Subcutaneously Administered Efalizumab (Anti-CD11a) Improves Signs and Symptoms of Moderate to Severe Plaque Psoriasis

  • Alice B. Gottlieb
  • Bruce Miller
  • Nicholas Lowe
  • William Shapiro
  • Charles Hudson
  • Ross Bright
  • Mark Ling
  • Anna Magee
  • Calvin O. McCall
  • Toivo Rist
  • Wolfgang Dummer
  • Patricia Walicke
  • Robert J. Bauer
  • Mark White
  • Marvin Garovoy
Basic/Clinical Science

Abstract

Background: Phase I and Phase II studies in patients with moderate to severe plaque psoriasis demonstrated that intravenous (IV) efalizumab improved clinical signs and symptoms and was well tolerated. Objective: To determine if subcutaneous (SC) delivery of efalizumab improves chronic plaque psoriasis and demonstrates an acceptable safety profile. Methods: This was a Phase I, open-label, single- and multiple-dose, escalating-dose study. Subjects received a single dose of efalizumab (0.3 mg/kg/wk SC) or escalating multiple doses of efalizumab (0.50–2.0 mg/kg/wk SC). Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI), target lesion assessment, and Physician’s Global Assessment (PGA). Safety was assessed by evaluating adverse events, clinical laboratory test results, physical examination results, immunologic responses, and vital signs. Results: PASI score, target lesion assessment, and PGA showed improvement of approximately 40%–60% in signs and symptoms of plaque psoriasis by day 56. Mean PASI scores were still declining at the end of the eight-week dosing period, suggesting that longer duration of treatment would be more effective. By day 91, mean PASI scores were 16.2 vs. 14.6 at day 56 in the 0.5–1.0-mg/kg/wk group and 11.7 vs. 10.1 in the 1.0–2.0-mg/kg/wk group. This demonstrates that, on average, patients maintained their treatment benefit during the 42-day followup period. Overall, there were considerably fewer adverse events than in previous IV studies. These consisted principally of mild to moderate headache, pain, and rhinitis. No allergic reactions were observed. Antibodies to efalizumab were observed in only one subject (2%) and did not have any clinical relevance. Conclusion: The SC administration of eight weekly doses of efalizumab improves signs and symptoms of psoriasis. The treatment was safe and very well tolerated. In comparison to previously published results with IV efalizumab, SC administration of efalizumab improves overall safety and tolerability, with the additional advantage of greater convenience.

Antécédents: Les études de phase I et de phase II sur des patients souffrant de formes modérées à graves de psoriasis en plaques ont démontré que l’administration intraveineuse d’Efalizumab a amélioré les signes cliniques et les symptômes tout en étant bien totérée. Objectif: Déterminer si l’administration sous-cutanée (SC) d’Efalizumab améliore le psoriasis en plaques chronique et présente un profil d’innocuité acceptable. Méthodes: Il s’agit de la phase I d’un essai ouvert, à doses uniques et multiples croissantes. Les sujets ont reçu soit une dose unique d’Efalizumab (0,3 mg/kg/semaine SC) soit des doses multiples croissantes d’Efalizumab (de 0,5 à 2,0 mg/kg/semaine SC). L’efficacité du traitement a été évaluée au moyen de l’index de surface et de sévérité du psoriasis (PASI), de l’évaluation des lésions en forme de cocarde et de l’évaluation générale du médecin. L’innocuité a été jugée selon les événements indésirables, les résultats des tests du laboratoire clinique, les résultats de l’examen physique, les réponses immunologiques et les signes vitaux. Résultats: Le score PASI, l’évaluation des lésions et l’évaluation générale du médecin ont montré une amélioration des signes et symptômes du psoriasis en plaques par environ 40% à 60% à la 56e journée. À la fin de la période de huit semaines de dosage, les scores PASI moyens continuaient de décliner, suggérant qu’un traitement de longue durée serait plus efficace. À la 91e journée, les scores PASI moyens étaient de 16,2 contre 14,6 à la 56e journée chez le groupe recevant les doses 0,5 à 1,0-mg/kg/semaine et de 11,7 contre 10,1 chez le groupe recevant les doses 1,0 à 2,0-mg/kg/semaine. Ces résultats démontrent que les effets du traitement se sont maintenus durant la période de suivi de 42 jours. En général, il y a eu considérablement moins d’événements indésirables que dans des études précédentes sur l’administration intraveineuse. Les événements indésirables étaient principalement des maux de tête modérés, des douleurs et de la rhinite. Aucune réaction allergique n’a été décelée. Des anticorps d’Efalizumab se sont formés chez un seul sujet (2%) et n’avaient aucun intérêt clinique. Conclusion: L’administration sous-cutanée pendant huit semaines de doses hebdomadaires d’Efalizumab améliore les signes et symptômes du psoriasis. Le traitement était très bien toléré et son innocuité établie. Comparativement à d’autres résultats publiés impliquant l’administration intraveineuse d’Efalizumab, l’administration sous-cutanée est plus sécuritaire et mieux tolérée, en plus d’être plus facile à livrer.

Notes

Acknowledgements

The authors of this study gratefully acknowledge the efforts of the HUPS254 Study Group coordinators: Judy Campbell, Paulette Chadwell, Kim Hall, Brian Hamblen, Karen Mangieri, Nancy McClintock, Karen Mudurian, Joyce Powell, Dalia Rizk, Amelia Sherr, Caryn Shulman, Galina Solodkina, and Jean L. Thomas.

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Copyright information

© Canadian Dermatology Association 2003

Authors and Affiliations

  • Alice B. Gottlieb
    • 1
  • Bruce Miller
    • 2
  • Nicholas Lowe
    • 3
  • William Shapiro
    • 4
  • Charles Hudson
    • 5
  • Ross Bright
    • 6
  • Mark Ling
    • 7
  • Anna Magee
    • 8
  • Calvin O. McCall
    • 9
  • Toivo Rist
    • 10
  • Wolfgang Dummer
    • 11
  • Patricia Walicke
    • 11
  • Robert J. Bauer
    • 12
  • Mark White
    • 12
  • Marvin Garovoy
    • 12
  1. 1.Clinical Research CenterUniversity of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick, New JerseyUSA
  2. 2.Oregon Medical Research Center, Portland, OregonUSA
  3. 3.Clinical Research Specialists, Santa Monica, CaliforniaUSA
  4. 4.nTouch Research Corporation, San Diego, CaliforniaUSA
  5. 5.Hill Top Research, Inc., Evansville, IllinoisUSA
  6. 6.Psoriasis Research Institute, Palo Alto, CaliforniaUSA
  7. 7.Medaphase Inc., Newnan, GeorgiaUSA
  8. 8.Charlottesville Medical Research Center, Charlottesville, VirginiaUSA
  9. 9.Emory University School of Medicine, Atlanta, GeorgiaUSA
  10. 10.Clinical Research Center of Dermatology Associates of Knoxville, Knoxville, TennesseeUSA
  11. 11.Genentech Inc., South San Francisco, CaliforniaUSA
  12. 12.XOMA (US) LLC, Berkeley, CaliforniaUSA

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