This study aims to compare the urate-lowering response rate of febuxostat and allopurinol in gout patient using a model-based meta-analysis. The literature search identified 22 clinical trials of gout with a total of 43 unique treatment arms that met our inclusion criteria, and a total of 6 365 gout patients were included in the study. The response rates of allopuriol and febuxostat were characterized by Tmax model and Emax model respectively, and the effect of baseline serum uric acid (sUA) and patient type on the drug effect was tested. The results showed that allopurinol can reach an average maximum response rate of 50.8% while febuxostat can reach a 100% response rate within a very short time, and the ED50 was 34.3 mg. Covariate analysis revealed that baseline sUA has a negative effect on response rate of allopurinol, and a positive effect on the predicted ED50 of febuxostat. For patients who had shown inadequate response to prior allopurinol treatment, the average response rate was about half that of the allopurinol responder patients.
Allopurinol ; therapeutic use ; Febuxostat ; Gout ; blood ; drug therapy ; Gout Suppressants ; therapeutic use ; Humans ; Thiazoles ; therapeutic use ; Uric Acid ; blood

A 52-year-old man was referred to our department with a 2-year history of polyarthritis. He was diagnosed as gout due to acute arthritis of bilateral feet dorsum 2 years ago,but he didn't receive any standard treatment. 1 year ago,there were more and more joints evolved during the gout attack, and many subcutaneous nodules occurred. When he presented to our clinic 1 month ago,the urate acid level was as high as 715 μmol/L. Moreover, we could find bone erosion in the X rays of his hand and foot,as well as synovitis,double contour sign and tophus on the ultrasound examination. The diagnosis of gout was clearly and definitely. However, he had leukocytosis and thrombocytosis for 4 years in the past history, and the urate acid level was only 400 μmol/L at that time. He also had well-controlled hypertension. The family history was unremarkable. Furthermore, we found megalosplenia on his physical examination. The bone marrow examination showed myelofibrosis and JAK2 V617F gene was positive. He was diagnosed as primary myelofibrosis and treated with interferon-α, together with urate acid-lowing therapy (febuxostat 60 mg once daily). Following-up for 1 year,the dosage of febuxostat decreased to 40 mg once daily, and the patient didn't have gout attack again, some of the tophus diminished, and the urate acid level ranged from 400 to 500 μmol/L. Gout is a common disease in clinical practice,usually combined with metabolic syndrome,chronic renal failure and specific drugs using (diuretic and calcineurin inhibitors). However,it is relatively rare to see gout associated with myeloproliferative diseases, including polycythemia vera, primary thrombocythemia, primary myelofibrosis and chronic myelocytic leukemia. In these diseases, the turnover of nucleic acids is greatly augmented, and an excess of purine metabolites, including uric acid, is released. In the natural course of gout, the appearance of tophus from the first onset of arthritis usually takes several years. This patient only had one traditional risk factor, but his urate acid level was remarkably high and he developed tophus in a short term. After treatment of primary myelofibrosis, the symptom of gout partially alleviated. Careful physical examination and medical history taking lead to the diagnosis of secondary gout, which should be reminded in the daily practice.
Arthritis, Gouty/etiology* ; Febuxostat/therapeutic use* ; Gout/etiology* ; Gout Suppressants/therapeutic use* ; Humans ; Male ; Middle Aged ; Primary Myelofibrosis/complications* ; Uric Acid

Animals ; Chronic Disease ; Febuxostat ; Heart Failure ; drug therapy ; metabolism ; Humans ; Reactive Oxygen Species ; Thiazoles ; pharmacology ; therapeutic use ; Xanthine Oxidase ; antagonists & inhibitors