Allopurinol, the first-line drug for serum urate-lowering therapy in gout, is approved by the US Food and Drug Administration for a dose up to 800 mg/d and is available as a low-cost generic drug. However, the vast majority of allopurinol prescriptions are for doses < or = 300 mg/d, which often fails to adequately treat hyperuricemia in gout. This situation has been promoted by longstanding, non-evidence-based guidelines for allopurinol use calibrated to renal function (and oxypurinol levels) and designed, without proof of efficacy, to avoid allopurinol hypersensitivity syndrome. Severe allopurinol hypersensitivity reactions are not necessarily dose-dependent and do not always correlate with serum oxypurinol levels. Limiting allopurinol dosing to < or = 300 mg/d suboptimally controls hyperuricemia and fails to adequately prevent hypersensitivity reactions. However, the long-term safety of elevating allopurinol dosages in chronic kidney disease requires further study. The emergence of novel urate-lowering therapeutic options, such as febuxostat and uricase, makes timely this review of current allopurinol dosing guidelines, safety, and efficacy in gout hyperuricemia therapy, including patients with chronic kidney disease.

Intraarticular corticosteroid injections are an effective short-term treatment for symptomatic knee OA compared to placebo. Patients with noninflammatory characteristics on ultrasound had a more prolonged benefit from IA corticosteroids compared to inflammatory patients.

This IPD meta-analysis demonstrates that patients with severe knee pain at baseline derive more benefit from IA glucocorticoid injection at short-term follow-up than those with less severe pain at baseline.

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Objective To evaluate efficacy and safety of poseltinib (formerly LY3337641/HM71224), an irreversible covalent inhibitor of Bruton’s tyrosine kinase from a 2-part, Phase-2 trial (RAjuvenate) in adults with active rheumatoid arthritis (RA). Methods In Part A, 36 patients with mildly active RA were randomized 1:1:1:1 to oral poseltinib 5-, 10-, or 30-mg or placebo once-daily for 4 weeks to assess safety/tolerability. No safety signals precluded moving to Part B where 250 patients with moderate-to-severe RA were randomized 1:1:1:1 to oral poseltinib 5- (N=63), 10- (N=62), or 30-mg (N=63) or placebo (N=62) once-daily for 12 weeks. Parts A and B permitted stable doses of background disease-modifying antirheumatic drugs. The primary endpoint in Part B was proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12. Logistic regression compared each poseltinib dose to placebo for primary/secondary endpoints. Nonresponder imputation was used for missing data. Results After interim analysis showed low likelihood of demonstrating significant efficacy, the sponsor discontinued Part B of the study. 189 (76%) patients completed 12 weeks in Part B; 61 discontinued study treatment (27 [44%] due to study termination by sponsor). There was no statistically significant difference in ACR20 response between any dose of poseltinib and placebo at Week 12 (p>0.05 for all comparisons). Five serious adverse events occurred (n=2, placebo; n=3, 30-mg); there was 1 death due to a fall. Conclusion While no safety findings precluded continuation, the study was terminated after interim data demonstrated low likelihood of benefit in RA.