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Abstract
Objective To determine whether comorbidity is associated with clinical (relapses, disability worsening) and MRI outcomes in multiple sclerosis (MS) by conducting a secondary analysis of the CombiRx clinical trial.
Methods CombiRx compared interferon beta-1a, glatiramer acetate, and the combination of these agents. For participants eligible for evaluation of 6-month confirmed disability worsening, we used medical history, concomitant medications, and adverse events to ascertain comorbidity status. Comorbid conditions evaluated included hypertension, dyslipidemia, diabetes mellitus, depression, anxiety disorders, and migraine. Clinical outcomes included disease activity consisting of protocol-defined relapses, disability worsening, and MRI activity. We summarized the prevalence of these comorbid conditions and their association with disease activity and its components using multivariable Cox regression.
Results Of the 1,008 participants randomized, 959 (95.1%) were eligible for assessment of 6-month disability worsening; for this subgroup, the median length of follow-up was 3.4 years (range 0.5–6.9 years). Overall, 55.1% of participants had ≥1 comorbidity at enrollment. After adjustment, anxiety (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.01–1.55) and dyslipidemia (HR 1.32, 95% CI 1.01–1.72) were associated with an increased hazard of any disease activity, while migraine (HR 0.80, 95% CI 0.67–0.97) was associated with a decreased hazard.
Conclusions In this large trial population with rigorously obtained outcomes, comorbid conditions were common among participants and influenced disease outcomes, including relapses. The comorbidity burden of clinical trial participants with MS may be an important factor in the outcome of clinical trials. Additional investigations of the impact of comorbidity on clinical trial outcomes and response to disease-modifying therapies are warranted.
Glossary
- CI=
- confidence interval;
- CUA=
- combined unique lesion activity;
- EDSS=
- Expanded Disability Status Scale;
- FSS=
- functional system score;
- GA=
- glatiramer acetate;
- HR=
- hazard ratio;
- IFN=
- interferon beta-1a;
- MS=
- multiple sclerosis
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 193
- Received November 13, 2019.
- Accepted in final form February 26, 2020.
- © 2020 American Academy of Neurology
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- Author response: Comorbidity is associated with disease activity in MS: Findings from the CombiRx trial
- Reader response: Comorbidity is associated with disease activity in MS: Findings from the CombiRx trial
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