From diagnosis to treatment: patterns in disease-modifying therapy initiation in multiple sclerosis

Background: Over recent decades, several high-efficacy disease-modifying therapies (DMTs) have been approved for multiple sclerosis (MS), prompting a shift from an escalation strategy toward early high-efficacy treatment. Yet, DMT initiation patterns and safety profiles remain unexplored in research relying solely on patient self-reports and have not been examined in Switzerland. Objectives: To investigate (1) time from MS diagnosis to first DMT, (2) temporal trends in initial DMT use, (3) number of suspected adverse drug reactions (sADRs) following the first DMT, and (4) occurrence of any severe sADR. Design: Retrospective cohort study using longitudinal, patient-reported data from the Swiss MS Registry (SMSR) between 1995 and 2024. Methods: We analyzed data from SMSR participants with relapsing-remitting MS or clinically isolated syndrome diagnosed after 1995. Time from diagnosis to first DMT was analyzed using Kaplan-Meier analysis. Temporal trends were assessed through annual distributions of first DMTs. sADR burden was modeled with a two-part zero-inflated negative-binomial model, and severe sADRs (⩾1 severe sADR) were assessed with logistic regression. All models were adjusted for sex and age at DMT initiation. Results: Median time from diagnosis to first DMT decreased from 4.5 months (95% confidence interval (CI): 2-6) in the 1995-2004 diagnosis group to 2 months (95% CI: 1-2) in more recent groups (⩾2010). First DMT use shifted from predominantly low-efficacy to moderate (2013-2020) and, since 2020, to high-efficacy DMTs. Compared to low-efficacy DMTs, moderate (incidence risk ratio (IRR) = 0.63, 95% CI: 0.48-0.84) and high-efficacy DMTs (IRR = 0.55, 95% CI: 0.31-0.98) were associated with fewer sADRs, and high-efficacy DMTs had higher odds of reporting zero sADRs (OR = 8.61, 95% CI: 2.34-31.76). We observed signals of a higher likelihood of severe sADRs in high-efficacy DMTs (OR = 1.41, 95% CI: 0.55-3.24) compared to low-efficacy DMTs, although this was not statistically significant. Conclusion: Patient self-reports can reliably capture trends in DMT use. In Switzerland, the first DMT use has evolved, with patients starting DMTs earlier and more frequently with higher-efficacy DMTs. While moderate and high-efficacy DMTs were associated with fewer sADRs, they may also carry a higher risk of severe sADRs, underscoring the need to balance personal preferences, efficacy, and safety in first-line MS treatment.