A greater reduction in radiographic progression after initial combination therapy with ADA and MTX was seen at week 48, even after discontinuation of ADA treatment at week 24. This sustained effect was not found at the primary endpoint (DAS28 reduction).
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.
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
Background To study the prolonged effect on disease activity by an early induction therapy with adalimumab (ADA) plus methotrexate (MTX) versus MTX alone in DMARD naïve patients (pts) with early RA (designated HIT HARD, funded by the German Ministry of Science). Methods In a double-blind randomized controlled trial, RA pts (disease duration of ≤12 months, ≥6 swollen, ≥6 tender joints, and CRP≥10 mg/l) were randomized into two groups: placebo (PBO) plus MTX (n=85), given s.c. at 15 mg/week (w) versus MTX 15 mg/w s.c. plus 40 mg ADA s.c. eow over 24w (n=87). After w24, both groups were treated only with MTX up to w48. The primary outcome measure was the DAS28-response at w48. Secondary outcomes was the pts in remission (DAS28<2.6), ACR responses, HAQ, SF36 and radiographic progression. Statistical analysis was based on the ITT population. To improve power, analysis of covariance (ANCOVA) with baseline (BL) status as covariable was applied to compare DAS28, HAQ between groups. Non-parametric ANCOVA was used to compare van der Heijde modified Sharp (Sharp vdH) scores. Multiple imputation method was used to replace missing data. Results Mean disease duration at BL was 1.7 years, 91 (53%) were ACPA positive and 114 (63%) IgM RF positive. DAS28 was 6.2±0.8 (ADA/MTX) and 6.3±0.9 (PBO/MTX) (p=0.60). Outcome parameters at w24 and w48 are presented in tables 1. During the induction phase, ADA/MTX reduced disease activity to a significantly greater extent than PBO/MTX (Table 1). After termination of ADA or PBO and continuation with MTX alone, the differences between both groups in clinical outcome parameters (DAS28, remission, ACR50 response, HAQ, SF36 mental score) decreased at w24/48 and did not reach statistical significance at w48. Nevertheless, combination therapy significantly reduced radiographic progression as demonstrated by the Sharp vdH erosion score (p=0.010) as compared to the combination group, joint space narrowing score (p=0.035) and Sharp vdH total score (p=0.003); Ratingen score (p=0.012) compared to MTX alone when analyzed after w48. Table 1. Comparison of clinical parameters at w 24 and w 48 Week 24Week 48 Variable/GroupsADA/MTXPBO/MTXpADA/MTXPBO/MTXp DAS283.0±1.23.6±1.40.0093.2±1.43.4±1.60.41 Remission (%)47.929.50.02142.436.80.47 ACR50 (%)63.848.70.04952.651.40.88 ACR70 (%)48.026.80.00640.534.00.40 HAQ, mean±SD0.49±0.60.72±0.60.00140.61±0.60.66±0.60.40 SF36 mental score, mean±SD48.8±9.848.9±8.80.5150.0±9.647.9±9.60.37 SF36 physical score, mean±SD44.0±11.139.8±9.90.000241.4±12.442.0±10.30.79 Values are means and standard deviations if not otherwise specified. Conclusions Superiority in reduction of radiographic progression after initial combination therapy with ADA and MTX was seen at w 48, even after discontinuation of ADA treatment at w 24. Such a sustained effect was not found regarding the primary endpoint (DAS28 reduction). Disclosure of Interest J. Detert Grant/Research support from: Abbott & Co GmbH, Speakers Bureau: Abbott & Co GmbH, H. Bastian Speakers Bureau: Abbott & Co GmbH, J. Listing:...
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