Treatments for Rheumatoid Arthritis Don’t Appear to Prevent Parkinson’s

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by Steve Bryson, PhD |

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Medications used to treat rheumatoid arthritis, an autoimmune disorder, do not affect a person’s risk of developing Parkinson’s disease, a Finnish study, funded by the Michael J. Fox Foundation for Parkinson’s Research, reported.

Rheumatoid arthritis has been associated with a lower Parkinson’s risk, but exposure to arthritis therapies did not explain this association, its researchers found.

An exception was the use of chloroquine or hydroxychloroquine, which was linked to a 26% lower relative risk of Parkinson’s. Future studies should investigate this further, they added.

The study, “Disease-Modifying Antirheumatic Drugs and Risk of Parkinson Disease: Nested Case-Control Study of People With Rheumatoid Arthritis,” was published in the journal Neurology.

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Rheumatoid arthritis (RA) is caused by a mistaken immune attack on the lining of the joints, resulting in inflammation and pain, particularly in the hands, knees, or ankles.

Some studies suggest that people with rheumatoid arthritis are at a lower risk of developing Parkinson’s disease. This observation may be due to the use of disease-modifying anti-rheumatic drugs (DMARDs), which are designed to suppress inflammation. As such, they may modify the altered immune responses reported in Parkinson’s patients.

Scientists at the University of Eastern Finland examined the use of DMARDs by people diagnosed with rheumatoid arthritis at least three years before they were also found to have Parkinson’s.

Participants were recruited from the FINPARK study, a nationwide registry of 22,189 community-dwelling Finns with Parkinson’s. Among them, 315 people (63.2% women) were diagnosed with both rheumatoid arthritis and Parkinson’s, referred to by researchers as cases. They ranged in age from 46 to 93, and their median duration of rheumatoid arthritis before a Parkinson’s diagnosis was 12.6 years.

A group of 1,571 adults with rheumatoid arthritis but not Parkinson’s, matched by age, sex, and regions of residence, served as controls. The prevalence of co-existing medical conditions, such as cardiovascular diseases, were comparable between the two groups.

Data on DMARDs and anti-inflammatory corticosteroids purchased at least three years before a Parkinson’s diagnosis were collected. This lagtime was introduced to control for early non-specific Parkinson’s symptoms or ongoing Parkinson’s assessments that may affect therapy exposure, as well as newly diagnosed rheumatoid arthritis or changes in rheumatoid arthritis medications.

Data were also adjusted for co-existing medical conditions thought to be associated with the medicines or outcomes, including asthma or chronic obstructive pulmonary disease (COPD), stroke, diabetes, cardiovascular diseases, substance abuse, and head injury.

In both cases and controls, the most common DMARDs were sulfasalazine, methotrexate, and chloroquine or hydroxychloroquine. Gold preparations, used to treat RA, were prescribed about 25% of the time, while immunosuppressants were least commonly used. Corticosteroids were given to nearly two-thirds of cases and controls.

Overall, the use of DMARDs or corticosteroids was not associated with a Parkinson’s risk. Biological DMARDs — treatments produced by living cells that target specific immune proteins — were used by less than 3% of cases and controls, and also not linked to Parkinson’s.

“These results,” however, “should be interpreted cautiously due to limited number of users in our study,” the researchers wrote.

Similar results were found when the researchers considered any therapy at any time before a Parkinson’s diagnosis, as well as treatments within the three-year lag time.

Notably, patients prescribed chloroquine or hydroxychloroquine had a 26% lower relative risk of Parkinson’s. When the use of these medicines was considered at any time before Parkinson’s diagnosis, a 31% lower relative risk was seen.

Researchers speculated that the immunomodulatory effects of chloroquine and hydroxychloroquine may have influenced inflammatory processes in Parkinson’s. However, because methotrexate, the first-line DMARD for rheumatoid arthritis, is a more powerful immunosuppressant than hydroxychloroquine, “the protective association of chloroquine/hydroxychloroquine might be explained by other reasons than its immunosuppressive effects,” they wrote.

An examination of DMARD changes found the most common medication was sulfasalazine, used by 10% of both cases and controls, followed by the combination of chloroquine or hydroxychloroquine, methotrexate, and sulfasalazine. No relationships between different exposure histories for DMARDs and Parkinson’s risk were found.

“The hypothesis that decreased risk of [Parkinson’s disease] among rheumatoid arthritis patients could be explained by use of DMARDs was not confirmed in our study,” the researchers concluded. “Further studies on newer DMARDs, especially on bDMARDs [biological DMARDS] … and assessment of dose-response relations between DMARDs” and Parkinson’s risk are needed.

“The potential ability of chloroquine/hydroxychloroquine to modify the [Parkinson’s disease] disease process should be studied further,” they added.