Hydroxychloroquine in patients with inflammatory and erosive osteoarthritis of the hands (OA TREAT): study protocol for a randomized controlled trial

Abstract

BackgroundOsteoarthritis (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/DesignOA 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.DiscussionThe 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].Trial registrationISRCTN46445413, date of registration: 05-10-2011.

The Role of Hydroxychloroquine in the Age of COVID-19: A Periodic Systematic Review and Meta-Analysis

“…In this situation, medications transposition is a critical need to find effective anti-inflammatory agents in order to decrease the cytokines and pro-inflammatory factors production (14). In this regard, HCQ has been known as an effective anti-inflammatory agent for a long time (since the 1950s), especially in autoimmune disorders (15). Besides, outcome of a new experimental study conducted by Liu et al has been mentioned in the title of their publication as follows: "Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro".…”

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases

“…The results of this study should better delineate whether HCQ is an effective treatment for the pain and synovitis associated with OA and, interestingly, whether HCQ offers any longterm structural benefit in patients with OA. Another prospective study (OA-TREAT) is proposed by an investigator-led German-based group in a randomised (in a ratio of 1:1) double-blind investigation in a total of 510 patients comprising a relatively subset or erosive hand OA; these patients will receive either 400 or 200 mg HCQ or placebo (Detert et al 2014). …”

“…Of these, 7 were prospective studies and 3 were retrospective reviews. Additionally, our search produced a study protocol for an RCT that is currently underway (Detert et al 2014).…”

Emerging targets in osteoarthritis therapy

“…The disease manifestations in the joint are well characterized, including progressive loss of articular cartilage, cartilage calcification, osteophyte formation, subchondral bone remodeling, and mild to moderate inflammation of the synovial lining. Many therapeutic clinical trials have been conducted with designs based on subject selection related to the joint location or on whether the disease is primary or secondary to other types of arthritis [1–3]. Most trials, including those addressing targeted therapies, have evaluated patient-reported outcomes of function and pain at later stages of disease when there is radiographic evidence of damage, i.e., joint space narrowing and osteophytes.…”