Differences in national strategies for the treatment of relapsing-remitting multiple sclerosis significantly associated with disability outcomes during follow-up

1. The use of highly effective disease-modifying treatments for relapsing-remitting multiple sclerosis was significantly more prevalent in Swedish patients compared to Danish patients and was associated with significant reductions in the rate of confirmed disability worsening and relapse rates.

2. The findings demonstrated that differences in national treatment strategies and clinical guidelines had a significant association with disability outcomes during long-term follow-up.

Evidence Rating Level: 2 (Good)

Study Rundown: The discovery of new disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has led to different treatment strategies among nations and their respective health systems and even individual centers. The most common treatment strategy is one of escalation, beginning with safer first-line options and adding more effective but toxic agents as the disease progresses, keeping in mind the patient’s individual goals and balancing risks and safety. Among Scandinavian countries, there are marked differences between the national strategies of Denmark and Sweden, where their association with clinical outcomes in multiple sclerosis (MS) is unknown. This retrospective cohort study, using data extracted from the Swedish and Danish MS registries, sought to investigate whether national treatment recommendations and clinical practice guidelines were associated with disability outcomes after 3 to 7 years of follow-up. The primary endpoint was time to 24-week confirmed disability worsening. Secondary endpoints included 24-week confirmed disability improvement, rate of reaching Expanded Disability Status Scale (EDSS) scores of 3 and 4, annualized relapse rate, time to first relapse, and treatment modifications. Among 2,700 Swedish and 2,161 Danish patients, the use of highly effective DMTs was significantly more prevalent in the Swedish population and was associated with significant reductions in the rate of confirmed disability worsening and relapse rates. These findings demonstrated that differences in national treatment strategies and clinical guidelines had a significant impact on disability outcomes during long-term follow-up. A limitation of this study was the use of various measures of disability progression as primary and secondary endpoints. Although disability progression is a hallmark of MS disease progression and often more reliable than relapse rate for the evaluation of MS treatment response, the Danish patients in this study received significantly more EDSS assessments than Swedish patients, decreasing the overall interrater and intrarater reliability and sensitivity of the Danish cohort.

Click to read the study in JAMA Neurology

Relevant Reading: Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study

In-Depth [retrospective cohort]: This cohort study included a total of 4,861 patients with 2,700 patients from the Swedish MS registry (1,867 women [69.2%]; mean [SD] age, 36.1 [9.5] years) and 2,161 patients from the Danish MS registry (1,472 women [68.1%]; mean [SD] age, 37.3 [9.4 years]). All eligible patients were observed from the date of index DMT initiation between January 2013 and December 2016 until the last recorded visit at time of data extraction in October 2019, for a mean (SD) of 4.1 (1.5) years. Data was analyzed using inverse probability of treatment weighting-based models via a propensity score to weight and corrected comparison for the imbalance of confounders observed at baseline between the 2 countries. In Danish patients, 1,994 (92.3%) initiated a low to moderately effective DMT (teriflunomide, 907 [42.0%]) and 165 (7.6%) initiated a highly effective DMT. Comparatively, 1,769 patients (65.5%) initiated a low to moderately effective DMT (teriflunomide, 64 [2.4%]) and 931 (34.5%) initiated a highly effective DMT from the Swedish registry, a strategy associated with a 29% reduction in the rate of postbaseline 24-week confirmed disability worsening relative to the Danish treatment strategy (HR, 0.71; 95%CI, 0.57-0.90; P = .004). For secondary outcomes, the Swedish treatment approach was associated with a 24% and 25% reduction in the rate of reaching an expanded disability status scale score of 3 and 4 respectively (HR, 0.76; 95%CI, 0.60-0.97; P = .03; HR, 0.75; 95%CI, 0.61-0.96; P = .01) compared to Danish patients.

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