Olga Alexeeva

A Multicenter, Randomized, Double-Blind Trial of Everolimus Versus Azathioprine and Placebo to Maintain Steroid-Induced Remission in Patients With Moderate-to-Severe Active Crohn's Disease

OBJECTIVES:A prospective study was undertaken to compare the efficacy of everolimus versus azathioprine or placebo in maintaining steroid-induced remission in active Crohns disease (CD) and assess the safety and pharmacokinetics of everolimus.METHODS:This was a randomized, double-blind, placebo-controlled, proof-of-concept study in adults with moderate-to-severe active CD. The patients received oral steroids for a rapid induction of remission plus everolimus 6 mg/day, azathioprine 2.5 mg/kg/day, or placebo as maintenance treatment. The main outcome measure was the treatment success, defined as a steroid-free remission by the end of month 3 and maintained until study cutoff without the use of prohibited efficacy treatments.RESULTS:Following an interim analysis, the study was terminated before enrollment was completed due to the lack of efficacy. The full intent-to-treat population comprised 138 patients. Only 96 patients who entered the study ≥7 months prior to data cutoff were included in the primary efficacy population. The treatment success was achieved in 13 of 38 everolimus patients, 22 of 36 azathioprine patients, and 8 of 22 placebo patients. Using the Kaplan–Meier estimates at month 7, the incidence of treatment success was 22.0% with everolimus group (95% confidence interval [CI] 6.7–37.3%, P = 0.610 vs placebo), 38.3% with azathioprine group (95% CI 20.6–55.9%, P = 0.500 vs placebo), and 28.8% with placebo group (95% CI 7.7–49.9%). The type and incidence of adverse events in the everolimus cohort were similar to those reported in the approved transplantation indications.CONCLUSIONS:The safety and tolerability of everolimus (6 mg/day) in patients with active CD were comparable to azathioprine. At this dose, everolimus is not more efficacious in achieving a steroid-free remission in active CD than the comparators.

The Reflux Improvement and Monitoring (TRIM) Program Is Associated With Symptom Improvement and Weight Reduction for Patients With Obesity and Gastroesophageal Reflux Disease.

Objectives:Current healthcare systems do not effectively promote weight reduction in patients with obesity and gastroesophageal reflux disease (GERD). The Reflux Improvement and Monitoring (TRIM) program provides personalized, multidisciplinary, health education and monitoring over 6 months. In this study we aimed to (i) measure the effectiveness of TRIM on GERD symptoms, quality of life, and weight, and (ii) examine patient health beliefs related to TRIM.Methods:This prospective mixed methods feasibility study was performed at a single center between September 2015 and February 2017, and included adult patients with GERD and a body mass index ≥30 kg/m2. Quantitative analysis consisted of a pre- to post-intervention analysis of TRIM participants (+TRIM Cohort) and a multivariable longitudinal mixed model analysis of +TRIM vs. patients who declined TRIM (−TRIM Cohort). Primary outcomes were change in patient-reported GERD symptom severity (GerdQ) and quality of life (GerdQ-DI), and change in percent excess body weight (%EBW). Qualitative analysis was based on two focus groups of TRIM participants.Results:Among the +TRIM cohort (n=52), mean baseline GerdQ scores (8.7±2.9) decreased at 3 months (7.5±2.2; P<0.01) and 6 months (7.4±1.9; P=0.02). Mean GerdQ-DI scores decreased, but did not reach statistical significance. Compared with the −TRIM cohort (n=89), reduction in %EBW was significantly greater at 3, 6, and 12 months among the +TRIM cohort (n=52). In qualitative analysis, patients unanimously appreciated the multidisciplinary approach and utilized weight loss effectively to improve GERD symptoms.Conclusions:In this mixed methods feasibility study, participation in TRIM was associated with symptom improvement, weight reduction, and patient engagement.

Electronic Clinical Decision Support Tools for Obesity and Gastroesophageal Reflux Disease: The Provider’s Perspective

Electronic clinical decision support (CDS) in the medical record is a potentially powerful tool to improve patient outcomes. Although CDS is increasingly utilized, limited data exist on the utilization, strengths, and drawback of CDS tools in the management of gastrointestinal disease [1–3]. We recently described the design and effective implementation of The Reflux Improvement and Monitoring (TRIM) program, which leveraged CDS to provide a 6-month patient-centered weight loss counseling program tailored to patients with gastroesophageal reflux disease (GERD) and administered by trained health educators [4]. While we reported patient health beliefs regarding TRIM, we did not explore provider perspectives. In this study, we aimed to assess provider factors and perspectives related to the CDS and TRIM in order to better inform future CDS implementation. In this study, we first prospectively examined the association between provider level factors and CDS acceptance defined as the percentage of CDS firings that led to a signed referral order between October 2015 and September 2017 in general internal medicine (GIM) and gastroenterology (GI) outpatient clinics at a single academic medical center. Next, we evaluated provider satisfaction with and perceptions of the CDS through a survey study. Surveys were distributed in email or paper form to 102 providers in the GIM and GI clinics between March and May 2017. The 13-item survey utilized Likert and modified Likert scales, multiple choice selection, and free response. Among 2361 unique triggered CDS alerts for patients with obesity and GERD, 503 (21.3%) were accepted and led to referral orders being placed for TRIM. Female providers were significantly more likely to refer compared to male providers (OR 1.9, CI 1.5–2.3; p < 0.01) and GI providers were significantly more likely to refer compared to GIM providers (OR 2.5, CI 2.0–3.1, p < 0.001). Provider age did not influence likelihood of referral. Survey response rate was 42% (43/102). The majority of providers (76%) agreed or strongly agreed that TRIM was an effective intervention for their patients with obesity and GERD. Providers were most likely to offer TRIM to patients that displayed high motivation for weight loss, and with more severe obesity. The top reported barrier to referral for GIM providers was a lack of time to consider the CDS, which appeared for them mixed in with other CDS in a dedicated section of the patient chart. When asked what would encourage them to refer more patients to TRIM, 60% of GIM providers selected satisfied patient/provider testimonials, and 40% selected having TRIM referral orders available outside of the CDS. Only 11% believed that having CDS appear more often would encourage them to refer more patients, suggesting that increased CDS must be balanced against the potential for alert fatigue. This post-hoc analysis provides the following important lessons for future CDS implementation: (1) satisfied patient and provider testimonials should be integrated into program promotion, (2) promotion should be particularly emphasized to providers in departments outside of the implementers’ home department, and (3) empowering and educating providers to place referrals outside of CDS is essential.