Certain Treatments Linked to Lower Risk of Secondary Progressive MS, Study Shows

Initial treatment of relapsing-remitting multiple sclerosis (RRMS) with Gilenya (fingolimod), Tysabri (natalizumab), or Lemtrada (alemtuzumab) is associated with a lower risk of conversion to secondary progressive multiple sclerosis (SPMS), compared with interferon beta or Copaxone (glatiramer acetate), a study reports.

Findings also showed that early treatment — especially within five years of disease onset — delayed progression to SPMS. These results may help guide decisions on selecting disease-modifying treatments for patients with RRMS.

The study, “Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis,” was published in the journal JAMA.

According to the research team, within 20 years of disease onset, 4 out of 5 untreated RRMS patients convert to SPMS — a phase of the disease where disability irreversibly increases; this stage is characterized by worsening physical and mental capacity, and reduced quality of life.

The relationship between disease-modifying treatments (DMTs) and conversion to SPMS has not been studied in depth, or much at all. In fact, much of the research on SPMS so far has been done without a unifying definition of the disease form.

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In 2016, researchers validated an objective definition of SPMS diagnosis based on the Expanded Disability Status Scale — a method of quantifying disability in MS — and information about preceding relapses.

Using this definition of SPMS, a team led by researchers at The Royal Melbourne Hospital and The University of Melbourne in Australia and the University of Cambridge in the U.K. investigated the association between SPMS and DMTs.

Their goal was to better understand the association between the risk of conversion to SPMS and the use, type of, and timing of DMTs.

For this purpose, data from 1,555 RRMS patients from 21 countries were analyzed. All patients started DMT or clinical monitoring between 1988 and 2012, and were followed for a minimum of four years. The data were primarily obtained from the MS base project, an international online registry for neurologists studying MS and other neuro-immunological diseases.

Analyzed DMTs included: interferon beta (under-the-skin or intramuscular injection, available under several brand names, such as Avonex, Betaferon, Extavia, Plegridy, and Rebif), Copaxone (marketed by Teva Pharmaceuticals), Gilenya (marketed by Novartis), Tysabri (marketed by Biogen), and Lemtrada (marketed by Sanofi Genzyme).

Results showed that treatment with a DMT was associated with a lower risk of conversion to SPMS, compared with patients not receiving any treatment. Interestingly, among the DMTs analyzed, Gilenya, Tysabri, and Lemtrada were associated with a significantly lower risk of conversion to SPMS than treatment with Copaxone or interferon beta, with a hazard ratio of 0.66, meaning a 39.8% lower probability of conversion.

The risk of SPMS conversion was also significantly lower for early treatment compared with late treatment. This was true for patients starting Copaxone or interferon beta treatment within five years of disease onset, versus later treatment, but also when escalating from Copaxone or interferon beta to Gilenya, Tysabri, or Lemtrada treatment within five years of disease onset versus later escalation.

“People who converted from relapsing MS to secondary progressive MS experience gradual and mostly irreversible worsening of disability,” Tomas Kalincik, PhD, one of the study’s lead authors, said in a press release. “Most of the therapies that we use to treat MS have no effect once people have converted to SPMS. This study shows us how important it is to treat relapsing MS early and pro-actively.”

Kalincik is the head of the MS Service at The Royal Melbourne Hospital and the Clinical Outcomes Research unit at the University of Melbourne.

Gowri, a Royal Melbourne patient diagnosed with MS in her 20s, is receiving monthly infusions to treat her disease. Knowing that there is available data to prove that current treatments are effective have helped her feel optimistic about her future.

“It’s fantastic — it makes you feel very grateful that the treatment is working,” said Gowri, whose full name was not disclosed in the release. “I had a great General Practitioner who referred me straight away to a neurologist. My treatment started very quickly. This year will be 20 years since I was diagnosed, and even though I have some symptoms and I have been in hospital — particularly after the birth of my daughter, I’m able to work, catch up with friends and have a normal life.”

According to Kalincik, the results of the study are reassuring for both neurologists and patients with MS.