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1.  Tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanalysis of efficacy and safety 
Background
To analyse available evidence on the efficacy and safety of anti-TNFα drugs (infliximab, etanercept and adalimumab) for treating rheumatoid arthritis (RA).
Methods
We searched systematically for randomised controlled clinical trials on treatment of RA with anti-TNFα drugs, followed by a systematic review with metaanalysis. Trials were searched from MEDLINE, EMBASE and Cochrane Library databases. The American College of Rheumatology (ACR) efficacy response criteria were used. Safety parameters provided by the trials were also assessed. Positive and undesired effects were estimated using combined relative risks (RR), number needed to treat (NNT) and number needed to harm (NNH). Heterogeneity was evaluated by Cochrane's Q and I2 statistics.
Results
Thirteen trials (7087 patients) met the inclusion criteria. The combined RR to achieve a therapeutic response to treatment with recommended doses of any anti-TNFα drug was 1.81 (95% CI 1.43–2.29) with a NNT of 5 (5–6) for ACR20. NNT for ACR50 [5 (5–6)] and ACR70 [7 (7–9)] were similar. Overall therapeutic effects were also similar regardless of the specific anti-TNFα drug used and when higher than recommended doses were administered. However, lower than recommended doses elicited low ACR70 responses (NNT 15). Comparison of anti-TNFα drugs plus methotrexate (MTX) with MTX alone in patients with insufficient prior responses to MTX showed NNT values of 3 for ACR20, 4 for ACR50 and 8 for ACR70. Comparison of anti-TNFα drugs with placebo showed a similar pattern. Comparisons of anti-TNFα drugs plus MTX with MTX alone in patients with no previous resistance to MTX showed somewhat lower effects. Etanercept and adalimumab administered as monotherapy showed effects similar to those of MTX. Side effects were more common among patients receiving anti-TNFα drugs than controls (overall combined NNH 27). Patients receiving infliximab were more likely to drop out because of side effects (NNH 24) and to suffer severe side effects (NNH 31), infections (NNH 10) and infusion reactions (NNH 9). Patients receiving adalimumab were also more likely to drop out because of side effects (NNH 47) and to suffer injection site reactions (NNH 22). Patients receiving etanercept were less likely to drop out because of side effects (NNH for control versus etanercept 26) but more likely to experience injection site reactions (NNH 5).
Conclusion
Anti-TNFα drugs are effective in RA patients, with apparently similar results irrespective of the drug administered. Doses other than those recommended are also beneficial. The main factor influencing therapeutic efficacy is the prior response to DMARD treatment. The effect of treatment with etanercept or adalimumab does not differ from that obtained with MTX. The published safety profile for etanercept is superior but the fact that no patients are treated with higher than recommended doses requires explanation.
doi:10.1186/1471-2474-9-52
PMCID: PMC2377247  PMID: 18419803
2.  Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout 
Annals of the Rheumatic Diseases  1998;57(9):545-549.
OBJECTIVES—To study the efficacy of allopurinol and benzbromarone to reduce serum urate concentrations in patients with primary chronic gout.
METHODS—Prospective, parallel, open study of 86 consecutive male patients with primary chronic gout. Forty nine patients (26 normal excretors and 23 under excretors) were given allopurinol 300 mg/day and 37 under excretors benzbromarone 100 mg/day. After achieving steady plasma urate concentrations with such doses, treatment was then adjusted to obtain optimal plasmatic urate concentrations (under 6 mg/dl).
RESULTS—Patients receiving allopurinol 300 mg/day showed a mean reduction of plasmatic urate of 2.75 mg/dl (from 8.60 to 5.85 mg/dl) and 3.34 mg/dl (from 9.10 to 5.76 mg/dl) in normal excretors and under excretors respectively. Patients receiving benzbromarone 100 mg/day achieved a reduction of plasmatic urate of 5.04 mg/dl (from 8.58 to 3.54 mg/dl). Fifty three per cent of patients receiving allopurinol and 100% receiving benzbromarone achieved optimal plasma urate concentrations at such doses. The patients with poor results with allopurinol 300 mg/day achieved a proper plasma urate concentration with allopurinol 450 to 600 mg/day, the mean final dose being 372 mg/day. Renal fuction improved and no case of renal lithiasis was observed among benzbromarone treated patients, whose mean final dose was 76 mg/day.
CONCLUSION—Benzbromarone is very effective to control plasma urate concentrations at doses ranging from 50 to 100 mg/day. Uricosuric treatment is a suitable approach to the treatment of patients with gout who show underexcretion of urate.

 Keywords: gout; gout suppressants; allopurinol; benzbromarone
PMCID: PMC1752740  PMID: 9849314

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