Impact of adalimumab on disease burden in moderate-to-severe ulcerative colitis patients: The one-year, real-world UCanADA study.

BACKGROUND: A gap remains in documenting the impact of anti-tumor necrosis factor therapy on disease burden in ulcerative colitis (UC) patients treated in a real-world setting. The use of patient-reported outcomes (PROs) has been discussed as a primary endpoint in the context of the FDA PRO Guidance, for labelling purposes. Specifically, the efficacy and safety of adalimumab have been demonstrated in pivotal trials; however, data are needed to understand how clinical results translate into improvements in key aspects of the daily lives of UC patients, such as symptoms, health-related quality of life (HRQoL), and disability. AIM: To assess real-world effectiveness of adalimumab on PRO measures in patients with moderate-to-severe UC. METHODS: UCanADA was a single arm, prospective, 1-year multicenter Canadian post-marketing observational study in which multiple PRO questionnaires were completed-with psychologic distress/depression symptoms as the primary endpoint-by patients with moderate-to-severe UC. Assessments were performed during patients' routine care visit schedule, which was at the initiation of adalimumab (baseline), after induction (approximately 8 wk), and 52 wk after baseline. Additional optional assessments between weeks 8 and 52 were collected at least once but no more than two times during this period. Serious safety events and per-protocol adverse events were collected. RESULTS: From 23 Canadian centres, 100 patients were enrolled and 48 completed the study. Measured with the Patient Health Questionnaire-9 items at week 52, 61.5% (40/65) [95% confidence interval (CI): 49.7%-73.4%] of the patients improved in psychologic distress/depression symptoms, which was slightly higher in completers [65.9% (29/44); 95%CI: 51.9%-79.9%)]. At week 52, clinical response and clinical remission were achieved respectively by 65.7% (44/73) and 47.8% (32/73) of the patients. The odds of improving depressive symptoms for those achieving a clinical remission at week 52 was 7.94 higher compared with those not achieving a clinical remission (CI: 1.42, 44.41; P = 0.018). Significant changes from baseline to weeks 8 and 52 were observed in disability, HRQoL, and fatigue. Meaningful improvement was reported in work impairment. CONCLUSION: At week 52, over 60% of the UCanADA patients had depressive symptoms significantly reduced, as well as HRQoL, fatigue symptoms, and work impairment improved. No new safety signals were detected.

Healthcare maintenance in elderly patients with inflammatory bowel disease.

The increasing number of older patients (age ≥60 years) with inflammatory bowel disease (IBD) highlights the importance of healthcare maintenance in this vulnerable population. Older IBD patients are more susceptible and have higher rates of many disease- and treatment-related adverse effects. Compared to younger IBD patients, older patients are at increased risk for infection, malignancy, bone disease, eye disease, malnutrition and thrombotic complications. Preventive strategies in the elderly differ from those in younger adults and are imperative. Changes to the immune system with aging can decrease the efficacy of vaccinations. Cancer screening guidelines in older IBD patients have to account for unique considerations, such as life expectancy, functional performance status, multimorbidity, financial status, and patient desires. Additionally, providers need to be vigilant in screening for osteoporosis, ocular disease, depression, and adverse events arising from polypharmacy.

Modified Delphi Process for the Development of Choosing Wisely for Inflammatory Bowel Disease.

BACKGROUND AND AIMS: The prevalence and incidence of inflammatory bowel disease (IBD) in North America is among the highest in the world and imparts substantial direct and indirect medical costs. The Choosing Wisely Campaign was launched in wide variety of medical specialties and disciplines to reduce unnecessary or harmful tests or treatment interventions. METHODS: The Choosing Wisely list for IBD was developed by the Canadian IBD Network for Research and Growth in Quality Improvement (CINERGI) in collaboration with Crohn's and Colitis Canada (CCC) and the Canadian Association of Gastroenterology (CAG). Using a modified Delphi process, 5 recommendations were selected from an initial list of 30 statements at a face-to-face consensus meeting. RESULTS: The 5 things physicians and patients should question: (1) Don't use steroids (e.g., prednisone) for maintenance therapy in IBD; (2) Don't use opioids long-term to manage abdominal pain in inflammatory bowel disease (IBD); (3) Don't unnecessarily prolong the course of intravenous corticosteroids in patients with acute severe ulcerative colitis (UC) in the absence of clinical response; (4) Don't initiate or escalate long-term medical therapies for the treatment of IBD based only on symptoms; and (5) Don't use abdominal computed tomography (CT) scan to assess IBD in the acute setting unless there is suspicion of a complication (obstruction, perforation, abscess) or a non-IBD etiology for abdominal symptoms. CONCLUSIONS: The Choosing Wisely recommendations will foster patient-physician discussions to optimize IBD therapy, reduce adverse effects from testing and treatment, and reduce medical expenditure.

Anal Neoplasia in Inflammatory Bowel Disease Is Associated With HPV and Perianal Disease.

OBJECTIVES: Literature describing the risk factors predisposing inflammatory bowel disease (IBD) patients to anal squamous neoplasia is very scarce. Case reports and small case series have implicated perianal Crohn's disease (CD), long-standing IBD, human papillomavirus (HPV) infection, and immunosuppressive treatment. In this study, we retrospectively examined the association between HPV infection and anal squamous neoplastic lesions among IBD patients from our center. METHODS: We reviewed the pathology records and slides of IBD patients diagnosed with anal squamous cell carcinomas (SCCs), high-grade squamous intraepithelial lesions (HSILs), and low-grade squamous intraepithelial lesions (LSILs) who presented at our center between 1 March 1994 and 9 September 2014. The HPV status of the neoplasms was assessed histologically, by immunohistochemical staining for p16 overexpression, and by global and type-specific HPV PCR. RESULTS: SCCs, HSILs, LSILs, and small cell carcinoma were identified, respectively, in six, nine, two, and one IBD patients. All six patients with SCC had CD with perianal involvement. HPV-related neoplasia was identified in 3/6 cases of SCC (all HPV-16), 1/1 small cell carcinoma (HPV-18), and 9/9 HSIL (7 HPV-16, 2 not typed); 2/2 LSILs were negative for high-risk HPV. CONCLUSIONS: In our experience, anal squamous neoplastic lesions in IBD are associated with HPV infection and SCC seem to be associated with perianal CD. Prospective studies are needed to confirm these results.

Converging goals of treatment of inflammatory bowel disease from clinical trials and practice.

It is important to have clear goals for treating inflammatory bowel disease in clinical practice and in research. Conventional end points for trials in ulcerative colitis and Crohn's disease have been based on composite indices, such as the Mayo Clinic Score and the Crohn's Disease Activity Index; these indices incorporate symptoms, signs, and findings from laboratory tests and sometimes endoscopic assessments. Although definitions of clinical response and remission have been based on these indices for regulatory purposes, they are difficult to apply to practice because they are complex and not intuitive to clinicians. This has caused a disconnect between clinical trials and practice. Recently, the use of composite indices in trials has been reevaluated in Food and Drug Administration-sponsored Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics workshops due to concerns about the validity of the indices. Alternative measures of outcome and definitions of response are being developed. Patient-reported outcomes are psychometric instruments created and defined by patients to quantify symptoms. A combination of end points, comprising patient-reported outcomes and objective evaluation of inflammation by endoscopy, offers a clinically meaningful and scientifically valid alternative to existing composite indices. Unlike composite indices, response definitions based on endoscopy and patient-reported outcomes can be readily applied in practice. This convergence of outcome assessment in clinical trials and practice could expedite implementation of "treat-to-target" algorithms, in which therapy is progressively intensified until a specific treatment goal is reached. This approach could improve patient care by reducing rates of disease-related complications, surgery, and hospitalization.

IBD across the age spectrum: is it the same disease?

IBD is a chronic disorder with disease onset ranging from early childhood to beyond the sixth decade of life. The factors that determine the age of onset currently remain unexplained. Is timing of occurrence a random event or is it indicative of different pathophysiological pathways leading to different phenotypes across the age spectrum? Over the past decade, several studies have suggested that the characteristics and natural history of IBD seem to be different according to age of onset. This heterogeneity suggests that the respective contributions of genetics, host immune system and environment to the aetiology and phenotype of Crohn's disease and ulcerative colitis are different across ages. Critical reviews that focus on differences characterizing IBD between age groups are scarce. Therefore, this Review updates the knowledge of the differences in epidemiology, clinical characteristics, and natural history of paediatric, adult and elderly-onset IBD. In addition, potential differences in host-gene-microbial interactions according to age are highlighted.

Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada.

BACKGROUND: Clinicians who treat patients with Clostridium difficile-associated diarrhea (CDAD) in Quebec, Canada, have noted an apparent increase in the proportion of patients who experience relapse. METHODS: To determine whether there was an increase in the frequency of treatment failure and of recurrence of CDAD after treatment, we reviewed data on cases that had been diagnosed in a hospital in the province of Quebec during the period 1991-2004. The frequency of recurrences within 60 days after the initial diagnosis was measured using Kaplan-Meier analysis, and Cox regression was used for multivariate analysis. RESULTS: Among patients who had initially been treated with metronidazole, the proportion whose regimens were switched to vancomycin or for whom vancomycin was added because of a disappointing response did not vary between 1991 and 2002 (66 [9.6%] of 688 patients overall) but more than doubled in 2003-2004 (112 [25.7%] of 435; P < .001). Among 845 patients treated with metronidazole only, the 60-day probability of recurrence increased dramatically in 2003-2004 (47.2%), compared with 1991-2002 (20.8%; P < .001). During 1991-2002, the probabilities of recurrence were 20.0%, 13.8%, and 28.9% among individuals aged 0-17, 18-64, and > or = 65 years, respectively; during 2003-2004, the probabilities were 25.0%, 27.1%, and 58.4%, respectively. CONCLUSION: In 2003-2004, there was an increase in the proportion of patients with CDAD believed, by their attending physicians, to have experienced metronidazole treatment failure, as well as an increase in the frequency of post-metronidazole therapy recurrences, especially among elderly persons.