Author Of 2 Presentations
P0198 - Comparative effectiveness of different DMT strategies in new onset RRMS; First results of the CombatMS trial (ID 1812)
Abstract
Background
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).
Objectives
To compare effectiveness of different DMT strategies for early RRMS, defined as treatment start latest two years after symptom onset.
Methods
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.
Results
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.
Conclusions
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.
P0491 - Safety Outcomes after Treatment with Alemtuzumab or Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis Patients (ID 584)
Abstract
Background
Induction therapy that cause long-term cessation of disease-specific inflammation is an emerging treatment option for multiple sclerosis (MS). Alemtuzumab was the first induction-type therapy to be approved for relapsing-remitting MS (RRMS) in 2013/2014, while autologous hematopoietic stem cell transplantation (AHSCT) is an induction-type medical procedure which has been used to treat MS since 1995 and was approved for use in RRMS in Sweden in 2016.
Objectives
This study aimed to assess safety outcomes for alemtuzumab and AHSCT, compared to non-induction disease-modifying therapies.
Methods
We performed a population-based cohort study linking the Swedish MS Register to national healthcare registers. Alemtuzumab, AHSCT, and a matched reference group of non-induction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. Main outcomes were death, thyroid disease, non-thyroid autoimmune disease, and infection.
Results
We identified 132 alemtuzumab and 139 AHSCT-treated patients, together with 2486 matched patients treated with non-induction therapies. Four patients in the alemtuzumab group died (incidence rate [IR] per 1000 person years=8.6, 95% confidence interval [CI]=2.3-22.0) compared to one patient in the AHSCT group (IR=1.7, 95% CI=0.0-9.6) and a mortality rate in the reference group of 0.7 (95% CI=0.3-1.3). Thyroid disease was most frequent in the alemtuzumab group (IR=109, 95% CI=75-154), but also occurred more often for AHSCT (IR=34, 95% CI=18-56) compared to the reference (IR=5.3 95% CI=3.9-7.1). The incidence of non-thyroid autoimmune disease was similar in all groups. IR for infection occurring ≥6 months from therapy initiation was 53 (95% CI=30-87) for alemtuzumab, 108 (95% CI=75-150) for AHSCT, and 51 (95% CI=46-57) for the reference.
Conclusions
We confirmed a high incidence of thyroid disease in alemtuzumab- and to a smaller extent also AHSCT-treated patients, and found a higher incidence of infections for AHSCT compared to both alemtuzumab and non-induction therapies. Interestingly, the incidence of first-ever non-thyroid autoimmune events was similar between the groups. Disorders relating to reproductive organs and fertility were common in the AHSCT group, especially in females. Other adverse events were rare. Overall mortality was slightly higher in the alemtuzumab group, but only one of the four deaths was clearly linked to the treatment.