MDF’s Patient-Focused Drug Development (PFDD) meeting, held in 2016 in conjunction with the U.S. Food and Drug Administration (FDA), highlighted the critical role of patients in developing clinically-meaningful outcome measures to facilitate drug development and approval. Identification of the symptoms regarded as most important to patients and caregivers, and the benefits they would most hope to derive from a therapy, provides critical guidance that must be included from the earliest stages of drug development.
Patient registries, like MDF’s Myotonic Dystrophy Family Registry, the National Registry for Myotonic Dystrophy & Facioscapulohumeral Dystrophy at the University of Rochester, the DM-Scope Registry in France, and the UK Myotonic Dystrophy Patient Registry, represent critically important data repositories to facilitate studies of the burden of disease for those living with myotonic dystrophy (DM).
The UK DM Patient Registry published a cross-sectional analysis of self-reported data from 556 myotonic dystrophy type 1 (DM1) patients with a confirmed diagnosis, representing approximately 8.5% of the estimated affected population in the United Kingdom (UK). Registered patients were also able to nominate healthcare specialists to enter their genetic and clinical data; these data augmented patient profiles and served to validate the patient-reported registry format.
Registrant gender was equally distributed (51% female) and a positive family history of DM was reported by 89% of registrants. Mean age of onset was 33 years. Fatigue/daytime sleepiness (79%) and myotonia (78%) were the most frequently reported symptoms—the occurrence of myotonia positively correlated with fatigue, dysphagia and ambulatory status. As in a prior report by the DM-Scope Registry, the UK cohort showed a higher frequency of severe myotonia in males, although fatigue did not show gender bias. Men also reported a higher frequency of cardiac abnormalities, non-invasive ventilation, and mobility impairments, while cataract surgery was more common in women. Most patients (65%) did not require assistive devices to walk. Severity of symptoms did not correlate with CTG repeat length obtained at the time of genetic testing.
While only one-third of patients reported having EKG, 48% of those were diagnosed with a cardiac conduction system abnormality and 36% had received an implanted cardiac device. Non-invasive ventilation was used regularly by 15% of patients. Of the patients with data available, 26% reported cataract surgery.
The UK group reported that the delays in receiving a genetic diagnosis of DM1 remain substantial and do not seem to have improved since the advent of genetic testing in 1996. They stress the importance of reducing the genetic diagnostic odyssey, not only to improve patient care and quality of life, but also to facilitate community readiness for interventional trials and approved therapies.
Taken together, knowledge of the symptoms that are most important to DM1 patients provides guidance not only for improved care, but also for the development of novel therapeutics. Studies such as that reported here, from the UK registry, provide an evidence-based underpinning that is essential for progress. An improved collaborative environment, whereby registry data is more readily shared, is a goal that will not only improve the science, but is in the best interests of those living with DM.
The UK Myotonic Dystrophy Patient Registry: Facilitating and Accelerating Clinical Research
Wood L, Cordts I, Atalaia A, Marini-Bettolo C, Maddison P, Phillips M, Roberts M, Rogers M, Hammans S, Straub V, Petty R, Orrell R, Monckton DG, Nikolenko N, Jimenez-Moreno AC, Thompson R, Hilton-Jones D, Turner C, Lochmüller H.
J Neurol. 2017 Apr 10. doi: 10.1007/s00415-017-8483-2. [Epub ahead of print]