Hydroxychloroquine for Knee Arthritis?


Pioneer Founding member

The Malaria drug hydroxychloroquine could now be the most controversial drug on the planet based on early suggestions that it might help people with COVID-19. However, the other day a patient asked if it also worked for knee arthritis. Turns out there is research on that topic, so let’s dig in.
What Is Hydroxychloroquine?
Hydroxychloroquine is a drug commonly used to treat malaria. It’s also used to treat certain autoimmune diseases such as lupus and rheumatoid arthritis. It’s in a drug class called Disease-Modifying Antirheumatic Drugs (DMARDs).

How does it work to help patients with rheumatoid arthritis? It’s believed that Hydroxychloroquine both interferes with the body attacking itself (a key feature of rheumatoid arthritis) and reduces the production of inflammatory cytokines that break down cartilage. That last part is interesting as it could also apply for osteoarthritis.

What Is Osteoarthritis?
Osteoarthritis is the wear and tear type arthritis that many of us get as we age or after traumatic injury. Here the cartilage between the bones begins to wear down. That’s in part due to a bad chemical environment in the joint where inflammatory and pro breakdown cytokines (chemicals) build-up. As the cartilage wears away, bone spurs crop up.

Does Hydroxychloroquine Work for COVID-19?
The real answer is that nobody knows. The NIH began a study of using both hydroxychloroquine and azithromycin (Z-pack antibiotic) to treat COVID-19 about a week ago (1). The most recent study which was not a controlled trial showed that hydroxychloroquine didn’t change the course of the hospitalization nor death for COVID-19 patients in the hospital (2). However, the study had a fatal flaw in that the patients who got hydroxychloroquine were more severe than the patients who didn’t. On the other hand, early research on the drug did show promise (3-5).

Does Hydroxychloroquine Work to Help Knee Arthritis?
In lab studies using cartilage cells from arthritis patients, hydroxychloroquine has been shown to inhibit those bad cytokines I mentioned earlier ( IL-1beta-induced inducible NO synthase (iNOS) and NO production). In a small 2013 human study, researchers used hydroxychloroquine in mild to moderate knee arthritis patients versus placebo (6). Almost all of the patients were middle-aged women. By two months, patients getting the real drug showed improvement in pain and function out to 6 months. The differences between the groups were fairly dramatic as shown here in a diagram from the study.

Side Effects?
Chloroquine and hydroxychloroquine have some common side effects like nausea, diarrhea, and loss of appetite. There has some concern about the drug’s cardiac effects, including heart rhythm problems. However, more research showed that this is less of an issue than previously thought (7.8). In addition, the World Health Organization has published guidelines showing that heart toxic effects are were rare (9).

The upshot? While hydroxychloroquine may or may not help cure COVID-19, it may just help your knee arthritis! While there isn’t a ton of data, if you find yourself on this drug and have knee pain, don’t be surprised if it gets better.


(1) National Institutes of Health. News Releases. NIH begins clinical trial of hydroxychloroquine and azithromycin to treat COVID-19. https://www.nih.gov/news-events/news-releases/nih-begins-clinical-trial-hydroxychloroquine-azithromycin-treat-covid-19 Accessed 5/20/20.

(2) Geleris J, Sun Y, Platt J, et al. Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 [published online ahead of print, 2020 May 7]. N Engl J Med. 2020;NEJMoa2012410. doi:10.1056/NEJMoa2012410

(3) Mediterranee Infection. RÉSULTATS DE L’ÉTUDE COCONEL : CORONAVIRUS ET CONFINEMENT – ENQUÊTE LONGITUDINALE. https://www.mediterranee-infection.com/resultats-de-letude-coconel-coronavirus-et-confinement-enquete-longitudinale/ Accessed 4/12/20.

(4) Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print, 2020 Mar 20]. Int J Antimicrob Agents. 2020;105949. doi:10.1016/j.ijantimicag.2020.105949

(5) Chen Z, Hu J, Zhang Z, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. Version 2. medRxiv 2020.03.22.20040758. [Preprint.] doi: 10.1101/2020.03.22.20040758

(6) Jokar M, Mirfeizi Z, Keyvanpajouh K. The effect of hydroxychloroquine on symptoms of knee osteoarthritis: a double-blind randomized controlled clinical trial. Iran J Med Sci. 2013;38(3):221‐226.

(7) Wozniacka A, Cygankiewicz I, Chudzik M, Sysa-Jedrzejowska A, Wranicz JK. The cardiac safety of chloroquine phosphate treatment in patients with systemic lupus erythematosus: the influence on arrhythmia, heart rate variability and repolarization parameters. Lupus. 2006;15(8):521-5. https://www.ncbi.nlm.nih.gov/pubmed/16942005

(8) Teixeira RA, et al. Evidence for cardiac safety and antiarrhythmic potential of chloroquine in systemic lupus erythematosus, EP Europace, Volume 16, Issue 6, June 2014, Pages 887–892, https://doi.org/10.1093/europace/eut290

(9) World Health Organization. The cardiotoxicity of antimalarials. Malaria Policy Advisory Committee Meeting. 22–24 March 2017, Geneva, Switzerland. https://www.who.int/malaria/mpac/mpac-mar2017-erg-cardiotoxicity-report-session2.pdf