Immunotherapy Slows Disability in Patients With Active Relapses During Secondary Progressive MS

In patients with active relapses in secondary progressive multiple sclerosis, disease-modifying therapies improved disability outcomes.

In patients with active relapses during secondary progressive multiple sclerosis (SPMS), treatment with disease-modifying therapies (DMTs) may slow the rate of disability accumulation, according to study results published in JAMA Neurology. Additionally, the study findings indicated that the rate of disability progression following disease onset was not dependent on early disease course/treatment.

There is limited data available regarding the association of relapses and DMTs with the rate of disability accumulation in patients with SPMS. The goal of this study was to analyze the relationship between relapses and disability accumulation rate in such patients. Additionally, study researchers sought to determine whether treatment prior to or during the secondary progressive stage could slow the progression of disability accumulation.

Australian researchers prospectively collected patient data from the MSBase cohort study ( Identifier: ACTRN12605000455662), an ongoing international registry focused on evaluating MS outcomes. Data of 53,680 patients with MS from 123 medical centers were obtained from the registry between January 1995 and February 2018. A total of 1621 patients with SPMS (mean age at MS onset, 33.9 years), at least 24 months between MS diagnosis and SPMS conversion, and at least 12 months of prospective follow up after SPMS conversion were identified and included in the study.

The study investigators assessed the association between disability accumulation and relapses as well as exposure to immunotherapy. The main outcomes were the rate of disability accumulation during the secondary progressive phase and the risk of becoming wheelchair dependent.

Approximately 40.8% (n=661) of patients had superimposed relapses during SPMS. Patients had an average follow-up of 5.6 years during SPMS.

Natalizumab and mitoxantrone were the most high-efficacy DMT exposures during early RRMS and SPMS. In contrast, most low-efficacy DMTs included interferon beta preparations and glatiramer acetate. Fingolimod and dimethyl fumarate were the primary medium-efficacy drug exposures.

Patients with higher rates of relapse during the secondary progressive stage had a significantly increased risk of becoming wheelchair dependent (hazard ratio [HR], 1.87; 95% CI, 1.17-3.00; P =.009). There was a significant association between a greater proportion of time receiving DMTs with a lower risk of becoming wheelchair dependent in patients with superimposed relapses during SPMS, including for low-efficacy therapies (HR, 0.78; 95% CI, 0.68-0.90; P <.001), medium-efficacy therapies (HR, 0.73; 95% CI, 0.55-0.96; P =.03), and high-efficacy therapies (HR, 0.73; 95% CI, 0.57-0.94; P =.02). A similar association was found with only medium-efficacy therapies in patients without relapses during SPMS (HR, 0.63; 95% CI, 0.44-0.89; P =.01).

Additionally, patients with superimposed relapses during SPMS had a reduced Multiple Sclerosis Severity Score progression slope during their disease if they received DMTs for a greater time during SPMS, including for low-efficacy therapies (95% CI, -0.039 to -0.012; P <.001) and high-efficacy therapies (95% CI, -0.056 to -0.013; P =.002).

Limitations of this study included its observational nature and lack of assessment of the implications associated with early aggressive therapy.

According to the investigators, these “results suggest that inflammatory disease activity remains a substantial yet modifiable component of SPMS.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Lizak N, Malpas CB, Sharmin S, et al. Association of sustained immunotherapy with disability outcomes in patients with active secondary progressive multiple sclerosis. JAMA Neurol. Published online July 27, 2020. doi:10.1001/jamaneurol.2020.2453