Is there any progress in treating secondary-progressive MS?
Many treatments are now available to treat the relapsing-remitting form of multiple sclerosis, but little help is available for people who develop secondary-progressive MS (SPMS). That may be changing as a number of novel therapies have now posted promising results.
Many people with relapsing-remitting MS (RRMS) go on to develop SPMS, which is characterized by fewer (or no) relapses but worsening disability. SPMS is determined by a neurologist, but it can be a difficult diagnosis to make. Inflammation, as shown by relapses and new lesions on an MRI, may still be present, and the development of worsening disability can be a slow process, so it isn’t always clear if a person is still in the relapsing-remitting phase or has transitioned to SPMS. As a result, it may take a few years before it can be confirmed that a person has SPMS.
The onset of SPMS has several important implications. Once it begins, the neurodegenerative aspects of MS become more prominent, and the inflammatory aspects (relapses, MRI lesions) play a lesser role. As a result, the medications used to treat RRMS – which primarily target inflammation – are less effective (or ineffective) for SPMS, so insurers may notify you that they’ll no longer reimburse the cost of treatment.
Early studies of beta-interferons (Rebif, Betaseron) showed that they had some effect in slowing the worsening of disability (SPECTRIMS Study Group. Neurology 2001;56:1496-1504; Kappos and colleagues. Neurology 2004;63:1779-1787). This effect appeared to be due largely to a reduction in inflammation, suggesting that people who are still having relapses may obtain some benefit if they stay on their interferon after transitioning to SPMS.
Unfortunately, since those early trials, most MS treatments have failed to show that they have any beneficial effects on disability. The most notable failure is Tysabri, which did not slow disability progression in the ASCEND trial of SPMS, although it did produce some improvement in arm function (Steiner and colleagues. American Academy of Neurology 2016; abstract P009). Tecfidera was being examined in the INSPIRE trial of SPMS, but that study was cancelled.
Since nerve damage is a prominent feature of SPMS, some researchers have tried medications that may be able to protect nerve fibres. Dronabinol, the active ingredient in marijuana, had no effect on disability (Zajicek and colleagues. Lancet Neurol 2013;12:857-865). The epilepsy drug Lamictal was also ineffective (Kapoor and colleagues. Lancet Neurol 2010;9:681-688). But early testing of other drugs retooled for use in MS showed some promise, such as the cholesterol-lowering drug Zocor, and the asthma drug ibudilast (Chataway and colleagues. Lancet 2014;383:2213-2221; Barkhof and colleagues. Neurology 2010;74:1033-1040). Ibudilast is now being studied in the ongoing SPRINT-MS trial of SPMS and primary-progressive MS (PPMS), and has been fast-tracked by the U.S. Food and Drug Administration as a possible treatment for progressive MS.
The latest candidate is siponimod (formerly called BAF312), a next-generation version of Gilenya. There have been early reports that in the phase III EXPAND trial, a large study that involved over 1,600 people, siponimod significantly reduced the risk of disability progression in people with SPMS. Results so far are preliminary, but additional details will be presented at the European Committee for Treatment and Research in MS (ECTRIMS) annual meeting in September.
MSology will be on-site at ECTRIMS 2016, providing daily coverage of new MS research. Watch for more information about the EXPAND study as well as other stories on msology.com, on Facebook and on our Twitter feed.
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