Disease modifying therapies likely to reduce conversion to secondary progressing multiple sclerosis

1. In this case-control cohort study, treatment with glatiramer acetate, interferon-beta, fingolimod, alemtuzumab, and natalizumab all led to reduced conversion to secondary progressive Multiple Sclerosis (MS) compared to no Disease-Modifying Treatment (DMT).

2. Treatment with fingolimod, alemtuzumab, and natalizumab had reduced conversion to secondary progressive MS compared to glatiramer acetate and interferon-beta.

Evidence Rating Level: 2 (Good)

Study Rundown: Patients with relapsing-remitting MS generally convert to secondary progressive MS within a few decades of initial diagnosis. Though Disease Modifying Therapies (DMTs) are well-validated to treat MS symptoms and prevent exacerbations, it is unclear if they similarly reduce the conversion to secondary progressive MS. In this case-control cohort with prospectively collected clinical data, patients who received any DMT had reduced conversion to secondary progressive MS than those who did not. Further, those who received DMT closer to symptom appearance tended to have reduced conversion compared to those who started DMT later. The more potent DMTs studied (fingolimod, alemtuzumab, and natalizumab) had reduced conversion compared to glatiramer acetate and interferon-beta.

This study utilizes the newly set consensus definition for secondary progressive MS, and thus may be more accurate than similar studies completed previously. However, the study was limited by its cohort design and strict exclusion criteria that greatly reduced the proportion of patients eligible for study.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

Relevant Reading: Long-term impact of interferon or Glatiramer acetate in multiple sclerosis: A systematic review and meta-analysis

In-Depth [case-control study]: 1555 matched patients with relapsing-remitting MS (out of 44,217 assessed for eligibility) were included in this observational cohort study with prospectively collected clinical data from 3 databases from the UK: untreated patients from a neuroinflammatory service database from the University Hospital of Wales, treated patients from MSBase, and atelezumab-treated patients from 5 European, non-MSBase centers. Patients were included if they had primary relapsing-remitting MS, complete MSBase minimal dataset, at least one Extended Disability Status Scale (EDSS) score 6 months before baseline, and at least 2 EDSS scores after baseline. Patients were excluded if they stopped their DMT at least 6 months within baseline and if they received an unlicensed therapy such as mitoxantrone, cladribine, rituximab, ocrelizumab, siponimod, or autologous stem cell transplant. Case and control matching was done via MatchIT. Treatment with each included therapy reduced the conversion to secondary progressive MS compared to no treatment: glatiramer acetate or interferon-beta (Hazard Ratio 0.71; CI₉₅ 0.61 to 0.81), fingolimod (HR 0.37; CI₉₅ 0.22 to 0.62), natalizumab (HR 0.61; CI₉₅ 0.43 to 0.86), and alemtuzumab (HR 0.52; CI₉₅ 0.32 to 0.85). Patients who received glatiramer acetate or interferon-beta within 5 years of symptom presentation had reduced conversion rates compared to those who received treatment after 5 years (HR 0.77; CI₉₅ 0.61 to 0.98). When treatment escalated from glatiramer acetate or interferon-beta to fingolimod, natalizumab, or alemtuzumab, there was a reduction in conversion rates compared to those who remained on initial DMT (HR 0.76; CI₉₅ 0.66 to 0.88). Patients who started fingolimod, natalizumab, or alemtuzumab had reduced conversion rates compared to those started on glatiramer acetate or interferon-beta (HR 0.66; CI₉₅ 0.44-0.99).

Image: PD

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