Hand Osteoarthritis: Hydroxychloroquine No More Effective Than Placebo

MedicalResearch.com Interview with:
Dr Sarah Kingsbury PhD
Osteoarthritis Strategic Lead
Deputy Section Head, Musculoskeletal Medicine and Imaging
Leeds Institute of Rheumatic and Musculoskeletal Medicine
University of Leeds

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Osteoarthritis of the hand is a painful and disabling condition, estimated to effect up to 31 per cent of people aged over 70. It can stop people from carrying out everyday activities and can limit their quality of life. The first-line pharmacological treatments for hand osteoarthritis, including paracetamol and non-steroidal anti-inflammatory drugs, are often not effective and are associated with side effects. Doctors have used hydroxychloroquine, an established treatment for rheumatoid arthritis, as an off-label alternative, supported by increasing evidence that inflammation is a factor in osteoarthritis. Until now, there has not been a large-scale study into whether using hydroxychloroquine works.

HERO was a 12 month randomised, double-blind, placebo controlled, pragmatic trial, designed with a view to replicate anecdotal reports of hydroxychloroquine use in clinical practice, and  powered to detect a moderate effect equivalent to that for NSAIDs in this population. The study involved 248 patients at 13 NHS hospitals in England: all had the condition for at least 5 years, had changes to the joints in their hands consistent with osteoarthritis and reported moderate to severe pain on at least half of the days in the previous three months to the study commencing.

Participants were randomised 1:1 to either hydroxychloroquine or placebo and followed up at 3 monthly intervals for 12 months. The study found that patients initially reported a small reduction in the severity of pain before the improvement plateaued. However, a similar amount of change was seen in both the group receiving hydroxychloroquine medication and the group taking the placebo.

MedicalResearch.com: What should readers take away from your report?

Response: The HERO trial found that hydroxychloroquine was not more effective than placebo in reducing symptoms or radiographic progression in people selected for moderate to severe hand pain and radiographic OA. These findings do not support the current practice for the off-label use of this drug in those with hand osteoarthritis, and provide evidence for change in practice. Increasingly as we understand that much hand pain is driven by tendon problems that improve with muscle strengthening, our focus should move away from pharmacological options. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: In an exploratory post-hoc analysis, we found a statistical association between patients who had a stronger grip strength and pain relief from hydroxychloroquine (p=0.033).  Weaker grip strength may predispose people to tenosynovitis or enthesitis, alternative (or additional) causes for hand pain in this population. Hydroxychloroquine would not be expected to have an effect on such pain. These findings suggest a need to consider grip strength in the population when planning further research and support the need for more detailed phenotyping of hand osteoarthritis to understand drivers of pain and identify potential therapeutic targets. Furthermore, they re-emphasise the importance of including strengthening exercises in the management of osteoarthritis, a core treatment recommended by the National Institute for Health and Care Excellence (NICE) and the American College of Rheumatology.  


Hydroxychloroquine Effectiveness in Reducing Symptoms of Hand OsteoarthritisA Randomized Trial
Sarah R. Kingsbury, PhD; Puvan Tharmanathan, PhD; Ada Keding, MSc; Sarah J. Ronaldson, MSc; Andrew Grainger, BMBS; Richard J. Wakefield, MD; Catherine Arundel, MSc; Fraser Birrell, PhD; Michael Doherty, MD; Tonia Vincent, PhD; Fiona E. Watt, PhD; Krysia Dziedzic, PhD; Terence W. O’Neill, MD; Nigel K. Arden, MD; David L. Scott, MD; John Dickson, MBChB; Toby Garrood, PhD; Michael Green, MBChB; Ajit Menon, MD; Tom Sheeran, MD; David Torgerson, PhD; Philip G. Conaghan, PhD
Published: Ann Intern Med. 2018.
DOI: 10.7326/M17-1430

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Last Updated on February 21, 2018 by Marie Benz MD FAAD