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Should RRMS Disease-Modifying Agents Be Used to Treat SPMS?

March 22, 2016

A question that faces clinicians is whether to continue treatment with disease-modifying drugs, effective in relapsing-remitting multiple sclerosis (RRMS), as the disease progresses to secondary progressive MS (SPMS). As the patient’s disease progresses into SPMS, the agents that worked so well in the past do not seem to work as well.

At the 10th World Congress on Controversies in Neurology in Lisbon, Portugal (March 17-20, 2016), Abhijit Chaudhuri, a consultant neurologist at Queens Hospital, London, U.K., and Jacek Losy from the Poznan University of Medical Science, Poland, discussed this important issue.

According to Dr. Chaudhuri, the lack of progress in SPMS treatment stems from the fact that the pathology of this disease form is inherently different from earlier disease stages. The progression to PPMS is mainly driven by neurodegenerative changes, in contrast to the principal inflammatory processes in RRMS. The cause of this neurodegeneration is not well explored, but it is likely dependent on several factors heavily influenced by metabolic brain changes.

“Neurodegeneration in SPMS is considered to be multi-factorial, diffuse, and significantly influenced by metabolic neuroaxonal changes,” Dr. Chaudhuri said in the debate. “Accumulation of disability in SPMS is driven by a neurodegenerative process which is independent of focal inflammatory changes.”

Since the underlying causes are different in the two MS stages, it is not surprising to find that current RRMS disease-modifying treatments have little effect on SPMS — and there is plenty of evidence that they do not, Dr. Chaudhuri said, citing several important studies.

Several clinical trials from 1988 onward, enrolling more than 6,000 patients and testing a multitude of both immunosuppressive and first-line disease-modifying drugs, have failed to show beneficial effects in SPMS patients. Together, these trials have investigated the efficiency of immune-suppressive drug therapies (ISDT) such as Azathioprine, Ciclosporin, Cyclophosphamide, Sulfasalazine, Linomide, Mitoxantrone and Cladribine; first-line disease modifying therapies like Interferon beta 1-a, Interferon 1-b and Glatiramer Acetate; and human intravenous immunoglobulin (IVIg), antiCD20 monoclonal antibody (Rituximab), Myelin Basic Protein (MBP), and cannabinoid (Dronabinol) for SPMS treatment.

Dr. Chaudhuri also mentioned a small trial investigating alemtuzumab (Lemtrada) in SPMS, which found no benefit in terms of Expanded Disability Status Scale (EDSS, a measure of disability) progression or rate of brain atrophy in MRI. Fingolimod (Gilenya) also failed to show efficacy in a trial for primary progressive MS, a disease form that likely shares underlying causes with SPMS.

Obviously there is an enormous unmet need for effective treatment in SPMS, but this is because the disease isn’t fully understood as of now. Many patients are frightened when told to stop treatment, and should be brought along slowly. The patients should then be informed about the on-going SPMS trials and allowed to enter one. While it is still preliminary, encouraging results have been found in studies involving Simvastatin and Biotin.

http://multiplesclerosisnewstoday.com/2016/03/21/cony-congress-scientists-debate-if-disease-modifying-treatment-should-be-stopped-in-secondary-progressive-ms/