E arrival of new products to treat gout (Figure 6). While these possibilities might be interesting, they are not testable hypotheses in our datasets. We considered other possible explanations for a steep increase such as the epidemic of obesity, increasing utilization of low-dose aspirin, and the higher utilization of high-fructose corn syrup or such dietary changes, but rejected them as the rate of increase was so obviously disproportionate to such long-term trends. To our knowledge, this is the first nationally representative study that reports time trends in the use of gout medications in the US population. Table 2 summarizes all the recent studies that have addressed the epidemiology of gout and gout medications PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26266977 in the ambulatory care settings. The designs, scope of enrollment and study duration are too heterogeneous to permit head to head comparison with our study. The proportion of patients/ visits with allopurinol prescriptions varies widely depending on the case definition used to identify gout. The proportion of visits of patients on colchicine seems to becomparable to the average proportion observed in the present study. The trends that we have documented in uratelowering medication are similar to those observed in the UK ambulatory-care settings with stable use of all medications except anti-inflammatory drugs, which showed a significant decline [18]. Ever since the ICG-001 site introduction of allopurinol as a therapy by Gertrude Elion, allopurinol had held sway as the mainstay of urate-lowering therapy for gout [15,19]. Nevertheless, allopurinol has been underprescribed and under-dosed, resulting in poor urate control and consequently worse health outcomes and higher costs of care [5,10,20-27]. Unlike the UK data where the proportion of patients with urate-lowering therapies was between 25 and 30 , the proportion of prescriptions for allopurinol in our study was much higher. Recently, uricosuric therapy has generated much interest on account of availability of newer agents [28-30]. Probenecid, an old uricosuric agent, gained popularity transiently in the past, but has fallen out of favor due to the dosing schedule, concerns about urolithiasis and reduced efficacy in the presence of azotemia [29]. In the present study probenecid prescriptions were observed to increase over time, but these increases were too few to reach statistical significance. The combination of xanthine oxidase inhibitors and uricosuric agents as a means to achieve better urate efficacy did not gain popularity in light of earlier pharmacokinetic studies suggesting that probenecid increases renal clearance of oxypurinol, the active metabolite of allopurinol [31]. The number of prescriptions for combination therapy of probenecid and allopurinol was negligible, although there are no explicit adverse effects associated with combination therapy, even though more recent clinicalNumber of citations100 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 YearFigure 6 Time trends in the number of publications in PubMed that mentioned gout in the title, abstract or Medical Subject Headings. Data source: Alexandru-Dan Corlan. Medline trend: automated yearly statistics of PubMed results for any query, 2004. Web resource at URL: http://dan.corlan.net/medline-trend.html. Accessed 14 February 2012, Archived by WebCite at http://www.webcitation.org/65RkD48SV.Krishnan and Chen Arthritis Research Therapy 2013, 15:R181 http://arthritis-research.com/content/15/6/RTable 2 C.
