RESUMEN
The objective of this study was to investigate confirmed progression independent of relapse activity in relapsing-remitting multiple sclerosis patients under long-term natalizumab treatment. We performed a retrospective, cross-sectional study of clinical data captured between 1994 and 2019 at two German multiple sclerosis tertiary referral centres. Data files of all relapsing-remitting multiple sclerosis patients treated with natalizumab for ≥24 months were analysed. Confirmed progression independent of relapse activity was defined as ≥12 week confirmed disability progression on a roving Expanded Disability Status Scale reference score by 1 point in patients with an Expanded Disability Status Scale score ≤3 or 0.5 in patients with an Expanded Disability Status Scale score ≥3.5 in the absence of a relapse. Cox proportional hazard models were used to analyse the probability of developing confirmed progression independent of relapse activity depending on both disease and natalizumab treatment duration. Among the 184 patients identified, 44 (24%) developed confirmed progression independent of relapse activity under natalizumab irrespective of the Expanded Disability Status Scale score at natalizumab onset. Time to confirmed progression independent of relapse activity was not affected by Expanded Disability Status Scale at natalizumab onset (categorized by Expanded Disability Status Scale score ≤3.5 versus >3.5) nor by duration of disease nor by duration of therapy. Confirmed progression independent of relapse activity occurred earlier in the disease course in patients with an earlier natalizumab therapy onset with regard to disease duration. A stepwise forward regression analysis revealed disease duration as the main factor for confirmed progression independent of relapse activity development (P = 0.005). Taken together, confirmed progression independent of relapse activity occurs in a substantial proportion of patients on long-term natalizumab treatment and independent of Expanded Disability Status Scale score at natalizumab onset. Our findings suggest that patients who are initiated on natalizumab early during disease course, usually in order to treat an aggressive clinical phenotype, have a higher risk of early confirmed progression independent of relapse activity.
RESUMEN
OBJECTIVE: The objective of the study was the analysis of adherence and self-perceived treatment response to long-term botulinum neurotoxin type A (BoNT-A) treatment in different neurological indications. METHODS: In this retrospective, monocentric, observational study, cross-sectional and longitudinal data of 1351 patients documenting 20705 injection appointments at the BoNT outpatient clinic of Heinrich Heine University Duesseldorf between 1989 and 2014 were retrospectively analyzed. Patients had been treated with BoNT for neurological conditions, including cervical dystonia (CD), blepharospasm (BSP), other dystonia (ODT), hemifacial spasm (HFS), and spasticity (SPAS). The parameters longitudinally analyzed for the entire cohort were therapy duration as well as the mean and cumulative BoNT-A dose. Cross-sectionally, for subgroups of at least 721, patients' global self-perceived quality of health and life, global self-perceived reduction of symptoms by BoNT-A treatment as well as the clinical global impression were evaluated. Furthermore, mouse hemidiaphragm assay antibodies (MHDA-ABs) were analyzed in a subgroup. RESULTS: The mean treatment duration was 4.58 years (95% CI 4.32-4.84), and 678 (50.2%) therapy dropouts of 1351 patients occurred within the first 8 years. Therapy adherence and self-perceived symptom reduction in long-term BoNT-A treatment over the years were significantly longer in BSP, HFS, and CD patients than in ODT and SPAS patients. INTERPRETATION: The treatment indication determines long-term adherence and self-perceived symptom reduction in BoNT-A therapy, which are better in BSP, HFS, and CD patients than in ODT and SPAS patients. MHDA-ABs had a significant impact on global self-perceived symptom reduction, but with only a limited degree.
