Influence of comorbidities on treatment considerations for first-line biologic prescribing in patients with inflammatory bowel disease in the UK.

Background: Anti-tumour necrosis factor (anti-TNF) therapies are the most commonly used biologics for inflammatory bowel disease (IBD), but for patients with a comorbidity, newer agents may be a more appropriate treatment choice. Aims: To investigate the impact of comorbidities in patients with IBD, on first-line biologic prescribing habits of IBD-specialist healthcare practitioners in the UK. Methods: IBD-specialist physicians and nurses were asked to answer an online survey, considering different prescribing scenarios in ulcerative colitis (UC) and Crohn's disease (CD). Respondents could indicate a preference for anti-TNFs or newer biologics, both in the absence and presence of 10 common comorbidities. Results: A total of 120 IBD-specialist healthcare professionals (HCPs) completed the survey. In the absence of comorbidities, anti-TNFs were favoured; infliximab was the preferred first-line biologic in both UC and CD (43% and 37% of respondents, respectively). On introducing comorbidities, the largest shift in prescribing behaviour was for vedolizumab, with preference increasing by 27% and 21%, compared with infliximab, which fell by 14% and 9% in UC and CD, respectively. Chronic/recurring infection (46%), congestive heart failure (≤44%) and malignancies (≤43%) were the most commonly selected comorbidities for vedolizumab treatment. Conclusions: Clinicians adapt their biologic prescribing habits in patients with IBD with comorbidities, considering known contraindications and precautions. A preference for vedolizumab is evident in many cases, however, for several comorbid scenarios, including demyelinating disorders, chronic obstructive pulmonary disease and malignancy, anti-TNFs are prescribed despite known risks. It is important that continual re-evaluation of the IBD treatment landscape is undertaken by HCPs, in alignment with recommendations in published guidelines.

Combination therapy for systemic sclerosis-associated pneumatosis intestinalis.

We present a case of a patient with pneumatosis intestinalis and pneumoperitoneum secondary to gastrointestinal systemic sclerosis, who presented following recurrent accident and emergency attendances with abdominal pain. Pneumatosis intestinalis is a rare complication of systemic sclerosis; management approaches focus largely on exclusion of life-threatening surgical pathologies and subsequent symptom control. To date, there are still no established gold-standard treatment strategy and no large-scale trial data to support a specific management strategy. We describe a case of successful medical management with a combination of antimicrobial, elemental diet and high-flow inhalation oxygen therapy, with supporting evidence of CT image confirming resolution. This case therefore contributes to the literature, being the first to report both symptomatic and radiological improvement following combination therapy without the need for surgical intervention.

Clinical Features and HLA Association of 5-Aminosalicylate (5-ASA)-induced Nephrotoxicity in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Nephrotoxicity is a rare idiosyncratic reaction to 5-aminosalicylate (5-ASA) therapies. The aims of this study were to describe the clinical features of this complication and identify clinically useful genetic markers so that these drugs can be avoided or so that monitoring can be intensified in high-risk patients. METHODS: Inflammatory bowel disease patients were recruited from 89 sites around the world. Inclusion criteria included normal renal function prior to commencing 5-ASA, ≥50% rise in creatinine any time after starting 5-ASA, and physician opinion implicating 5-ASA strong enough to justify drug withdrawal. An adjudication panel identified definite and probable cases from structured case report forms. A genome-wide association study was then undertaken with these cases and 4109 disease controls. RESULTS: After adjudication, 151 cases of 5-ASA-induced nephrotoxicity were identified. Sixty-eight percent of cases were males, with nephrotoxicity occurring at a median age of 39.4 years (range 6-79 years). The median time for development of renal injury after commencing 5-ASA was 3.0 years (95% confidence interval [CI] 2.3-3.7). Only 30% of cases recovered completely after drug withdrawal, with 15 patients requiring permanent renal replacement therapy. A genome-wide association study identified a suggestive association in the HLA region (p = 1×10(-7)) with 5-ASA-induced nephrotoxicity. A sub-group analysis of patients who had a renal biopsy demonstrating interstitial nephritis (n = 55) significantly strengthened this association (p = 4×10(-9), odds ratio 3.1). CONCLUSIONS: This is the largest and most detailed study of 5-ASA-induced nephrotoxicity to date. It highlights the morbidity associated with this condition and identifies for the first time a significant genetic predisposition to drug-induced renal injury.

Guidelines for the management of inflammatory bowel disease in adults.

The management of inflammatory bowel disease represents a key component of clinical practice for members of the British Society of Gastroenterology (BSG). There has been considerable progress in management strategies affecting all aspects of clinical care since the publication of previous BSG guidelines in 2004, necessitating the present revision. Key components of the present document worthy of attention as having been subject to re-assessment, and revision, and having direct impact on practice include: The data generated by the nationwide audits of inflammatory bowel disease (IBD) management in the UK in 2006, and 2008. The publication of 'Quality Care: service standards for the healthcare of people with IBD' in 2009. The introduction of the Montreal classification for Crohn's disease and ulcerative colitis. The revision of recommendations for the use of immunosuppressive therapy. The detailed analysis, guidelines and recommendations for the safe and appropriate use of biological therapies in Crohn's disease and ulcerative colitis. The reassessment of the role of surgery in disease management, with emphasis on the importance of multi-disciplinary decision-making in complex cases. The availablity of new data on the role of reconstructive surgery in ulcerative colitis. The cross-referencing to revised guidelines for colonoscopic surveillance, for the management of metabolic bone disease, and for the care of children with inflammatory bowel disease. Use of the BSG discussion forum available on the BSG website to enable ongoing feedback on the published document http://www.bsg.org.uk/forum (accessed Oct 2010). The present document is intended primarily for the use of clinicians in the United Kingdom, and serves to replace the previous BSG guidelines in IBD, while complementing recent consensus statements published by the European Crohn's and Colitis Organisation (ECCO) https://www.ecco-ibd.eu/index.php (accessed Oct 2010).

GPs have central role in managing IBD.

Ulcerative colitis and Crohn's disease are extremely variable in their presentation and course, and treatment can be difficult. It is important that GPs have a high index of suspicion of IBD and initiate appropriate treatment for patients undergoing relapse of the disease. GPs also have a vital role in the monitoring of patients, often in collaboration with gastroenterologists, particularly for those patients on immunosuppressant therapy.

Extraintestinal complications of inflammatory bowel disease.

Recent studies of extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) have demonstrated the importance of genetic predisposition in the etiology of musculoskeletal and cutaneous manifestations. In addition, small studies have shown infliximab to be effective in treating troublesome EIMs, particularly in pyoderma gangrenosum. Other trials have examined the safety of cyclooxygenase-2-specific nonsteroidal inflammatory drugs in IBD. Further work has been done on osteoporosis in IBD, and the American Gastroenterological Association has published a technical review and management guidelines for osteoporosis in a range of gastrointestinal disorders. However, despite further publications, debate remains concerning whether IBD patients with osteoporosis have a significant increase in fracture risk, and whether the bone loss is related to the disease or to its treatment.

Enteropathic arthritis.

Enteropathic arthritis is a form of arthritis associated with the chronic inflammatory bowel diseases, ulcerative colitis, and Crohn's disease. This form of arthritis is classified as one of the group of seronegative spondyloarthropathies, which also includes psoriatic arthritis, reactive arthritis, and idiopathic ankylosing spondylitis. Joint involvement also occurs with other gastrointestinal diseases such as Whipple's disease, celiac disease, and following intestinal bypass surgery for morbid obesity. In these conditions, abnormal bowel permeability and immunologic and genetic influences are probably involved in the pathogenesis of the joint disease, although the exact mechanisms remain uncertain.