NEW YORK (Reuters Health) – Hydroxychloroquine is no more effective than placebo for relieving moderate-to-severe hand pain due to osteoarthritis, researchers in the UK say.
“The first-line pharmacological treatments for hand osteoarthritis, including paracetamol and nonsteroidal anti-inflammatory drugs, are often not effective and are associated with side effects,” Dr. Sarah Kingsbury of Leeds Institute of Rheumatic and Musculoskeletal Medicine told Reuters Health.
“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,” she said by email. “Until now, there has not been a large-scale study into whether using hydroxychloroquine works.”
To investigate, Dr. Kingsbury and colleagues randomly assigned 248 participants (mean age, 63; 82% women) with symptomatic pain (at least 4 on a 0-to 10-point visual analog scale) and radiographic hand arthritis to either hydroxychloroquine (200 mg to 400 mg daily, depending on body weight) or placebo. All participants had the condition for at least five years and reported an inadequate response or side effects with drugs such as acetaminophen, oral NSAIDs and opioids.
As reported online February 19 in Annals of Internal Medicine, at six months, mean hand pain was similar in the two groups: 5.66 for hydroxychloroquine versus 5.49 for placebo. Results remained nonsignificant after adjustment for adherence, missing data and use of rescue medication.
No between-groups differences were observed at three, six or 12 months for secondary endpoints, including self-reported pain and function, quality of life, radiographic structure change and grip strength.
Although 94% of participants had at least one joint with synovitis on imaging at baseline, this finding was not associated with treatment response.
Of seven serious adverse events in the hydroxychloroquine group, three were medication-related: prolonged QT interval with ventricular arrhythmias; erythema multiforme; and acute generalized erythematous pustulosis.
Dr. Kingsbury said, “These findings do not support the current practice of off-label use of this drug in those with hand osteoarthritis, and provide evidence for a change in practice.”
“This can be a very frustrating problem for both patient and doctor,” she acknowledged. “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.”
“In an exploratory analysis,” she added, “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,” she said. “Hydroxychloroquine would not be expected to have an effect on such pain.”
“These findings re-emphasize the importance of including strengthening exercises in the management of osteoarthritis, a core treatment recommended by the (UK’s) National Institute for Health and Care Excellence (NICE) and the American College of Rheumatology,” she stressed.
“Further work is still needed to unravel the molecular mechanisms of inflammation in osteoarthritis and its role in symptoms and disease progression, and may provide alternative therapeutic targets for the focus of future research,” Dr. Kingsbury noted.
“In addition,” she said, “better patient phenotyping will improve our understanding of the drivers of hand pain and enable exclusion of other causes of hand pain such as tenosynovitis.”
Dr. Elena Losina of Brigham and Women’s Hospital in Boston, coauthor of a related editorial, told Reuters Health, “Hand osteoarthritis is a painful and prevalent condition. Currently there are no treatment options to arrest (its) progression.”
“Therefore,” she said by email, “every trial focused on treatments for this condition carries hopes and anticipated promise for positive outcome.”
Editorial coauthor Dr. Jeffrey N. Katz, also of Brigham and Women’s Hospital, added in the same email, “Negative findings are often viewed as discouraging. But every trial, even a negative one, given it is a well-done trial (like the current study), provides useful information.”
“Since hydroxychloroquine is a weak anti-inflammatory agent,” he said, “the negative findings from this trial should stimulate researchers to press on with investigations that attempt to examine more potent anti-inflammatory agents and, perhaps, continue to focus on better understanding mechanisms underlying hand osteoarthritis and test therapies that target these pathways.”
SOURCES: http://bit.ly/2BEQbSz and http://bit.ly/2Fhi3vY
Ann Intern Med 2018.
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