DDW 2017: News in Gastroenterology - Ulcerative Colitis

DDW 2017. Mo1652. IMPACT OF PROINFLAMMATORY CYTOKINES AND MESALAMINE ON THE EXPRESSION OF THE TIGHT JUNCTION PROTEIN CLAUDIN-1 IN INTESTINAL EPITHELIAL CELLS

 

Results: IFN and IL-13 had no effect on claudin-1 expression whereas stimulation of intestinal epithelial cells with IL-1, IL-6, TNF and a combination of IFN with TNF induced a dose- and time-dependent increase in claudin-1 expression. Concurrent treatment with mesalamine applied from the apical side of the monolayer partially prevented increased claudin-1 expression induced by proinflammatory cytokines. Data on the subcellular localization of claudin-1 and activation of key signaling pathways are currently under investigation and will be presented at the meeting.

Conclusions: Our results identify proinflammatory cytokines controlling claudin-1 expression in intestinal epithelial cells. The ability of mesalamine to counteract claudin-1 upregulation by these cytokines might provide a molecular basis for its suggested role as a chemo preventive agent in IBD-associated colorectal cancer.

CARE Faculty Perspective: This interesting study provides more fodder for the longstanding debate about the direct chemopreventive effects of 5-ASA. 

DDW 2017: News in Gastroenterology - Crohn's Disease

DDW 2017. 718. SUPERIOR ENDOSCOPIC AND DEEP REMISSION OUTCOMES IN ADULTS WITH MODERATE TO SEVERE CROHN'S DISEASE MANAGED WITH TREAT TO TARGET APPROACH VERSUS CLINICAL SYMPTOMS: DATA FROM CALM

 

Results:
Figure. Primary endpoint at 48 Weeks after Randomization

Conclusions: This is the first study showing that the treat to target approach leads to superior endoscopic and deep remission outcomes in CD compared with symptom-driven care.

CARE Faculty Perspective: This novel ‘treat to target’ concept involves monitoring patients with CD using biomarkers of inflammation, CRP, and FC, to assist in timely treatment. While this is a preliminary study, we may want to consider changing our treatment approach moving forward, as this study has demonstrated that T2T method leads to better outcomes than conventional symptom-driven care.

DDW 2017: News in Gastroenterology - Functional Gastrointestinal Disorders

DDW 2017. 263. INTESTINAL, NON-INTESTINAL, AND EXTRA-DIGESTIVE RESPONSE TO LINACLOTIDE IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH CONSTIPATION: RESULTS AT WEEK 4 PREDICT SUSTAINED RESPONSE

 

Results: 96 patients were eligible and treated (ITT analysis) after a 4-week screening period; 60 patients were included in the per protocol (PP) analysis. The majority were female (91; 95%) and mean age was 47 years. Mean baseline IBSSS score was 371 and mean time from diagnosis was 7.5 years (ITT). At Weeks 4 and 12, 23% and 25% of patients (ITT), and 32% and 37% of patients (PP), respectively, had a clinical response based on subjective improvement and IBSSS score. At Weeks 4 and 12, 64% and 55% of patients had subjective responses, and 24% and 32% had IBSSS score responses, respectively (ITT). If one of both criteria were considered, 61.5% (ITT) and 80% (PP) of patients obtained some benefit at Week 12. Baseline variables were not associated with response at Week 12, but response at Week 4 was independently associated with Week 12 response (OR: 6.5 [95% CI: 2.1, 19.8]). Digestive non-intestinal and extra-digestive symptom scores were significantly improved by Weeks 4 and 12 (Table). The most common adverse event was diarrhea (n=39; 21%). No serious adverse events occurred.

Table. Digestive non-intestinal and extra-digestive symptom scores (ITT population) 

 

Includes reflux and dyspepsia; bIncludes back pain, headaches, chest pain, dizziness, fainting spells, feeling heart pound or race, shortness of breath, pain or problems during sexual intercourse, pain in arms, legs, or joints, feeling tired or having low energy, menstrual cramps or other problems with periods (women only), and trouble sleeping *p=0.001 vs. baseline; **p<0.001 vs. baseline SD, standard deviation

Conclusions: Linaclotide relieves intestinal, non-intestinal, and extra-digestive symptoms in patients with clinically relevant IBS-C. Baseline characteristics were not predictive of response at Week 12, but response at Week 4 was independently associated with a sustained response at Week 12.

CARE Faculty Perspective: Linaclotide is an oral guanylate cyclase-C receptor antagonist approved in Canada for the treatment of moderate to severe IBS-C in adults. Previous trials have confirmed that linaclotide is a safe and effective agent that is able to reduce abdominal pain – one of the most highly reported reasons of why patients seek treatment.

Digestive non-intestinal and extra-digestive symptom scores were significantly improved already by week 4. From this study we can infer that if a patient responds to treatment at week 4, they are likely to have a sustained response at week 12.

DDW 2017: News in Gastroenterology - Functional Gastrointestinal Disorders

DDW 2017. Tu1612. IRRITABLE BOWEL SYNDROME PATIENT EXPERIENCE IN CANADA

 

Results: Respondents from every province and territory totalled 2,961. 90% were between 30-69 years of age, 86% female, 97% were adults with IBS. 53% had IBS for more than 10 years. 35% had IBS-D, 18% IBS-C, 41% IBS-M, and 6% unsure. In IBS-C patients, abdominal pain was identified as a distinct predominant symptom. Those with IBS-D experienced many symptoms, with abdominal pain, bloating, urgency, and diarrhea identified as highly concerning. 31% experienced severe abdominal pain in the last 3 months, with severe pain being constant in a high proportion. 62% of patients indicated they experienced pain continuing after bowel movement. The top factors driving patients to see their physician were pain/discomfort and impact of IBS on their personal/professional/daily life. Approximately 93% and 49% of patients consulted with a family doctor and gastroenterologist, respectively, for their IBS. 60% had a colonoscopy. 12% have been hospitalized for IBS. 76% indicated that their symptoms interfere with everyday life and 46% missed work or school due to IBS. Most IBS patients use ≥2 medications on a regular basis to control their symptoms yet only 21% are confident their symptoms are under control. Compounding the issue, 16% are unable to afford any of their prescribed medications, and 26% can only afford some of them.

Conclusions: Canadian IBS patients suffer from multiple symptoms, with the pain experienced by patients being the prime motivating factor to seek care. 79% have symptoms not under control. The conventional standard of care for IBS requires many different treatments to manage the multiple symptoms, with the majority of IBS patients requiring 2 or more treatments on a regular basis. IBS patients experience a wide range of symptoms and comorbidities. It can be a struggle for them to find treatments that are effective and affordable.

CARE Faculty Perspective: The most common complaints from patients include abdominal pain and constipation and/or diarrhea. Real-world data is limited, so this study aimed to look how IBS affects people in Canada. A questionnaire was distributed via the Gastrointestinal Society in Canada and included questions about symptom severity, medication use, experience with health care system, quality of life, etc.

The key finding from this survey is that 79% of patients do not have their IBS symptoms under control. This is a huge amount of people whose quality of life may be severely affected. More awareness on how to treat symptoms with appropriate treatment may be needed across Canada to ensure this rate is reduced.

DDW 2017: News in Gastroenterology - Upper Gastrointestinal Disorders

DDW 2017. 971: AGE OF HELICOBACTER PYLORI ERADICATION AND SUBSEQUENT RISK OF GASTRIC CANCER DEVELOPMENT: A POPULATION-BASED STUDY

Results: Among the 63,605 eligible HP-infected subjects (median age 54.8 years, 46.6% male) who had received a course of clarithromycin-based triple therapy, 169 (0.27%) developed GC with a median follow-up of 7.6 years (Incidence: 3.48 per 10,000 person-years). The incidence of gastric cancer in the youngest age group (<40 years) was very low (0.42 per 10,000 person-years) whereas the corresponding incidence rates in the 40-60 and >60-year age groups were 2.12 and 7.12 per 10,000 person-years, with a significant difference among the three groups (log rank p<0.001; Figure). When compared with the group who received HP therapy <40 years, there was a progressive increase in the risk of cancer in the older age groups (age group 40-60: HR 5.6, 95% CI 1.7-17.8; age group ≥60: HR 17.1, 95% CI 5.4-54.8).

Conclusions: In this large population-based study, we showed that the risk of gastric cancer development was very low in individuals who had received HP therapy before the age of 40. For prevention of gastric cancer, HP eradication shall be given before the age of 40.

CARE Faculty Perspective: The goal of this study was to determine the risk of developing gastric cancer after receiving HP eradication therapy among different age groups in a large cohort of HP infected subjects. It appears that patients over 60 have the highest rate of developing gastric cancer. In order to prevent this, HP eradication treatment should be given before the age of 40.

DDW 2017: News in Gastroenterology - Crohn's Disease

DDW 2017. 616. LONG-TERM SAFETY OF ADALIMUMAB IN PATIENTS WITH CROHN'S DISEASE: FINAL DATA FROM PYRAMID REGISTRY

Results: A total of 5025 pts were evaluated in this analysis (57.1% female, mean age 37.8 yrs at enrollment), representing 16680.4 PYs of ADA exposure over 6 yrs. The mean (SD) duration of ADA exposure during the registry was 1212.4 (835.4) days. A total of 2852 pts (56.8%) had prior biologic use, 1798 (35.8%) used immunomodulators (IMM), and 1463 (29.1%) used corticosteroids (CS) at registry baseline (BL). Overall, 3478 (69.2%) pts discontinued ADA or the registry. A total of 1853 pts (36.9%) reported 4129 treatment-emergent SAEs (24.8/100 PY). A total of 556 pts reported 792 treatment-emergent serious infections (SI) (4.7/100 PY). The only treatment-emergent SI reported by ≥1% of pts was perianal abscess (0.7/100 PY). The SI rate was higher for pts with concomitant medication at BL (ADA+CS, ADA+IMM, ADA+CS+IMM) vs ADA monotherapy (6.4, 4.8, 5.0 vs 4.2/100PY, respectively). A total of 116 pts experienced 134 treatment-emergent malignancy events (0.8/100 PY), of which 10 were lymphomas. No non-treatment-emergent lymphoma events were reported. The registry exposure-adjusted rate of lymphoma was 0.060/100 PY. The upper bound of the 1-sided 95% CI of this rate was 0.102/100 PYs and fell below 0.168/100 PYs (double the expected rate of 0.084/100 PYs). TEAEs leading to death were reported in 43 pts (0.3/100 PY). 

Conclusions: The registry achieved the goal of ruling out a doubling of lymphoma risk in pts with CD treated with ADA. No new safety signals were identified.

CARE Faculty Perspective: While immunosuppressive therapies have been associated with adverse events including infection and malignancy, this large-scale study determined that there is not a doubling of lymphoma risk for patients receiving adalimumab. The overall safety profile of adalimumab in this large registry is similar to that reported previously.

ECCO/CDDW 2017: Irritable Bowel Syndrome

CDDW 2017. A269. Irritable Bowel Syndrome Patient Experience in Canada 

G.P. Attara, J. Gray, G. Aumais

Results: Respondents from every province and territory totalled 2,961. 90% were between 30-69 years of age, 86% female, 97% were adults with IBS. 53% had IBS for more than 10 years. 35% had IBS-D, 18% IBS-C, 41% IBS-M, and 6% unsure. In IBS-C patients, abdominal pain was identified as a distinct predominant symptom. Those with IBS-D experienced many symptoms, with abdominal pain, bloating, urgency, and diarrhea identified as highly concerning. 24% experienced severe abdominal pain in the last 3 months, with severe pain being constant in a high proportion. 62% of patients indicated they experienced pain continuing after bowel movement. The top factors driving patients to see their physician were pain/discomfort and impact of IBS on their personal/professional/daily life. Approximately 93% and 49% of patients consulted with a family doctor and gastroenterologist, respectively, for their IBS. 60% had a colonoscopy. 12% have been hospitalized for IBS. 76% indicated that their symptoms interfere with everyday life and 46% missed work or school due to IBS. Most IBS patients use ≥2 medications on a regular basis to control their symptoms yet only 21% are confident their symptoms are under control. Compounding the issue, 16% are unable to afford any of their prescribed medications, and 26% can only afford some of them.

Conclusion: Canadian IBS patients suffer from multiple symptoms, with the pain experienced by patients being the prime motivating factor to seek care. 79% have symptoms not under control. The conventional standard of care for IBS requires many different treatments to manage the multiple symptoms, with the majority of IBS patients requiring 2 or more treatments on a regular basis. IBS patients experience a wide range of symptoms and comorbidities. It can be a struggle for them to find treatments that are effective and affordable.

CARE Faculty Perspective: IBS is a chronic functional gastrointestinal disorder that affects 13-20% of Canadians. There are a number of symptoms associated with IBS, and research has shown that abdominal pain and bloating are some of the most bothersome symptoms. Lifestyle interventions, such as increased dietary fiber, water intake, and exercise, for the treatment of IBS are universally recommended. However, lifestyle modifications are often not enough.

This study found that one of the main reasons patient seek treatment is due to pain. Linaclotide is approved for both IBS-C and CIC, and has shown to consistently provide abdominal pain relief. In the field of IBS-D, there are no currently approved agents however eluxadoline and rifaximin are currently being reviewed by Health Canada and appear to be promising.