July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Efficacy of IL-12/23 inhibition for the Treatment of Active Sight-Threatening Uveitis: A Pilot Study
Author Affiliations & Notes
  • Lotta Utriainen
    National Eye Institute, NIH, Bethesda, Maryland, United States
  • Jung Wha Lee
    National Eye Institute, NIH, Bethesda, Maryland, United States
  • Zhiyu Li
    National Eye Institute, NIH, Bethesda, Maryland, United States
  • Benjamin Chaon
    National Eye Institute, NIH, Bethesda, Maryland, United States
  • Ian Thompson
    National Eye Institute, NIH, Bethesda, Maryland, United States
  • Benjamin Chaigne-Delalande
    National Eye Institute, NIH, Bethesda, Maryland, United States
  • H Nida Nida Sen
    National Eye Institute, NIH, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Lotta Utriainen, None; Jung Wha Lee, None; Zhiyu Li, None; Benjamin Chaon, None; Ian Thompson, None; Benjamin Chaigne-Delalande, None; H Nida Sen, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5948. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Lotta Utriainen, Jung Wha Lee, Zhiyu Li, Benjamin Chaon, Ian Thompson, Benjamin Chaigne-Delalande, H Nida Nida Sen; Efficacy of IL-12/23 inhibition for the Treatment of Active Sight-Threatening Uveitis: A Pilot Study. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5948.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects. As both Th1 and Th17 cells are suggested to play a role in uveitis pathogenesis, Ustekinumab, by targeting the p40 subunit shared by both IL-12 and IL-23, offers a novel mechanism of action. We performed prospective, non-randomized, uncontrolled, single-center Phase I/II pilot study to investigate the safety, tolerability and potential efficacy of high-dose, frequent administration of subcutaneous ustekinumab as a treatment for active posterior segment uveitis.

Methods : A total of five patients are planned (four have been recruited) for this study. The eligible participants received three subcutaneous injections of ustekinumab at baseline, 4 weeks and 8 weeks at a dose of 90 mg per injection. The total study length was 28 weeks. Primary outcome was determined as the number of patients experiencing treatment response by week 16, defined as no active chorioretinal lesions and ≤0.5 AC cells or vitreous haze. Peripheral blood mononuclear cells (PBMC) and serum samples were collected, analyzed and stored at baseline, 4, 8, 16 and 28 weeks. To determine if Th1, Th17 and T regulatory (Treg) cell populations are affected by ustekinumab treatment, freshly isolated PBMCs were stimulated, and stained with a 14-color flow cytometry panel comprising of surface and intracellular markers associated with Th1, Th17 and Treg cells.

Results : Three out of four patients met the treatment response criteria by 16 weeks. A slight increase in the percentage of Tregs, defined as CD25+CD127loFoxp3+ cells, was seen in all patients by week 4 compared to baseline measurements. This persisted until week 8, when the percentage of Tregs started to decline. Percentage of Th17 cells, defined as CCR6+ IL-17+, slightly decreased by week 8 compared to baseline in two patients. IFNγ+ CD4+ T cells, most likely to be Th1 cells, showed no apparent changes in response to ustekinumab treatment.

Conclusions : In this small pilot study, repeated high dose subcutaneous injection of ustekinumab was tolerated well with no drug associated serious adverse events. Majority of patients experienced an improvement in their active posterior segment uveitis, which appeared to correlate with the expansion of Tregs. A larger placebo controlled study exploring efficacy and biological signatures associated with response to treatment is needed.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×