Dataset Information

Informing Medication Discontinuation Decisions among Older Adults with Relapsing-Onset Multiple Sclerosis.

ABSTRACT:

Background

For older adults with relapsing-onset multiple sclerosis (MS), limited information is available to inform if, or when, disease-modifying drugs (DMDs) may be safely discontinued.

Objective

The aim of this study was to project the outcomes of DMD discontinuation among older adults with relapsing-onset MS.

Methods

We projected the 10-year outcomes of discontinuation of a DMD (interferon-?, fingolimod, or natalizumab) among older adults (aged 55 or 70 years) who were relapse-free for 5 or more years and had not reached an Expanded Disability Status Scale (EDSS) score of 6. Outcomes included the percentage of people who had at least one relapse or reached EDSS 6, and quality-adjusted life-years (QALYs), which incorporated both relapses and disability. We used a simulation modeling approach. With increased age, relapses decreased and the effectiveness of DMDs for disability outcomes also decreased.

Results

We found lower projected benefits for DMD continuation at 70 years of age than at 55 years of age. Compared with discontinuation, the projected benefit of DMD continuation ranged from 0.007 to 0.017 QALYs at 55 years of age and dropped to 0.002-0.006 at 70 years of age. The annual projected benefits of DMD continuation (0.1-3.0 quality-adjusted life-days) were very low compared with typical patient preferences regarding treatment burden.

Conclusion

The benefits of DMDs may not be substantial among older adults with relapsing-onset MS. Direct clinical evidence remains limited and the decision of whether to discontinue a DMD should also take into account patient preferences. It is important to gain a better understanding of how age-related changes in the trajectory of relapsing-onset MS affect treatment effectiveness among older adults.

SUBMITTER: Schwehr NA

PROVIDER: S-EPMC7047543 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Informing Medication Discontinuation Decisions among Older Adults with Relapsing-Onset Multiple Sclerosis.

Schwehr Natalie A NA Kuntz Karen M KM Enns Eva A EA Shippee Nathan D ND Kingwell Elaine E Tremlett Helen H Carpenter Adam F AF Butler Mary M

Drugs & aging 20200301 3

<h4>Background</h4>For older adults with relapsing-onset multiple sclerosis (MS), limited information is available to inform if, or when, disease-modifying drugs (DMDs) may be safely discontinued.<h4>Objective</h4>The aim of this study was to project the outcomes of DMD discontinuation among older adults with relapsing-onset MS.<h4>Methods</h4>We projected the 10-year outcomes of discontinuation of a DMD (interferon-β, fingolimod, or natalizumab) among older adults (aged 55 or 70 years) who were ...[more]

PMID: 31916231

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Project description:Our inability to reliably predict disease outcomes in multiple sclerosis remains an issue for clinicians and clinical trialists. This study aims to create, from available clinical, genetic and environmental factors; a clinical-environmental-genotypic prognostic index to predict the probability of new relapses and disability worsening. The analyses cohort included prospectively assessed multiple sclerosis cases (N = 253) with 2858 repeated observations measured over 10 years. N = 219 had been diagnosed as relapsing-onset, while N = 34 remained as clinically isolated syndrome by the 10th-year review. Genotype data were available for 199 genetic variants associated with multiple sclerosis risk. Penalized Cox regression models were used to select potential genetic variants and predict risk for relapses and/or worsening of disability. Multivariable Cox regression models with backward elimination were then used to construct clinical-environmental, genetic and clinical-environmental-genotypic prognostic index, respectively. Robust time-course predictions were obtained by Landmarking. To validate our models, Weibull calibration models were used, and the Chi-square statistics, Harrell's C-index and pseudo-R 2 were used to compare models. The predictive performance at diagnosis was evaluated using the Kullback-Leibler and Brier (dynamic) prediction error (reduction) curves. The combined index (clinical-environmental-genotypic) predicted a quadratic time-dynamic disease course in terms of worsening (HR = 2.74, CI: 2.00-3.76; pseudo-R 2=0.64; C-index = 0.76), relapses (HR = 2.16, CI: 1.74-2.68; pseudo-R 2 = 0.91; C-index = 0.85), or both (HR = 3.32, CI: 1.88-5.86; pseudo-R 2 = 0.72; C-index = 0.77). The Kullback-Leibler and Brier curves suggested that for short-term prognosis (≤5 years from diagnosis), the clinical-environmental components of disease were more relevant, whereas the genetic components reduced the prediction errors only in the long-term (≥5 years from diagnosis). The combined components performed slightly better than the individual ones, although their prognostic sensitivities were largely modulated by the clinical-environmental components. We have created a clinical-environmental-genotypic prognostic index using relevant clinical, environmental, and genetic predictors, and obtained robust dynamic predictions for the probability of developing new relapses and worsening of symptoms in multiple sclerosis. Our prognostic index provides reliable information that is relevant for long-term prognostication and may be used as a selection criterion and risk stratification tool for clinical trials. Further work to investigate component interactions is required and to validate the index in independent data sets.

Dataset Information

Informing Medication Discontinuation Decisions among Older Adults with Relapsing-Onset Multiple Sclerosis.

Background

Objective

Methods

Results

Conclusion

Publications

Informing Medication Discontinuation Decisions among Older Adults with Relapsing-Onset Multiple Sclerosis.

Similar Datasets

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