Background Osteoarthritis (OA), particularly knee OA, is one of the most common causes of pain and disability in older people. Inflammation has been implicated in the pathogenesis of OA. Antimalarial agents such as hydroxychloroquine (HCQ) have been shown to have immunomodulatory and anti-inflammatory properties. Antimalarial agents also have antioxidant properties and may provide protection against tissue damage by free radicals.
Objectives A double-blind placebo-controlled trial was conducted to investigate the efficacy of HCQ in improving pain and mobility in older adults with moderate to severe knee OA.
Methods One hundred and sixty- six older adults with primary knee OA diagnosed according to the clinical and radiological criteria of the American College of Rheumatology with clinical signs of synovitis (warmth, joint margin tenderness, swelling or effusion) and the persistent knee pain (defined as >40 mm on VAS/daily pain during the month prior to study enrollment despite receiving maximum tolerated doses of conventional medical therapy (including paracetamol 4g/d and or a nonsteroidal anti-inflammatory drug) and a disease severity graded moderate to severe based on Kellgren-Lawrence radiographic system were randomized 1:1; 83 received 400 mg/day of HCQ and 83 received placebo for 36 weeks. Exclusion criteria included the presence of any cause of secondary OA, presence of other inflammatory diseases, history of hypersensitivity to antimalarial drugs and any eye disease. Primary outcome measures included pain reduction and improvement in physical function. Pain was assessed using the Visual Analogue pain Scale, (VAS, 0-100 mm). Synovitis was detected clinically and by ultrasound imaging at baseline and at the end of the study. Secondary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, activities of daily living (ADL) and analgesic use. Safety and tolerability to treatment were assessed.
Results There was a statistically significant reduction in knee pain (VAS) in the intervention group compared to the placebo group at 36 weeks The mean difference between treatment arms 95% CI was 10.2 (0.8 to 19.6), p<0.01. A significant improvement in physical function (WOMAC) and ADL scores; 8.6 (1.7 to 15.5) p<0.01 and 1.1 (0.1 to 2.1), p<0.05 respectively at 36 weeks in the intervention group when compared to the placebo group. A clinically relevant reduction in synovitis was noted in the HCQ group compared to the placebo group at 36 weeks. At 36 weeks there was a significant decrease in pain medication use in the HCQ group compared to the control group, p<0.01. The OMERACT-OARSI responder rate was (n=43) 52% in the HCQ group compared to (n=26) 31% in the placebo group, p<0.05. Mild to moderate drug side effects (skin rash, vertigo) were more frequent in the HCQ group, however no serious or life-threatening adverse events were reported.
Conclusions The findings of the present study showed that HCQ was effective in reducing knee pain and inflammation and in improving physical function in older patients with moderate to severe knee OA. HCQ may well be a beneficial addition to the therapeutic armamentarium of knee OA. Further larger long-term studies are however required.
Disclosure of Interest None declared