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Comparative effectiveness of disease-modifying therapies for highly active relapsing-remitting multiple sclerosis
Michael Köhler1, Friedemann Paul2, Kirsten Janke3
1Institute for Quality and Efficiency in Health Care (IQWiG), Cologne, Germany. michael.koehler@iqwig.de.
Background:
Comparative assessments of all available disease-modifying therapies (DMTs) in patients with highly active relapsing-remitting multiple sclerosis (RRMS) are lacking, even though some of these DMTs are restricted to this MS subpopulation. We therefore aimed to compare DMTs in patients with highly active RRMS using re-analyses of individual patient data (IPD) provided by study sponsors.
Methods:
We searched for randomised controlled trials (RCTs) that included adult patients with RRMS and directly compared alemtuzumab, cladribine, dimethyl fumarate, fingolimod, natalizumab, ocrelizumab, ofatumumab, ozanimod, ponesimod and teriflunomide, or compared these DMTs with other drugs or placebo. Re-analyses of IPD for subpopulations of patients with high disease activity despite previous DMT were included in network meta-analyses (NMAs). As there is no widely accepted definition of high disease activity in RRMS, criteria were chosen to cover as wide a range of definitions as possible, while being sufficiently similar across studies.
Results:
We identified 14 relevant RCTs, including only 3 head-to-head comparisons of DMTs, and no relevant studies on natalizumab. All studies were pivotal studies for approval. The available re-analyses of IPD did not allow comprehensive NMAs. The main reasons for this were the overall paucity of RCTs, especially head-to-head comparisons, and a high risk of bias. In addition, data on patient-relevant outcomes and long-term follow-up (> 2 years) were lacking.
Conclusion:
Based on the largest possible evidence base, including previously unpublished data, our systematic review shows substantial evidence gaps for DMTs in highly active RRMS. This indicates a need for further research beyond regulatory requirements.
Trial Registration:
Clinical trial number: not applicable.
Insights
Comparative assessments of disease-modifying therapies (DMTs) for highly active relapsing-remitting multiple sclerosis (RRMS) reveal significant evidence gaps. Further research is needed to inform treatment decisions for this patient population.
Area of Science:
- Neurology
- Immunology
- Pharmacology
Background:
- Highly active relapsing-remitting multiple sclerosis (RRMS) requires effective disease-modifying therapies (DMTs).
- Comparative data on available DMTs for highly active RRMS is limited, despite some therapies being exclusive to this subpopulation.
Purpose of the Study:
- To conduct a comparative assessment of disease-modifying therapies (DMTs) in patients with highly active relapsing-remitting multiple sclerosis (RRMS).
- To analyze individual patient data (IPD) from randomized controlled trials (RCTs) to compare DMT efficacy.
Main Methods:
- Systematic search for RCTs comparing approved DMTs (alemtuzumab, cladribine, dimethyl fumarate, fingolimod, natalizumab, ocrelizumab, ofatumumab, ozanimod, ponesimod, teriflunomide) in adult RRMS patients.
- Inclusion of re-analyses of IPD for network meta-analyses (NMAs) in subpopulations with high disease activity despite prior DMT.
- Application of broad criteria for high disease activity to encompass various definitions across studies.
Main Results:
- Identified 14 relevant RCTs, with only 3 direct head-to-head comparisons of DMTs; no studies found for natalizumab.
- Re-analyses of IPD were insufficient for comprehensive NMAs due to a scarcity of RCTs, particularly head-to-head trials, and a high risk of bias.
- Lack of data on patient-relevant outcomes and long-term follow-up (over 2 years) was noted.
Conclusions:
- A systematic review utilizing the largest available evidence base, including unpublished data, identified substantial evidence gaps for DMTs in highly active RRMS.
- The findings highlight a critical need for further research beyond regulatory requirements to better guide treatment strategies for this specific MS population.
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