Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol

Objectives: To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment. Methods: Prospective, multicentre, open-label, two-stage randomised controlled trial in gout patients with normal renal function. Enrolled patients were given 300 mg allopurinol for 2 months (stage 1). Those patients who could not tolerate allopurinol or who did not attain the target serum urate concentration (sUr) ⩽0.30 mmol/l (5.0 mg/dl), which was defined as successful, were randomised to benzbromarone 200 mg/day or probenecid 2 g/day for another 2 months (stage 2). Results: 96 patients were enrolled in stage 1. 82 patients (85%) were eligible for the analysis at the end of stage 1: there was a mean (SD) decrease in sUr concentration of 35 (11)% from baseline; 20 patients (24%) attained target sUr ⩽0.30 mmol/l; and 9 patients (11%) stopped allopurinol because of adverse drug reactions.62 patients were enrolled in stage 2. 27 patients received benzbromarone (3 patients not eligible for analysis) and 35 received probenecid (4 patients not eligible for analysis). Treatment with benzbromarone was successful in 22/24 patients (92%) and with probenecid in 20/31 patients (65%) (p = 0.03 compared with benzbromarone). Compared with baseline values, there was a mean (SD) decrease of sUr concentration of 64 (9)% with benzbromarone and 50 (7)% with probenecid (p<0.001). Conclusion: This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr ⩽0.30 mmol/l, following 2 months of treatment. In stage 2, benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day

Efficacy and tolerability of urate-lowering drugs in gout:a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol

OBJECTIVES: To investigate the efficacy and tolerability of allopurinol as first-choice antihyperuricemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment. METHODS: Prospective, multi-centre, open-label, randomised controlled trial of gout patients with normal renal function. Patients were given 300 mg allopurinol for 2 months (stage 1). When allopurinol was not tolerated or failed to attain target serum urate concentrations (sUr) </=0.30 mmol/L (5.0 mg/dl), which was defined as successful, patients were randomised to benzbromarone 200 mg/day or probenecid 2000 mg/day and treated for 2 months (stage 2). RESULTS: Ninety-six patients were enrolled in stage 1. Eighty-two patients (85%) were eligible for the analysis of stage 1: sUr concentrations decreased 36[+/-11]% (mean[+/-SD]) from baseline; twenty patients (24%) attained target sUr </=0.30 mmol/l; nine patients (11%) stopped allopurinol because of adverse drug reactions. Sixty-two patients were enrolled in stage 2: 27 patients received benzbromarone (3 lost to follow-up) and 35 received probenecid (4 lost to follow-up). With benzbromarone 22 out of 24 patients (92%) were treated successfully. Treatment success with probenecid was 20 out of 31 patients (65%) (p=0.03 compared with benzbromarone). Compared with baseline values, sUr decreased 64[+/-9]% applying benzbromarone and decreased 50[+/-7]% applying probenecid (p<0.001). CONCLUSION: This study demonstrates a poor efficacy and tolerability profile of allopurinol 300 mg/day to attain a biochemical predefined target level of sUr </=0.30 mmol/l after 2-months treatment. In stage 2, benzbromarone 200 mg/day is more effective and better tolerated than probenecid 2000 mg/day (controlled-trials.com number ISRCTN21473387)

Fatique in rheumatoid arthritis: The role of self-efficacy and problematic social support

OBJECTIVE: To examine the relationship of fatigue in people with rheumatoid arthritis (RA) with self-efficacy, positive and problematic aspects of social support, and demographic and disease-related variables. METHOD: Out-patients with at least 5 yr RA were studied. Fatigue was measured with a visual analogue scale. Other variables included were: positive social support [Social Support List- Interactions (SSL12-I)] and problematic social support; self-efficacy towards coping with RA and towards mobilizing support; health status (Dutch-AIMS2); and laboratory tests: erythrocyte sedimentation rate (ESR), haemoglobin (Hb) and rheumatoid factor (RF); and disease duration. RESULTS: A total of 229 out-patients were included. Fatigue correlated with all scales of the Dutch-AIMS2: with pain, physical function and affect (P < 0.001). There was no significant correlation with social support, but there was a highly significant correlation of fatigue with problematic social support (P < 0.001). Both forms of self- efficacy correlated strongly with fatigue: patients with high self- efficacy expectations towards coping with RA, and towards mobilizing the social network (P < 0.001), had less fatigue. In the regression analysis to explain the variation in fatigue, only pain, self-efficacy expectations towards coping with RA, and towards asking for help and problematic social support remained significant. CONCLUSIONS: Fatigue can to a large extent (37%) be explained by pain, self-efficacy towards coping with RA, and towards asking for help and problematic social support. It is known that self-efficacy can be enhanced by self- management courses and it may thus be possible to improve fatigue