The article by Jackson et al.1 and accompanying editorial by Corpechot and Poupon2 have raised the interesting question of practice variation in the diagnosis and treatment of primary biliary cirrhosis (PBC). In general, the variable use of effective medical therapies continues to be linked with the notion of inconsistent clinical outcomes for chronic disease overall.3 Given the available data, it is difficult to ignore the likelihood that ursodeoxycholic acid (UDCA) therapy has influenced the natural history of PBC in various populations. In addition, there is empiric evidence supporting the existence of practice variation in UDCA prescribing patterns for PBC within the United States.4 Specifically, the timing of UDCA therapy may be quite varied with at least 10% of patients beginning UDCA greater than 1 year after initial diagnosis.
Although specific details about provider adherence rates to weight-based dosing (13-15 mg/kg/day) remain unavailable, it is likely that significant variations exist in the United States, given the large dose range (from 1.5 to 23.1 mg/kg/day, median 11.5) reported by practicing gastroenterologists in the United Kingdom.5 Drug-related adverse event rates as high as 35% leading to UDCA discontinuation are also reported among U.S. residents with PBC.4 This far exceeds rates observed in published randomized controlled trials to date. Given the cohort used by Jackson et al., it would have been intriguing to know how often dose reduction and/or drug cessation occurred in their population. Finally, medical therapies with questionable or no benefit for PBC are prescribed by 10%-15% of providers based on published reports.5 Estimated rates of similar practices in the United States remain unknown.
Despite the overall rarity of PBC, these observations underscore the need to recognize differences in treatment patterns which may influence long-term outcome in PBC. Similarly, ongoing educational efforts to decrease the use of ineffective therapies with unfavorable risk/benefit profiles in altering the natural history of PBC would be welcomed.