Reema Mody

Effects of Gastroesophageal Reflux Disease on Sleep and Outcomes

BACKGROUND & AIMS Nighttime symptoms of gastroesophageal reflux disease (GERD) are prevalent and have negative effects on sleep quality. We quantified the effects of GERD symptoms on sleep difficulties and their effects on outcomes. METHODS Data were obtained from a patient-reported survey conducted in 2006 among the general US population. Respondents who had experienced GERD symptoms at least twice during the past month were categorized as GERD patients and were subclassified into groups on the basis of nighttime symptoms and sleep difficulties. Outcomes included health care resource use in past 6 months, work productivity and activity impairment (WPAI), and health-related quality of life (HRQOL) based on results of the Short-Form Health Survey (SF-8). Regression analysis was used to adjust for demographics and clinical characteristics. RESULTS Of 11,685 survey respondents with GERD, 88.9% experienced nighttime symptoms, 68.3% sleep difficulties, 49.1% difficulty initiating asleep (induction symptoms), and 58.3% difficulty maintaining sleep (maintenance symptoms). Respondents with nighttime GERD symptoms were more likely to experience sleep difficulties (odds ratio, 1.53) and difficulties with induction (odds ratio, 1.43) and maintenance (odds ratio, 1.56) of sleep (P < .001 for all). Sleep difficulties were associated with 0.9 additional provider visits, a 5.5% increase in overall work impairment, a 10.9% increase in activity impairment, and reductions of 3.1 and 3.6 points in SF-8 physical and mental summary scores, respectively. CONCLUSIONS Nighttime GERD symptoms are associated with interruption of sleep induction and maintenance and result in considerable economic burden and reduction in HRQOL.

The Effect of Dexlansoprazole MR on Nocturnal Heartburn and GERD-Related Sleep Disturbances in Patients With Symptomatic GERD

OBJECTIVES:Nocturnal heartburn and related sleep disturbances are common among patients with gastroesophageal reflux disease (GERD). This study evaluated the efficacy of dexlansoprazole MR 30 mg in relieving nocturnal heartburn and GERD-related sleep disturbances, improving work productivity, and decreasing nocturnal symptom severity in patients with symptomatic GERD.METHODS:Patients (N=305) with frequent, moderate-to-very severe nocturnal heartburn and associated sleep disturbances were randomized 1:1 in a double-blind fashion to receive dexlansoprazole MR or placebo once daily for 4 weeks. The primary end point was the percentage of nights without heartburn. Secondary end points were the percentage of patients with relief of nocturnal heartburn and of GERD-related sleep disturbances over the last 7 days of treatment. At baseline and week 4/final visit, patients completed questionnaires that assessed sleep quality, work productivity, and the severity and impact of nocturnal GERD symptoms.RESULTS:Dexlansoprazole MR 30 mg (n=152) was superior to placebo (n=153) in median percentage of nights without heartburn (73.1 vs. 35.7%, respectively; P<0.001). Dexlansoprazole MR was significantly better than placebo in percentage of patients with relief of nocturnal heartburn and GERD-related sleep disturbances (47.5 vs. 19.6%, 69.7 vs. 47.9%, respectively; P<0.001), and led to significantly greater improvements in sleep quality and work productivity and decreased nocturnal symptom severity. Adverse events were similar across treatment groups.CONCLUSIONS:In patients with symptomatic GERD, dexlansoprazole MR 30 mg is significantly more efficacious than placebo in providing relief from nocturnal heartburn, in reducing GERD-related sleep disturbances and the consequent impairments in work productivity, and in improving sleep quality/quality of life.

Long-term Efficacy of Vedolizumab for Ulcerative Colitis

Background and Aims The GEMINI long-term safety [LTS] study is a continuing phase 3 trial investigating the safety and efficacy of vedolizumab, an α4β7 integrin antagonist for ulcerative colitis [UC] and Crohns disease. We provide an interim analysis of efficacy in patients with UC. Methods Patients from the C13004 and GEMINI 1 studies and a cohort of vedolizumab-naïve patients received open-label vedolizumab every 4 weeks. Interim data were collected from May 22, 2009 to June 27, 2013. Clinical response and remission, evaluated using partial Mayo scores, and health-related quality of life [HRQL] were assessed for up to 152 weeks of cumulative treatment in the efficacy population. Results As of June 27, 2013, 63% of the efficacy population [n = 532/845] were continuing treatment. Among patients who responded to vedolizumab induction and had data available, 88% [n = 120/136] were in remission after 104 weeks of exposure (96% [n = 70/73] after 152 weeks). Among patients who withdrew from every-8-week vedolizumab maintenance in GEMINI 1 [n = 32] before week 52, increased dosing to every 4 weeks in GEMINI LTS resulted in response and remission rates of 41% and 28%, respectively, after 52 weeks, an increase from 19% and 6%, respectively, from before the dose increase. Similar benefits were demonstrated regardless of prior tumour necrosis factor-antagonist exposure. Durable benefits on HRQL were also observed. Conclusions Patients with UC experienced clinical and HRQL improvements with continued vedolizumab treatment. Increased dosing frequency to every 4 weeks was beneficial in patients who had loss of response to 8-weekly dosing.

Long-term Efficacy of Vedolizumab for Crohn’s Disease

Background and Aims Vedolizumab is a gut-selective α4β7 integrin antagonist therapy for ulcerative colitis and Crohns disease. The GEMINI long-term safety [LTS] trial is an ongoing open-label study investigating the safety of vedolizumab. We present interim exploratory analyses of efficacy in patients with Crohns disease. Methods Patients from the C13004, GEMINI 2 and GEMINI 3 studies and vedolizumab-naïve patients could enrol in GEMINI LTS and received vedolizumab every 4 weeks. Data were collected from May 22, 2009 to June 27, 2013. Outcomes of clinical response and remission, defined by the Harvey-Bradshaw Index, and health-related quality of life [HRQL] were assessed for up to 152 weeks of treatment in the efficacy population. Results Among patients with response at week 6 in GEMINI 2 who received vedolizumab continuously, 83% [n=100/120] and 89% [n=62/70] of patients with available data were in remission after 104 and 152 weeks, respectively. Increased dosing frequency from every 8 weeks [GEMINI 2] to every 4 weeks [GEMINI LTS] improved outcomes in patients who had withdrawn early from GEMINI 2, with 47% [n=27/57] experiencing clinical response and 32% [n=18/57] in remission at week 52 of GEMINI LTS [up from 39% and 4% before the dose increase]. Similar improvements were observed regardless of prior tumour necrosis factor [TNF] antagonist exposure. Long-term benefits of HRQL were also observed. Conclusions The clinical benefits of vedolizumab continued with long-term treatment regardless of prior TNF antagonist exposure. Increased dosing frequency might improve outcomes in patients who lose response to conventional 8-weekly dosing.

Impact of noncompliance with urate-lowering drug on serum urate and gout-related healthcare costs: administrative claims analysis*

ABSTRACT Objective: To determine the association between allopurinol compliance and serum urate (sUA) level; and examine the association between sUA and gout-related healthcare costs in a large managed care population. Research design and methods: This retrospective administrative claims analysis examined subjects with gout (≥2 medical claims with ICD-9-CM diagnosis code 274.xx or ≥1 claim with a gout diagnosis and ≥1 pharmacy claim for allopurinol, probenecid, colchicine, or sulfinpyrazone) between January 1, 2002 and March 31, 2004. Each subject was observed during 1-year pre-index and 1-year post-index periods. Main outcome measures: Outcomes were allopurinol medication possession ratio (MPR) and compliance (MPR ≥ 0.80), sUA (mg/dL), and gout-related healthcare costs. ‘Post-allopurinol’ sUA was measured during three periods after the first observed allopurinol fill: 30–89 days; 90–149 days; ≥150 days. A baseline sUA on or before the start of the post-index period was also identified. Outcomes were stratified by post-allopurinol or baseline sUA and compliance. Generalized linear modeling (GLM) regression measured the impact of baseline sUA on gout-related healthcare costs, controlling for demographic and health status variables. Results: The study sample comprised 18 243 subjects with mean age of 53.9 years. In all, 55% (n = 10 073) of subjects used allopurinol. There were 1473 (8.1%) subjects with a post-allopurinol sUA and 2438 (13.4%) subjects with a baseline sUA result. Among all subjects with a post-allopurinol sUA, 45.6% were compliant; between 49.3% and 56.8% of compliant subjects had an sUA < 6.0 mg/dL compared with 22.5–27.8% of non-compliant subjects, depending on the post-allopurinol time period (all p < 0.001). GLM results showed gout-related costs associated with baseline sUA ≥ 6.0 and < 9.0 mg/dL were 58% higher (95% confidence interval (CI): 1.012 –2.456; p = 0.044) than were costs for sUA < 6.0 mg/dL. There was no significant difference in gout-related costs between baseline sUA < 6.0 mg/dL and ≥9.0 mg/dL. Conclusions: Analysis revealed an important associations between allopurinol compliance, sUA, and gout-related costs: compliance was positively associated with favorable sUA (<6.0 mg/dL) in unadjusted comparisons. GLM showed that baseline sUA < 6.0 was inversely associated with gout-related costs relative to baseline sUA ≥ 6.0 and <9.0 mg/dL. Nevertheless, a substantial portion of subjects, even compliant ones, did not achieve sUA < 6.0 mg/dL. These results should be interpreted carefully in light of study limitations, including incomplete laboratory data, the potentially incorrect inference that medications were taken as prescribed, and lack of generalizability from Medicare managed care enrollees to the broader Medicare population.

Treatment patterns and symptom control in patients with GERD: US community-based survey

ABSTRACT Background: Proton pump inhibitors (PPIs) are the most commonly used pharmacological treatment for gastroesophageal reflux disease (GERD). Objective: To examine the utilization patterns of PPIs and other GERD-related medications, satisfaction with PPI treatment and presence of GERD symptoms. Patients and methods: GERD patients using prescription PPIs were identified from a mixed-model HMO health plan. Utilization patterns of PPIs and other GERD medications, satisfaction with PPI treatment and presence of GERD symptoms were assessed using questionnaires. Results: Among the 617 patients who completed the survey, 71.0% used PPIs once a day (QD), 22.2% used twice a day (BID) and 6.8% more than twice a day or on an as-needed basis. Approximately 42.1% of all patients supplemented their prescription PPIs with other GERD medications, including over-the-counter medications and H2-receptor antagonists. Over 85% of the patients still experienced GERD symptoms and 82.7% nighttime symptoms. Overall, 72.8% of all patients were satisfied or very satisfied with their PPI treatment. Limitations: The study used self-reported data which may have been subject to recall bias. As the study was conducted in a specific region of the US, the results may have limited generalizability to other US regions or countries. Conclusions: Patients on PPI treatment often experience GERD symptoms and supplement their prescription PPIs with other GERD medications. A substantial proportion of GERD patients receiving PPI treatment are on a BID regimen. Furthermore, more than a quarter of the patients are not completely satisfied with their PPI treatment.

Health-related quality of life, work productivity and health care resource use associated with constipation predominant irritable bowel syndrome

Abstract Objectives: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. Prevalence estimates of IBS vary widely, from 10 to 15%, in the U.S. However, few studies have examined constipation predominant IBS (IBS-C), a subtype of IBS. The aim of this study was to assess the effect of IBS-C on health-related quality of life (HRQOL), work productivity and activity impairment, and health care resource use. Methods: Using data from the 2007 U.S. National Health and Wellness Survey, IBS-C patients (n = 789) were compared to a propensity-score matched comparison group (n = 789). Differences between the groups were examined on HRQOL (SF-12v2), work productivity and activity impairment (WPAI questionnaire), and self-reported resource use in the last 6 months. Results: Patients with IBS-C reported significantly lower levels of HRQOL (physical component summary score: 41.55 [95% CI: 40.72–42.37] versus 44.49 [95% CI: 43.67–45.31]; mental component summary score: 40.58 [95% CI: 39.75–41.40] vs. 45.87 [95% CI: 45.04–46.70]) and significantly higher mean levels of presenteeism (31.72% [95% CI: 28.25%–35.61%] vs. 21.43% [95% CI: 19.03%–24.15%]), overall work impairment (35.54% [95% CI: 31.76%–39.76%] vs. 25.29% [95% CI: 22.59%–28.30%]), and activity impairment (45.78% [95% CI: 43.08%–48.66%] vs. 33.03% [95% CI: 31.08%–35.11%]) than matched comparators (all P values < 0.01). Patients with IBS-C reported significantly more provider visits (8.07 [95% CI: 7.38–8.82] vs. 5.55 [95% CI: 5.07–6.08]) and emergency room visits (0.57 [95% CI: 0.46–0.70] vs. 0.36 [95% CI: 0.29–0.45]) in the past 6 months (all Ps < 0.01). No statistically significant differences between the groups were observed in absenteeism or the number of the days hospitalized. Conclusions: IBS-C was associated with poorer HRQOL, greater work productivity loss and activity impairment, and greater healthcare resource use. Limitations include the study’s cross-sectional design and its self-reported nature. Nevertheless, improved management of IBS-C may reduce the humanistic and economic burden of the condition and benefit patients, employers, and the healthcare system.

Risk of developing colorectal cancer and benign colorectal neoplasm in patients with chronic constipation

Chronic constipation (CC) is a highly prevalent health problem, potentially associated with increased risk of colorectal cancer (CRCancer).

The development and validation of a Nocturnal Gastro-oesophageal Reflux Disease Symptom Severity and Impact Questionnaire for adults

Aliment Pharmacol Ther 2010; 32: 591–602

Real-world assessment of therapy changes, suboptimal treatment and associated costs in patients with ulcerative colitis or Crohn's disease

Treatments for Crohns disease (CD) and ulcerative colitis (UC) are not uniformly effective, thus necessitating dose changes, switching, and augmentation and carry adverse event risk, often requiring discontinuation, which reduces treatment benefits.