The following are additional highlights from the Americas Committee for Treatment and Research in MS (ACTRIMS) Forum, held February 25-27, 2021.
NEDA-strengths and limitations: The combined metric of no evidence of disease activity (NEDA) has been shown to be predictive of future disability in some but not all studies. NEDA was defined as no relapses, new/enlarging MRI lesions or 6-month confirmed disability progression. A meta-analysis of 14 real-world studies of NEDA (N=4794) with a minimum follow-up of four years (mean 6.4 years) reported that the positive predictive value (PPV) of NEDA for no EDSS worsening was 87.1% (Solomon et al. ACTRIMS 2021; P035). PPV was similar in patients treated with a platform disease-modifying therapy or a high-efficacy DMT. However, the probability of worsening EDSS with evidence of disease activity was low (34.7%). The authors suggested that additional measures may be needed to guide treatment switches.
Ozanimod post-hoc analysis: An analysis of phase III trials (RADIANCE, SUNBEAM) reported that ozanimod, a selective S1P agonist, was superior to interferon-β-1a IM in all subgroups stratified by baseline EDSS score (Hartung et al. ACTRIMS 2021; P046). ARR was 59% lower in the group with baseline EDSS <2.0, 42% lower for EDSS 2.0-3.5, and 37% lower for EDSS 4.0-5.0. New/enlarging T2 lesion counts at 24 months were significantly lower with ozanimod except in the group with baseline EDSS <2.0. There was no significant treatment difference on 3- or 6-month confirmed disability progression by baseline EDSS score.
Why switch DMTs? A retrospective study at the University of Alberta examined 190 treatment switches/discontinuations over a four-month period in 105 RRMS patients (Chu et al. ACTRIMS 2021; P074). Overall, an inadequate treatment response was the most common reason for switching. For those on an injectable DMT, the most common reasons were treatment failure (37%), patient preference (22%) and side effects (16%). For those on an oral DMT, the most common reasons were treatment failure (33%), side effects (31%) and laboratory abnormalities (18%). Treatment failure was a less common reason for switch in the infusion DMT group (6%); common reasons for switch were laboratory abnormalities (38%), patient preference (37%) and side effects (13%).
Obesity and MS risk: A Mendelian randomization analysis examined the effects of different measures of obesity on MS risk (Misicka et al. ACTRIMS 2021; P095). This type of analysis selects genetic variants from genome-wide association studies to determine if genetic effects are related to outcomes. Genetic variants associated with body-mass index (BMI) were positively associated with MS risk, however, variants for waist-hip ratio were not. The authors suggest that the biological mechanisms related to body mass rather than to waist-hip ratio are more closely linked to the development of MS.
Vascular disease and MS: Vascular disease risk factors (VDRF, i.e. hypertension, hyperlipidemia, obesity, diabetes) are associated with an increased risk of disability worsening in MS (Tettey et al. J Neurol Sci 2014;347:23-23). An MR spectroscopy study examined alterations in brain metabolism that may contribute to disability worsening in MS patients with VDRF (mean age 56 years) and without VDRF (mean age 52 years) (Yadav et al. ACTRIMS 2021; P127). The VDRF group had significantly higher BMI (30.4 vs. 23.5 kg/m2) and waist circumference (103.5 vs. 87.9 cm). Mean EDSS score was 4.0 vs. 3.5, respectively, at baseline. Patients with VDRF had significantly reduced brain ATP vs. patients without VDRF. The authors hypothesized that ATP depletion may reflect mitochondrial dysfunction and cerebral blood flow abnormalities, which may contribute to worsening MS progression.