Synovitis is prevalent in osteoarthritis (OA) and associated with pain. Hydroxychloroquine (HCQ) is used routinely for treating synovitis in inflammatory arthritis. The primary aim of the HERO randomized controlled trial was to determine the effectiveness of HCQ as an analgesic treatment for hand OA, and secondarily to determine if synovitis was associated with treatment response, effects on structural progression and cost-effectiveness.
248 participants with symptomatic (VAS pain ≥4/10) and radiographic hand OA recruited across UK primary and secondary care were randomized to HCQ or placebo for 12 months. Daily HCQ dose ranged from 200-400 mg according to ideal body weight. The primary endpoint was average hand pain during the previous 2 weeks (numerical rating scale, NRS) at six months. Secondary endpoints included other self-reported pain and function (NRS and VAS scales, AUSCAN), grip strength, quality-of-life measures (OAQol, SF-12) and radiographic structural change (on Kallman score) at 12 months. The effects of baseline radiographic severity were also assessed. In a sub-study, n=143 participants had ultrasound performed at baseline on small joints of a single hand. Longitudinal mixed models compared changes between groups. Analyses were conducted on intention-to-treat basis. A health economics analysis was also performed.
Follow-up was 84.7% at 6 months and 76.6% at 12 months. The mean initial HCQ dose for the intervention arm (n= 114) was 320 mg. At the primary endpoint, the treatment difference estimate between HCQ and Placebo was -0.16 points on the NRS pain scale (95% CI: -0.72 to 0.41, p=0.584). There were no significant treatment differences at 3, 6 or 12 months for any secondary outcomes including radiographic outcomes. Baseline structural damage did not affect response to HCQ. On ultrasound, 94% had ≥1 joint positive for greyscale synovitis, 59% were Power Doppler positive; synovitis did not impact on treatment group differences. The economic analysis found that HCQ was less costly but produced a smaller quality-adjusted life year (QALY) gain than placebo, saving £6,545 per QALY lost, and was not considered to be cost-effective.
HCQ was not more effective than placebo in reducing symptoms or radiographic progression in people selected for moderate to severe hand pain and radiographic OA; HCQ is therefore not recommended for this patient group. Given the analgesic benefits of other anti-inflammatory therapies, these findings may reflect the mild anti-inflammatory action of HCQ, differing drug effects on certain OA pathologies, and also inclusion criteria in hand OA trials.