Parakkal Deepak

Radiological Response Is Associated With Better Long-Term Outcomes and Is a Potential Treatment Target in Patients With Small Bowel Crohn's Disease

OBJECTIVES:Crohns disease (CD) management targets mucosal healing on ileocolonoscopy as a treatment goal. We hypothesized that radiologic response is also associated with better long-term outcomes.METHODS:Small bowel CD patients between 1 January 2002 and 31 October 2014 were identified. All patients had pre-therapy computed tomography enterography (CTE)/magnetic resonance enterography (MRE) with follow-up CTE or MRE after 6 months, or 2 CTE/MREs≥6 months apart while on maintenance therapy. Radiologists characterized inflammation in up to five small bowel lesions per patient. At second CTE/MRE, complete responders had all improved lesions, non-responders had worsening or new lesions, and partial responders had other scenarios. CD-related outcomes of corticosteroid usage, hospitalization, and surgery were assessed using Kaplan–Meier survival analysis and multivariable Cox models.RESULTS:CD patients (n=150), with a median disease duration of 9 years, had 223 inflamed small bowel segments (76 with strictures and 62 with penetrating, non-perianal disease), 49% having ileal distribution. Fifty-five patients (37%) were complete radiologic responders, 39 partial (26%), and 56 non-responders (37%). In multivariable Cox models, complete and partial response decreased risk for steroid usage by over 50% (hazard ratio (HR)s: 0.37 (95% confidence interval (CI), 0.21–0.64); 0.45 (95% CI, 0.26–0.79)), and complete response decreased the risk of subsequent hospitalizations and surgery by over two-thirds (HRs: HR, 0.28 (95% CI, 0.15–0.50); HR, 0.34 (95% CI, 0.18–0.63)).CONCLUSIONS:Radiological response to medical therapy is associated with significant reductions in long-term risk of hospitalization, surgery, or corticosteroid usage among small bowel CD patients. These findings suggest the significance of radiological response as a treatment target.

Incremental diagnostic yield of chromoendoscopy and outcomes in inflammatory bowel disease patients with a history of colorectal dysplasia on white-light endoscopy.

BACKGROUND AND AIMSnChromoendoscopy (CE) identifies dysplastic lesions with a higher sensitivity than white-light endoscopy (WLE). The role of CE in the management of dysplasia on surveillance WLE in inflammatory bowel disease (IBD) remains unclear.nnnMETHODSnA retrospective cohort of IBD patients with colorectal dysplasia on WLE who subsequently underwent CE between January 1, 2006 and August 31, 2013 was identified. Endoscopic and histologic findings were compared among the index WLE, first CE, and subsequent CE. Outcomes assessed included endoscopic lesion removal, surgery or repeat CE, and diagnosis of colorectal cancer.nnnRESULTSnNinety-five index cases were identified. The median duration of IBD was 18 years (interquartile range 9.3-29.8); 78 patients had ulcerative colitis. Dysplasia was identified in 55 patients during the index WLE with targeted biopsies of 72 lesions. The first CE visualized dysplastic lesions in 50 patients, including 34 new lesions (not visualized on the index examination). Endoscopic resection was performed successfully of 43 lesions, most in the cecum/ascending colon (n = 20) with sessile morphology (n = 33). After the first CE, 14 patients underwent surgery that revealed 2 cases of colorectal cancer and 3 cases of high-grade dysplasia. Multiple CEs were performed in 44 patients. Of these, 20 patients had 34 visualized lesions, 26 of which were new findings.nnnCONCLUSIONnInitial and subsequent CE performed in IBD patients with a history of colorectal dysplasia on WLE frequently identified new lesions, most of which were amenable to endoscopic treatment. These data support the use of serial CEs in this high-risk population.

Radiographical evaluation of ulcerative colitis

Radiographical modalities have become important diagnostic tools in cases of ulcerative colitis (UC). Imaging can be used non-invasively to determine the extent of involvement, severity of disease and to detect disease-related complications and extra-intestinal inflammatory bowel disease (IBD) manifestations. While abdominal X-rays and barium enemas still retain their relevance in specific clinical settings, the use of computed tomography enterography (CTE) or magnetic resonance enterography (MRE) are now used as first-line investigations to exclude active small bowel disease in IBD patients and can be utilized to detect active colonic inflammation. Additionally, CT colonography and MR colonography are emerging techniques with potential applications in UC. Ultrasonography, leukocyte scintigraphy and positron emission tomography are novel abdominal imaging modalities currently being explored for IBD interrogations. This plethora of radiological imaging options has become a vital component of UC assessments.

Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy

Crohn’s disease is characterized by a dysregulation of both innate and adaptive immunity responses. Interleukin-12/23 (IL-12/23) pathway has been found to be a major driver of inflammation in adaptive immune responses. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23 and prevents their interaction with their cell surface receptor and further cytokine activation. It is currently approved in the management of plaque psoriasis and psoriatic arthritis. Very promising data have emerged through phase II and phase III trials (UNITI-1, UNITI-2, and IM-UNITI) for both induction and maintenance of clinical response and remission in moderate-to-severe Crohn’s disease, resulting in approval by the Food and Drug Administration for this condition. This article reviews the immunology of the IL-12/23 pathway, available data regarding the initial designing of ustekinumab, drug development through clinical trials including pharmacokinetics, efficacy, and safety, and its potential place in the treatment of Crohn’s disease.

Computed Tomography and Magnetic Resonance Enterography in Crohn's Disease: Assessment of Radiologic Criteria and Endpoints for Clinical Practice and Trials.

Abstract:Early recognition of Crohns disease with initiation of disease-modifying therapy has emerged as a prominent inflammatory bowel disease management strategy. Clinical practice and trials have often focused on patient symptoms, and more recently, serologic tests, stool inflammatory markers, and/or endoscopic inflammatory features for study entry criteria, treatment targets, disease activity monitoring, and to assess therapeutic response. Unfortunately, patient symptoms do not correlate well with biological disease activity, and endoscopy potentially misses or underestimates disease extent and severity in small bowel Crohns disease. Computed tomography enterography and magnetic resonance enterography (MRE) are potential tools to identify and quantify transmural structural damage and disease activity in the small bowel. In this review, we discuss the role of computed tomography enterography and MRE in disease management algorithms in clinical practice. We also compare the currently developed MRE-based scoring systems, their strengths and pitfalls, as well as the role for MRE in clinical trials for Crohns disease.

Assessing the likelihood of new-onset inflammatory bowel disease following tumor necrosis factor-alpha inhibitor therapy for rheumatoid arthritis and juvenile rheumatoid arthritis.

AbstractnThe association between inhibition of tumor necrosis factor-alpha (TNF-α) in patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and the onset of inflammatory bowel disease (IBD) is unclear. We sought to evaluate this association by analyzing adverse events (AEs) reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) with a standardized scoring tool for drug-induced AEs. A search of the FAERS for RA or JRA (January 2003–December 2011) reported with adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab was performed. This dataset was then queried for cases indicating IBD. Full-length reports were accessed using the Freedom of Information Act and organized by age, sex, concomitant medications, co-morbidities, type of TNF-α inhibitor used, and diagnosis/treatment details. The Naranjo score was used to determine whether the drug-induced AEs were definite, probable, possible, or doubtful. There were 158 cases of IBD after TNF-α inhibitor exposure in RA or JRA patients. Use of the Naranjo score revealed that, in a majority of the cases (71.5xa0%), TNF-α inhibitor exposure was considered a ‘possible’ cause. A majority of the ‘probable cases’ in JRA were reported with etanercept (40 patients, 90.91xa0%). There were no ‘definite’ cases of anti-TNF-induced IBD. After applying the Naranjo scale, a weak association between new-onset IBD and TNF-α inhibitor therapy in RA patients and a moderately strong association especially with etanercept exposure in JRA patients was observed. However, causality cannot be determined due to limitations of the FAERS and the Naranjo score.

Effect of Tumor Necrosis Factor–α Inhibitors on Drug-Induced Pancreatitis in Inflammatory Bowel Disease

Background: Mesalamine and thiopurines (6-mercaptopurine and azathioprine) have been shown to increase the risk of developing acute pancreatitis in inflammatory bowel disease (IBD) patients. Tumor necrosis factor-α (TNF-α) inhibitors have been shown to protect against pancreatitis in animal models. Objective: To determine the risk of pancreatitis when comparing thiopurine monotherapy, mesalamine monotherapy, and thiopurine and mesalamine dual therapy to identical treatments but with the addition of a TNF-α inhibitor. Methods: Using a case-control design, the Food and Drug Administration Adverse Event Reporting System was queried for cases of pancreatitis and control reactions in IBD patients on a thiopurine or mesalamine. The proportional reporting ratio method was used to compare the different therapy regimens with the same regimen combined with a TNF-α inhibitor. Results: In all, 549 cases and controls were identified. When comparing thiopurine monotherapy with thiopurines combined with a TNF-α inhibitor, the odds of pancreatitis were lower in those on combination therapy (odds ratio [OR] = 0.04; 95% CI = 0.01-0.12). A similar trend was seen when comparing mesalamine monotherapy to mesalamine combined with a TNF-α inhibitor (OR = 0.08; 95% CI = 0.04-0.14) and when comparing those on both a thiopurine and mesalamine with those on all 3 therapies (OR = 0.04; 95% CI = 0.01-0.16). Conclusions: Combination therapy with TNF-α inhibitors appears to be associated with a lower risk of pancreatitis in IBD patients on mesalamine, thiopurines, or a combination of both. Physicians should consider using TNF-α inhibitors in those with the greatest risk of pancreatitis, although prospective studies are needed.

Crohn’s disease diagnosis, treatment approach, and management paradigm: what the radiologist needs to know

Crohn’s disease is one of the major subtypes of idiopathic inflammatory bowel disease and is characterized by chronic transmural intestinal inflammation of the gastrointestinal tract anywhere from mouth to the anus, with a predilection for the small bowel. Cross-sectional imaging with computed tomography and magnetic resonance enterography plays a key role in confirming diagnosis, identifying and managing complications, assessing disease severity, and identifying response to medical therapy. This review will focus on the role of radiologists in the diagnosis and assessment of Crohn’s disease. Additionally, a review of current medical therapy approaches, available medications, and side effects will be discussed. The review will also highlight key complications of medical therapy and associated diseases that should be evaluated by the radiologist with cross-sectional imaging.

Update on the Medical Management of Crohn’s Disease

The medical management of Crohn’s disease is a rapidly evolving field with expanding therapeutic drug options and treatment strategies. In addition to corticosteroids, immunomodulators, and anti-tumor necrosis (anti-TNF) agents, a new anti-adhesion medication (vedolizumab) has been approved. Individualized patient-based dosing of immunomodulators and biologic agents is now possible with therapeutic drug monitoring (TDM). There is a changing paradigm in treatment goals to achieve deeper remission identified by composite clinical and endoscopic endpoints. More aggressive treatment strategies in the postoperative setting have been proposed due to emerging data on medication efficacy in this setting. Management algorithms that stratify CD patients into risk groups to balance treatment benefit against adverse events and costs are being developed to translate research into clinical practice. This review provides an update on these new developments for practicing gastroenterologists.

De-novo Inflammatory Bowel Disease After Bariatric Surgery: A Large Case Series

BackgroundnCase reports of inflammatory bowel diseases [IBD] have been reported in patients with a history of bariatric surgery. Our aim was to characterize patients who were diagnosed with IBD after having undergone bariatric surgery.nnnMethodsnElectronic medical records were reviewed at two institutions to identify patients who developed de-novo Crohns disease or ulcerative colitis [UC] after bariatric surgery. Data on demographics, type of bariatric surgical procedure, IBD subtype, phenotype and medication usage were obtained. The incidence rate of de-novo IBD after bariatric surgery [per 100000 person-years] and standardized incidence ratio [SIR] were estimated from a prospective bariatric surgery database.nnnResultsnA total of 44 patients with de-novo IBD after bariatric surgery were identified [31 Crohns disease, 12 UC, one IBD unclassified]. Most patients were female [88.6%], with median age at IBD onset of 44 years [IQR, 37-52] and median time to IBD diagnosis after bariatric surgery of 7 years [IQR, 3-10]. Sixty-eight per cent underwent Roux-en-Y gastric bypass. In the prospective database, the incidence of IBD in patients who underwent bariatric surgery was 26.7 per 100000 person-years [4.5 for UC and 22.3 for Crohns disease]. The age-adjusted SIR ranged from 3.56 in the 40-49 year age group to 4.73 in the 30-39 year age group.nnnConclusionnWe described a case series of patients developing de-novo IBD after bariatric surgery. There appears to be a numerically higher incidence of Crohns disease in this population. Confirmation of causality is required in larger patient cohorts.