Filgotinib in Active Noninfectious Uveitis

JAMA Ophthalmology, vol. 142, pp. 789

Abstract

Importance: Noninfectious uveitis is a leading cause of visual impairment with an unmet need for additional treatment options. Objective: To assess the efficacy and safety of filgotinib, a Janus kinase 1 (JAK1) preferential inhibitor, for the treatment of noninfectious uveitis. Design, Setting, and Participants: The HUMBOLDT trial was a double-masked, placebo-controlled, phase 2, randomized clinical trial conducted from July 2017 to April 2021 at 26 centers in 7 countries. Eligible participants (aged ≥18 years) had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite at least 2 weeks of treatment with oral prednisone (10-60 mg per day). Interventions: Participants were randomly assigned 1:1 to receive filgotinib, 200 mg, or placebo orally once daily for up to 52 weeks. Main Outcomes and Measures: The primary end point was the proportion of participants experiencing treatment failure by week 24. Treatment failure was a composite end point represented by assessment of the presence of chorioretinal and/or retinal vascular lesions, best-corrected visual acuity, and anterior chamber cell and vitreous haze grades. Safety was assessed in participants who received at least 1 dose of study drug or placebo. Results: Between July 26, 2017, and April 22, 2021, 116 participants were screened, and 74 (mean [SD] age, 46 [16] years; 43 female [59.7%] of 72 participants, as 2 participants did not receive treatment doses) were randomly assigned to receive filgotinib (n = 38) or placebo (n = 36). Despite early termination of the trial for business reasons ahead of meeting enrollment targets, a significantly reduced proportion of participants who received filgotinib experienced treatment failure by week 24 vs placebo (12 of 32 participants [37.5%] vs 23 of 34 participants [67.6%]; difference vs placebo -30.1%; 95% CI, -56.2% to -4.1%; P = .006). Business reasons were unrelated to efficacy or safety. Adverse events were reported in 30 of 37 participants (81.1%) who received filgotinib and in 24 of 35 participants (68.6%) who received placebo. Serious adverse events were reported in 5 of 37 participants (13.5%) in the filgotinib group and in 2 of 35 participants (5.7%) in the placebo group. No deaths were reported during the trial. Conclusions and Relevance: Results of this randomized clinical trial show that filgotinib lowered the risk of treatment failure in participants with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis vs placebo. Although the HUMBOLDT trial provided evidence supporting the efficacy of filgotinib in patients with active noninfectious uveitis, the premature termination of the trial prevented collection of additional safety or efficacy information of this JAK1 preferential inhibitor. Trial Registration: ClinicalTrials.gov Identifier: NCT03207815.

Authors 16

1. Sunil K. Srivastava corresponding

   Cleveland Clinic

   Affiliation as printed

   Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio

2. Timothy R. Watkins

   Gilead Sciences (United States)

   Affiliation as printed

   Gilead Sciences, Inc, Foster City, California

3. Quan Dong Nguyen

   Stanford University

   Affiliation as printed

   Byers Eye Institute, Stanford University, Palo Alto, California

4. Sumit Kumar Sharma

   Cleveland Clinic

   Affiliation as printed

   Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio

5. David K. Scales
   Affiliation as printed

   Retina & Uveitis Consultants of Texas PA, San Antonio

6. Mark S. Dacey
   Affiliation as printed

   Colorado Retina Associates, Denver

7. Rajiv E. Shah

   Atrium Health Wake Forest Baptist

   Affiliation as printed

   Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina

8. David Chu
   Affiliation as printed

   Metropolitan Eye Research and Surgery Institute, Palisades Park, New Jersey

9. Dilraj Singh Grewal

   Duke University

   Affiliation as printed

   Department of Ophthalmology, Duke University, Durham, North Carolina

10. Eric B. Suhler

    Oregon Health & Science University · VA Portland Health Care System

    Affiliation as printed

    Oregon Health & Science University and VA Portland Health Care System, Portland

11. Mark C. Genovese

    Gilead Sciences (United States)

    Affiliation as printed

    Gilead Sciences, Inc, Foster City, California

12. Ying Guo

    Gilead Sciences (United States)

    Affiliation as printed

    Gilead Sciences, Inc, Foster City, California

13. William Barchuk

    Gilead Sciences (United States)

    Affiliation as printed

    Gilead Sciences, Inc, Foster City, California

14. Robin Besuyen Aachen Galapagos BV

    Galapagos (Netherlands)

    Affiliation as printed

    Galapagos BV, Leiden, the Netherlands

15. Andrew D. Dick

    University of Bristol · UCL Biomedical Research Centre · University College London

    Affiliation as printed

    Bristol Medical School and School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom

    National Institute of Health Research Moorfields Biomedical Research Centre, UCL Institute of Ophthalmology, University College London, London, United Kingdom

16. James Todd Rosenbaum

    Legacy Health

    Affiliation as printed

    Legacy Devers Eye Institute, Portland, Oregon