Outcomes are better for people with relapsing-remitting multiple sclerosis (RRMS) initially treated with higher efficacy disease-modifying therapies (DMTs) than for those who begin with lower efficacy DMTs and escalate to more effective treatments as the disease progresses, according to a real-world analysis of patient registry data. Findings also showed that the side effects of higher efficacy therapy generally did not lead patients to switch to other DMTs. Rather, a lack of efficacy was cited as the main reason for moving off of a low-efficacy DMT, and the researchers questioned whether these therapies are the best choice for a first-line RRMS treatment. The study, “Does initial high efficacy therapy in multiple sclerosis surpass escalation treatment strategy? A comparison of patients with relapsing-remitting multiple sclerosis in the Czech and Swedish national multiple sclerosis registries,” was published in the journal Multiple Sclerosis and Related Disorders. Escalation approach often taken with MS disease-modifying therapies. The use of DMTs can slow disability progression in people with multiple sclerosis (MS). Some DMTs are highly effective at slowing progression but are associated with a high risk of side effects and can be more expensive. Others have lower efficacy, meaning they are less effective at slowing disease, but they also have fewer side effects. The standard approach is to start with a lower efficacy DMTs and escalate to more effective therapies following a breakthrough in disease activity. However, studies suggest that early treatment with high-efficacy DMTs may be a better approach to slow disability. A recent population-based study consistently showed that RRMS patients in Sweden who started on high-efficacy DMTs had better outcomes than those in Denmark, who typically began with low-efficacy DMTs. To confirm these findings, researchers in the Czech Republic conducted a similar analysis comparing Swedish and Czech RRMS patients given first-line DMTs between 2013 and 2016. Most patients in the Czech Republic receive low-efficacy DMTs as initial therapy, an approach supported by cost reimbursement criteria. Data collected from national MS registries showed that 3,327 of the 3,487 patients in the Czech registry (95.4%) and 1,771 out of 2,923 patients in the Swedish registry (60.6%) began treatment with a low-efficacy DMT. The remaining patients received moderate- to high-efficacy DMTs as an initial therapy. Lower efficacy DMTs included Tecfidera (dimethyl fumarate), glatiramer acetate (sold as Copaxone, among others), Aubagio (teriflunomide), or interferon-based medications. Moderate- and high-efficacy DMTs included Ocrevus (ocrelizumab), Tysabri (natalizumab), Lemtrada (alemtuzumab), Gilenya (fingolimod), Ponvory (ponesimod), and rituximab, which is used off-label in MS. Researchers' analysis covered 2,991 Czech registry patients — 2,877 or 96.19% starting on lower efficacy therapies — and 1,529 people in the Swedish registry, with 642 (41.99%) starting on a moderate- or high-efficacy DMT. Particular focus was given to the Czech group with an initial lower efficacy DMT and the Swedish group with an initial higher efficacy treatment. After a mean follow-up of 6.6 years in the Czech group and 5.9 years in the Swedish group, no significant differences were seen in the time to confirmed disability worsening, defined by an increase in Expanded Disability Status Scale (EDSS) scores. Therapy effectiveness cited more with switches than side effects. However, the risk of progressing to an EDSS score of 4 or higher — representing considerable disability — was significantly lower, by 26%, in Swedish compared with Czech patients. The risk of relapse also was significantly reduced, by 66%, in Swedish patients, who experienced a mean of 0.056 relapses per year compared with 0.266 annual relapses in the Czech group. Furthermore, the likelihood of confirmed disability improvement, meaning an easing in disability, was three times higher in Swedish patients. “It is reasonable to ask why such a significant reduction in the risk of relapse did not translate into a change in the long-term outcome of [confirmed disability worsening],” the researchers wrote. “Our hypothesis is that the evaluation methods of EDSS might differ between the countries.” Patients in Sweden moved from low-to-moderate to high-efficacy treatment much sooner than those in the Czech Republic. After eight years of follow-up, 68% of Swedish patients had not switched their high-efficacy DMT, compared with 40% of Czech patients on low-efficacy DMTs. Over half (54%) of Czech patients in the registry were switched due to a lack of efficacy, followed by side effects (28.8%). In the Swedish registry, a lack of effectiveness accounted for 37.8% of DMT switches. When only Swedish patients undergoing high-efficacy DMT were examined, 15% switched due to side effects. “The possibility that an early switch of [moderate-to-high-efficacy] DMTs may increase the incidence of side effects was not confirmed,” the researchers noted. Overall, this analysis “confirmed a better prognosis for patients in Sweden, where a significant proportion of patients received [moderate-to-high-efficacy] DMTs as initial therapy,” the researchers concluded.