up with various dosages of subcutaneous (SC) or intravenous efalizumab or placebo in 7 previous efalizumab phase I, II, or III clinical studies. A minimum efficacy response after the first course of efalizumab therapy was not required for eligibility for

Patient disposition and demographic and psoriasis characteristics

In total, 365 patients from 7 eligible studies qualified for efalizumab retreatment with 1 mg/kg/wk (n = 202) or 2 mg/kg/wk (n = 163). Not all patients received sufficient exposure to efalizumab during their previous efalizumab clinical trial to allow for determination of their response to efalizumab. Of the 282 patients who received 12 weeks of prior efalizumab therapy, 110 (39.0%) achieved a PASI-75 response and 208 (73.8%) achieved PASI-50. The baseline characteristics are described in Table

Discussion

As demonstrated by the PASI responses, the majority of patients experienced clinical benefit with efalizumab retreatment. Although there was no placebo control for comparison, the proportions of patients achieving PASI-75 and PASI-50 in this open-label study were comparable with those of other phase III, randomized, placebo-controlled studies (Fig 1). Moreover, the percentage mean improvement from baseline was very similar for patients who received efalizumab retreatment and those who received

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C.L. Leonardi et al.
Extended efalizumab therapy improves chronic plaque psoriasis: results from a randomized phase III trial
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T-cell modulation for the treatment of chronic plaque psoriasis with efalizumab (Raptiva): mechanisms of action
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Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial
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A novel targeted T-cell modulator, efalizumab, for plaque psoriasis
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Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis
Arch Dermatol
(2005)

There are more references available in the full text version of this article.

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Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory Disorders
2018, Clinical Gastroenterology and Hepatology
Citation Excerpt :
Although other biologic combinations with etanercept have been described, these have not been targeted agents used in the treatment of IBD and the rates of AEs have been variable. Efalizumab is an antiadhesion molecule that binds to and decreases expression of CD11a on leukocytes, thereby preventing interaction with intercellular adhesion molecule-1 and leukocyte trafficking into tissue.14 Initially approved to treat psoriasis, it was removed from the market in 2009 because of an association with progressive multifocal leukoencephalopathy.
Current therapies used in the treatment of inflammatory bowel disease (IBD) are not effective in all patients. Biologic agents result in approximately 40% remission rates at 1 year in selected populations, prompting a growing interest in combining biologic therapy to improve outcomes. There are limited published data regarding the efficacy and safety of combination targeted therapy in IBD specifically, which include only 1 exploratory randomized control trial and 3 case reports or series. This review evaluates the published literature regarding this therapeutic paradigm in IBD and its extensive utilization in the treatment of other immune-mediated inflammatory disorders. The combination of biologic therapies demonstrates variable degrees of efficacy and highlights some safety concerns, depending upon the agents used and the disease state treated. A trial (Clinical Trials.gov Identifier: NCT02764762) combining vedolizumab and adalimumab is currently underway evaluating the effectiveness and safety of this approach in patients with Crohn’s disease, which should provide further insight into this treatment concept. While combination biologic therapy is an attractive strategy, the lack of consistent superior efficacy as well as safety concerns militates the need for further trials prior to its general application in IBD.
Clinical characteristics and disease course in patients treated with efalizumab following suspension of marketing authorization by the European Medicines Agency: A multicenter observational study
2011, Actas Dermo-Sifiliograficas
La reciente resolución de la EMEA con respecto a la suspensión de efalizumab, ocurrida en febrero del año 2009, ha proporcionado una oportunidad única para comprobar la evolución de un grupo de pacientes en cuya selección no intervinieron los filtros ni los sesgos habituales de los estudios pivotales. El objetivo planteado fue evaluar el curso de la psoriasis tras la suspensión forzosa de efalizumab en un grupo de pacientes tratados en el ámbito clínico. Como objetivos secundarios se planteó investigar su perfil clínico, la respuesta y evolución durante el tratamiento y el curso evolutivo a las 12 y 24 semanas tras la suspensión.
Se recogió información procedente de un grupo de pacientes tratados con efalizumab referida al perfil epidemiológico, al curso de la dermatosis durante el tratamiento y a su evolución al suspenderlo. Se llevaron a cabo estudios estadísticos con vistas a identificar variables predictivas de los distintos objetivos investigados.
Se incluyeron 147 pacientes procedentes de 12 centros hospitalarios nacionales. Durante el tratamiento un 4% de los pacientes fue diagnosticado de exacerbación inflamatoria generalizada. La mayor parte de los pacientes pudieron ser clasificados como buenos respondedores (55%) o respondedores moderados (18%). Un 30% de los pacientes presentaron rebote tras la suspensión de efalizumab. La probabilidad de rebote fue independiente del perfil clínico, la respuesta al tratamiento o la actitud terapéutica del dermatólogo al suspenderlo.
Se comprobó una elevada ocurrencia de fenómeno de rebote tras la suspensión de efalizumab, superior a la descrita en los ensayos clínicos pivotales y especialmente significativa si se tiene en cuenta la elevada incidencia de buenos respondedores durante el tratamiento, considerados de mejor pronóstico. Otros datos significativos son la superior perspectiva de respuesta clínica —presumiblemente condicionada por el tiempo medio de tratamiento—, y la elevada incidencia de episodios de exacerbación inflamatoria generalizada.
The withdrawal of marketing authorization for efalizumab by the European Medicines Agency in February, 2009 provided a unique opportunity to assess the course of disease in patients who were not subject to the selection criteria and biases that were common in the pivotal trials. The aim of this study was to evaluate the course of psoriasis following forced suspension of efalizumab in a group of patients treated in normal clinical practice. As secondary objectives, we sought to assess the relationships between clinical characteristics, treatment response, and disease course during efalizumab treatment and 12 and 24 weeks after suspension.
Information on the epidemiological profile and disease course during treatment and following suspension of the drug was collected from a group of patients treated with efalizumab. Statistical analyses were performed to identify predictive factors.
One hundred forty-seven patients from 12 Spanish hospitals were included in the study. During treatment, 4% of patients were diagnosed with generalized inflammatory flares. Most patients could be classified as having a good (55%) or moderate (18%) response to treatment. Rebound following withdrawal of efalizumab was observed in 30% of patients. The likelihood of rebound was independent of clinical characteristics, treatment response, or therapeutic approach used by the dermatologist following suspension.
There was a high frequency of rebound following suspension of efalizumab, exceeding the rate reported in pivotal trials. This is particularly noteworthy given the large proportion of patients with a good response to treatment and therefore believed to have a better prognosis. Other significant findings were the higher frequency of positive treatment response than observed in previous studies (possibly influenced by the mean treatment duration) and the high frequency of generalized inflammatory flares.
Effectiveness of chondroitin sulphate in patients with concomitant knee osteoarthritis and psoriasis: A randomized, double-blind, placebo-controlled study
2010, Osteoarthritis and Cartilage
Citation Excerpt :
Results of this clinical trial are encouraging and warrant further studies in patients with psoriasis to assess the effects of CS treatment for a longer period of time. Current therapies for psoriasis are limited, therefore there is a need for effective and safe treatment options42. The need for alternative therapies is reinforced by the demographic change in age distribution that will lead to more elderly people with psoriasis with an increasing number of coexisting conditions43, and so it may be expected that a large percentage of patients with psoriasis will suffer from OA in adulthood.
The aim of the trial was to assess the efficacy of chondroitin sulphate (CS) on symptomatic knee osteoarthritis (OA) associated to psoriasis.
In this randomized, double-blind, placebo (PBO)-controlled clinical trial 129 patients with symptomatic knee OA and concomitant psoriasis were randomized into two groups receiving 800 mg daily of CS or PBO for 3 months. The primary efficacy outcome for knee OA was the Huskisson’s visual analogue scale (VAS) and for psoriasis was the Psoriasis Area and Severity Index (PASI). Additionally, other secondary efficacy criteria for both conditions were assessed.
After 3 months of treatment, CS was more effective than PBO, relieving pain VAS (CS −26.9 ± 24.8 vs PBO −14.23 ± 20.8 mm, P < 0.01), decreasing the Lequesne index (CS −4.8 ± 3.4 vs PBO −3.3 ± 3.5, P < 0.05) and reducing the number of patients using acetaminophen as rescue medication (CS 43% vs PBO 64%, P < 0.05). Regarding PASI, Overall Lesion Severity Scale and Physician’s Global Assessment of Change no statistically significant changes were detected in front of PBO. However, CS improved plantar psoriasis compared to PBO (CS 87% vs PBO 27%, P < 0.05). Quality of life improved significantly in CS-treated patients according to the Short Form-36 health survey and the Dermatology Life Quality Index (DLQI). CS tolerability was excellent. Adverse events were infrequent and evenly distributed among groups. The incidence of psoriatic flares did not increase after treatments.
This study confirms the efficacy and safety of CS as a symptomatic slow-acting drug in patients with knee OA and shows that CS improves plantar psoriasis. The use of CS could represent a special benefit in patients with both pathologies since non-steroidal anti-inflammatory drugs have been reported to induce or exacerbate psoriasis.
FDA Clinical Trials Government Identifier: NCT00669123.
A new era in the management of psoriasis? The biologics: facts and controversies
2010, Clinics in Dermatology
Citation Excerpt :
The duration of remission achieved with biologics can be considered quite similar to those of traditional systemic drugs, being alefacept among the biologics and PUVA among the traditional therapies the only ones that can be considered as remitive (vs suppressive) therapies. Concerns about the intermittent use of biologic therapy include the rebound phenomenon reported with some of them after the treatment is discontinued (particularly with efalizumab in up to 14% of patients27) and a decreased degree of response compared with the first treatment (particularly with infliximab24), even though most patients responded well to reintroduction of the biologic agents.28,29 Therefore, due to these concerns and the short duration of remission, biologic agents seem to work better in a continuous than in an as-needed setting.30
During the last 30 years, the tremendous progress in our knowledge of the pathogenesis of psoriasis has led to the development of new agents, the so-called biologics, that have revolutionized the management of severe psoriasis. Dermatologists and patients see this emerging therapy as a new perspective in the state of the art in managing moderate to severe psoriasis. After a few years of use in daily practice, we may begin to analyze the power of the currently available biologic agents in the management of severe psoriasis from the perspective of facts.
Spanish evidence-based guidelines on the treatment of moderate-to-severe psoriasis with biologic agents
2009, Actas Dermo-Sifiliograficas
Psoriasis vulgaris is an inflammatory skin disease that is generally chronic and that affects between 1% and 2% of the population in industrialized Western countries. It is associated with a marked decline in quality of life. A wide range of treatments are currently available, although surveys conducted before the advent of biologic agents reflected a strong degree of dissatisfaction with the treatments then available. Extensive scientific evidence has been gathered on the safety of biologic agents, and this has led to a review of the role of systemic treatment in general and has allowed new therapeutic goals and strategies to be contemplated in patients with moderate to severe psoriasis. In this new situation, there is a need for Spanish guidelines on the treatment of moderate to severe psoriasis with biologic agents, drafted by consensus among specialists and ratified by the Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology (AEDV). These guidelines should be evidence-based with regard to the pharmacologic characteristics, mechanism of action, administration route and regimen, efficacy, contraindications, adverse effects, and cost estimates of biologic agents approved for the treatment of moderate to severe psoriasis in Spain.
La psoriasis vulgar es una enfermedad cutánea inflamatoria, de curso habitualmente crónico, que afecta a un 1-2% de la población en los países occidentales industrializados, y produce una reducción marcada de la calidad de vida de los pacientes. Pese a la diversidad de tratamientos disponibles, las encuestas efectuadas antes del advenimiento de los agentes biológicos demuestran un alto grado de insatisfacción con respecto a los tratamientos disponibles. Se ha acumulado abundante evidencia científica con respecto a la eficacia y seguridad de los agentes biológicos, que ha llevado a revisar el papel del tratamiento sistémico en general y ha permitido contemplar nuevos objetivos y estrategias terapéuticas en los pacientes con psoriasis moderada a grave. En este contexto nuevo se hace necesario establecer, de forma consensuada por especialistas expertos y ratificada por los integrantes del Grupo Español de Psoriasis de la Academia Española de Dermatología y Venereología (AEDV), unas directrices para el tratamiento de la psoriasis moderada a grave con agentes biológicos, que incluyan información basada en la evidencia científica disponible acerca de las características farmacológicas, mecanismo de acción, vía y pautas de administración, eficacia, contraindicaciones, efectos adversos y estimaciones del coste de los agentes biológicos aprobados para el tratamiento de la psoriasis moderada a grave en España
Biologic therapies in the treatment of psoriasis
2009, Presse Medicale
Le psoriasis altère significativement les différents domaines de la qualité de vie.
Les traitements systémiques classiques ont une efficacité inconstante et une toxicité dose-dépendante limitant leur utilisation prolongée.
Depuis 2004, quatre biothérapies – l’infliximab, l’étanercept, l’éfalizumab et l’adalimumab – ont obtenu l’autorisation de mise sur le marché dans le psoriasis modéré à sévère avec échec, intolérance ou contre-indication d’au moins deux traitements systémiques classiques parmi la photothérapie, le méthotrexate, la ciclosporine.
Le taux de patients atteignant le PASI75 à 3 mois est estimé à : environ 80 % sous infliximab (protocole d’induction classique S0, S2, S6) ; environ 33 % et 50 % sous étanercept, respectivement, 25 et 50 mg, 2x/semaine ; environ 25 % sous éfalizumab (1 injection hebdomadaire de 1 mg/kg) ; environ 70 % sous adalimumab 40 mg, respectivement, hebdomadaire et toutes les 2 semaines.
L’efficacité des biothérapies à moyen terme (au-delà de 12 mois) est mal documentée dans le psoriasis.
La tolérance des biothérapies à long terme (au-delà de 5 ans) n’est pas documentée.
De nouvelles biothérapies sont en cours d’évaluation dans le psoriasis en plaques : ustekinumab (CNTO-1275), ABT-874, certolizumab (CDP-870), golimumab (CNTO-148). L’ustékinumab a obtenu l’AMM européenne pour le psoriasis (même libéllé que pour les autres biothérapies) en janvier 2009 et devrait obtenir l’AMM en France courant 2009.
Psoriasis impairs significantly the quality of life.
Systemic treatments have inconstant efficiency and dose-dependant toxicity.
Since 2004, four biologic therapies – infliximab, etanercept, éfalizumab and adalimumab – are approved in Europe for the treatment of moderate to severe psoriasis, with failure, intolerance or contra-indication to at least 2 “classical” systemic treatments, including phototherapy, methotrexate and ciclosporin.
The estimated rate of patients reaching PASI75 at month 3 are as follow: about 80% under infliximab (classical W0-W2-W6 regimen); about 33% and 50% under etanercept, respectively, 25 and 50 mg, twice weekly; about 25% under éfalizumab (1 mg/kg, weekly); about 70% under adalimumab (40 mg, every other week).
The 12-month efficiency of biologic therapies in psoriasis is poorly documented.
The long term (5-year or more) safety of biologic therapies is not documented.
New biologic therapies are under investigation in the treatment of psoriasis: ustekinumab (CNTO-1275), ABT-874, certolizumab (CDP-870), golimumab (CNTO-148). Ustekinumab is approved in Europe since January 2009.

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Supported by Genentech Inc and Serono International SA.

Disclosures: Dr Miller has no conflict of interest to disclose. Dr Caro, Dr Kwon, and Mr Compton are stock shareholders and employees of Genentech Inc. Dr Gordon has received research support and honoraria from Genentech Inc. Dr Leonardi has received educational grant support from and served on the speakers bureau and advisory board for Genentech Inc. Dr Papp is a consultant, an investigator, and an advisory board member for Genentech Inc, Serono International SA, and Xoma, LLC; he is on the Serono International SA speakers bureau. Helix Medical Communications LLC was contracted by Genentech Inc and Serono International SA to provide editorial support for manuscript development.

Presented in part as posters at the 12th Congress of the European Academy of Dermatology and Venereology; Florence, Italy; November 17-21, 2004; and the Meeting of the American Association of Dermatology; San Francisco, Calif; March 21-26, 2003.

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ReportEfalizumab retreatment in patients with moderate to severe chronic plaque psoriasis

Background

Objective

Methods

Results

Limitations

Conclusion

Section snippets

Study design

Patient disposition and demographic and psoriasis characteristics

Discussion

J Am Acad Dermatol

Raptiva [efalizumab] [package insert]

T-cell modulation for the treatment of chronic plaque psoriasis with efalizumab (Raptiva): mechanisms of action

Dermatology

Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial

JAMA

A novel targeted T-cell modulator, efalizumab, for plaque psoriasis

N Engl J Med

Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis

Arch Dermatol

Report
Efalizumab retreatment in patients with moderate to severe chronic plaque psoriasis