A phase 2 randomized controlled trial of the Janus Kinase (JAK) inhibitor filgotinib in patients with noninfectious uveitis

Abstract

Purpose : Noninfectious uveitis (NIU) is a major cause of visual impairment with limited treatment options. We performed a randomized, placebo-controlled, double-masked trial of filgotinib, a JAK1 preferential inhibitor, to assess its efficacy and safety in NIU.

Methods : Adults with intermediate-, posterior- or pan-uveitis that was active despite at least 2 weeks of treatment with 10-60 mg prednisone were eligible for this trial. Patients were randomized 1:1 to receive either filgotinib, 200 mg daily, or placebo for up to 52 weeks. On study day 1, all patients began a protocolized prednisone taper beginning at 60 mg to 0 mg by the beginning of Week 15. The primary endpoint was the proportion of patients failing treatment by week 24. Treatment failure was defined as a new chorioretinal and/or retinal vascular lesion, worsening of best corrected visual acuity by ≥15 letters, or an inability to achieve an anterior chamber cell or vitreous haze grade 0.5+ at week 6 or a 2-step increase after week 6. Patients who took study drug and completed at least week 6 of the study were considered evaluable. While in progress, the trial was terminated before full enrollment (planned N = 248) for business reasons. As a result, all hypothesis testing was done without multiplicity adjustment.

Results : Seventy-four (74) patients were randomized. The majority (57%) had idiopathic uveitis. Patients with missing data were imputed as treatment failures. Of the 66 evaluable patients, the proportion failing treatment was 12 of 32 (38%) in the filgotinib arm and 23 of 34 (68%) in the placebo arm (p = 0.006). The median time to treatment failure was 22 weeks in the placebo arm and was not estimable in the filgotinib arm as more than half the patients in the filgotinib arm did not have treatment failure (hazard ratio 0.309; 95% CI [0.144 to 0.663]) [Figure]. Adverse events were reported more frequently in patients who received filgotinib than placebo (81% v. 69% adverse events and 14% v. 6% serious adverse events). There were no arterial or venous thromboembolic events, no major adverse cardiovascular events, no opportunistic infections and no cases of tuberculosis or herpes zoster reported.

Conclusions : In patients with vision threatening NIU, filgotinib 200 mg reduced the risk of uveitis flare compared to placebo and was generally well tolerated.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.