Is disease-modifying treatment in primary progressive multiple sclerosis effective after all?


Is disease-modifying treatment in primary progressive multiple sclerosis effective after all?

1703 2560 Anna Stelling, PhD

Until now, several randomised controlled trials and real-world studies could not show the clinical benefit of disease‑modifying treatments (DMTs) in primary progressive multiple sclerosis (PPMS).1-4 However, some recently published results point towards a potentially positive effect on disability milestones after sustained DMT exposure. During this year’s “2020 joint ACTRIMS/ECTRIMS meeting”, Mattia Fonderico (Department NEUROFARBA, University of Florence, Italy), virtually presented his real-world study data on the potential effects of DMTs in PPMS patients.

Study designed to assess wheelchair dependence

Dr Fonderico and his team aimed to assess the effectiveness of DMTs by evaluating wheelchair dependence in Italian PPMS patients (N=1214). The primary outcome of the study was the risk of becoming wheelchair dependent, assessed via multivariable Cox regression models, and reached when the Expanded Disability Status Scale (EDSS) score was equal to or above 7. Treatments included moderately effective DMTs (Interferon Beta 1a/1b, glatiramer, dimethyl fumarate, teriflunomide, methotrexate and azathioprine) and highly effective DMTs (Monoclonal antibodies, mitoxantrone, cladribine and fingolimod).

Longer treatment decreases risk of wheelchair dependence

After a mean follow-up of 11.7 years, the study group found that patients who were treated earlier after symptom onset showed a trend towards a lower risk of wheelchair dependence. In addition, the data revealed that patients who were exposed to DMTs for the longest period (>7.51 years) had a significantly lower risk of becoming wheelchair dependent (P=0.014) compared to untreated and shorter-treated patients. Dr Fonderico mentioned that their study had some limitations like the exclusion of magnetic resonance imaging (MRI) variables, a missing analysis of superimposed relapses, as well as active progressive PPMS patients being defined as those who had relapsed within two years before the defined baseline.

Further studies needed

Dr Fonderico stated that, “despite the limitations, we can conclude that in our cohort treatment persistence delayed time to wheelchair in patients with a primary progressive phenotype.” His group is currently looking at the long-term effect of superimposed relapses. However, he says that more real-world studies will be needed to determine the long-term safety of the treatments. In particular, it is important to see if there is a possibility to determine the value of DMT in PPMS patients at certain points during the course of treatment.

For more coverage from “2020 joint ACTRIMS/ECTRIMS meeting”, please click here.

    1. Wolinsky JS et al. Ann Neurol. 2007;61:14-24
    2. Hawker K et al. Ann Neurol. 2009;66:460-71
    3. Lublin F et al. Lancet. 2016;387:P1075-84
    4. Lorscheider J et al. Eur J Neurol. 2019;26:363-70


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