Patterns of 6-mercaptopurine and azathioprine maintenance therapy among a cohort of commercially insured individuals diagnosed with Crohn’s disease in the United States

Abstract

Background and aims

Thiopurines, including 6-mercaptopurine (6-MP) and azathioprine (AZA), are the mainstay of maintenance therapy for Crohn’s disease (CD). However, studies examining their effectiveness in routine practice among diverse patient populations are lacking. Among a cohort of new users of 6MP/AZA, we described treatment patterns and changes in subsequent therapy.

Methods

Using the Truven Health Analytics databases, we identified all individuals diagnosed with CD and initiating 6-MP/AZA monotherapy from 2001–2008 (n=3,657). We estimated the proportion of CD patients remaining on 6-MP/AZA monotherapy, using Kaplan–Meier methods, and identified predictors of treatment noncontinuation, using multivariable Cox regression. Among the “noncontinuers,” we described subsequent patterns of maintenance therapy and summarized the diagnosis and procedure codes and prescription drug claims preceding treatment discontinuation.

Results

The 1-year 6-MP/AZA treatment continuation rate was 42%. Children (age ≤18 years) and individuals with no prior anti-tumor necrosis factor (TNF) use were more likely to continue 6-MP/AZA, while those dispensed more (>4) outpatient prescriptions for any drug before initiation of 6-MP/AZA were less likely to continue maintenance treatment. Overall, 1,128 (39%) and 105 (4%) individuals experienced a clinical event potentially indicating active disease or 6-MP/AZA-intolerance prior to discontinuation, respectively. Most patients discontinued therapy; among the remaining patients who failed to continue 6-MP/AZA, most augmented with an anti-TNF.

Conclusion

Most patients initiating 6-MP/AZA monotherapy did not continue beyond 1 year. In contrast to trial evidence showing 1-year remission rates of 40%–80%, this study observed a lower effectiveness of 6-MP/AZA treatment, possibly due to differences in disease severity, patient demographics, comorbidity, adherence, and health care utilization.

Keywords:

• immunomodulators
• outcomes research/measurement
• inflammatory bowel disease
• patterns of care

Supporting information

Table S1 Administrative codes used to identify an initial 6-MP/AZA treatment discontinuation, switch, and augmentation

Table S2 Administrative codes used to identify possible indicators of intolerance or active disease

Author contributions

SFC, MDK, and JLL conceived and designed the study. CFC and JKA acquired and analyzed the data. JLL, MDK and SFC interpreted the data. JLL, MDK, CFC, JKA, and SFC drafted the article or revised it critically for important intellectual content. All authors approved the final version of the manuscript.

Disclosure

Results of this study were presented at the 28th International Conference on Pharmacoepidemiology and Therapeutic Risk Management in Barcelona, Spain on August 23–26, 2012. SFC, JKA, and CFC are employees of GlaxoSmithKline. JLL and MDK are consultants to GlaxoSmithKline. As such, the study sponsor had involvement in all aspects of the study including, study design, analysis, and interpretation of data, in the writing of the manuscript, and in the decision to submit the manuscript for publication; the study sponsor did not have a role in data collection. The authors report no other conflicts of interest.