A study in Israel stratified PPMS patients according to the speed of progression (Legarda et al. ECTRIMS 2016; abstract P276). Overall, 53% were “fast progressing,” defined as EDSS >3 within 2 years of onset; 26% were “slow progressing,” defined as EDSS >3 at >5 years. Among fast progressing subjects, 16% were persistently fast, defined as EDSS >6 within 5 years.
An analysis at the Rocky Mountain MS clinic, Colorado, reported that PPMS patients had lower brain-parenchymal fraction (BPF) and thalamic volume compared to RRMS patients, although the number of progressive patients was small (Honce et al. ECTRIMS 2016; abstract P1003).
A number of studies have suggested that frequent early relapses are prognostic of earlier disability. A 7-year follow-up study found that relapse frequency in the first two years after diagnosis was associated with an increasing risk of SPMS (Scalfari et al. ECTRIMS 2016; abstract P464). Overall, 13.8% of patients with 1 relapse, 30.2% with 2 relapses, and 54.0% with ≥ 3 relapses developed SPMS. The inter-attack interval was also prognostic. More frequent relapses were associated with a higher accrued volume of cortical lesions and more severe cortical atrophy.
The clinical usefulness of NEDA assessments is controversial. But a new study suggests that NEDA at 1 year is predictive of time to SPMS (Kappos et al. ECTRIMS 2016; abstract P1217). The analysis was based on data from the FREEDOMS/FREEDOMS II extensions of fingolimod at month 96. A further observation: patients who did not develop SPMS had higher brain volumes at baseline.
Natalizumab: In the ASCEND trial, natalizumab failed to meet its primary endpoint of delayed disability progression on a composite measure comprising EDSS, T25FW and 9HPT (Steiner et al. AAN 2016; abstract P009). A post-hoc analysis found that a higher proportion of patients on natalizumab improved on at least one disability measure compared to placebo (33% vs. 23%) (Giovannoni et al. ECTRIMS 2016; abstract P1270). A second post-hoc analysis reported a slowing in upper-limb disability as measured by the 9HPT, but only in the subgroups with more advanced disability (baseline EDSS >6), and without inflammatory activity (no relapses in the prior 12 or 24 months) (Kapoor et al. ECTRIMS 2016; abstract P1656).
Fingolimod: In the INFORMS trial, fingolimod was associated with a small reduction in the proportion of patients with 3-month confirmed disability progression (77.2% vs. 80.3%); differences were not significant (hazard ratio 0.95) (Lublin et al. Lancet 2016;387:1075-84). A post-hoc analysis of patient subgroups found a greater treatment effect in patients with inflammatory activity at baseline (risk reduction 7.1% for Gd+, 2.65% for Gd- for the composite endpoint of EDSS/T25FW/9HPT), but results were not significant (Lublin et al. ECTRIMS 2016; abstract P1283). There was a weak trend in risk reduction with fingolimod for EDSS (19.5%) in the subgroup with relapses at baseline. Results of the SPMS trial of siponimod (BAF312), a second-generation sphingosine-1-receptor modulator, will be presented in an upcoming issue of NeuroSens.
Ocrelizumab: In an analysis of the ORATORIO trial of PPMS, treatment was associated with a 25% reduction in 6-month confirmed disability progression (Giovannoni et al. ECTRIMS 2016; abstract P746). There was a 27% reduction in the risk of 6-month confirmed worsening (>20%) in Timed 25-foot walk (T25FW), and risk of worsening (>20%) on the 9-Hole Peg Test (9HPT), indicating a lower risk of deterioration in ambulation and upper limb function.