Sequencing of high-efficacy disease-modifying treatments in MS

Given the chronic nature of MS and sub-optimal treatment response occurring frequently, sequencing of multiple treatments has become routine practice. The aim is to maximise the benefit–risk balance of treatment. One of the reasons this poses a challenge, is that real-world evidence for the numerous possible strategies is scarce.

A number of studies on this subject were presented at the AAN 2019 meeting:

• A real-world study looked at discontinuation and effectiveness of dimethyl fumarate (n=428) and fingolimod (n=358) over 36 months in 786 MS patients [1]. More patients on dimethyl fumarate discontinued than on fingolimod (58.3% vs 45.2%; OR 1.81; P<0.001). The main cause was intolerance. Within 12 months of discontinuation, one third of patients had switched to high efficacy therapy (natalizumab, rituximab, ocrelizumab, alemtuzumab), while 39-48% switched to a first-line injectable or oral disease-modifying treatment. After switching to high efficacy therapy, 6% of the dimethyl fumarate group and 11.9% of the fingolimod group relapsed; after switching to an injectable/oral disease-modifying treatment, relapses were more common: 14.2% and 18.4%, respectively. There were also fewer Gd+ lesions after escalation to high efficacy therapy.
• An analysis of the PANGAEA 2.0 database revealed a benefit within 12 months of treatment and sustained effectiveness over 24 months in patients on dimethyl fumarate, teriflunomide or daclizumab who switched to fingolimod [2]. Mean reduction in annualised relapse rate at 24 months was 73.5% in the oral disease-modifying treatment group, and 72.5% in the dimethyl fumarate group.
• In a prospective, observational, multicentre study, alemtuzumab proved to be safe and effective in controlling disease activity in patients who switched from fingolimod [3]. After 12 months (n=51), the annualised relapse rate was reduced from 1.35 to 0.16 (P<0.001). The proportion of patients who developed new Gd+ lesions decreased from 59% to 3%. After 24 months (n=24), the annualised relapse rate had decreased from 1.46 to 0.16 (P<0.01). There was a reduction from 71% to 14% in the proportion of patients who developed new Gd+ lesions. Infections were detected in 55% and 52% of patients, respectively; 6% and 21% of patients developed thyroid disease.
• In the OCTAVE study, patients on ocrelizumab previously treated with natalizumab are followed. At 6 months, all 16 evaluated patients were free of relapses, EDSS progression, and MRI changes [4]. However, there were 4 serious adverse events, including 1 case each of breast cancer and acute cystitis. The authors found these possibly treatment-related events concerning, given the small number of patients.

1. Hersh C, et al. AAN 2019, P3.2-065.
2. Ziemssen T, et al. AAN 2019, P3.2-075.
3. Gonzalez I, et al. AAN 2019, P3.2-050.
4. Smoot K, et al. AAN 2019, P3.2-056.

Posted on 30 July 201915 March 2021