Hydroxychloroquine Delays Disability for Least Treatable Form of Multiple Sclerosis

Summary: Hydroxychloroquine shows promise for reducing some of the debilitating systems associated with primary progressive multiple sclerosis, a new study reports.

Source: University of Calgary

A University of Calgary study has found promising results for the generic drug hydroxychloroquine when used to treat the evolution of disability of primary progressive multiple sclerosis (MS), the least treatable form of the autoimmune disease.

MS affects about 90,000 Canadians with about 15 percent of those diagnosed with primary progressive MS, one of the highest rates in the world.

Cumming School of Medicine research teams led by Dr. Marcus Koch, MD, Ph.D., and Dr. Wee Yong, Ph.D., found hydroxychloroquine helped to slow the worsening of disability during the 18-month study involving participants at the MS clinic in Calgary.

The research was published in Annals of Neurology.

“With primary progressive MS, there is no good treatment to stop or reverse the progression of disease. The disability progressively worsens through time,” says Koch, a clinician-investigator in the Department of Clinical Neurosciences and member of the Hotchkiss Brian Institute (HBI).

“Dr. Yong’s research team, with whom we closely collaborate, has been screening a large number of generic drugs over several years and the results with hydroxychloroquine show some promise. Our trial is a preliminary success that needs further research. We hope sharing these results will help inspire that work, specifically larger scale clinical trials, into the future.”

The experimental study, known as a single-arm phase II futility trial, followed 35 people between November 2016 and June 2021. Researchers expected to see at least 40 percent, or 14 participants, experience a significant worsening of their walking function, but at the end of the trial only eight participants had worsened. Hydroxychloroquine was generally well-tolerated.

Hydroxychloroquine is an anti-malaria medication more commonly used to manage the symptoms of rheumatoid arthritis and autoimmune conditions such as lupus. It was chosen because it is widely used in rheumatological diseases and generally well-tolerated.

This shows a brain
MS affects about 90,000 Canadians with about 15 percent of those diagnosed with primary progressive MS, one of the highest rates in the world. Image is in the public domain

“Based on research in our lab on models of MS, we predicted that hydroxychloroquine would reduce disability in people living with MS. Calgary has a vibrant bench-to-bedside MS program and the work from Dr. Koch’s trial offers further evidence which we were pleased to see,” says Yong, a professor in the Department of Clinical Neurosciences and HBI member.

The cause of MS remains unknown. It’s a disease in which the body’s immune system attacks its own tissues and is generally long-lasting, often affecting the brain, spinal cord and the optic nerves in your eyes. It can cause problems with vision, balance and muscle control, although the effects are different for everyone who has the disease.

The MS Clinical Trials team’s work is supported in part by philanthropic contributions from donors including The Westman Charitable Foundation and the Swartout family. This specific study was also funded through a grant from the MS Translational Clinical Trials Program of the Hotchkiss Brain Institute.

Dr. Koch and the research team have been studying the impact of hydroxychloroquine on primary progressive MS for several years and that work continues, including its potential to achieve even greater results as a therapy in combination with select other generic drugs.

About this multiple sclerosis and neuropharmacology research news

Author: Press Office
Source: University of Calgary
Contact: Press Office – University of Calgary
Image: The image is in the public domain

Original Research: Closed access.
Hydroxychloroquine for Primary Progressive Multiple Sclerosis” by Marcus W. Koch et al. Annals of Neurology


Hydroxychloroquine for Primary Progressive Multiple Sclerosis


Primary progressive multiple sclerosis (PPMS) does not respond well to immunomodulatory or immunosuppressive treatment. Chronic activation of microglia has been implicated in the pathophysiology of PPMS. The antimalarial drug hydroxychloroquine (HCQ) reduces the activity of human microglia and has neuroprotective effects in vitro.


We conducted a single-arm, phase II futility trial of 200 mg oral HCQ twice daily for 18 months. In an effort to investigate disability worsening in the absence of overt focal inflammation, we excluded participants with contrast enhancing lesions on a screening magnetic resonance imaging (MRI). The primary end point was ≥20% worsening on the timed 25-foot walk measured between 6 and 18 months of follow-up.


Based on original trial data, 40% of the cohort were expected to worsen. We used a Simon 2-stage design to compare a null hypothesis of 40% of the cohort worsening against the one-sided alternative of 20%. Using a 5% type 1 error rate and 80% power, HCQ treatment would be deemed successful if fewer than 10 of 35 participants experienced clinically significant worsening. The study met its primary end point, as only 8 of 35 participants worsened between 6 and 18 months. HCQ was overall well-tolerated, with adverse events in 82% and serious adverse events in 12% of participants. All serious adverse events were unlikely related to HCQ use.


HCQ treatment was associated with reduced disability worsening in people with PPMS. HCQ is a promising treatment candidate in PPMS and should be investigated further in randomized controlled clinical trials.

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