#AANAM – Progression May Be Evident in About 1.5 Years of Radicava Start

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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ALS progression study

Editor’s note: The ALS News Today team is providing in-depth coverage of the 2021 Virtual AAN Annual Meeting, April 17–22. Go here to read the latest stories from the conference.

Amyotrophic lateral sclerosis (ALS) patients require walking aids, ventilation support, and/or speech generation devices about 1.5 years after starting treatment with Radicava (edaravone), according to data from U.S. insurance health claims.

These real-world findings may help to inform patients, caregivers, and healthcare providers in estimating the time to disease progression milestones, and help to optimize Radicava’s use, the researchers noted.

Data were presented by Melissa Hagan, PhD, the director of Health Economics and Outcomes Research at Mitsubishi Tanabe Pharma America (MTPA), Radicava’s developer, in a poster presentation at the recent American Academy of Neurology annual meeting.

The poster was titled, “Time to Event Milestones in Patients With Amyotrophic Lateral Sclerosis Treated With IV Edaravone: Results From a US Administrative Claims Analysis.”

Radicava, administered directly into the bloodstream, works by reducing oxidative stress, which is thought to be one of the drivers of nerve cell death in ALS. Oxidative stress is an imbalance between the production of potentially harmful free radicals and a cell’s ability to detoxify them.

The therapy was approved in the U.S. to treat ALS in May 2017, based on clinical data showing that Radicava effectively slowed disease progression and functional decline by 33% compared with a placebo.

However, there is limited real-world data on Radicava’s effectiveness.

To gain insight on outcomes in Radicava-treated patients in the clinical setting, MTPA, along with Princeton Pharmatec, evaluated time to progression milestones for insured adults with ALS who started using Radicava between August 2017, when the therapy became available to U.S. health providers, and June 2019.

Researchers retrospectively analyzed patients’ data using Optum’s de-identified Clinformatics Data Mart Database of administrative health claims spanning all U.S. states for members with commercial or Medicare Advantage insurance.

Included patients had to have at least six months of data before starting with Radicava, and at least one year of later data in the database.

Milestones focused on clinical outcomes associated with ALS progression: the use of canes, walkers, or wheelchairs; artificial nutrition; non-invasive ventilation; invasive ventilation; speech-generating devices; and hospice care.

A total of 117 Radicava-treated patients were included in the analysis: 75 (64.1%) covered by Medicare Advantage plans and 42 (35.9%) by commercial insurance.

Their mean age was 64.4, more than half (53%) were men, and most (84.6%) were also using riluzole, an ALS approved therapy marketed as Rilutek, Tiglutik, and Exservan.

Patients had the disease for a median of 190 days (about six months) before initiating Radicava, and treatment was taken for a median of 419 days (over a year).

Before Radicava, the most commonly reported symptoms were those related to bulbar function, or that linked to chewing, swallowing, speaking, and breathing (84.6% of patients), followed by motor symptoms (78.6%), respiratory problems (60.7%), and nerve symptoms (23.1%).

“As ALS progressed, the number of months to milestones decreased, indicating general increased physical disability,” the researchers wrote.

“After the initiation of [Radicava], patients progressed to the use of canes/walkers/wheelchairs, as well as the use of invasive ventilation/speech devices after an average of 19.8 months,” Hagan said.

In addition, patients took a mean of 16.3 months to need a feeding tube, 19.3 months to require non-invasive ventilation, and 21.4 months to start hospice care.

This study was “the first to analyze the time in which it takes ALS patients to progress to key milestones after [Radicava] has been initiated,” Hagan said, adding that the data “provide critical information that may be helpful to patients, caregivers, and providers in estimating the time to key ALS milestones [and] helping to optimize [Radicava] treatments.”

Hagan noted, however, that these data are limited to patients within the Optum’s database, meaning that they “may not be generalizable to all ALS patients.” This patient group “may represent a relatively healthier ALS population, since the present data did not capture ALS patients who were no longer covered by commercial health insurance or who had died.”

In another meeting poster, titled “Time Trajectories of Critical Events in Amyotrophic Lateral Sclerosis Progression,” researchers at the Mayo Clinic and University of Waterloo provided evidence that a new modeling system, called tollgate-based ALS staging system (TASS), may help assess time trajectories of ALS progression.

Disease progression is often evaluated through changes in total scores of the ALS Functional Rating Scale-Revised (ALSFRS-R). However, this type of functional scales may not place sufficient focus on key milestones in progression, and they miss some of them.

In the new system, tollgates refer to a set of critical clinical events, such as having slight weakness in arms, needing a wheelchair, and needing a feeding tube. It includes five functional segments (leg and arm strength, speech, swallowing, and breathing), each scored with one of six tollgates (0 to 5), with higher scores indicating greater disability.

The researchers first specified which tollgates were passed, according to the ALSFRS-R scores of 514 ALS patients. These people were followed at the ALS Clinic of Mayo Clinic-Rochester between 2006 and 2016.

Patients gradually passed tollgates for each functional domain, highlighting progressively greater disability over time, as expected for ALS.

The team then mapped the ALSFRS-R data of 3,264 patients from the Pooled Resource Open-Access ALS Clinical Trials database into TASS information to derive time trajectories of ALS progression in a larger patient population.

Results showed that most ALS patients were predicted to have impaired arm function (67%) and require walking aids (53%) by the second year after ALS onset. By the third year, most (74%) patients would occasionally use a wheelchair, while 49% would need assistive speech devices, and 30% feeding tubes.

Nearly half (48%) of ALS patients would be wheelchair-dependent by the fourth year.

Patients with bulbar onset disease (that first affecting the muscles involved in swallowing, chewing, speaking, and breathing) also showed a faster loss of the ability to talk and to eat independently, relative to those with a disease first affecting the limbs.

These findings further support the new system’s potential to help predict progression trajectories in this patient population. Future studies using larger datasets may help to analyze the different trajectories of ALS patients based on several factors, and assist clinicians with planning and counseling patients.

“The estimated time trajectories assist clinicians in better understanding general ALS progression pathways, while extending these estimations to various risk subgroups in future studies may facilitate personalized ALS management,” the researchers wrote.