Hydroxychloroquine offers no analgesic benefit for hand osteoarthritis
The addition of the antirheumatic agent hydroxychloroquine to a regular pain regimen does not provide clinically-relevant pain relief for patients with moderate-to-severe hand osteoarthritis, according to the HERO* trial.
A total of 248 patients (mean age 62.7 years, 82 percent female) with long-standing, symptomatic hand osteoarthritis (VAS** pain score of ≥4) were randomized 1:1 to receive hydroxychloroquine 200–400 mg or placebo for 12 months. Ultrasonography was done to evaluate the association between baseline inflammation and drug response. [Ann Intern Med 2018;doi:10.7326/M17-1430]
Mean NRS*** score for hand pain was similar between hydroxychloroquine and placebo recipients at 6 months (5.66 vs 5.49 points), generating a mean difference of -0.16 points (95 percent confidence interval, -0.73 to 0.40; p=0.57).
“The failure of [hydroxychloroquine] as an analgesic [could suggest] that the level or type of inflammation in our population did not match the mechanism of [hydroxychloroquine],” said the researchers. This finding could also reflect the mild anti-inflammatory activity or suboptimal dosing of hydroxychloroquine, they said.
Although subgroup results revealed the presence of synovitis in 93.7 percent and 58.7 percent of participants with baseline grayscale and power Doppler ultrasonography, respectively, there was no association between baseline synovitis and treatment effect, noted the researchers.
Despite evidence showing hydroxychloroquine to be well-tolerated and effective for other inflammatory diseases (ie, rheumatoid arthritis, systemic lupus erythematosus), the current findings failed to show a favourable reduction in symptoms or radiographic progression of moderate-to-severe hand osteoarthritis. [Ann Rheum Dis 2010;69:1004-1009; BMJ 2015;350:h1225; Ann Rheum Dis 2017;76:1269-1278; Arthritis Care Res (Hoboken) 2012;64:465-474]
What went wrong?
As the cohort comprised patients with moderate-to-severe disease level and established radiographic changes, the researchers indicated that they might have missed an early window of opportunity for hydroxychloroquine to have therapeutic benefit, citing evidence reflecting the more inflammatory nature of early vs established osteoarthritis. [Rheum Dis 2005;64:1263-1267]
Overall, the results do not support the off-label use of hydroxychloroquine; therefore, hydroxychloroquine should not be considered within the management plan in this patient group, the researchers concluded.
“The negative findings in this carefully done trial beg the question of what went awry,” said Dr Elena Losina and Dr Jeffrey Katz from the Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, US in a commentary. [Ann Intern Med 2018;doi:10.7326/M18-0035]
“Did [hydroxychloroquine] fail to reduce inflammation, or did reduced inflammation not translate to pain relief? This question could have been addressed more directly had the investigators opted for a more mechanistic design … [using] 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,” they pointed out.
While the findings did not reveal an association between synovitis and treatment effect, Losina and Katz underscored that the potential role of inflammation in the pathogenesis of hand osteoarthritis should not be dismissed. Further evaluation is recommended using more potent agents to specifically target inflammatory pathways for this condition, they added.
“Although the [hydroxychloroquine] battle resulted in defeat, the campaign to identify effective osteoarthritis therapies continues,” said Losina and Katz.