ABSTRACT
OBJECTIVE: To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy. METHODS: Patients were randomised to receive two infusions of placebo (n=63), rituximab 500 mg (n=62), or rituximab 1000 mg (n=60) intravenously on days 1 and 15. MRI scans and radiographs of the most inflamed hand and wrist were acquired at baseline, weeks 12 (MRI only), 24 and 52. The primary end point was the change in MRI erosion score from baseline at week 24. RESULTS: Patients treated with rituximab demonstrated significantly less progression in the mean MRI erosion score compared with those treated with placebo at weeks 24 (0.47, 0.18 and 1.60, respectively, p=0.003 and p=0.001 for the two rituximab doses vs placebo) and 52 (-0.30, 0.11 and 3.02, respectively; p<0.001 and p<0.001). Cartilage loss at 52 weeks was significantly reduced in the rituximab group compared with the placebo group. Other secondary end points of synovitis and osteitis improved significantly with rituximab compared with placebo as early as 12 weeks and improved further at weeks 24 and 52. CONCLUSIONS: This study demonstrated that rituximab significantly reduced erosion and cartilage loss at week 24 and week 52 in MTX-inadequate responder patients with active RA, suggesting that MRI is a valuable tool for assessing inflammatory and structural damage in patients with established RA receiving rituximab. TRIAL REGISTRATION NUMBER: NCT00578305.
Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Rituximab/therapeutic use , Adult , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/pathology , Cartilage, Articular/pathology , Disease Progression , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Radiography , Rituximab/administration & dosage , Rituximab/adverse effects , Severity of Illness Index , Treatment OutcomeABSTRACT
The effects of conjugated linoleic acid isomers (CLA) and endurance training on lean body mass are expected to result from their action on tissue protein metabolism. The aim of this study was to analyze their effects on protein metabolism in 2 muscles, the small intestine and liver of adult rats. Four-month-old male Wistar rats were fed diets containing either no CLA, cis-9, trans-11 CLA isomer (1 g.100 g(-1)), trans-10, cis-12 CLA isomer (1 g.100 g(-1)) or both isomers (1 g.100 g(-1) each) for 6 weeks. Half of the rats were subjected to endurance training by running on a treadmill. At the end of this period, the rats were injected with a flooding dose of (13)C-valine to determine protein synthesis rates in the post-absorptive (experiment 1) and in the post-prandial (experiment 2) states. No effect of CLA or endurance training were detected in the small intestine. Training reduced food intake and protein synthesis rates in the liver but no effect was found on the protein synthesis rates in muscles. In the post-absorptive state, protein synthesis rate was increased by feeding the trans-10, cis-12 CLA isomer alone in the liver (+9%) or in combination with the cis-9, trans-11 isomer in the gastrocnemius (+30%), mostly in sedentary rats. In the post-prandial state, the cis-9, trans-11 CLA isomer tended to reduce the protein synthesis rate in the gastrocnemius muscle. However, no effect of CLA was found on muscle protein amounts. In conclusion, CLA isomers would have limited but differential effects on tissue protein metabolism in adult rats.
Subject(s)
Linoleic Acids, Conjugated/administration & dosage , Physical Conditioning, Animal/physiology , Protein Biosynthesis/drug effects , Proteins/drug effects , Proteins/metabolism , Animals , Carbon Isotopes , Intestine, Small/metabolism , Isomerism , Linoleic Acids, Conjugated/chemistry , Linoleic Acids, Conjugated/metabolism , Liver/metabolism , Male , Muscle Proteins/metabolism , Postprandial Period , Protein Biosynthesis/physiology , Random Allocation , Rats , Rats, WistarABSTRACT
Dietary CLA isomers were shown to reduce adipose tissues in growing animals, mainly in mice, but their effects in adult animals remain unclear. This study was conducted to determine whether these effects depend on the isomer fed, on physical activity, or on the initial level of body fat. Male Wistar rats (4 mo old) were fed for 6 wk diets containing either no CLA, the cis-9, trans-11 CLA isomer (10 g/kg), the trans-10, cis-12 CLA isomer (10 g/kg), or both isomers (10 g/kg each). Half of the rats were assigned to exercise by treadmill running (1 h/d, 22 m/min). The initial body fat level was normal (12.7%) in a first trial, and high (18.9%) in a second trial. Chemical and anatomical body compositions were determined by chemical analysis and organ dissection. In both trials, the CLA diets, whatever the isomer, had no effect on food intake and body weight changes, on body chemical composition (fat, protein and water contents or gains), or on the body anatomical composition (weights or gains in epididymal and perirenal adipose tissues, in liver and in 4 muscles). There was no interaction between CLA treatment and physical activity. In conclusion, adult male rats do not appear to be responsive to the fat-to-lean partitioning effect of CLA described in growing rats. This was not affected by exercise or initial body fat level.
