Measuring PFS Outcome Might Help Researchers Evaluate Huntington’s Progression, Study Suggests

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by Alice Melão |

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Identifying Huntington’s disease progression can be a challenge in clinical trials. Now, an international team of researchers proposes in an article published in JAMA Neurology the use of a new composite measure to help evaluate disease progression prior to a motor diagnosis.

Progression of Huntington’s disease is characterized by the occurrence of motor and cognitive impairment and behavioral changes. The prediction of disease incidence is possible before any signs or symptoms appear. A simple genetic test can detect whether a person is a carrier of the mutation in the HTT gene that causes Huntington’s.

Early genetic screening can help identify those who will develop Huntington’s symptoms, giving clinicians the means to improve the follow-up, treatment, and care of patients.

Diagnosing Huntington’s disease is based mainly on the evaluation of motor skills through the Unified Huntington’s Disease Rating Scale (UHDRS). The rating scale can identify whether the motor symptoms a person displays are caused by Huntington’s with a 99% degree of confidence.

However, the use of motor diagnosis during clinical trials as a measurement of treatment effectiveness can be difficult, because Huntington’s is a slow, progressive illness. In most cases, the occurrence of motor events does not happen in the typical period a clinical trial lasts.

In the study, “Survival End Points for Huntington Disease Trials Prior to a Motor Diagnosis,” an international team of researchers evaluated the potential of analyzing progression-free survival (PFS), which is widely used in oncology studies, for use as an alternative measurement of Huntington’s disease progression.

“Progression-free survival is defined as the time elapsed from treatment initiation to the first event of HD [Huntington’s disease] progression or motor diagnosis, whichever comes first,” the researchers wrote in their report.

The team determined PFS primarily by time for motor diagnosis. In the absence of this diagnosis, they considered the time for detection of clinically meaningful changes (CMC) on the UHDRS total motor score, total functional capacity, the symbol digit modalities test, and the Stroop word test.

In the study, researchers analyzed nearly seven years of follow-up data, collected between January 2008 and November 2014, from a total of 167 individuals with identified HTT mutations and 156 non-carriers.

In addition, they tested the PFS approach for Huntington’s progression evaluation in a group of 366 people with and without HTT mutations whose clinical data were collected between February 2006 and December 2009.

With the use of the composite evaluation of PFS, the researchers were able to estimate Huntington’s progression in patients who did not have a motor diagnosis. In addition, they showed that the CMC evaluation they propose in the study was valid in the two groups of patients included in the study. This suggests that the PFS determination can be applied to the general Huntington’s population to define disease progression.

“This approach is especially appealing when a researcher wants to examine whether a treatment delays motor onset,” researchers wrote.

The team highlights that use of PFS can help in the planning of clinical trials, especially those that are designed for evaluating preventive therapies for patients who are carriers of HTT mutations but have not yet received a motor diagnosis.