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STOCKHOLM, Sweden – Wearable technology such as Fitbit may be able to play a role in determining how well patients diagnosed with multiple sclerosis are doing, researchers suggested here at the 35th congress of the European Committee for Treatment and Research in Multiple sclerosis.
In an ongoing Phase 3 study investigating the efficacy and safety of MD1003 – high-dose pharmaceutical grade biotin in patients with primary and secondary progressive multiple sclerosis, participants were given Fitbit step counters to help analyze movement at a more granular level, said Valerie Block, PT, a post-graduate fellow at the Weill Institute for Neurosciences at the University of California, San Francisco, California.
“A person living with multiple sclerosis who needs a cane to get around and is classified on the Expanded Disability Status Scale with a score of 6.5. Despite needing a cane, some of these people can walk 7,000 steps a day while another person with the same EDSS classification may only walk 500 steps,” said Block.
“This is the first study to use remote active monitoring in a large Phase 3 study,” Block said. The number of steps taken by participants in the trial appear to correlate with clinical measures of ambulation, cognitive function, brain and spinal cord MRI atrophy metrics and quality of life, she said.
Block said that by using Fitbit technology, the average daily step count (STEPS) will give researchers a representation of what people actually do in their ecological environment, rather than what they are capable of doing in a clinic setting. She also noted, “STEPS can capture change when traditional methods are unresponsive.”
She said that previous work has shown that step counts do reflect changes over time in the EDSS, with lower step counts related to increased disability in the patients scores on the scale.
The trial has enrolled 492 patients, of whom 311 have been diagnosed with secondary progressive multiple sclerosis; 53.3 percent of the cohort are women; the average age in the study is 52.7 years; the median EDSS score is 6; the average length of diagnosis of multiple sclerosis is 10.6 years. The average STEPS count in the first 30 days of the trial was 3,699.
Block said that STEPS appeared to have significant correlation with overall disability; walking speed; patient reported physical health; cognitive impairment and patient-reported mental health. It also correlated with MRI findings such as normalized brain volume, brain grey matter volume and brain T1 lesion volume.
“These data support the study of STEPS as an exploratory outcome measure in clinical trials for progressive multiple sclerosis,” Block said.
The MedDay Pharmaceuticals study is ongoing.
New drugs look good
In twin Phase 3 studies, the anti-CD20 monoclonal antibody ofatumumab outperformed the multiple sclerosis drug teriflunomide in patients diagnosed with the relapsing-remitting form of the disease. In the ASCLEPIOS 1 and AESCLEPIOS 2, the annualized relapse rate was halved with treatment with ofatumumab, reported Stephen Hauser, MD, professor and director of the UCSF Weill Institute for Neurosciences.
“Ofatumumab with monthly 20 mg subcutaneous dosing regimen demonstrated high efficacy and a favorable safety profile,” Dr. Hauser said.
The annualized relapse rate among the 452 patients assigned to teriflunomide in ASCLEPIOS 1 was 0.22 and that was reduced to a rate of 0.11 among the 454 patients assigned to receive ofatumumab at 50.5 percent relative reduction, he reported. The results were much the same in ASCLEPIOS 2, in which the 469 patients assigned to teriflunomide experienced an annualized relapse rate of 0.25, while the 469 patients assigned to ofatumumab had an annualized relapse rate of 0.10, a 58.5 percent relative reduction (p<.001).
In the pooled analysis, treatment with ofatumumab was associated with a 10.9 percent rate of patients experienced confirmed disability worsening at 3 months compared with 15 percent of the patients on teriflunomide – a 34.4 percent relative risk reduction (P=.002). Dr. Hauser also said 8.1 percent of patients on ofatumumab experienced 6-month confirmed disability worsening compared with 12 percent of the patients on teriflunomide – a 32.5 percent relative risk reduction (P=.002).
Dr. Hauser also illustrated that treatment with ofatumumab was associated with a reduction in gadolinium-enhancing T1 lesions. In ASCLEPIOS 1, new lesions occurred in an average of 0.4523 patients on teriflunomide compared with 0.0115 – a 97.5 percent reduction in these lesions (p<.001). In ASCLEPIOS 2, the lesions occurred at a rate of 0.5141 in patients on teriflunomide and at a rate of 0.0317 in patients on ofatumumab, a decrease of 93.8 percent (p<.001). T2 lesions were reduced 82 percent in ASCLEPIOS 1 and by 84.5 percent in ASCLEPIOS 2 among patients treated with ofatumumab (p<.001).
Dr. Hauser reported that 84.2 percent of teriflunomide patients reported adverse events, 7.9 percent of those were classified as serious events; 83.6 percent of the ofatumumab patients experienced adverse events, but 9.1 percent were considered serious events. The most common adverse events were infections, occurring in 1.8 percent of teriflunomide patients and in 2.5 percent of ofatumumab patients. The only fatality in the study occurred as the result of an aortic hemorrhage in a teriflunomide patient.
Patients were randomized to receive either ofatumumab 20 mg in subcutaneous injections every 4 weeks, following an initial loading regimen of 20 mg subcutaneous doses on Days 1, 7 and 14; or were assigned to receive teriflunomide 14 mg orally once daily, for up to 30 months.
The patients were recruited from 37 countries. Their mean age was about 38; mean duration of multiple sclerosis was about 8 years; mean Expanded Disability Status Scale score at baseline was 2.9.
The study was sponsored by Novartis Pharma AG, Basel, Switzerland.
In another study with the drug siponimod, patients diagnosed with secondary progressive multiple sclerosis and treated with the agent appear to be able to extend the time until they require a wheelchair for mobility if they are treated with siponimod rather than placebo.
The percentage of patients requiring a wheelchair after progressing from assisted ambulatory status on the Expanded Disability Status Scale (EDSS) who were treated with placebo was 26.1 percent compared with a rate of 19.2 percent for patients who had been assigned to siponimod (p=.0365) in the so-called EXPAND trial, reported Patrick Vermersch, MD, PhD, vice-dean of faculty at the University of Lille, France.
“Siponimod significantly reduced the risk of progression to a wheelchair versus placebo,” Dr. Vermersch said.
In a substudy analysis, researchers followed outcomes in 293 patients who had demonstrated an EDSS score of 6.5 and had been given siponimod and 119 patients who had been randomized to placebo, he said. If they progressed to a score of 7 of higher on the EDSS, it means that are confined to a wheelchair for mobility.
That 36-month results was similar to the overall study population. After adjusting the survival analysis for baseline EDSS, the risk reduction of 31 percent for patients on siponimod strongly trended toward significance (p=.0585), Dr. Vermersch reported.
The substudy tested the ‘time to wheelchair” – measured as the length of time until the patients progresses to an EDSS of 7 or greater based on sustained progression until the last examination in the core part of the trial, up to 3 years. I
In a modeling exercise, Dr. Vermersch suggested that the time to transition from ambulatory status to becoming wheelchair-bound would be extended by 4.3 years if a patients was taking placebo rather than the active drug.
“Time to wheelchair is a highly clinically relevant endpoint,” he said. “Results from this analysis translate to potential long-term benefit beyond the core part of the EXPAND trial. Data further support the clinical relevance of the effect of siponimod on delaying disability progression in patients with secondary progressive multiple sclerosis.”
He noted that the modeling exercise was limited by the fact that it looked at outcomes beyond the study duration. About 30 percent of the patients in the study were followed for about 6 years.
The study was supported by Novartis.