New study posts positive results in progressive MS
One of the great failures of MS research has been the inability to find an effective treatment for people with progressively disabling disease. This progression can be either a steady worsening of disability from the outset (called primary-progressive, or PPMS), or after an initial period of relapsing-remitting MS (called secondary-progressive, or SPMS). One reason for this failure is that current MS therapies primarily target inflammatory flare-ups, as shown by relapses and MRI lesions, whereas damage to nerve fibres rather than inflammation is what drives disability during the progressive phase. So it has been unclear how much benefit medications that target inflammation can achieve in slowing down disability.
Up until now, the conventional MS medications have been shown to be largely ineffective in progressive MS. Failed trials have included OLYMPUS (PPMS, rituximab), PROMISE (PPMS, Copaxone), INFORMS (PPMS, Gilenya), ASCEND (SPMS, Tysabri), and a phase II study of bone-marrow transplantation. Some studies suggested that treatment had some effect, and researchers have now made the suggestion that it may take 2-3 years before any benefit is seen (Sormani and colleagues. ECTRIMS 2016; abstract 215).
However, two recent studies have now shown that some medications in development do have the ability to slow the development of disability. Last year, the infusion drug ocrelizumab (the successor to rituximab) reported that treatment reduced the risk of worsening disability by 24% compared to a placebo in people with PPMS in the ORATORIO study (Montalban and colleagues. ECTRIMS 2015; abstract LB228) (see Ocrelizumab: promising results in relapsing and progressive MS, MSology, October 22, 2015).
A second trial, called EXPAND, is the largest study to date involving people with SPMS and has also reported very promising results. Subjects received either a placebo or siponimod, a new drug that is similar to Gilenya. About one-half of the people had an EDSS score of 6 or more, meaning that they needed the use of a cane or other device to help them walk. About 21 months later, there was a 21-26% reduction in the progression of disability (Kappos et al. ECTRIMS 2016; abstract 250). Siponimod also appeared to slow the loss of nerve fibres in the brain by about 23%, which may explain in part its beneficial effect on disability.
These promising studies are just the beginning. MS societies have joined forces in a Progressive MS Alliance to speed up the pace of development. And a number of novel therapies, such as lipoic acid, ibudilast and masitinib, are currently being tested in progressive MS. The hope is that one or more therapies will become available soon for people living with worsening MS.
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