Abstract
Purpose :
Pathogenic variants in ALPK1 have been shown to cause a dominantly inherited disease termed ROSAH for the association with retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, headache. Previously, our team reported improvement in intra-ocular inflammation associated with tocilizumab (TCZ) treatment in 2 of 2 patients with ROSAH. The present study aims to evaluate the efficacy of IL6 inhibition in a larger cohort of patients with ROSAH.
Methods :
This study is a retrospective analysis of patients with ROSAH enrolled onto ClinicalTrials.gov ID NCT00001373.
Results :
A total of 28 patients (15 female) with ROSAH were enrolled onto our clinical trial. Fourteen of these individuals had been initiated on an IL6 inhibitor (TCZ (n=13), sarilumab (n=1)). Two individuals who were on TCZ for less than 8-weeks were excluded from this analysis. Among the 12 remaining individuals, 4 were prescribed TCZ for ocular indications and 8 were prescribed IL6 inhibitor for primarily non-ocular indications (e.g., fatigue, arthritis). In the subgroup with ocular inflammation as the primary indication for treatment, all 4 individuals showed improvement in macular edema after tocilizumab initiation and a reduction on vascular leakage was noted in those with fluorescein angiography (FA) available for review. Three of these individuals remain on TCZ and TCZ was discontinued in 1 secondary to a perceived lack of an ongoing inflammatory process. Of the 12 individuals initiated on an IL6-inhibitor for non-ocular indications, 1 had therapy discontinued secondary to severe neutropenia. All 11 individuals who remained on treatment reported improvement in the parameter identified as the primary indication for treatment initiation.
Conclusions :
IL6 inhibition may be an appropriate therapeutic option for select patients with ROSAH including individuals with active intra-ocular inflammation. Further investigations are needed to determine whether IL6 inhibition can influence the progression of retinal degeneration and/or optic nerve edema. However, within this non-randomized context, discerning whether observed changes result from treatment effects or inherent disease variability poses a significant challenge. Therefore, undertaking a comprehensive study to elucidate the natural history of ROSAH is imperative, as it will be instrumental in providing the necessary context for a more meaningful interpretation of treatment outcomes.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.