Shannon Chang

Disease monitoring in inflammatory bowel disease

The optimal method for monitoring quiescent disease in patients with Crohns disease (CD) and ulcerative colitis is yet to be determined. Endoscopic evaluation with ileocolonoscopy is the gold standard but is invasive, costly, and time-consuming. There are many commercially available biomarkers that may be used in clinical practice to evaluate disease status in patients with inflammatory bowel disease (IBD), but the most widely adopted biomarkers are C-reactive protein (CRP) and fecal calprotectin (FC). This review summarizes the evidence for utilizing CRP and FC for monitoring IBD during clinical remission and after surgical resection. Endoscopic correlation with CRP and FC is evaluated in each disease state. Advantages and drawbacks of each biomarker are discussed with special consideration of isolated ileal CD. Fecal immunochemical testing, traditionally used for colorectal cancer screening, is mentioned as a potential new alternative assay in the evaluation of IBD. Based on a mixture of information gleaned from biomarkers, clinical status, and endoscopic evaluation, the best treatment decisions can be made for the patient with IBD.

In vivo diagnostic accuracy of high resolution microendoscopy in differentiating neoplastic from non-neoplastic colorectal polyps: a prospective study

OBJECTIVES:High-resolution microendoscopy (HRME) is a low-cost, “optical biopsy” technology that allows for subcellular imaging. The purpose of this study was to determine the in vivo diagnostic accuracy of the HRME for the differentiation of neoplastic from non-neoplastic colorectal polyps and compare it to that of high-definition white-light endoscopy (WLE) with histopathology as the gold standard.METHODS:Three endoscopists prospectively detected a total of 171 polyps from 94 patients that were then imaged by HRME and classified in real-time as neoplastic (adenomatous, cancer) or non-neoplastic (normal, hyperplastic, inflammatory).RESULTS:HRME had a significantly higher accuracy (94%), specificity (95%), and positive predictive value (PPV, 87%) for the determination of neoplastic colorectal polyps compared with WLE (65%, 39%, and 55%, respectively). When looking at small colorectal polyps (less than 10 mm), HRME continued to significantly outperform WLE in terms of accuracy (95% vs. 64%), specificity (98% vs. 40%) and PPV (92% vs. 55%). These trends continued when evaluating diminutive polyps (less than 5 mm) as HRMEs accuracy (95%), specificity (98%), and PPV (93%) were all significantly greater than their WLE counterparts (62%, 41%, and 53%, respectively).CONCLUSIONS:In conclusion, this in vivo study demonstrates that HRME can be a very effective modality in the differentiation of neoplastic and non-neoplastic colorectal polyps. A combination of standard white-light colonoscopy for polyp detection and HRME for polyp classification has the potential to truly allow the endoscopist to selectively determine which lesions can be left in situ, which lesions can simply be discarded, and which lesions need formal histopathologic analysis.

Optimizing pharmacologic management of inflammatory bowel disease

ABSTRACT Introduction: As our medical armamentarium for IBD continues to expand, it is essential that clinicians understand both optimizing and sequencing of individual and combination therapeutic approaches with available medications. Areas covered: This review summarizes dosing strategies and therapeutic drug monitoring for pharmacologic optimization in IBD. Aminosalicylates remain first-line therapies for mild-to-moderate UC but have limited evidence of efficacy in CD. Budesonide provides an alternative to aminosalicylates when targeted to appropriate sites in the distal small bowel and colon, as do conventional corticosteroids when applied rectally. Systemic steroids are highly efficacious but burdened by toxicity. Thiopurines or methotrexate can be utilized as steroid-sparing agents. Biologic agents targeting TNF remain important for steroid-sparing therapy in moderate-to-severe UC and CD. Newer biologics targeting lymphocyte trafficking and lymphocyte activation are also efficacious for moderate-to-severe IBD. Near future conventional drug options include oral agents such as tofacitinib and mongersen. Expert commentary: Positioning therapies according to the location, phenotypes, and severity, as well as the use of therapeutic and clinical targets, will improve outcomes and minimize toxicities and therapeutic futilities. Future IBD treatment should focus on personalized therapy plans based on genetic determinants, targeted mechanisms of action, and pharmacologic optimization.

Extrapolation and Interchangeability of Infliximab and Adalimumab in Inflammatory Bowel Disease

Opinion statementInfliximab and adalimumab biosimilars have been approved by the FDA and European Medicines Agency and have already been introduced to the international market. Availability into the US market is imminent. Biosimilars are highly similar to the reference biologic product but should not be referred to as, nor equated with, generic medications as no two biosimilars can ever be identical. Regulatory pathways for biosimilar approval consider the totality of evidence for biosimilar approvals, but the preponderance of development relies on analytic and functional testing and allows extrapolation between indications to reduce the financial burden of completing comparative clinical trials for each indication. Neither CT-P13 (infliximab biosimilar) nor ABP 501 (adalimumab biosimilar) was clinically tested in patients with inflammatory bowel disease prior to being submitted for approval by regulatory agencies. The body of available evidence suggests that these drugs will perform similarly to their originators. The pathway for interchangeability of biosimilars has yet to be clarified by federal regulators and currently remains determined by states within the USA. However, preliminary data suggests that switching from originator to biosimilar is safe with minimal differences in clinical efficacy.

In vivo classification of colorectal neoplasia using high-resolution microendoscopy: Improvement with experience.

High‐resolution microendoscopy (HRME) is a novel, low‐cost “optical biopsy” technology that allows for subcellular imaging. The study aim was to evaluate the learning curve of HRME for the differentiation of neoplastic from non‐neoplastic colorectal polyps.

Vedolizumab for Ulcerative Colitis: Treatment Outcomes from the VICTORY Consortium

OBJECTIVES: We aimed to quantify the safety and effectiveness of vedolizumab (VDZ) when used for UC, and to identify predictors of response to treatment. METHODS: Retrospective review (May 2014‐December 2016) of VICTORY Consortium data. Adults with follow‐up after starting VDZ for clinically active UC were included. Primary effectiveness outcomes were cumulative rates of clinical remission (resolution of all UC‐related symptoms) and endoscopic remission (Mayo endoscopic sub‐score 0). Key secondary effectiveness outcomes included cumulative rates of corticosteroid‐free remission and deep remission (clinical remission and endoscopic remission). Cox proportional hazard analyses were used to identify independent predictors of treatment effectiveness. Non‐response imputation (NRI) sensitivity analyses were performed for effectiveness outcomes. Key safety outcomes were rates of serious infection, serious adverse events, and colectomy. RESULTS: We included 321 UC patients (71% prior TNF&agr; antagonist exposure, median follow‐up 10 months). The 12‐month cumulative rates of clinical remission and endoscopic remission were 51% and 41%, respectively. Corresponding rates for corticosteroid‐free remission and deep remission were 37% and 30%, respectively. Using NRI, 12‐month rates were 20% (n = 64/321) for clinical remission, 17% (n=35/203) for endoscopic remission, 15% (n=30/195) for corticosteroid‐free remission, and 14% (n = 28/203) for deep remission. A majority of the patients without adequate follow‐up at 12 months who were deemed non‐responders using NRI had already achieved clinical remission (n = 70) or a significant clinical response (n=36) prior to 12 months. VDZ discontinuation prior to 12 months was observed in 91 patients, for lack of response (n =56), need for surgery (n=29), or adverse event (n=6). On multivariable analyses, prior exposure to a TNF&agr; antagonist was associated with a reduced probability of achieving clinical remission (HR 0.53, 95% CI 0.38–0.75) and endoscopic remission (HR 0.51, 95% CI 0.29–0.88). Serious adverse events and serious infections were reported in 6% and 4% of patients, respectively. Overall cumulative rates of colectomy over 12 months were 13%, with lower rates observed in patients naive to TNF&agr; antagonist therapy (2%) than those who had been exposed to TNF&agr; antagonists (19%). CONCLUSION: In this large real‐world cohort we observed that VDZ was well tolerated and effective in achieving key clinical outcomes.

The nocebo effect and patient perceptions of biosimilars in inflammatory bowel disease

We read with great interest a recent paper by Boone et al. [1]. In this 1-year observational study, the authors sought to quantify the nocebo rate in individuals with an immune-mediated inflammatory disease who were switched from the originator infliximab to a biosimilar for a non-medical reason. Patients were provided informed consent and voluntarily agreed to transition to the infliximab biosimilar. The patients in this study were stable on infliximab, with the average duration of infliximab treatment being more than 3 years prior to switching. The results demonstrated an overall nocebo response of 12.8%, (12.5% for rheumatologic disorders and 12.9% for inflammatory bowel disease (IBD)). Patients with a nocebo response endorsed Bless exerted effect,^ chills during infusions, numbness, and tingling, and headache. All nocebo-response patients were able to be re-initiated on the infliximab originator. The authors concluded that non-medical switching may have a negative impact on patient’s perceived disease burden and sense of well-being. The investigators hypothesized that shared decision-making and patient education may decrease the nocebo-response rate. However, there is currently limited data regarding patient perception and knowledge of biosimilars to help physicians address potential concerns with their patients [2, 3]. The infliximab biosimilar was approved in the USA in 2016, but penetration into our marketplace has only recently accelerated. As such, we recently performed a small, prospective study aimed at gauging IBD patients’ initial perceptions of biosimilars. In 2017, we surveyed 132 adult patients with IBD at two university-affiliated gastroenterology clinics regarding their current impression of biosimilars. A standardized cover sheet was included with the 14-question survey which described the purpose of the study and a brief explanation of biosimilars. We found that a large proportion of surveyed participants (75%), despite themajority beingwell-educated with a university education or more, had never heard of biosimilar medications. In regard to participant concerns with biosimilars, 81% were concerned with the efficacy, 74% were concerned with the side effects, and 70% were concerned with the safety of these medications. Significantly more biologic-experienced participants were concerned about the effectiveness and the safety of biosimilars when compared to biologic-naive participants (86 vs 62%, p = 0.003 and 75 vs 55%, p = 0.041, respectively). Regarding switching, 58% of all participants were uncomfortable exchanging their current medication for a biosimilar. Not surprisingly, significantly more patients currently or previously on a biologic were uncomfortable switching to a biosimilar compared to patients not currently on a biologic (61 vs 45%, p = 0.032). Our study highlights a lack of awareness of biosimilars as well as main concerns regarding these medications. These findings can be used to help physicians to construct a patient-centered approach to introducing biosimilars. For the most part, the decision to switch to a biosimilar will be driven by economics rather than patient preference. Patients who switch to the biosimilar are at risk of nocebo effects given concerns regarding efficacy, side effects, and safety. In the study by Boone et al., patients voluntarily switched to the biosimilar. In real-world practice, the nocebo response may be higher in patients who do not voluntarily switch. We agree with Boone et al. that patient education is paramount to limiting patient noncompliance and the nocebo effect. * Shannon Chang shannon.chang@nyumc.org

Making the Cut: An Isolated Filiform Polyp

75-year-old woman with a remote history of sigAmoidectomy for perforated diverticulitis, as well as benign colonic polyps found during colonoscopy 4 years prior, presented for surveillance colonoscopy. During colonoscopy, an isolated, 3 cm in length, pedunculated, worm-like polyp was discovered at 40 cm proximal to the anus (Figure A). Initial hot snare polypectomy, set at 25 W, cut through the outermost layer of stalk tissue but failed to cut through the central fibrous-appearing core. Of note, the stalk of the polyp was noted to contract with application of current. By using the autocut function set at 180 W, the central core was successfully cut (Figure B). The polyp was retrieved, and hemostatic clips were placed to prevent post-polypectomy bleeding. Pathologic examination revealed a finger-like polyp lined by benign reactive colonic epithelium and containing a central fibrovascular core, which was negative for dysplasia (Figure C). There were no post-procedural adverse events. Filiform polyps are most commonly associated with inflammatory bowel disease but may also be seen with diverticulitis and malignancy. Differing from this case, filiform polyps more commonly are found as a group of polyps or even as mass-like agglomerations. Histologic examination of filiform polyps reveals nonspecific inflammation of colonic mucosa with a core that is often fibrovascular but can also contain disordered smooth muscle fascicles and nerves. These muscle fascicles are believed to be the cause of polyp contraction with application of current during this case. Filiform polyps generally are not thought to have malignant potential. However, endoscopists should consider polypectomy or biopsy if the polyp is of uncertain histology. This was an atypical, isolated filiform polyp found during colonoscopy, and thus the endoscopists chose to proceed with polypectomy. A previous report suggested a snare and cautery technique for removal of suspected filiform polyps. However, because of the fibrovascular and muscular core of these polyps, autocut may be more successful for polypectomy of a suspected filiform polyp.

Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease

Background We quantified loss of response (LOR) to vedolizumab (VDZ) in clinical practice and assessed the effectiveness of VDZ dose intensification for managing LOR. Methods Retrospective review (May 2014-December 2016) of a prospectively maintained inflammatory bowel disease (IBD) registry. Kaplan-Meier estimates were used to determine rates of LOR to VDZ . Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. Success of recapturing response (>50% reduction in symptoms from baseline) and remission (complete resolution of symptoms) after dose intensification was quantified. Results Cumulative rates for VDZ LOR were 20% at 6 months and 35% at 12 months, with slightly lower rates in Crohns disease than in ulcerative colitis (6 months 15% vs 18% and 12 months 30% vs 39%, P = 0.03). On multivariable analysis, LOR to a tumor necrosis factor (TNF) antagonist before VDZ use was associated with an increased risk for LOR to VDZ [hazard ratio (HR) 1.93; 95% confidence interval (CI) 1.25-2.97] in all patients. For Crohns disease patients specifically, higher baseline C-reactive protein concentration was associated with increased risk for LOR to VDZ (HR 1.01 per mg/dL increase, 95% CI 1.01-1.02). Shortening of VDZ infusion interval from 8 to every 4 or 6 weeks recaptured response in 49% and remission in 18% of patients. Conclusions LOR to a TNF antagonist before VDZ use and higher baseline C-reactive protein are important predictors of VDZ LOR. Treatment response can be recaptured in almost half of these patients with VDZ infusion interval shortening.

Outcomes and Management of the Ileal Pouch-Anal Anastomosis in the Elderly

Purpose of ReviewIleal pouch-anal anastomosis (IPAA) is the preferred surgical treatment for patients undergoing colectomy to maintain intestinal continuity. Earlier studies have suggested that outcomes are worse in elderly patients who underwent IPAA. However, more recent reports have shown that IPAA outcomes in the elderly are comparable to younger patients. We review the recent medical literature regarding outcomes and treatments for common complications in elderly IPAA patients.Recent FindingsCompared to younger patients, IPAA in the elderly is not associated with increased major surgical complications, but is associated with increased length of stay and re-admission rate for dehydration in older patients. Rates of fecal incontinence after IPAA were similar between younger and older patients. Sacral nerve stimulation has shown early promise as a possible treatment for fecal incontinence after IPAA, but more research is needed. Pouchitis is a common complication, and antibiotics remain first-line treatment options. Other treatment options include mesalamines, steroids, immunomodulators, and biologics. The efficacy of newer biologics such as vedolizumab and ustekinumab has been reported, but more data is needed.SummaryIPAA is safe in the elderly with high self-reported patient satisfaction. However, the elderly IPAA patient warrants special consideration regarding outcomes and management.