Ibudilast reduced retinal atrophy in primary progressive MS

Ibudilast was associated with reduced retinal atrophy compared with placebo in patients with primary progressive MS (PPMS) but not in patients with secondary progressive MS (SPMS). The ganglion cell and ganglion cell-inner plexiform layer (GCIPL) were mostly responsible for the detected differences in retinal layer thickness between participants [1].

Ibudilast is an amino-modulatory, small molecule inhibitor targeting phosphodiesterase and toll-like receptor 4. The phase 2, randomised, placebo-controlled SPRINT-MS trial (NCT01982942) demonstrated retinal conserving qualities of ibudilast in patients with progressive MS [2]. The current post-hoc analysis aimed to compare the thickness of several retinal layers between ibudilast receivers and placebo receivers, measured by optical coherence tomography (OCT). Retinal layers included were GCIPL, the inner nuclear layer (INL), and the outer nuclear layer (ONL). Subgroup analyses were performed to differentiate between PPMS and SPMS patients. Analyses were adjusted for differences in baseline characteristics. Results were compared with MRI brain measures. In total, 248 participants and 2,217 OCT scans were assessed. Dr Henrik Ehrhardt (Johns Hopkins University, MD, USA) presented the findings.

GCIPL atrophy rates were significantly higher in placebo participants (-0.272 μm/year; 95% CI -0.471 to -0.074) than in ibudilast participants (-0.20; 95% CI -0.220–0.181; P<0.003). Subgroup analysis revealed that this declined atrophy rate was present in PPMS patients (ibudilast -0.081; 95% CI -0.372–0.209, placebo -0.598; 95% CI -0.884 to -0.312; P<0.001), but not in SPMS patients (ibudilast -0.196 vs placebo -0.119; P=0.543). Dr Ehrhardt added that future research should aim to unravel the observed differences in atrophy rates between MS subtypes.

Furthermore, baseline GCIPL thickness, age, sex, and disease duration were not associated with atrophy rates in patients with PPMS or SPMS. No significant associations were found between INL or ONL atrophy rates and the treatment arms. Finally, results of OCT scans of retinal layer atrophy and MRI measures (brain parenchymal fraction, grey matter fraction, white matter fraction) correlated significantly in this population. “These findings support the use of OCT measures in similar trials and may provide information on the relation between damage in various parts of the CNS,” Dr Ehrhardt concluded.

1. Ehrhardt H, et al. Ibudilast slows retinal atrophy in progressive multiple sclerosis: post-hoc analyses of the SPRINT-MS Phase II randomized controlled trial. OP151, ECTRIMS 2021 Virtual Congress, 13–15 October.
2. Robert JF, et al. N Engl J Med 2018;379(9):846–855.

 

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Posted on 9 December, 20219 December, 2021