Objective. To investigate whether disease control can be achieved in early active rheumatoid arthritis (RA) by treatment with methotrexate and intraarticular betamethasone, and whether the addition of cyclosporine to the regimen has any additional effect.Methods. Patients (n ؍ 160) were randomized to receive methotrexate 7.5 mg/week plus cyclosporine 2.5 mg/kg of body weight/day (combination therapy) or methotrexate plus placebo-cyclosporine (monotherapy). At weeks 0, 2, 4, 6, and 8 and every 4 weeks thereafter, betamethasone was injected into swollen joints (maximum 4 joints or 4 ml per visit). Beginning at week 8, if synovitis was present, the methotrexate dosage was increased stepwise up to 20 mg/week, with a subsequent stepwise increase in the cyclosporine or placebo-cyclosporine dosage up to 4 mg/kg. Results. At 52 weeks, 20% improvement according to the American College of Rheumatology criteria (ACR20) was achieved in 85% of the combination therapy group versus 68% of the monotherapy group (P ؍ 0.02). The median individual overall ACR response (ACR-N) in the 2 groups was 80.0% (interquartile range 40.1-91.8%) and 54.5% (interquartile range 2.4-87.8%), respectively (P ؍ 0.025). At 48 and 52 weeks, ACR remission criteria were met in 35% of the combination therapy group and 28% of the monotherapy group. Progression in the Larsen score at 52 weeks was -0.2 ؎ 6.5 and 0.4 ؎ 6.9 (mean ؎ SD) in the combination therapy and monotherapy groups, respectively. Serum creatinine levels increased by 7%, and hypertrichosis was more prevalent, in the combination therapy group.
Conclusion. Combined treatment with methotrexate and intraarticular glucocorticoid showed excellentSupported by a grant from the Danish Rheumatism Association. Novartis Healthcare Denmark A/S kindly provided cyclosporine and placebo-cyclosporine and sponsored an independent good clinical practice monitor. Nycomed provided methotrexate, folic acid, and calcium/vitamin D. Schering-Plough provided injectable betamethasone. Merck, Sharp, & Dohme provided alendronate.
Early and strict synovitis suppressive treatment with MTX and intra-articular GC lead to high remission rates and halting of erosive progression at 5 years. No additional effect of initial combination therapy with CSA was found. The results parallel those reported for tumour necrosis factor α antagonists. Baseline MRI-bone oedema, TSS and anti-CCP predicted radiographic progression.
Continuous methotrexate and intra-articular corticosteroid treatment resulted in excellent clinical response and disease control at 2 years, and the radiographic erosive progression was minimal. Addition of ciclosporine during the first 76 weeks resulted in significantly better ACR20 and ACR50 responses, but did not have any additional effect on remission rate and radiographic outcome.
Dual energy x-ray absorptiometry (DEXA) offers the possibility of assessing regional soft tissue composition, i.e. lean mass (LM) and fat mass: LM may be considered a measure of muscle mass. We examined age-related differences in LM, percentage fat (%fat) and muscle strength in 100 healthy non-athletic women aged 18-87 years. Relationships between muscle strength and leg LM in 20 elite female weight lifters and in 18 inactive women with previous hip fractures were also studied. The LM and %fat of the whole body, trunk, arms and legs were derived from a whole body DEXA scan. Isokinetic knee extensor strength (KES) and flexor strength (KFS) at 30 degrees.s-1 were assessed using an isokinetic dynamometer. The women aged 71-87 years had 35% lower KES and KFS than the women aged 18-40 years (P < 0.0001). Differences in LM were less pronounced. The LM of the legs, for instance, was 15% lower in the old than in the young women (P < 0.0001). In a multiple regression analysis with age, body mass, height and leg LM or KES as independent variables and KES or leg LM as the dependent variable, age was the most important predictor of KES (r(partial) = -0.74, P < 0.0001). The same applied to KFS. Body mass, not age, was the most important predictor of leg LM (r(partial) = 0.65, P < 0.0001) and of LM at all other measurement sites. The LM measured at different regions decreased equally with increasing age. The KES:leg LM ratio was negatively correlated with age (r = -0.70, P < 0.0001). The weight lifters had significantly higher KES:leg LM ratios than age-matched controls (+ 12%, P < 0.0001) and vice versa for the women with previous hip fractures (-36%, P < 0.0001). In conclusion, from our study it would seem that in healthy nonathletic women, age is a more important determinant of muscle strength than is LM as measured by DEXA. Muscle strengthening exercises and inactivity seem to have a considerably stronger influence on muscle strength than on LM.
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