HERO – Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis: an RCT

Our trial tested whether treating patients with symptomatic hand osteoarthritis (OA) with hydroxychloroquine compared to placebo reduced synovitis and pain. Differences in hand pain severity between treatment groups were small and neither statistically significant nor clinically meaningful.

Why did we do this research?

OA is common and causes significant joint pain and disability. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We proposed that treating patients with symptomatic hand OA with hydroxychloroquine would be a practical and safe treatment to reduce synovitis and pain.

What did we do?

We carried out a multicentre, randomized, double-blind, placebo-controlled trial. Patients with symptomatic hand OA were randomized to active treatment with hydorxychloroquine or placebo for 12 months. Daily medication dose ranged from 200 to 400 mg according to ideal body weight. 

The primary outcome was change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months post randomisation. Secondary outcomes included other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. An ultrasound substudy examined baseline levels of synovitis.

Who was involved?

A total of 248 participants (82% women; mean age, 62.7 years) with symptomatic and radiographic hand OA were recruited from primary and secondary care sites in the UK and randomised.

What did we find?

Hydroxychloroquine was no more effective than placebo for pain relief in patients with moderate to severe hand pain and radiographic osteoarthritis. Differences in hand pain severity between treatment groups were small at each follow-up and not statistically significant or clinically meaningful.

Publications

• Kingsbury SR, Tharmanathan P, Keding A, et al. Hydroxychloroquine Effectiveness in Reducing Symptoms of Hand Osteoarthritis: A Randomized Trial. Ann Intern Med. 2018 Mar 20;168(6):385-395. https://doi.org/10.7326/M17-1430  Epub 2018 Feb 20. PMID: 29459986.
• Ronaldson SJ, Keding A, Tharmanathan P, Arundel C, Kingsbury SR, Conaghan PG, Torgerson DJ. Cost-effectiveness of hydroxychloroquine versusplacebo for hand osteoarthritis: economic evaluation of the HERO trial. F1000Res. 2021 Aug 17;10:821. https://doi.org/10.12688/f1000research.55296.1 . PMID: 34950454.
• Losina E, Katz JN. Hydroxychloroquine: Another Battle Lost in the Campaign to Find Effective Therapies for Hand Osteoarthritis. Ann Intern Med. 2018 Mar 20;168(6):442-443. https://doi.org/10.7326/M18-0035  Epub 2018 Feb 20. PMID: 29459984.
• Kingsbury, S.R., Tharmanathan, P., Adamson, J. et al. Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis (HERO): study protocol for a randomized controlled trial. Trials 14, 64 (2013). https://doi.org/10.1186/1745-6215-14-64