Efficacy and Safety of Dual Biologic Therapy in Patients With Inflammatory Bowel Disease: A Review of the Literature.

Using 2 or more treatment modalities to achieve a synergistic effect in patients with refractory inflammatory bowel disease (IBD) has been an area of focus for many years. This methodology, known as combination therapy, has been proposed for various therapeutic agents, most commonly biologics and immunomodulators. Although the mainstay of biologic therapy for IBD has traditionally focused on agents targeting tumor necrosis factor, the development of newer biologics with different targets, such as vedolizumab and ustekinumab, has introduced the possibility of concomitant dual biologic therapy. Dual biologic therapy has been proposed in the treatment algorithm for 2 types of patients with IBD: those with well-controlled luminal IBD and uncontrolled extraintestinal symptoms (secondary indications such as arthritis or psoriasis) and those with refractory, uncontrolled IBD. Thus far, the data on the efficacy and safety of dual biologic therapy as a treatment for Crohn's disease or ulcerative colitis remain quite limited. In fact, the overwhelming majority of the literature consists of case reports and case series. Given this paucity of high-level data, physicians have looked to larger studies on dual biologic therapy in other fields of medicine, such as rheumatology and dermatology. The goal of this article is to summarize the current literature on the use of dual biologics in IBD, address the potential adverse effects or risks associated with combination therapy, and highlight future directions in the use of this therapeutic modality.

The Cost-Effectiveness of Vedolizumab for Inflammatory Bowel Disease: A Review of the Current Literature.

The United States spends a greater share per gross domestic product on health care than any other developed country in the world. Cost-conscious, high-value care has an important role in the practice of medicine. Inflammatory bowel disease (IBD) affects 1.6 million people in the United States and is responsible for significant health care costs, with estimates as high as $31.6 billion annually, a large portion of which is attributable to the use of biologic therapies. As the number of therapeutic targets for IBD expands, gastroenterologists can anticipate the arrival of novel therapeutic agents on the market, and these may carry significant costs. Vedolizumab, a monoclonal antibody directed against the gut-selective integrin α4ß7, is a novel biologic agent approved for the treatment of Crohn's disease and ulcerative colitis. Cost-effectiveness is an area of research that aims to assess the added value (in terms of both cost and utility) of diagnostic or therapeutic interventions. This article reviews the current literature evaluating the cost-effectiveness of vedolizumab for the treatment of IBD.

Bone, inflammation, and inflammatory bowel disease.

Osteoporosis is a leading cause of morbidity in patients with inflammatory bowel disease (IBD). Bone loss is an early systemic process and occurs even before clinical disease manifests. Bone disease is attributed to vitamin D deficiency, steroid use, and/or systemic inflammation. In this review, we discuss the molecular pathways of bone loss mediated by inflammatory cytokines and other mediators. Further research will hopefully clarify the mechanisms of inflammation-induced bone loss in IBD and guide effective treatment modalities.

Chromoendoscopy-targeted biopsies are superior to standard colonoscopic surveillance for detecting dysplasia in inflammatory bowel disease patients: a prospective endoscopic trial.

OBJECTIVES: Patients with extensive, longstanding chronic ulcerative or Crohn's colitis face greater risks of developing colorectal cancer. Current standard surveillance relies on detecting dysplasia using random sampling at colonoscopy but may fail to detect dysplasia in many patients. Dye spraying techniques have been reported to aid in detecting otherwise subtle mucosal abnormalities in the setting of colitis. We prospectively compared dye-spray technique using methylene blue to standard colonoscopic surveillance in detecting dysplasia. METHODS: One hundred fifteen patients were referred to the Chromoendoscopy Study Group and prospectively screened for the study. One hundred two (64 M, 38 F) (79 UC 23 CC) patients meeting the inclusion criteria were enrolled. Following a standard bowel preparation, each patient was examined using standard office endoscopic equipment by three methods: (a) standard surveillance colonoscopy with four random biopsies every 10 cm (for a total of at least 32 samples); (b) a targeted biopsy protocol; and finally (c) methylene blue (0.01%) dye spray was segmentally applied throughout the colon and any pit-pattern abnormality or lesion rendered visible by the dye spray was targeted and biopsied. Each patient had a single examination, which included two passes of the colonoscope. Specimens were reviewed in a blinded fashion by a single gastrointestinal pathologist. The three methods were then compared with each patient serving as his or her own control. RESULTS: Targeted biopsies with dye spray revealed significantly more dysplasia (16 patients with low grade and 1 patient with high grade) than random biopsies (3 patients with low-grade dysplasia) (P= 0.001) and more than targeted nondye spray (8 patients with low-grade and 1 patient with high-grade dysplasia) (P= 0.057). Targeted biopsies with and without dye spray detected dysplasia in 20 patients compared with 3 using Method (a) (P= 0.0002, two-tailed exact McNemar's Test). There were no adverse events. CONCLUSIONS: Colonoscopic surveillance of chronic colitis patients using methylene blue dye-spray targeted biopsies results in improved dysplasia yield compared to conventional random and targeted biopsy methods. Accordingly, this technique warrants incorporation into clinical practice in this setting and consideration as a standard of care for these patients. The value of multiple random biopsies as a surveillance technique should be revisited.

Medical management of the pregnant patient with inflammatory bowel disease.

Gastroenterologists are not infrequently faced with questions regarding pregnancy when advising or treating their patients with inflammatory bowel disease (IBD). To advise patients effectively, the following factors must be considered: (1) the inheritance patterns of IBD for accurate counseling and family planning; (2) the effects of active IBD versus medications or surgery on fertility; (3) the effects of pregnancy on the course of IBD; (4) the effects and potential risks of active IBD versus those of diagnostic tests, medical treatments, and surgical treatments on the developing fetus; (5) approach to delivery; and (6) the risks of breast-feeding while receiving treatment for IBD.