A randomised trial of colchicine for osteoarthritis of the hand (COLAH)

BACKGROUND: Osteoarthritis (OA) is the most common joint disease and frequently involves the hand. Painful hand OA is associated with a significant disease burden and reduced quality of life. Indeed, the effect of symptomatic hand OA on quality of life is comparable to rheumatoid arthritis, but affects considerably more people (prevalence ~20% versus ~1% in older adults). With an ageing population, the burden and health-care costs related to hand OA will increase. Patients often rely on NSAIDs or opiates with concomitant adverse effects in this age group to control pain. Hand OA is a heterogeneous condition with approximately 50% of patients having evidence of synovitis. This phenotype of hand OA with inflammatory signs i.e. those with evidence of synovitis is associated with increased pain. In addition, hand OA joints with synovitis are 3.5 times more likely to experience rapid joint destruction and radiographic progression than those without synovitis. Ultrasound (US) has been shown to reliably detect synovitis in the joints of the hand when performed by an experienced technician. Therefore, this is the subgroup of patients with hand OA that are most in need of evidence-based therapies. Previous study to assess treatments for hand OA using of plaquenil, etanercept or adalimumab found not superior to placebo to alleviate pain. There is possible effect if structural modification with etanercept and adalimumab has been shown to be beneficial in erosive and inflamed hand OA. The cost however of these medications in 20K/per year, therefore there use is an expensive alternative. Currently, there are no proven pharmacological treatments for hand OA. The lack of categorization of hand OA according to inflammatory phenotype may have contributed to previous negative outcomes in clinical trials. Cost-effective therapies targeting synovitis may offer a novel approach for reducing disease burden from hand OA. Colchicine is a low cost drug which has long been used in the anti-inflammatory treatment of acute gout. There has been recent renewed interest in this ancient drug, particularly its effects in cardiovascular diseases such as pericarditis. The primary mechanism of action of colchicine is tubulin disruption leading to subsequent down-regulation of multiple inflammatory pathways and modulation of innate immunity. Preliminary studies in knee OA have indicated that colchicine may have a beneficial effect on pain and a larger randomized clinical trial of colchicine in knee OA is currently underway. No studies of colchicine have been undertaken in hand OA. STUDY AIMS Primary hypothesis: Colchicine decreases pain (assessed by 100mm VAS) by 10mm more than identical placebo over 12 weeks in patients with clinical hand OA. STUDY DESIGN Randomised, placebo-controlled double-blind clinical trial. This study will be carried out at The Queen Elizabeth Hospital and Royal Adelaide Hospital.