Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: Long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration

Robert B. Nussenblatt, Darby J.S. Thompson, Zhuqing Li, Jan S. Peterson, Randy R. Robinson, Richard S. Shames, Sudha Nagarajan, Meina Tao Tang, Michelle Mailman, Gisela Velez, Chandra Roy, Grace A. Levy-Clarke, Eric B. Suhler, Ali Djalilian, Hatice Nida Sen, Shadi Al-Khatib, Roxana Ursea, Sunil Srivastava, Allison Bamji, Susan MellowPushpa Sran, Thomas A. Waldmann, Ronald R. Buggage

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

Therapy for severe uveitis is frequently long-term immunosuppression using systemic corticosteroids and cytotoxic agents, but side effects make long-term therapy difficult. A long-term (>4 year) Phase I/II single armed interventional study using intravenous anti-IL-2 receptor alpha treatments (daclizumab) and a short-term Phase II study evaluating the use of a subcutaneous daclizumab formulation were conducted. Patients were tapered off their systemic immunosuppressive therapy and received daclizumab infusions or subcutaneous injections at intervals varying from 2 to 6 weeks. In the long-term study, seven of ten enrolled patients were tapered from their original immunosuppressive medications and maintained exclusively on repeated daclizumab infusions for control of their uveitis for over 4 years. No patient was permanently removed from therapy for an adverse event ascribed to the medication. The use of 6-week infusion intervals led to recurrence of uveitis, while 2- to 4-week intervals did not. Only one patient developed measurable anti-daclizumab antibodies but this disappeared when subcutaneous therapy was begun. In the short-term study, four of the five patients receiving the subcutaneous formulation met the study endpoints for success within the first 12 weeks. All five were successful by 26 weeks. These studies provide preliminary evidence that regularly administered long-term daclizumab therapy can be given in lieu of standard immunosuppression for years to treat severe uveitis and that subcutaneously administered daclizumab appeared to be a clinically viable treatment strategy. These studies suggest that anti-IL-2 receptor blockade could be useful in the treatment of Th1-mediated autoimmune conditions.

Original languageEnglish (US)
Pages (from-to)283-293
Number of pages11
JournalJournal of Autoimmunity
Volume21
Issue number3
DOIs
StatePublished - Nov 2003

Keywords

  • Autoimmunity
  • Daclizumab
  • IL-2 receptor
  • Immunosuppression
  • Inflammation
  • Uveitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Nussenblatt, R. B., Thompson, D. J. S., Li, Z., Peterson, J. S., Robinson, R. R., Shames, R. S., Nagarajan, S., Tang, M. T., Mailman, M., Velez, G., Roy, C., Levy-Clarke, G. A., Suhler, E. B., Djalilian, A., Sen, H. N., Al-Khatib, S., Ursea, R., Srivastava, S., Bamji, A., ... Buggage, R. R. (2003). Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: Long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration. Journal of Autoimmunity, 21(3), 283-293. https://doi.org/10.1016/S0896-8411(03)00113-6