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
ObjectivesHand osteoarthritis (OA) is a condition characterised by cartilage degradation and frequently erosive changes. Analgesics and non-steroidal anti-inflammatory drugs are used for symptomatic relief but are often poorly tolerated or contraindicated. Previous publications suggest hydroxychloroquine (HCQ) as a possible treatment for hand OA. The OA-TREAT study aimed to investigate the efficacy and safety of HCQ in patients with inflammatory and erosive hand OA (EOA).MethodsOA-TREAT was an investigator-initiated, multicentre, randomised, double-blind, placebo (PBO)-controlled trial. Patients with inflammatory and EOA, according to the ACR criteria, with radiographically erosive disease were randomised 1:1 to HCQ 200–400 mg/day or PBO for 52 weeks (W52). Both groups received stable standard therapy. The primary endpoint was Australian Canadian Hand Osteoarthritis Index (AUSCAN) for pain and hand disability at W52.Results75 patients were randomised to HCQ and 78 to PBO. At W52, mean AUSCAN pain was 26.7 in HCQ and 26.5 in PBO patients (p=0.92). Hand disability measured by AUSCAN function (mean) was 48.1 in HCQ and 51.3 in PBO patients (p=0.36). Changes in radiographic scores did not differ significantly (p>0.05) between treatment groups. There were 7 serious adverse events in the HCQ and 15 in the PBO group.ConclusionsOA-TREAT is the first large randomised PBO controlled trial focusing on EOA. 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.
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.
Biologics, possibly in combination with a conventional disease-modifying antirheumatic drug (DMARD) – preferably methotrexate (MTX), are used in accordance with the recommendations of the international rheumatological societies. However, in clinical practice, this recommendation is often problematic, as many rheumatologists know from personal experience. The quality of life of the patient is affected mainly by drug-induced intolerances (eg, MTX). Thus, the acceptance of the patient to treatment is often so inadequate that a discontinuation of the drug is necessary. In daily practice, approximately 30% of patients with biological therapy receive no concomitant DMARD according to the register data.
ObjectivesVitamin D (VitD) deficiency is a health problem prevalent not only in the elderly but also in young adults. The primary objective of our observational pilot study “MUVY” (Mood, UVR, Vitamin D in Young women) was to test both the short-term and long-term effects of a series of three suberythemal UV radiation (UVR) exposures on the VitD status and well-being of young healthy women during winter in a repeat measure design.Methods20 healthy young women (Fitzpatrick skin types I–III, aged 21–25 years) received three full body broad band UVR exposures with an escalating erythemally weighted dose schedule during one week in winter, and completed self-report questionnaires monitoring symptoms of depression (Beck Depression Inventory, BDI) and affective state/well-being (Profile of Mood States, POMS) at baseline and three days after the last UVR exposure. 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in serum at baseline, and at study days 8, 36 and 50.ResultsMean baseline 25(OH)D level was 54.3 nmol/L (standard deviation (s.d.) = 24.1), with seven women having VitD deficient status. Relevant symptoms of depression, as indicated by low BDI total scores (0–8), were absent. After the three UVR exposures the increment of 25(OH)D was an average of 13.9 nmol/L (95% confidence interval (CI) = 9.4–18.4) and 26.2 pmol/L (95%CI = 7.2–45.1) for 1,25(OH)2D. Δ25(OH)D, and corresponding baseline levels were significantly and inversely associated (rho = -0.493, p = 0.027). Only 25(OH)D remained significantly increased above baseline for at least six weeks after the last UVR exposure. A strong inverse correlation of the POMS subscale “Vigor/Activity” and the increment in 1,25(OH)2D was found (rho = -0.739, p<0.001) at day 8.ConclusionsThree suberythemal whole body UVR exposures during one week are a simple and suitable method for improving 25(OH)D levels during winter, for at least six weeks, and especially in young women with VitD deficient status.Trial RegistrationGerman Clinical Trials Register (Deutsches Register Kinischer Studien) DRKS00009274
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