by Antonella Macerollo
For October 2021, we have selected: Spelman T. el al Treatment Escalation vs Immediate Initiation of Highly Effective Treatment for Patients With Relapsing-Remitting Multiple Sclerosis: Data From 2 Different National Strategies. JAMA Neurol 2021 Aug 16;e212738 | doi: 10.1001/jamaneurol.2021.2738. Online ahead of print
Our research paper of the month is a cohort study, comparing data from the Danish and Swedish national multiple sclerosis (MS) registries to investigate the association of national difference in disease-modifying treatment (DMT) strategies for relapsing-remitting multiple sclerosis (RRMS) with clinical outcomes.
While Denmark and Sweden have similar socioeconomic standards and healthcare systems, there are notable differences in the choice of DMT and the treatment strategy for RRMS between the two countries. The objective of this retrospective cohort study, based on data obtained from the Swedish and Danish MS registries, was to investigate whether national treatment recommendations and clinical practice are associated with disability outcomes after 3 to 7 years of follow-up.
Denmark and Sweden have developed nationwide MS registries with coverage of more than 90% and 80% of patients, respectively. The study used data from the date of index DMT initiation (between January 1, 2013, and December 31, 2016) until the last recorded visit at time of data extraction (October 2, 2019).
A total of 2700 patients from the Swedish registry (1867 women [69.2%]; mean [SD] age, 36.1 [9.5] years) and 2161 patients from the Danish MS registry (1472 women [68.1%]; mean [SD] age, 37.3 [9.4 years]) met the inclusion criteria and started a DMT between 2013 and 2016 were included in the analysis.
The analysis included adult patients aged 18 to 55 years at baseline with clinically isolated syndrome or RRMS, who initiated DMT for the first time between January 1, 2013, and December 31, 2016. Patients with primary progressive MS or secondary progressive MS at baseline were excluded. To limit confounding from comorbid conditions and the relative unresponsiveness to DMT associated with increasing age, the authors also excluded patients older than 55 years. Data were extracted from the registries on October 2, 2019, meaning the maximum follow-up period was seven years.
The authors’ analysis showed that the Swedish treatment strategy was associated with a 29% reduction in the rate of postbaseline 24-week confirmed disability worsening relative to the Danish treatment strategy (hazard ratio, 0.71; 95% CI, 0.57-0.90; P = .004). The Swedish treatment strategy was also associated with a 24% reduction in the rate of reaching an expanded disability status scale score of 3 (hazard ratio, 0.76; 95% CI, 0.60-0.97; P = .03) and a 25% reduction in the rate of reaching an expanded disability status scale score of 4 (hazard ratio, 0.75; 95% CI, 0.61-0.96; P = .01) relative to Danish patients.
During an observational time of three to seven years, Swedish patients had a significantly lower rate of disability progression than Danish patients, and fewer Swedish patients reached thresholds of clinically evident disability compared with Danish patients.
Danish patients almost exclusively started treatment with a conventional first-line DMT, primarily teriflunomide, whereas one-third of Swedish patients initiated treatment with a highly effective DMT, mostly rituximab and natalizumab. This difference may explain why more Danish patients discontinued and subsequently switched from the index DMT to another DMT and why breakthrough disease was more often recorded as the reason for the DMT switch for Danish than Swedish patients. In addition, Swedish patients switched to a highly effective DMT more often than Danish patients did, which might have been associated with the more favourable disability outcomes among Swedish patients.
Our authors conclude that the differences in national treatment recommendations and strategies had a clear association with disability outcomes after a few years of follow-up. Starting with a more effective therapy and switching to a more effective DMT at treatment discontinuation, irrespective of reason, seemed to be superior to commencing a conventional first-line DMT and escalation.