Off-label hydroxychloroquine no more effective than placebo when added to usual care for osteoarthritis hand pain

Hydroxychloroquine (HCQ) is no more effective than placebo for relieving moderate to severe hand pain and radiographic osteoarthritis when added to usual care, a study found.

Researchers at 13 primary and secondary care centers in England randomly assigned 248 participants (82% women; mean age, 62.7 years) with symptomatic pain of 4 or more on a 0- to 10-point visual scale and radiographic hand osteoarthritis in a double-blind, placebo-controlled clinical trial to either hydroxychloroquine (200 to 400 mg) or placebo for 12 months with ongoing usual care.

The primary end point was average hand pain during the previous two weeks on a 0- to 10-point numerical rating scale at six months. Secondary end points included self-reported pain and function, grip strength, quality of life, radiographic structural change, and adverse events. Baseline ultrasonography was done. Results were published Feb. 19 by Annals of Internal Medicine.

There were 210 (84.7%) participants at six months. Mean hand pain at this time was 5.49 points in the placebo group and 5.66 points in the hydroxychloroquine group, with a treatment difference of −0.16 point (95% CI, −0.73 to 0.40 point; P=0.57). No significant treatment differences existed at three, six, or 12 months for any secondary outcomes. The percentage of participants with at least one joint with synovitis was 94% (134 of 143 participants) on grayscale ultrasonography and 59% on power Doppler. Neither baseline structural damage nor synovitis affected treatment response. Fifteen serious adverse events were reported, seven in the hydroxychloroquine group (three of which were possibly drug-related) and eight in the placebo group.

According to the researchers, the findings do not support the current practice of off-label use of hydroxychloroquine in patients with hand osteoarthritis. The researchers also noted that hand pain may be caused by tendon problems, rather than arthritis, so hydroxychloroquine would not have helped.

The authors wrote, “Our findings in this full-scale pragmatic trial do not support the current practice of off-label use of HCQ in patients with hand osteoarthritis.”

That hydroxychloroquine did not prove superior to placebo in the trial should not deter research and drug development communities, an editorial stated, citing this study's design. A more mechanistic study design might have used baseline and follow-up ultrasonography or magnetic resonance imaging to determine whether hydroxychloroquine-treated participants had greater reduction in inflammatory changes than placebo-treated participants, the editorialist said.

“HCQ is safe, it is also a weak anti-inflammatory agent seldom used in contemporary practice as a solo disease-modifying therapy for rheumatoid arthritis and other inflammatory conditions,” the editorialist wrote. “Further therapeutic studies of the effects of anti-inflammatory therapy on nodal hand osteoarthritis will need to use more potent agents or compounds developed to more specifically target the inflammatory pathways documented in this condition.”