Groene Hart Ziekenhuis

Author Of 2 Presentations

Biostatistical Methods Poster Presentation

P0018 - Variability of the response to immunotherapy among sub-groups of patients with multiple sclerosis (ID 1239)

Abstract

Background

Our current understanding of demographic and clinical modifiers of the effectiveness of multiple sclerosis (MS) therapies is limited.

Objectives

To assess whether patients’ response to disease modifying therapies (DMT) in MS varies by disease activity (annualised relapse rate, presence of new MRI lesions), disability, age, MS duration or disease phenotype.

Methods

Using the international MSBase registry, we selected patients with MS followed for ≥1 year, with ≥3 visits, ≥1 visit per year. Marginal structural models (MSMs) were used to compare the hazard ratios (HR) of 6-month confirmed worsening and improvement of disability (EDSS), and the incidence of relapses between treated and untreated periods. MSMs were continuously re-adjusted for patient age, sex, pregnancy, date, time from first symptom, prior relapse history, disability and MRI activity.

Results

Among 23 687 patients with relapsing MS, those on DMT experienced 20% greater chance of disability improvement [HR 1.20 (95% CI 1.0-1.5)], 47% lower risk of disability worsening [HR 0.53 (0.39-0.71)] and 51% reduction in relapses [HR 0.49 (0.43-0.55)]. The effect of DMT on relapses and EDSS worsening was attenuated with longer MS duration and higher prior relapse rate. The effect of DMT on EDSS improvement and relapses was more evident in low EDSS categories. DMT was associated with 51% EDSS improvement in patients without new MRI lesions [HR 1.51 (1.00-2.28)] compared to 4% in those with MRI activity [HR 1.04 (0.88-1.24)]. Among 26329 participants with relapsing or progressive MS, DMT was associated with 25% reduction in EDSS worsening and 42% reduction in relapses in patients with relapsing MS [HR 0.75 (0.65-0.86) and HR 0.58 (CI 0.54-62), respectively], while evidence for such beneficial effects of treatment in patients with progressive MS was not found [HR 1.11 (0.91-1.46) and HR 1.16 (0.91-1.46), respectively].

Conclusions

DMTs are associated with reduction in relapse frequency, progression of disability, and increased chance of recovery from disability. In general, the effectiveness of DMTs was most pronounced in subgroups with shorter MS duration, lower EDSS, lower relapse rate and relapsing MS phenotype.

Collapse
Observational Studies Poster Presentation

P0862 - Disability accrual in primary-progressive & secondary-progressive multiple sclerosis (ID 1232)

Abstract

Background

Some cohort studies have reported similar onset age and disability accrual in primary and secondary progressive MS (PPMS, SPMS); others have reported later onset and faster disability accrual in SPMS. Comparisons are complicated by differences in baseline disability and exposure to disease-modifying therapies (DMT), and by lack of a standardized definition of SPMS.

Objectives

We compared hazards of disability accrual in PPMS and SPMS patients from the MSBase cohort using multivariable Cox models, applying validated diagnostic criteria for SPMS (Lorscheider et al., Brain 2016).

Methods

Inclusion required adult-onset progressive MS; ≥ 3 recorded Expanded Disability Status Scale (EDSS) scores; and, for SPMS, initial records with EDSS ≤ 3 to allow objective identification of SPMS conversion. Phenotypes were subgrouped as active (PPMS-A, SPMS-A) if ≥ 1 progressive-phase relapse was recorded, and inactive (PPMS-N, SPMS-N) otherwise. Disability accrual was defined by sustained EDSS increases confirmed over ≥ 6 months. Hazard ratios (HR) for disability accrual were obtained using Andersen-Gill Cox models, adjusted for sex and time-varying age, disability, visit frequency, and proportion of time on DMT or immunosuppressive therapy. Sensitivity analyses were performed using (1) PPMS and SPMS diagnosed since 1995, and (2) physician-diagnosed SPMS. Cumulative probability of reaching EDSS ≥ 7 (wheelchair required) was assessed (Kaplan-Meier).

Results

5461 patients were included (1257 PPMS-N; 1308 PPMS-A; 1731 SPMS-N; 1165 SPMS-A). Age at progression onset was older in SPMS than PPMS (47.2 ± 10.2, vs. 41.5 ± 10.7 [mean ± SD]), and in the inactive subgroups of each phenotype. Hazard of disability accrual was decreased in SPMS relative to PPMS (HR 0.85; 95% CI 0.78–0.92); decreased by proportion of time on DMT (HR 0.99 per 10% increment; 0.98–0.99); and higher in males (1.18; 1.12–1.25). Relative to PPMS-N, hazard was decreased in SPMS-A (0.79; 0.71–0.87) but similar for PPMS-A (1.01; 0.93–1.10) and SPMS-N (0.94; 0.85–1.05). Sensitivity analyses corroborated these results. However, patients with SPMS-A reached EDSS ≥ 7 at younger ages (cumulative probability 30% by 57, vs. 64–66 for SPMS-N, PPMS-A, PPMS-N).

Conclusions

Progressive phase onset is later in SPMS than PPMS. Hazard of disability accrual during the progressive phase is lower in SPMS than PPMS. However, patients with SPMS-A reach wheelchair requirement younger than other progressive phenotypes, reflecting earlier progression onset versus SPMS-N, and greater disability at onset versus PPMS

Collapse