Dataset Information

Long-term clinical outcomes in patients with multiple sclerosis who are initiating disease-modifying therapy with natalizumab compared with BRACETD first-line therapies.

ABSTRACT:

Background

Aggressive disease control soon after multiple sclerosis (MS) diagnosis may prevent irreversible neurological damage, and therefore early initiation of a high-efficacy disease-modifying therapy (DMT) is of clinical relevance.

Objectives

Evaluate long-term clinical outcomes in patients with MS who initiated treatment with either natalizumab or a BRACETD therapy (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate).

Design

This retrospective analysis utilized data from MSBase to create a matched population allowing comparison of first-line natalizumab to first-line BRACETD.

Methods

This study included patients who initiated treatment either with natalizumab or a BRACETD DMT within 1 year of MS diagnosis and continued treatment for ⩾6 months, after which patients could switch DMTs or discontinue treatment. Patients had a minimum follow-up time of ⩾60 months from initiation. A subgroup analysis compared the natalizumab group to patients in the BRACETD group who escalated therapy after 6 months. Outcomes included unadjusted annualized relapse rates (ARRs), time-to-first relapse, time-to-first confirmed disability improvement (CDI), and time-to-first confirmed disability worsening (CDW).

Results

After 1:1 propensity score matching, 355 BRACETD patients were matched to 355 natalizumab patients. Patients initiating natalizumab were less likely to experience a relapse over the duration of follow-up, with ARRs [95% confidence interval (CI)] of 0.080 (0.070-0.092) for natalizumab patients and 0.191 (0.178-0.205) for BRACETD patients (p < 0.0001). A Cox regression model of time-to-first relapse showed a reduced risk of relapse for natalizumab patients [hazard ratio (95% CI) of 0.52 (0.42-0.65); p < 0.001] and a more favorable time-to-first CDI. The risk of CDW was similar between groups. The subgroup analysis showed an increased relapse risk as well as a significantly higher risk of CDW for BRACETD patients.

Conclusion

Early initiation of natalizumab produced long-term benefits in relapse outcomes in comparison with BRACETD, regardless of a subsequent escalation in therapy.

SUBMITTER: Butzkueven H

PROVIDER: S-EPMC10898303 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Long-term clinical outcomes in patients with multiple sclerosis who are initiating disease-modifying therapy with natalizumab compared with BRACETD first-line therapies.

Butzkueven Helmut H Kalincik Tomas T Patti Francesco F Slee Mark M Weinstock-Guttman Bianca B Buzzard Katherine K Skibina Olga O Alroughani Raed R Prat Alexandre A Girard Marc M Horakova Dana D Havrdova Eva Kubala EK Van der Walt Anneke A Eichau Sara S Hyde Robert R Campbell Nolan N Bodhinathan Karthik K Spelman Tim T

Therapeutic advances in neurological disorders 20240226

<h4>Background</h4>Aggressive disease control soon after multiple sclerosis (MS) diagnosis may prevent irreversible neurological damage, and therefore early initiation of a high-efficacy disease-modifying therapy (DMT) is of clinical relevance.<h4>Objectives</h4>Evaluate long-term clinical outcomes in patients with MS who initiated treatment with either natalizumab or a BRACETD therapy (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate).<h4>Design</h4>This retrospective an ...[more]

PMID: 38414723

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Project description:BackgroundLimited information exists on the healthcare resource utilization (HCRU) associated with real-world natalizumab used as a first-line (1L) versus later-line (2L+) treatment in multiple sclerosis (MS).ObjectivesTo describe natalizumab use in newly diagnosed MS patients treated as 1L or 2L+ and evaluate unadjusted annualized relapse rates (ARR) and MS-related HCRU before and after treatment initiation.DesignThis retrospective observational study utilized Komodo Health Sentinel claims data from October 2015 to August 2022. The study included adults diagnosed with incident MS who initiated natalizumab treatment, with insurance coverage for at least 12 months before diagnosis and 24 months after. The index date was the first natalizumab claim on or after the diagnosis. Baseline was defined as the 365 days prior to the index date, truncated at the time of diagnosis. Follow-up ended at the earliest occurrence of death, insurance disenrollment, treatment discontinuation (gap ⩾45 days), switch to another disease-modifying therapy before natalizumab discontinuation, or study end.MethodsRelapses and HCRU were assessed using person-time methods to account for varying follow-up times. Relapses were identified using a validated claims-based algorithm, and time to first relapse was analyzed using Kaplan-Meier methods. Hazard ratios for relapse were estimated using univariate Cox models. Mean differences (MD) in HCRU between baseline and follow-up and between 1L and 2L+ treatment groups were calculated.ResultsA total of 1174 patients in the 1L group (mean age 39.0, 72.0% female) and 394 in the 2L+ group (mean age 39.7, 79.4% female) were included. Patients in the 1L group had a significantly higher baseline ARR (1.48 vs 0.92, p < 0.001) and lower on-treatment ARR (0.28 vs 0.41 for 2L+, p < 0.001). HCRU decreased significantly in the 1L group from baseline to follow-up: hospitalizations (MD 17.01 visits/year), length of stay (LOS; MD 20.96 days/year), emergency room visits (MD 9.83 visits/year), non-natalizumab outpatient visits (MD 12.11 visits/year) and long-term care facility stays (MD 22.18 days/year, p = 0.002). The 1L group showed greater reductions in inpatient visits (MD 10.01 visits//year), LOS (MD 16.73 days/year) and non-natalizumab outpatient visits (MD 11.64 visits/year) compared to the 2L+ group.ConclusionNatalizumab as a first-line treatment was associated with greater reductions in ARR and MS-related HCRU compared to later-line use.

Project description:ImportanceModerately effective therapies (METs) have been the main treatment in pediatric-onset multiple sclerosis (POMS) for years. Despite the expanding use of highly effective therapies (HETs), treatment strategies for POMS still lack consensus.ObjectiveTo assess the real-world association of HET as an index treatment compared with MET with disease activity.Design, setting, and participantsThis was a retrospective cohort study conducted from January 1, 2010, to December 8, 2022, until the last recorded visit. The median follow-up was 5.8 years. A total of 36 French MS centers participated in the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort. Of the total participants in OFSEP, only treatment-naive children with relapsing-remitting POMS who received a first HET or MET before adulthood and at least 1 follow-up clinical visit were included in the study. All eligible participants were included in the study, and none declined to participate.ExposureHET or MET at treatment initiation.Main outcomes and measuresThe primary outcome was the time to first relapse after treatment. Secondary outcomes were annualized relapse rate (ARR), magnetic resonance imaging (MRI) activity, time to Expanded Disability Status Scale (EDSS) progression, tertiary education attainment, and treatment safety/tolerability. An adapted statistical method was used to model the logarithm of event rate by penalized splines of time, allowing adjustment for effects of covariates that is sensitive to nonlinearity and interactions.ResultsOf the 3841 children (5.2% of 74 367 total participants in OFSEP), 530 patients (mean [SD] age, 16.0 [1.8] years; 364 female [68.7%]) were included in the study. In study patients, both treatment strategies were associated with a reduced risk of first relapse within the first 2 years. HET dampened disease activity with a 54% reduction in first relapse risk (adjusted hazard ratio [HR], 0.46; 95% CI, 0.31-0.67; P < .001) sustained over 5 years, confirmed on MRI activity (adjusted odds ratio [OR], 0.34; 95% CI, 0.18-0.66; P = .001), and with a better tolerability pattern than MET. The risk of discontinuation at 2 years was 6 times higher with MET (HR, 5.97; 95% CI, 2.92-12.20). The primary reasons for treatment discontinuation were lack of efficacy and intolerance. Index treatment was not associated with EDSS progression or tertiary education attainment (adjusted OR, 0.51; 95% CI, 0.24-1.10; P = .09).Conclusions and relevanceResults of this cohort study suggest that compared with MET, initial HET in POMS was associated with a reduction in the risk of first relapse with an optimal outcome within the first 2 years and was associated with a lower rate of treatment switching and a better midterm tolerance in children. These findings suggest prioritizing initial HET in POMS, although long-term safety studies are needed.

Dataset Information

Long-term clinical outcomes in patients with multiple sclerosis who are initiating disease-modifying therapy with natalizumab compared with BRACETD first-line therapies.

Background

Objectives

Design

Methods

Results

Conclusion

Publications

Long-term clinical outcomes in patients with multiple sclerosis who are initiating disease-modifying therapy with natalizumab compared with BRACETD first-line therapies.

Similar Datasets

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