Increasing evidence suggest that early initiation of highly effective disease modulatory therapies (DMTs) reduce disability progression in relapsing-remitting MS (RRMS), but few studies strive to identify the most successful DMT strategy for new onset RRMS by also including drug survival. The CombatMS study is a Swedish nationwide observational drug trial involving all Sweden´s University Clinics (NCT03193866).
To compare effectiveness of different DMT strategies for early RRMS, defined as treatment start latest two years after symptom onset.
The CombatMS population comprises 3500 RRMS patients starting a first DMT or doing a first DMT switch between Jan 1st 2011 to Oct 31st 2018, who from study start (June 2017) undergo an annual structured follow up with EDSS, patient reported outcomes and imaging. For this study we selected patients aged 18 to 50 years starting a first DMT within two years from symptom onset with a previously registered EDSS score ≤ 12 months before or ≤ 2 months after treatment start. We restricted the analysis to the four most frequent DMT choices in this category: interferons (INF), natalizumab (NTZ), dimethyl fumarate (DMF) and rituximab (RTX), resulting in total study population of 954 patients. We used an ever-treated approach, disregarding if the patient later switched or stopped therapy. Two-year disability progression was determined by comparing the baseline EDSS score to the EDSS score closest to two years, while relapse rate and drug survival were measured for a two-year follow-up period from treatment start.
The proportion of patients experiencing disability progression was 7.3 % (NTZ), 7.6 % (RTX), 12.4 % (DMF) and 19.2 % (INF). After adjusting for baseline differences in age, sex, region of residence, baseline EDSS, relapse rate before DMT start, and follow-up time, only the difference between RTX and INF remained significant. Two-year drug survival ranged from 38.3 % (INF) to 92.4 % (RTX), with these two extremes being significantly different from all other DMTs. Annualized relapse rates varied from 0.04 (RTX) to 0.27 (INF), with significant difference between all other DMTs and INF and between RTX and DMF.
We observe relatively large differences in two-year outcomes across the studied DMTs, where the most striking findings are that patients initiating INF perform worse and those starting RTX better in most comparisons. Longer observation times will be needed to inform on risk-benefit with different DMT choices beyond two years.