OP0186 HYDROXYCHLOROQUINE IN PATIENTS WITH INFLAMMATORY AND EROSIVE OSTEOARTHRITIS OF THE HANDS: RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED, MULTI-CENTRE, INVESTIGATOR-INITIATED TRIAL (OA TREAT)

Abstract

Background:Hand osteoarthritis (OA) is a very common condition with cartilage degradation and frequently erosive bone changes. It may be very painful and can greatly affect everyday activities. Common analgesics and NSAIDs are used for symptomatic relief but are often poorly tolerated or contraindicated especially in elderly patients. There is no effective and proven disease modifying therapy available. Previous publications and anecdotal reports suggest hydroxychloroquine (HCQ) as a possible treatment, and some physicians use HCQ off-label for the treatment of OAObjectives:To investigate the efficacy and safety of HCQ in patients with inflammatoryanderosive hand OA in a randomized, double-blind, placebo controlled, multi-centre, investigator-initiated trialMethods:Patients with inflammatory and erosive hand OA, according to the ACR criteria, with radiographically proven erosive disease were randomized 1:1 to HCQ 200-400mg per day or matching placebo (PBO) for 52 weeks. Both groups received standard therapy (stable NSAIDs). The primary endpoint was AUSCAN for pain and hand disability at week 52 (W52). A secondary endpoint was radiographic progression from baseline (BL) to W52. A multiple endpoint test and analysis of covariance was used to compare changes between groups. All analyses were conducted on an intention-to-treat baseResults:Of 156 patients 3 were excluded and 75 were randomized to HCQ and 78 to PBO. Mean age was 52.4 (SD 8.1) in the HCQ and 50.2 (SD 6.6) years in the PBO group. 68 (90.7%) of the patients were female in the HCQ and 60 (76.9%) in the PBO group. Disease duration was 9.5 (SD 7.5) in HCQ and 10.8 (SD 8.8) years in PBO group. CRP and ESR were normal in both groups. BL pain (AUSCAN) was 31.1 (SD 8.2) and 30.7 (SD 8.9), BL function (AUSCAN) was 58.5 (SD 15.5) in HCQ and 57.8 (SD 17.1) in PBO patients. Table 1 shows clinical and functional parameters at W52. Only morning stiffness was significantly reduced in the HCQ group (p=0.001). Changes in radiographic scores did not differ significantly (p>0.05) between treatment groups. There were 7 SAE in the HCQ and 15 in the PBO group. No new safety issues were detectedTable 1.Results of the covariance analysis (ANCOVA)-adjusted mean values and 95%-confidence intervals for primary and secondary outcomes at W52, as well as a p-value for group comparisonOutcomeAdj. Mean HCQ95%-CI HCQAdj. Mean PBO95%-CI PBOP-value HCQ x PBOAUSCAN Function48.14353.351.346.6560.36AUSCAN Pain26.723.929.426.523.929.10.92tender joint6.44.87.97.15.48.70.49swollen joint21.32.72.11.42.70.93ESR (mm/h)8.26.99.611.710.113.5<0.01HAQ0.90.810.80.70.90.46Phys. Global3.22.83.63.533.90.39Pat. Global4.53.95.15.24.65.80.14SF36 mental48.846.65150.848.752.80.22SF36 physical39.83841.639.938.241.60.95Morning Stiffness (min)30.22436.316.310.322.30.001Modif. Kallmann Score53.652.155.152.851.454.20.24The associated BL value or, if available, a mean value from BL and screening was included in the ANCOVA model as a covariate.Conclusion:The OATREAT trial examined the clinical and radiological efficacy and safety of HCQ as a treatment option for inflammatory and erosive OA over 52 weeks. OATREAT is the first large randomized PBO controlled trial focusing on erosive hand OA. HCQ was no more effective than PBO for changes in pain, function and radiographic scores in the 52-week period. Overall safety findings were consistent with the known profile of HCQ. Thus, our data failed to show that HCQ is effective in patients with inflammatory, erosive hand OADisclosure of Interests:Claudia Kedor Consultant of: Advisory Board for Novartis Pharma GmbH, Jacqueline Detert: None declared, Rolf Rau: None declared, Siegfried Wassenberg: None declared, Joachim Listing: None declared, Pascal Klaus Employee of: Pfizer Pharma GmbH, Tanja Braun: None declared, Walter Hermann: None declared, Stefan Weiner: None declared, Martin Bohl-Bühler: None declared, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi., Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma