29 Nov SVC As Marker of Respiratory Decline in Amyotrophic Lateral Sclerosis

MedicalResearch.com Interview with:

Dr. Andrews

Jinsy Andrews, MD, MS
Director of Neuromuscular Clinical Trials
Columbia University
The Neurological Institute
New York, NY 10032 

MedicalResearch.com: What is the background for this study?

Response: The importance of respiratory function in Amyotrophic Lateral Sclerosis (ALS) has long been recognized. Despite ALS being a clinical diagnosis with variable presentation and variable rates of disease progression, all patients experience respiratory symptoms and inevitably die typically from respiratory failure. At present there is no validated biomarker of disease progression or clinical staging system. Direct measure of respiratory function in ALS is important and can be measured using vital capacity. Although the forced maneuver (FVC) has been widely used in patients with ALS, it can underestimate the actual lung capacity by causing fatigue or inducing bronchospasm in patients with ALS. More recently, the slow maneuver (SVC) has been used since it can be obtained from patients with advancing disease which can potentially minimize missing data and may reduce any underestimation of actual lung capacity due to a forceful effort. However, the prognostic value of the decline in SVC is unclear in patients with ALS.

MedicalResearch.com: What are the main findings?

Response: The main findings in this study of 893 placebo treated patients with Amyotrophic Lateral Sclerosis from 3 independent data sets (2 clinical trials and an ALS clinical trial database) is that these datasets had similar rates of SVC decline averaging –2.73 to –2.90 percentage points per month. Additionally, using the placebo group of the largest of the 3 datasets, the faster rate of SVC decline was associated with older age at onset and lower functional scores. The rate of decline in SVC was also associated with meaningful clinical events including respiratory failure, tracheostomy and death suggesting that it is an important indicator of clinical disease progression.

MedicalResearch.com: What should readers take away from your report?

Response: In a disease that is highly variable in presentation and progression, the rate of decline in SVC provides an objective way to assess clinical disease progression and is associated with clinical events later in the disease such as respiratory failure, tracheostomy and death. 

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Limitation of this study is that was retrospective. Further studies evaluating the change over time and its relationship to respiratory symptoms reported by the patient may add to the relevance of SVC both clinically and for clinical trials.

MedicalResearch.com: Is there anything else you would like to add?

Response: These data characterize the natural history of decline in SVC over time in patients with ALS and may be a more sensitive marker of clinical progression and may have the potential to be an outcome measure in clinical trials that can allow for more efficient trial design that could be shorter in duration or evaluating smaller cohorts of patients in the future.

Disclosures: I am a former employee of Cytokinetics and am currently a consultant for Cytokinetics. I have received research grants from Neuraltus and Roche.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Jinsy A. Andrews, Lisa Meng, Sarah F. Kulke, Stacy A. Rudnicki, Andrew A. Wolff, Michael E. Bozik, Fady I. Malik, Jeremy M. Shefner. Association Between Decline in Slow Vital Capacity and Respiratory Insufficiency, Use of Assisted Ventilation, Tracheostomy, or Death in Patients With Amyotrophic Lateral Sclerosis. JAMA Neurol. Published online November 27, 2017. doi:10.1001/jamaneurol.2017.3339

https://jamanetwork.com/journals/jamaneurology/fullarticle/2663747

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on November 29, 2017 by Marie Benz MD FAAD