title: Hydroxychloroquine in patients with inflammatory and erosive osteoarthritis of the hands (OA TREAT): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Osteoarthritis (OA) is a heterogeneous group of conditions with disturbed integrity of articular cartilage and changes in the underlying bone. The pathogenesis of OA is multifactorial and not just a disease of older people. Hydroxychloroquine (HCQ) is a disease-modifying anti-rheumatic drug (DMARD) typically used for the treatment of various rheumatic and dermatologic diseases. Three studies of HCQ in OA, including one abstract and one letter, are available and use a wide variety of outcome measures in small patient populations. Despite initial evidence for good efficacy of HCQ, there has been no randomized, double-blind, and placebo-controlled trial in a larger patient group. In the European League Against Rheumatism (EULAR), evidence-based recommendations for the management of hand OA, HCQ was not included as a therapeutic option because of the current lack of randomized clinical trials.
  
  
  METHODS
  OA TREAT is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial. A total of 510 subjects with inflammatory and erosive hand OA, according to the classification criteria of the American College of Rheumatology (ACR), with recent X-ray will be recruited across outpatient sites, hospitals and universities in Germany. Patients are randomized 1:1 to active treatment (HCQ 200 to 400 mg per day) or placebo for 52 weeks. Both groups receive standard therapy (non-steroidal anti-inflammatory drugs [NSAID], coxibs) for OA treatment, taken steadily two weeks before enrollment and continued further afterwards. If disease activity increases, the dose of NSAID/coxibs can be increased according to the drug recommendation. The co-primary clinical endpoints are the changes in Australian-Canadian OA Index (AUSCAN, German version) dimensions for pain and hand disability at week 52. The co-primary radiographic endpoint is the radiographic progression from baseline to week 52. A multiple endpoint test and analysis of covariance will be used to compare changes between groups. All analyses will be conducted on an intention-to-treat basis.
  
  
  CONCLUSIONS
  The OA TREAT trial will examine the clinical and radiological efficacy and safety of HCQ as a treatment option for inflammatory and erosive OA over 12 months. OA TREAT focuses on erosive hand OA in contrast to other current studies on symptomatic hand OA, for example, HERO [Trials 14:64, 2013].
  
  
  BACKGROUND
  ISRCTN46445413, date of registration: 05-10-2011.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. jacqueline.detert@charite.de.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Detert
authors.forename: Pascal
authors.initials: P
authors.lastname: Klaus
authors.forename: Joachim
authors.initials: J
authors.lastname: Listing
authors.forename: Vera
authors.initials: V
authors.lastname: Höhne-Zimmer
authors.forename: Tanja
authors.initials: T
authors.lastname: Braun
authors.forename: Siegfried
authors.initials: S
authors.lastname: Wassenberg
authors.forename: Rolf
authors.initials: R
authors.lastname: Rau
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001696:Biomechanical Phenomena; D002985:Clinical Protocols; D004185:Disability Evaluation; D004311:Double-Blind Method; D005858:Germany; D050823:Hand Joints / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D010003:Osteoarthritis / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D011859:Radiography; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D006886:Hydroxychloroquine