Hydroxychloroquine as a Potential Treatment for Primary Progressive MS

A Canadian study conducted at the University of Calgary MS Clinic examined the use of the antimalarial drug, hydroxychloroquine (HCQ), for the treatment of people living with primary progressive MS (PPMS) in a phase II futility trial and found that treatment was associated with reduced disability worsening of the treated cohort.

There is a need for effective treatments for PPMS. One potential therapeutic strategy would be to inhibit the chronic activation of microglia, immune cells in the central nervous system, and to prevent neurodegeneration, both of which are implicated in PPMS. HCQ is a generic drug with a known safety profile widely used in the treatment of malaria, rheumatoid arthritis, and systematic lupus erythematosus. HCQ has been shown to reduce the activity of human microglia and has neuroprotective effects. In this study, researchers examined whether treatment with HCQ can decrease or delay the worsening of disability in people with PPMS.

To assess HCQ, researchers conducted a single-arm, phase II futility trial where participants took 200 mg of oral HCQ twice daily for 18 months. Phase II futility trials are small to mid-size, open label, single-arm trials comparing a treated cohort to historical control data. The primary end point of the futility trial was 20% or more worsening on the timed 25-foot walk (T25W) measured between 6 and 18 months of follow-up. Based on historical data on worsening, the researchers expected that 40% of trial participants would experience clinically significant worsening of their T25W performance between 6 and 18 months. If fewer than 10 of the 35 participants experienced clinically significant worsening of the T25FW between 6 and 18 months, the treatment would be deemed successful. The trial met the primary end point by demonstrating that 8 of 35 participants experienced clinically significant worsening. Additionally, HCQ was generally well-tolerated with adverse events reported in 82% and serious adverse events reported in 12% of participants.

Overall, HCQ treatment is a potential treatment to reduce disability worsening in people with PPMS and warrants further investigation in randomized controlled clinical trials. Researchers are also investigating potential combinations of existing medications that target multiple facets of progressive MS, such as the combination of indapamide (a diuretic medication) and HCQ. Repurposing of existing drugs, like HCQ, is a promising strategy to identify new treatment candidates for PPMS.


  • Full text article published in ANNALS of Neurology – Hydroxychloroquine for Primary Progressive Multiple Sclerosis. Link to article - https://onlinelibrary.wiley.co... 
  • Full text article published in Neurotherapeutics - Combination of Hydroxychloroquine and Indapamide Attenuates Neurodegeneration in Models Relevant to Multiple Sclerosis. Link to article - https://www.ncbi.nlm.nih.gov/p...