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Behandlung der Plaque-Psoriasis mit Biologics

Eine Metaanalyse randomisierter kontrollierter Studien

Treatment of Plaque Psoriasis with Biologics. A Meta-Analysis of Randomized Controlled Trials

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Zusammenfassung

Hintergrund und Ziel:

Die Entwicklung verschiedener biologischer Therapien (sog. Biologics) ist ein großer Fortschritt für die Behandlung der Psoriasis vulgaris. Diese Metaanalyse fasst die Evidenz aus randomisierten kontrollierten Studien (RCTs) der in Deutschland zur Behandlung der mittelschweren bis schweren Psoriasis vulgaris zugelassenen Biologics zusammen.

Material und Methodik:

Systematisches Review und Metaanalyse aller RCTs, in denen im Januar 2008 in Deutschland zur Behandlung der mittelschweren bis schweren Psoriasis vulgaris zugelassene Biologics geprüft wurden. Identifikation relevanter Studien durch systematische elektronische Literaturrecherche in MEDLINE, EMBASE, Cochrane Library und Scopus. Primärer Endpunkt: Anteil an Patienten mit mindestens 75%iger Reduktion im Psoriasis Area and Severity Index (PASI) Score (PASI75-Responder), sekundäre Endpunkte: klinisch relevante Besserung der Lebensqualität, monatliche Inzidenz an Studienabbrüchen und unerwünschten Ereignissen. Die Prozentsätze der PASI75-Responder wurden als Risikodifferenz (RD) dargestellt und statistisch zusammengefasst.

Ergebnisse:

25 Artikel zu 16 RCTs mit insgesamt 8 057 Patienten mit mittelschwerer bis schwerer Psoriasis vulgaris wurden qualitativ analysiert. 15 doppelblinde, plazebokontrollierte Studien wurden in die Metaanalyse eingeschlossen. Infliximab war wirksamer als alle anderen biologischen Optionen als Kurztherapie für die mittelschwere bis schwere Psoriasis vulgaris (RD [95%-Konfidenzintervall, CI] 76% [72–80%]). Adalimumab (RD [95%-CI] 59% [45–73%]) war wirksamer als Efalizumab (RD [95%-CI] 24% [19–30%]) und Etanercept. Bei Etanercept bestand ein deutlicher Dosis-Wirkungs-Effekt (2 × 50 mg wöchentlich: RD [95%-CI] 44% [40–48%]; 2 × 25 mg wöchentlich: RD [95%-CI] 30% [25–35%]). Die Behandlung mit allen untersuchten Biologics verbesserte die Lebensqualität der Psoriasispatienten. Die monatliche Rate an Studienabbrüchen aufgrund unerwünschter Ereignisse betrug bei Infliximab 1,2%, bei Etanercept 0,5%, bei Efalizumab 1,0% und bei Adalimumab 0,5%.

Schlussfolgerung:

Der klinische Nutzen der einzelnen derzeit zur Behandlung der mittelschweren bis schweren Psoriasis vulgaris zugelassenen Biologics unterscheidet sich beträchtlich. Infliximab ist die wirksamste Therapieoption, gefolgt von Adalimumab. Große kontrollierte Studien deuten auf eine hohe Sicherheit aller Präparate in der Kurzzeittherapie hin. Kürzlich etablierte Register werden weitere wichtige Daten zur Sicherheit unter Alltagsbedingungen liefern.

Abstract

Background and Purpose:

The development of different biological therapies (so-called biologics) is a great progress for the treatment of the psoriasis vulgaris. The evidence from randomized controlled trials (RCTs) of biologics, which have been licensed in Germany for the treatment of moderate-to-severe psoriasis vulgaris, were pooled in this meta-analysis.

Material and Methods:

Systematic review and meta-analysis of all RCTs, in which biologics licensed in Germany as of January 2008 for the treatment of moderate-to-severe psoriasis vulgaris were examined. Relevant trials were identified by systematic electronic literature search in MEDLINE, EMBASE, Cochrane Library, and Scopus. Primary endpoint: proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI) Score (PASI75 responder), secondary endpoints: clinically relevant improvement in the quality of life, monthly incidences of study withdrawals and adverse events. PASI75 response rates were statistically pooled and represented as risk differences (RD).

Results:

25 articles on 16 RCTs totaling 8,057 patients with moderate-to-severe psoriasis vulgaris were qualitatively analyzed. 15 double-blind and placebo- controlled trials were compared by meta-analysis. Infliximab had the highest efficacy in the short-term therapy of moderate-to-severe psoriasis vulgaris (RD [95% confidence interval, CI] 76% [72–80%]). Adalimumab (RD [95% CI] 59% [45–73%]) was more effective than efalizumab (RD [95% CI] 24% (19–30%]) and etanercept. Treatment with etanercept showed a clear dose-response effect (50 mg twice weekly: RD [95% CI] 44% (40–48%]; 25 mg twice weekly: RD [95% CI] 30% (25–35%]). All biologics improved the quality of life of psoriasis patients. Monthly incidence rates of withdrawals due to adverse events were 1.2% for infliximab, 0.5% for etanercept, 1.0% for efalizumab, and 0.5% for adalimumab.

Conclusion:

A patient’s chance to reach considerable clinical benefit differs significantly between the different biological therapies currently approved for moderate-to-severe psoriasis vulgaris. Infliximab is most effective, followed by adalimumab. Large controlled studies indicate a high safety of all biologics in the short-term treatment. Recently established registers will provide additional important safety data under real-life conditions.

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Authors and Affiliations

  1. Institut für Klinische Pharmakologie, Medizinische Fakultät „Carl Gustav Carus“, Technische Universität Dresden, Dresden, Germany

    Zhengguang Zhang MPH & Wilhelm Kirch

  2. Klinik und Poliklinik für Dermatologie, Medizinische Fakultät „Carl Gustav Carus“, Technische Universität Dresden, Dresden, Germany

    Jochen Schmitt & Gottfried Wozel

  3. Institut für Klinische Pharmakologie, Medizinische Fakultät „Carl Gustav Carus“, Technische Universität Dresden, Fetscherstraße 27, 01307, Dresden, Germany

    Zhengguang Zhang MPH

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  1. Zhengguang Zhang MPH
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  3. Gottfried Wozel
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  4. Wilhelm Kirch
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Correspondence to Zhengguang Zhang MPH.

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Zhang, Z., Schmitt, J., Wozel, G. et al. Behandlung der Plaque-Psoriasis mit Biologics. Med Klin 104, 125–136 (2009). https://doi.org/10.1007/s00063-009-1024-8

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  • DOI: https://doi.org/10.1007/s00063-009-1024-8

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