Long-term DMT Use Seen to Lower Likelihood of RRMS Progressing to SPMS in Study

Long-term DMT Use Seen to Lower Likelihood of RRMS Progressing to SPMS in Study

Long-term treatment with disease-modifying therapies (DMTs) appears to lessen the risk of disease worsening in relapsing-remitting multiple sclerosis (RRMS) patients, an 18-year follow-up study suggests.

But these therapies were not seen to benefit those who had progressed to secondary progressive multiple sclerosis (SPMS).

The study, “Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies,” was published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.

Disease-modifying therapies (DMTs) are treatments that aim to reduce MS progression from relapsing–remitting forms of the disease to SPMS.

Researchers conducted a retrospective analysis of 1,709 patients registered at the Group for Research and Treatment of Multiple Sclerosis (GITEM) Registry in Valencia, Spain.

Out of the initial 1,709 patients, 225 were clinically diagnosed with MS and 204 received treatment with first-line DMTs — interferon beta (Biogen‘s Avonex, among other brand names) or glatiramer acetate (sold as Teva‘s Copaxone).

Treatment with DMTs began when patients experienced at least one relapse in the previous year or two relapses within the previous three years. RRMS patients were followed for a median of 18.1 years.

Patients who failed to respond to treatment were given second-line therapies, namely the immune suppressants Novantrone (mitoxantrone), cyclophosphamide, or selective second-line DMTs, such as Tysabri (natalizumab) or Gilenya (fingolimod).

Study participants were evaluated regularly — every three to six months — for changes in their Expanded Disability Status Scale (EDSS) scores, relapse rates, and for side effects or decisions to stop treatment.

Progression to SPMS was confirmed “when patients with a previous EDSS score of 3.0 or greater experienced a six-month worsening to EDSS 4.0 or greater without evidence of relapse,” the researchers wrote.

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An EDSS score of 4 is characterized by significant disability, although patients are still able to walk without aid.

In total, 204 patients were treated with DMTs for a median of 12 years. Of these, 88 (43.1%) switched to second-line therapies because of treatment failure, and 29 switched from interferon beta to glatiramer acetate due to side effects that included “flu-like syndrome” (17 people) and “dermatological events” (11).

A total of 109 patients (53.4%) reached an EDSS of 3.0 within 14.1 years, and 74 (36.3%) progressed to SPMS in eight years (median age 42.6). Forty patients took a mean of about 20 years to reach an EDSS score of 6.0, which notes disability at a level that requires a walking aid.

Predictors of disease progression included multifocal relapse, being older than age 34 at disease onset (older patients had a four times greater risk of progressing to SPMS), and failure to respond to first-line disease-modifying therapy.

These parameters also predicted shorter times to reach EDSS 3.0 or EDSS 6.0 scores.

Fifty-two patients (64.7%) were treated with second-line DMTs after they progressed to SPMS; they reached an EDSS score of 6 within 12 years of the first MS event.

But RRMS patients given first-line DMTs took 21 years to reach an EDSS of 6, and only 9.5% of those who switched to second-line therapies progressed to SPMS.

These results compared to other natural history studies, the researchers said, suggesting that treatment with DMTs might slow disease progression in RRMS patients.

In this study, 36.3% of RRMS patients worsened to SPMS after 18 years of follow-up, compared to 58% and 66.3% of patients whose disease progressed during a similar follow-up in two independent studies.

But in patients whose disease progressed to SPMS, disease-modifying therapies had no effect.

“[W]e consider it likely that long-term treatment with DMTs might reduce the number of patients who will develop SPMS,” the researchers concluded. “However, in patients who do convert to SPMS, time to conversion, age of transition and subsequent cumulative disability are not influenced by current therapies.”


  1. A. Al-Shaar says:

    I have been on Rebif for 9 years. However, disability has increased in use of arm, hand and leg on left side of body. Doctor recommendation is to change DMT. Gelinya is z likely choice. Do you concur or do you propose any alternate DMT? Can you advise / feedback?

  2. Barbara Donnahoe says:

    I’m 65. I was diagnosed in 2007 with PP. Tried Rebif. That messed up my liver. Tried Copoxane even tho I was told that it wasn’t for my type. Hurting myself by giving shots was not my answer and it didn’t seem to help. Had stem cell replacement in 2017 and started following Dr. Terry Wahls MS diet. Not only do I feel better, I lost some weight too. Why don’t they try to find out what causes MS instead of just putting bandaids on it and treating symptoms?

  3. Panse says:

    But Tecfidera can cause infection of JC /BK virus which can be detrimental. As such it is advisable to conduct JC/BK virus tests on CS fluid before switching over to Tecfidera.

    • Cheryl says:

      I have RRMS that now they think might be SPMS. I have been taking Ampyra for 2 yrs. it helps a little but I have a weak right leg and foot drop. I keep trying to go off if ampyra but when I do I can’t walk as good as when I take it. I kinda wish sometimes that I never started taking it. I feel like I have some of the side effects , tired change in balance.

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