Early intensive versus escalation treatment in patients with relapsing-remitting multiple sclerosis in Austria.

OBJECTIVES: To compare the effectiveness of early intensive treatment (EIT) versus escalation treatment (ESC) in a nationwide observational cohort of almost 1000 people with relapsing-remitting multiple sclerosis (RRMS). MATERIALS AND METHODS: The EIT cohort started with alemtuzumab (AZM), cladribine (CLAD), fingolimod (FTY), natalizumab (NTZ), ocrelizumab (OCR), or ozanimod (OZA); whereas, the ESC cohort was escalated from dimethylfumarate (DMF) or teriflunomide (TERI) to AZM, CLAD, FTY, NTZ, OCR, or OZA within the Austrian MS Treatment Registry. Patients had to stay on therapy for at least 3 months and up to 16 years. The EIT cohort included 743 and the ESC cohort 227 RRMS patients. We used multinomial propensity scores for inverse probability weighting in generalized linear (GLM) and Cox proportional hazards models to correct for the bias of this non-randomized registry study. RESULTS: Estimated mean annualized relapse rates (ARR) were 0.09 for EIT and 0.4 for ESC patients. The incidence rate ratio (IRR) in the GLM model for relapses showed a decreased relapse probability of 78% for the EIT versus ESC cohort [IRR = 0.22, 95% CI (0.16-0.30), p < 0.001]. Analyzing the time to the first relapse by Cox regression, a hazard ratio (HR) of 0.17 [95% CI (0.13-0.22), p < 0.001] revealed a decreased risk of 83% for the EIT group. Regarding sustained Expanded Disability Status Scale (EDSS) progression for 12 weeks, a HR of 0.55 [95% CI (0.40-0.76), p < 0.001] showed a decreased probability of 45% for the EIT cohort. CONCLUSIONS: ESC treatment after DMF and TERI revealed a higher relapse and EDSS progression probability compared to EIT in Austrian RRMS patients. Therefore, an early intensive treatment should be started in patients with an active or highly active disease course.

Effects of horizontal versus vertical switching of disease-modifying treatment after platform drugs on disease activity in patients with relapsing-remitting multiple sclerosis in Austria.

OBJECTIVES: To compare in a nationwide observational cohort the effectiveness, frequency and reasons for treatment interruption of dimethylfumarate (DMF) and teriflunomide (TERI) (horizontal switchers) versus alemtuzumab (AZM), cladribine (CLAD), fingolimod (FTY), natalizumab (NTZ), ocrelizumab (OCR) and ozanimod (OZA) (vertical switchers) in patients with relapsing-remitting multiple sclerosis (pwRRMS) and prior interferon beta (IFN-beta) or glatiramer-acetate (GLAT) treatment. MATERIALS AND METHODS: The "horizontal switch cohort" included 669 and the "vertical switch cohort" 800 RRMS patients. We used propensity scores for inverse probability weighting in generalized linear (GLM) and Cox proportional hazards models to correct for bias in this non-randomized registry study. RESULTS: Estimated mean annualized relapse rates (ARR) were 0.39 for horizontal and 0.17 for vertical switchers. The incidence rate ratio (IRR) in the GLM model showed an increased relapse probability of 86% for horizontal versus vertical switchers (IRR = 1.86; 95% CI 1.38-2.50; p < 0.001). Analyzing the time to the first relapse after treatment switch by Cox regression, a hazard ratio of 1.58 (95% CI 1.24-2.02; p < 0.001) indicated an increased risk of 58% for horizontal switchers. The hazard ratios for treatment interruption comparing horizontal versus vertical switchers were 1.78 (95% CI 1.46-2.18; p < 0.001). CONCLUSIONS: Horizontal switching after a platform therapy resulted in a higher relapse and interrupt probability and was associated with a trend towards less EDSS improvement comparing to vertical switching in Austrian RRMS patients.

Long-term outcome and predictors of long-term disease activity in natalizumab-treated patients with multiple sclerosis: real life data from the Austrian MS Treatment Registry.

OBJECTIVES: To evaluate long-term effectiveness of natalizumab (NTZ) and to determine demographic, clinical, and radiological predictors regarding long-term disease activity (≥ 7 years) in a nationwide observational cohort, using data collected prospectively in a real-life setting. MATERIALS AND METHODS: We analysed data from 230 patients from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), who had started treatment with NTZ at any time since 2006 and stayed on NTZ for at least 7 years without treatment gap of more than three months. RESULTS: Estimated mean annualised relapse rates (ARR) over a mean treatment period of 9.3 years were 0.07 for NTZ. Sustained EDSS progression for 12 weeks was observed in 36 (19%) patients and for 24 weeks in 31 (16.3%) cases. Sustained EDSS regression for 12 and 24 weeks was seen in 45 (23.7%) and 42 (22.1%) cases. The baseline parameters ≥ 1 Gadolinium-enhancing MRI lesion(s) [incidence rate ratio (IRR) of 0.409 (95% CI 0.283-0.593), p = 0.001], ARR ≤ 1 in the prior 12 month before treatment initiation with NTZ [IRR of 0.353 (95% CI 0.200-0.623), p = 0.001] and EDSS ≤ 1 [incidence rate ratio (IRR) of 0.081 (95% CI 0.011-0.581), p = 0.012] were significantly associated with a reduced relapse risk, whereas a disease duration ≤ 5 years increased significantly the ARR [IRR of 1.851 (95% CI 1.249-2.743), p = 0.002]. The only predictive baseline parameter for experiencing EDSS progression (sustained for 12 and 24 weeks) was age > 35 years [HR of 2.482 (95% CI 1.110-5.549), p = 0.027, and HR of 2.492 (95% CI 1.039-5.978), p = 0.041, respectively]. CONCLUSIONS: These real-life data show a stable disease course regarding relapse activity and disease progression under NTZ treatment for more than 7 years. The main predictors for disease activity were higher relapse rate before treatment initiation, higher disability, shorter disease duration and absence of Gadolinium-enhancing MRI lesions at baseline. Older age at NTZ start was the only significant risk factor for disease progression over long-term.

Oral therapies for treatment of relapsing-remitting multiple sclerosis in Austria: a 2-year comparison using an inverse probability weighting method.

OBJECTIVES: To compare the efficacies, frequencies and reasons for treatment interruption of fingolimod (FTY), dimethyl fumarate (DMF) or teriflunomide (TERI) in a nationwide observational cohort. MATERIALS AND METHODS: Two cohorts of patients with relapsing-remitting multiple sclerosis (RRMS) having started treatment with FTY, DMF or TERI documented in the Austrian MS Treatment Registry (AMSTR) since 2014 and either staying on therapy for at least 24 months (24 m cohort) or with at least one follow-up visit after start of treatment (total cohort). The 24 m cohort included 629 RRMS patients: 295 in the FTY, 227 in the DMF and 107 in the TERI group. We used multinomial propensity scores for inverse probability weighting in generalized linear and Cox proportional hazards models to correct for the bias of this non-randomised registry study. RESULTS: Estimated mean annualized relapse rates (ARR) over 24 months were 0.13 for FTY, 0.09 for DMF and 0.11 for TERI treatment. For TERI in comparison with DMF, we observed higher probability for treatment interruption (p = 0.023) and reduced sustained EDSS regression for 12 (p = 0.016) and 24 weeks (p = 0.031) and, for the comparison of DMF versus FTY, a reduced sustained EDSS progression for 12 weeks (p = 0.02). CONCLUSIONS: Relapse rates with treatment with FTY, DMF and TERI were similar. Patients treated with DMF showed less sustained disability progression for 12 weeks than FTY-treated patients. However, FTY and DMF treatment was associated with more likely EDSS regression for 12 and 24 weeks and a lower probability for treatment interruption as compared to TERI-treated patients.

Correction to: Switching from natalizumab to fingolimod treatment in multiple sclerosis: real life data from the Austrian MS Treatment Registry.

The original version of this article unfortunately contained a mistake. First and last names of the authors were interchanged. The correct author names are given below.

Switching from natalizumab to fingolimod treatment in multiple sclerosis: real life data from the Austrian MS Treatment Registry.

OBJECTIVES: To compare the efficacy of natalizumab (NTZ) and fingolimod (FTY) in the treatment of relapsing-remitting multiple sclerosis (MS) in sequential use in common and as a function of transition periods in a nationwide observational cohort using prospectively collected data from a real-life setting. MATERIALS AND METHODS: We included 195 patients from the Austrian MS Treatment Registry, who had started treatment with NTZ at any time since 2006 and stayed on NTZ for at least 24 months, switched afterwards within 1 year to FTY and stayed on FTY for at least another 12 months. Transition periods between NTZ and FTY were grouped into three different intervals: < 3 months (135 patients), 3-6 months (44 patients), and 6-12 months (16 patients). RESULTS: Estimated mean annualized relapse rates (ARR) over a mean treatment period of 44 months were 0.26 for NTZ and 0.32 for FTY (p = 0.381) over 46 months. In the treatment gap, differences were found concerning the relapse probability, seven (5.2%) patients in the < 3 months group, six (13.6%) in thef 3-6 months group, and seven (43.8%) in the 6-12 months group (p < 0.001). After this treatment gap, no significant differences concerning ARR, EDSS change, EDSS progression, and regression were observed regardless the proceeding transition periods. Significantly higher efficacy of NTZ compared to FTY in sequential use was found regarding EDSS change, EDSS progression, and EDSS regression sustained for 12 and 24 weeks. CONCLUSIONS: First, we here show an increased short-time risk for relapses during the treatment gap between NTZ and FTY therapy, dependent on the length of transition time. Second, the disease course after switching to FTY remained stable in the long-term evaluation. Therefore, switching from NTZ to FTY in a real-world setting appears efficacious and safe, but this data advocate for a short switching gap of 3 months or less.

Real-life use of oral disease-modifying treatments in Austria.

OBJECTIVES: To compare the efficacy, frequencies and reasons for treatment interruption of fingolimod, dimethyl fumarate (DMF) or teriflunomide in a nationwide observational cohort using prospectively collected data. MATERIALS AND METHODS: Two cohorts of patients with relapsing-remitting multiple sclerosis (RRMS) starting treatment with fingolimod, dimethyl fumarate or teriflunomide documented in the Austrian MS Treatment Registry (AMSTR) since 2014 and either staying on therapy for at least 12 months (12m cohort) or having at least one follow-up visit (total cohort). The 12m cohort included 664 RRMS patients: 315 in the fingolimod, 232 in the DMF and 117 in the teriflunomide group. Multinomial propensity scores were used for inverse probability weighting to correct for the bias of this non-randomised registry study. RESULTS: Estimated mean annualized relapse rates (ARR) over 12 months were 0.21 for fingolimod, 0.20 for DMF and 0.19 for teriflunomide treatment, causing an incidence rate ratio (IRR) of 1.01 for fingolimod vs DMF (P = 0.96) and 0.92 for teriflunomide vs DMF (P = 0.84). No differences were found regarding the probability for experiencing a relapse, EDSS change, EDSS progression and EDSS regression, except regarding less sustained EDSS progression for 12 weeks concerning DMF vs fingolimod (P = 0.02). The hazard ratio for treatment interruption comparing fingolimod vs DMF was 1.03 (P = 0.86) and 1.07 comparing teriflunomide vs DMF (P = 0.77). CONCLUSIONS: In the AMSTR, there was no difference concerning ARR, probability for a relapse, EDSS change, treatment interruption, EDSS progression or regression between oral DMTs, except regarding less sustained EDSS progression for 12 weeks concerning DMF vs fingolimod.