Antimalarial (AM) treatments, such as chloroquine (CQ) and hydroxychloroquine (HCQ), have been used to treat autoimmune disorders for over sixty years. It has been an effective treatment of autoimmune inflammatory disorders like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by decreasing the body’s inflammatory response. However, recent research is reexamining the effects of the drug, specifically on skeletal muscle. 

In a systematic review and meta-analysis published by Nature March 23rd, 2021, scientists found that the toxic effect of CQ and HCQ on skeletal muscles is an under-diagnosed side effect. Researchers determined that the chronic use of CQ or HCQ can be a risk for drug-induced myopathy, muscle disease resulting in muscle weakness.  

While antimalarial drugs were not designed to treat inflammatory diseases, the cellular characteristics of CQ and HCQ allow them to accumulate in lysosomes and autophagosomes of leukocytes. This affects the self-antigen presentation in the cells, interfering with the production and release of pro-inflammatory cytokines. In short, it decreases the cell’s inflammatory response. 

However, CQ and HCQ can accumulate in other cells, including liver, kidney, retina, skeletal, and cardiac muscle cells. While HCQ is preferred for long-term use as it has lower toxicity than CQ, its side effects in retinopathy, skeletal myopathy, and cardiomyopathy are comparable. They can both damage muscle fibres. 

The review found that past studies on the side effects of the medication, specifically muscle toxicity, are underdiagnosed in geriatric patients with a mean age above 62 years. 

It hypothesizes that the under-diagnosis is due to erroneous attribution of symptoms to other age-related causes, such as ischemic cardiomyopathy and sarcopenia, the progressive loss of skeletal muscle due to age. The average age of patients affected by drug-induced myopathy matches the population developing sarcopenia. 

The review suggests an investigation on the hypothesis about sarcopenia as a co-factor affecting the quality of the muscle. The review also calls for new clinical studies focusing on the population using chronic treatment with CQ and HCQ to observe the long-term effects of AM drugs.

Dr. Paul Fortin, a senior scientist of rheumatology and epidemiology at Arthritis Research Canada agrees that there are still aspects of the drug that require more investigation, but he believes that the effect of HCQ and CQ on muscles is very rare. 

According to Dr. Fortin, HCQ and CQ have a mild to moderate effect in treating RA. It is typically used in combination with methotrexate to better control the inflammation, and it would be a form of long-term treatment. 

“Any drug you would take for a long time can deposit in tissues,” Dr. Fortin said. 

According to Dr. Fortin, “[AM treatment] is considered one of the safest drugs in the choices we have.”  

Antimalarial medication is the primary treatment for SLE, and used as a combined treatment for RA.

An article published in Arthritis Care & Research on January 7th, 2021, found that SLE patients who followed AM therapy had a 71% lower risk of death than patients who did not follow it, and an 83% lower risk of death than patients who discontinued AM. 

While Dr. Fortin believed that a lot of papers have been written on AM drugs, he agreed there are different dimensions to consider, such as the effect of AM drugs on patients with RA and SLE’s immune risk to Covid-19. 

Dr. Fortin is currently researching the impact of AM drugs in arthritis patients exposed to Covid-19. Alongside Dr. Deborah Da Costa, a scientist at McGill University’s Health and Centre researching psychosocial and psychological impacts of RA, they are investigating the physical and psychosocial impacts of Covid-19 on patients with autoimmune inflammatory diseases undergoing AM treatment. 

This research began in July 2020 and is projected to be completed in June 2022. 

“The opportunity arose at the beginning of 2020 when the pandemic started since we already had these patients enrolled,” Dr. Fortin said. 

Given that Canada had several ongoing research studies that followed patients with RA and SLE taking AM drugs before Covid-19, Dr. Fortin and Dr. Da Costa did not need to find new participants. 

The study will follow 3,000 patients from across Canada with RA or SLE, comparing those who take AM drugs to those who are not, and look at how they are affected by Covid-19. 

People with RA or SLE have impaired immune systems, but it is unknown if those on AM treatment would be more or less susceptible to Covid-19. 

Dr. Fortin said that the AM medication can suppress the immune system, but it is unclear if this would be beneficial or negative for the patient. By suppressing the immune system, AM drugs control inflammation. However, the patient could be more susceptible to infection. 

“We don’t know which way it’s going to go,” Dr. Fortin said. 

In the meantime, the recent vaccine development adds a new component to their research. Dr. Fortin said they will also look at how patients taking AM medication will respond to the vaccine.