Things are happening. After many years of no real therapeutic options for chronic progressive Multiple Sclerosis and many therapy studies have been negative, two substances have now actually shown significant effects on disability progression in large approval studies. Although the effects are only moderate, the mere fact that efficacy in this disease phase could be demonstrated on the delay of disease progression is very good news.For Ocrelizumab, a B-cell depleting antibody, the effect on primary chronic progressive MS (PPMS) was already reported at last year’s ECTRIMS in Barcelona. The ORAORIO study showed that treatment with Ocrelizumab can reduce the relative risk of disability progression (measured by the EDSS) by 24% (see also DocBlog New from ECTRIMS 2015).
The data from the study has since been further evaluated – the analysis was presented at this year’s ECTRIMS. For the evaluation of the study a new “compound parameter” was introduced, i.e. a measuring size which is composed of different individual measured values. In analogy to the NEDA concept in relapsing MS (no evidence of disease progression = no evidence of disease activity), the NEP parameter (no evidence of progression = no evidence of progression) was evaluated. It consists of the disability progression on the EDSS scale, changes in the nine-hole-peg test (tests finger dexterity) and changes in the 7.6 meter walking distance (evaluation of mobility). The parameters were first combined in pairs (EDSS and changes in the 7.6 meter walking distance, EDSS and changes in the nine-hole-peg test and combination of nine-hole-peg test and 7.6 meter walking distance). For each pair a significant risk reduction in relation to progression of the parameter could be determined in the treatment group, with the effects being particularly pronounced in the area of mobility. Even with the combination of all three, a highly significant prevention of progression was found with therapy with Ocrelizumab – compared to placebo, a relative risk reduction of 47% was found compared to the placebo group. This is ultimately an impressive result – perhaps even more pronounced and relevant in practice than expected from the consideration of the primary study endpoint (confirmed EDSS progression). In light of these results, treatment with Ocrelizumab will certainly play a role in the future treatment of primarily chronic progressive patients. However, the new evaluations suggest that patients who are treated relatively early in the course (i.e. still with preserved walking ability) will benefit the most.
Another good news is the positive result of the EXPAND study. The study investigated the effect of Siponimod on secondary-chronic progressive MS (SPMS). Siponimod is a further development of Fingolimod, is considered more selective and therefore has a different side effect profile. Siponimod has so far only been tested in progressive patients – a relatively bold decision by the manufacturing company. But the courage was rewarded, because the study significantly reduced the disability progression in the treatment group by 21% compared to the placebo group. Interestingly, the primary endpoint was achieved in all predefined subgroups, i.e. regardless of the presence of relapses, MRI activity, age of the patients, initial EDSS or duration of the disease. This result suggests that a mechanism beyond inflammation inhibition actually plays a role. No new safety aspects have emerged. Therefore, given the lack of other immunotherapeutic options, approval for the treatment of SPMS can be expected.
