Summary: Hydroxychloroquine appears to slow some measures of disability progression in people with primary progressive multiple sclerosis, according to a University of Calgary study.
Source: University of Calgary
Researchers at the University of Calgary report encouraging early results for hydroxychloroquine, a widely available generic medication, when used to treat disability progression in primary progressive multiple sclerosis (PPMS), a form of MS that is notoriously difficult to treat.
Multiple sclerosis affects an estimated 90,000 Canadians, and roughly 15 percent of those individuals have the primary progressive form of the disease—one of the higher national rates worldwide.
Teams from the Cumming School of Medicine led by Dr. Marcus Koch, MD, Ph.D., and Dr. Wee Yong, Ph.D., tested hydroxychloroquine in an 18-month clinical study at the MS clinic in Calgary and found fewer participants experienced measurable worsening of mobility than expected. The study was published in Annals of Neurology.
“There are currently very limited options that reliably stop or reverse decline in primary progressive MS,” says Dr. Koch, a clinician-investigator in the Department of Clinical Neurosciences and a member of the Hotchkiss Brain Institute. “This trial is an early-stage result that suggests hydroxychloroquine may slow clinical worsening in some people with PPMS. It’s an encouraging signal that deserves further testing in larger, randomized trials.”
The single-arm phase II futility trial enrolled 35 participants between November 2016 and June 2021. Investigators had anticipated that about 40 percent of the group—approximately 14 individuals—would show significant decline in walking ability during the study’s 18 months. Instead, only eight participants met that threshold. Overall, hydroxychloroquine was generally well tolerated by study participants.
Hydroxychloroquine is an antimalarial drug that is also commonly prescribed to manage symptoms of autoimmune conditions such as rheumatoid arthritis and lupus. It was chosen for this study because laboratory work showed it can reduce activation of microglia—immune cells in the brain—and it has a long record of clinical use in rheumatology with an acceptable safety profile.
“Our laboratory studies predicted that hydroxychloroquine would reduce inflammatory activation in the central nervous system, which could translate into less disability over time,” says Dr. Wee Yong, professor in the Department of Clinical Neurosciences and member of the Hotchkiss Brain Institute. “The clinical findings from Dr. Koch’s team align with those preclinical observations and support moving forward to larger trials.”
The cause of multiple sclerosis remains unknown. MS is an immune-mediated condition in which the body’s immune system attacks the central nervous system, often affecting the brain, spinal cord and optic nerves. Symptoms vary widely but commonly include problems with vision, balance, coordination and muscle control. Primary progressive MS is characterized by steady worsening of neurological function without the clear relapses and remissions seen in other MS types.
This clinical work was supported in part by philanthropic donations, including contributions from The Westman Charitable Foundation and the Swartout family, and by a grant from the MS Translational Clinical Trials Program of the Hotchkiss Brain Institute. The research team continues to explore hydroxychloroquine’s potential—alone and in combination with other generic agents—to determine whether it can offer meaningful clinical benefit for people living with PPMS.
About this multiple sclerosis and neuropharmacology research news
Author: Press Office
Source: University of Calgary
Contact: Press Office – University of Calgary
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Original Research: Closed access. “Hydroxychloroquine for Primary Progressive Multiple Sclerosis” by Marcus W. Koch et al. Annals of Neurology
Abstract
Hydroxychloroquine for Primary Progressive Multiple Sclerosis
Objective
Primary progressive multiple sclerosis typically shows limited response to current immunomodulatory and immunosuppressive therapies. Chronic activation of microglia has been implicated in the disease process for PPMS. Hydroxychloroquine, an antimalarial agent, has been shown in laboratory studies to reduce microglial activity and to exert neuroprotective effects in vitro, motivating its evaluation in people living with PPMS.
Methods
The investigators conducted a single-arm, phase II futility trial administering 200 mg of oral hydroxychloroquine twice daily for 18 months. To focus on progression occurring without clear focal inflammation, individuals with contrast-enhancing lesions on screening MRI were excluded. The primary outcome was a clinically meaningful worsening—defined as a 20 percent or greater decline—on the timed 25-foot walk, assessed between months 6 and 18 of follow-up.
Results
Based on historical data, the study team expected 40 percent of participants to worsen during the observation period. Using a Simon two-stage design and statistical parameters chosen to detect a reduction in that rate, the trial predefined success as fewer than 10 of 35 participants experiencing significant walking decline. The study met this endpoint: eight of 35 participants worsened between months 6 and 18. Hydroxychloroquine was generally well tolerated; adverse events occurred in 82 percent of participants and serious adverse events in 12 percent, but investigators judged the serious events to be unlikely related to hydroxychloroquine use.
Interpretation
In this single-arm phase II futility trial, hydroxychloroquine treatment was associated with a lower-than-expected rate of disability worsening in people with primary progressive multiple sclerosis. These results identify hydroxychloroquine as a promising candidate for PPMS therapy and support advancing to randomized, controlled clinical trials to confirm efficacy and further characterize safety.