Date Published: June 23, 2016
Publisher: Public Library of Science
Author(s): Akbar K. Waljee, Wyndy L. Wiitala, Shail Govani, Ryan Stidham, Sameer Saini, Jason Hou, Linda A. Feagins, Nabeel Khan, Chester B. Good, Sandeep Vijan, Peter D. R. Higgins, Fabio Cominelli.
Corticosteroids are effective for the short-term treatment of inflammatory bowel disease (IBD). Long-term use, however, is associated with significant adverse effects. To define the: (1) frequency and duration of corticosteroid use, (2) frequency of escalation to corticosteroid-sparing therapy, (3) rate of complications related to corticosteroid use, (4) rate of appropriate bone density measurements (dual energy X-ray absorptiometry [DEXA] scans), and (5) factors associated with escalation and DEXA scans.
Retrospective review of Veterans Health Administration (VHA) data from 2002–2010.
Of the 30,456 Veterans with IBD, 32% required at least one course of corticosteroids during the study time period, and 17% of the steroid users had a prolonged course. Among these patients, only 26.2% underwent escalation of therapy. Patients visiting a gastroenterology (GI) physician were significantly more likely to receive corticosteroid-sparing medications. Factors associated with corticosteroid-sparing medications included younger age (OR = 0.96 per year,95%CI:0.95, 0.97), male gender (OR = 2.00,95%CI:1.16,3.46), GI visit during the corticosteroid evaluation period (OR = 8.01,95%CI:5.85,10.95) and the use of continuous corticosteroids vs. intermittent corticosteroids (OR = 2.28,95%CI:1.33,3.90). Rates of complications per 1000 person-years after IBD diagnosis were higher among corticosteroid users (venous thromboembolism [VTE] 9.0%; fragility fracture 2.6%; Infections 54.3) than non-corticosteroid users (VTE 4.9%; fragility fracture 1.9%; Infections 26.9). DEXA scan utilization rates among corticosteroid users were only 7.8%.
Prolonged corticosteroid therapy for the treatment of IBD is common and is associated with significant harm to patients. Patients with prolonged use of corticosteroids for IBD should be referred to gastroenterology early and universal efforts to improve the delivery of high quality care should be undertaken.
Corticosteroids are powerful, non-selective systemic anti-inflammatory drugs that are frequently used to treat autoimmune conditions. In inflammatory bowel disease (IBD), corticosteroids are the mainstay of “rescue” therapy for patients who are experiencing a disease flare. Despite the efficacy of these medications in the short-term, corticosteroids are known to cause serious adverse effects with long term use including bone loss , venous thromboembolism (VTE)  and poor wound healing . Corticosteroids often lead to rapid resolution of IBD symptoms, which aligns with patient preferences for treatment. However, this may lead to inappropriate use of these medications for maintenance when other treatment options may be better in the longer-term. Escalation of therapy to corticosteroid-sparing maintenance therapy such as immunomodulators [4, 5] or biological agents [6, 7] can improve disease outcomes and avoid the complications of prolonged steroid use. Underutilization of corticosteroid-sparing medications and failure to monitor for complications of corticosteroid use have motivated professional subspecialty societies to advocate for reduction in corticosteroid use and early initiation of corticosteroid-sparing therapy . Indeed, early use of corticosteroid-sparing medications is now viewed as an increasingly important measure of the quality of IBD care . These measures of the quality of the process of IBD care are aimed at optimizing medication use and improving patient safety by minimizing exposure to medications associated with both short and long term complications . According to Plevy et al. patients with two corticosteroid courses within one year should escalate to corticosteroid-sparing maintenance therapy . The American Gastroenterological Association (AGA) recommends dual X-ray absorptiometry (DEXA) scan evaluation of bone density in any patient on corticosteroids for at least 3 months or recurrent courses, any male with IBD over the age of 50 or any post-menopausal female. [12, 13].
Descriptive statistics were used to compare patient characteristics among the corticosteroid and non-corticosteroid groups comparing the patient age and whether or not a visit with a GI specialist occurred. Demographic and clinical variables were compared between the corticosteroid groups and additional supplementary analysis was done among the various patterns of corticosteroid users (CS, IS, AS) and NS (no corticosteroid users). Independent sample t-tests were used to compare corticosteroid user groups on continuous measures. Negative binomial regression models were used to estimate the effects of corticosteroid users on count outcomes. Pearson’s chi-square tests were used to test the relationship between corticosteroid users and categorical measures. In the event that cell sizes dropped below n = 5, Fisher’s exact test was used to test for statistical significance. We used Poisson regression models to assess the impact of IBD corticosteroid use on complications, adjusting for age, male gender, Charlson comorbidity index, and exposure time (IBD diagnosis date or corticosteroid initiation date to the end of the study period). To assess escalation of therapy and DEXA scan use within one year of corticosteroid initiation, we used logistic regression to evaluate Veteran predictors (age, gender and GI visit pre-corticosteroid initiation) of outcomes and adjusting for clustering by facility. In addition, we conducted a multilevel logistic regression model, adjusting for Veteran level covariates (age, gender), to assess the facility-level variation in escalation of therapy for Veterans among all corticosteroids users (CS, IS, AS). All data analysis was performed using Stata 13.1 (StataCorp, College Station, TX).
We identified 30,456 patients with IBD over the study period. The mean (±SD) age was 60 (15) years. The majority of Veterans were male (94%) and Caucasian (69%). Additional baseline characteristics are provided in Table 1 and Supplementary Table A in S1 Tables for the various patterns of corticosteroid users.
In this large cohort of Veteran IBD patients, we found that one-third are treated with corticosteroids at least once during the study period and 15% of the total corticosteroid users were exposed to continuous corticosteroid use. Among these patients with a prolonged exposure, three-quarters did not receive any form of corticosteroid-sparing therapy. The negative effect of corticosteroid exposure was seen in corticosteroid related complications such as VTE, fragility fractures and infections. Additionally, there was a low rate of utilization of DEXA scans according to society guidelines even accounting for bisphosphonate use.
Prolonged corticosteroid therapy for the treatment of IBD is common and may be associated with significant harm to patients. Despite this, there was low utilization of preventative measures such as DEXA scans. No individual-level or facility-level factors were specifically associated with use of corticosteroid-sparing medications; however, a gastroenterology visit was associated with an increased likelihood of using corticosteroid-sparing medications. Patients with prolonged use of corticosteroids for IBD should be referred to gastroenterology early and universal efforts to improve the delivery of high quality care should be undertaken.