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Kyoto (ptp011/19.09.2017/09:00) - A number of promising new drugs and treatment strategies have emerged over the course of the past decade which slow the progression of multiple sclerosis (MS) and improve quality of life for those affected. "To put it in a nutshell, current therapeutic strategies for all forms of MS aim to preserve body function and cognitive performance in patients by supressing disease activity to the fullest extent possible," explained Prof William Carroll of the University of Western Australia in Perth, who is also Vice-President of the World Federation of Neurology (WFN).
At the XXIII World Congress of Neurology (WCN) in Kyoto he gave an overview of current treatments and new and established medications with proven effectiveness and emerging treatment approaches. "Each new class of medication has informed on the mechanisms of brain and spinal cord injury in MS and together with identified biomarkers and improved access to effective therapies will lead to improved outcomes, particularly reduced disability," he noted.
The International Progressive MS Alliance is carrying out vital work to aid understanding of the underlying mechanisms of progressive MS. It is leading a concerted effort to develop treatment for patients with progressive worsening of the condition despite apparent suppression of MRI-visible inflammation. The aim is to decode the mechanisms behind progression and identify new therapeutic approaches. "Increased efforts are also being made in the important area of symptom control among MS patients with permanent and - at present - irreversible injury. Locomotor, sphincteric and cognitive functions and fatigue and pain management are primary targets," said Prof Carroll.
Oral medication provides improved quality of life
For many years, interferons beta 1a and beta 1b injections have been the agents of choice for the basic treatment of relapsing-remitting MS. They slow progression of the disease, reduce the frequency of relapses and reduce their severity. Glatiramer acetate, a mix of synthetic polypeptides likewise administered by injection, prevents inflammatory reactions, has a neuroprotective effect and was and is used in relapsing MS. Mitoxantrone has been used when injectables have seemed ineffective. "While its effectiveness for secondary progressive MS has been proven, this agent is being used much less frequently, since therapy requires monitoring of heart function, close attention to the upper dosage limit, can only be administered in specialist centres and may limit subsequent treatment options," Prof Carroll explained.
Over the past decade, new drugs in capsule or tablet form, such as fingolimod, dimethyl fumarate and teriflunomide have helped improve quality of life for MS patients. "Siponimod, a variation of fingolimod, has been approved in various countries following positive phase III results. The new drug should also make immunotherapy possible in secondary chronic progressive multiple sclerosis with ongoing relapse activity, and bring about a 25-30 percent delay in progression," Prof Carroll reported. In studies, cladribine has shown significant effects on MRI findings, relapse activity and progression of the disease. Although approved in Australia and Russia in 2010 for the treatment of relapsing-remitting MS, a European approval application was withdrawn in 2011 and the medication removed from the market in Australia and Russia as a result. In 2017 the European Medicines Agency issued a positive opinion for approval, meaning that the medicine could quickly become available in Europe and other parts of the world.
Monoclonal antibodies shown to be highly effective
The development of monoclonal antibody therapy with alemtuzumab, natalizumab and daclizumab has opened the door to a range of highly selective influences of the immune system for the first time and, as a result, highly-effective therapy for multiple sclerosis. "Alongside the highly promising therapeutic outcomes, uncommon side effects which are severe in some cases should not be overlooked when taking any possible benefits into account," Prof Carroll cautioned. Ocrelizumab, a fully humanised monoclonal antibody targeting mainly B-cells and which is a successor of the arthritis and cancer medication rituximab, is a new addition to this group of medicines. "Positive results in the phase III study give rise to hopes that ocrelizumab will not only be an option for relapsing-remitting MS, but also for certain subgroups with progressive multiple sclerosis," added Prof Carroll.
Autologous blood stem cell transplants
Autologous blood stem cell transplantation is another form of therapy for MS, and is used when otherwise highly effective medicines fail to deliver the desired treatment outcomes. While this approach has been shown to keep MS in check, the side effects are considerable. There are also currently very few long-term data demonstrating how long the progression of MS can be arrested for but trends are encouraging. "The risks and benefits of this stem cell therapy must be carefully weighed up with those of the new medicine-based therapy options," said Prof Carroll.
Realistic MS treatment goals
"When it comes to relapsing-remitting MS, additional studies and large-scale register-based data surveys show that achieving NEDA-4 (No Evidence of Disease Activity) is currently a realistic target," Prof Carroll explained. For patients this means freedom from relapses, no new inflammations in MRI scans, no progression of disability (including cognitive) and normalised rates of cerebral atrophy. The WFN vice-president hopes that new, effective treatments administered at an early stage will be able to prevent disability. "The degree of disability as measured on the Expanded Disability Status Scale (EDSS) could potentially be halted and in some cases reduced."
A similar development has also emerged for progressive MS. Administration of ocrelizumab for the primary form and siponimod for the secondary form could represent a new, effective treatment programme. "Although it has not been definitively proven that MS can be brought to a halt and any further progress prevented using these medicines, it is worth pursuing these therapeutic options further at this time. To wait and see is to deny the possibility of future newly arriving treatments to be used when potential disability has been reduced," Prof Carroll concluded.
Sources: Carroll, W: Therapeutic Overview of MS - Emerging Goals. Abstract WCN17-3716; http://www.progressivemsalliance.org
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