The effect of infliximab dose escalation in inflammatory bowel disease patients with antibodies to infliximab.

BACKGROUND: Infliximab dose escalation (DE) can be used in inflammatory bowel disease patient; however, the long-term benefit remains unclear, especially in those with antibodies to infliximab (ATI). The aim was to assess the effect of DE in patients with ATI on drug level, clinical response and ATI status. METHODS: All patients undergoing infliximab DE (a reduction in dose interval between infusions <8 weeks ± an increase in dose up to 10 mg/kg) at a referral centre between April 2016 and August 2019 were included. RESULTS: Ninety-two patients were DE: 51 were men, 50 had CD and 63 were receiving immunosuppression. A total of 87 people received DE for a median of 44 weeks (range 4-176). Five stopped infliximab after 1 dose of DE: 2 for loss of response and 3 for infusion reaction. In patients with ATI ≤10 vs. >10 AU/mL, DE significantly increased drug levels: median infliximab levels of 1.4 and 0.9 at baseline, respectively, to 3.2 and 3.5 at week 24. After DE, 21/35 ATI-positive patients had a fall in ATI ≤10 AU/mL. At week 24 following DE 62/92 patients were in clinical remission. Duration of clinical remission was shorter in those with ATI >10 AU/mL (median 24 weeks, range 0-88) than in those with transient/ATI ≤10 AU/mL (median 36 weeks, range 0-126, P = 0.06). CONCLUSIONS: A strategy of DE for selected patients receiving infliximab is associated with an increase in drug levels and reduced ATI positivity. This is associated with clinical remission in approximately 70% of patients at 6 months.

Polymerase chain reaction for detection of mucosal cytomegalovirus infection in patients with acute ulcerative colitis.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with acute exacerbations of ulcerative colitis (UC) but its clinical relevance remains uncertain. The primary aim of this study was to assess the prevalence of CMV infection in UC patients using viral polymerase chain reaction (PCR) analysis of mucosal biopsy samples. Secondary aims were to establish whether the disease was due to a primary infection or reactivation and to note associated risk factors and clinical outcomes. METHODS: Since 2011, a policy of biopsy for CMV infection was adopted for severe UC patients in a large tertiary center. A retrospective review was undertaken to identify patients with mucosal biopsies for exacerbations of UC from October 2011 through January 2014. RESULTS: Sixty biopsies for CMV PCR were obtained from 52 patients, 15 of whom were positive. In these patients, 9/9 tested were seropositive for anti-CMV IgG, while none were seropositive for anti-CMV IgM. Steroid refractory disease was a significant predictor of CMV positivity; however, there was no difference between the CMV-positive and -negative groups in rates of immunosuppression, or clinical and endoscopic severity. Six patients in the CMV-positive group received infliximab; all received concurrent antiviral therapy and did not require surgery. CONCLUSIONS: PCR of mucosal biopsies detected CMV infection due to viral reactivation in almost a third of patients with deteriorating or acute severe UC. Steroid refractory disease was significantly associated with CMV positivity, but no significant relationship was demonstrated with either disease severity or immunosuppression in our cohort. Treatment with anti-tumor necrosis factor agents was administered safely in combination with antiviral drugs.

Clinical utility of double-balloon enteroscopy in suspected Crohn's disease: a single-centre experience.

BACKGROUND: Small bowel Crohn's disease has a heterogeneous presentation leading to a delay in diagnosis. Capsule endoscopy is now a well-established diagnostic tool; however, few studies have evaluated the role of double-balloon enteroscopy (DBE) in patients with suspected Crohn's disease. Histology obtained at DBE is useful in addition to clinical symptoms, blood parameters and capsule endoscopy findings to aid diagnosis and further management. OBJECTIVE: The aim of this study was to evaluate the impact of DBE and histology on the management of patients with suspected small bowel Crohn's disease. METHODS: DBE procedures including histology for suspected Crohn's disease from 2006 to 2014 were retrospectively reviewed. Follow-up data for all patients were collected. RESULTS: In our series of 399 double-balloon enteroscopies, 122 procedures were performed in 100 patients for suspected Crohn's disease. Positive DBE findings were found in 60% of patients. Forty-five per cent of patients were treated as Crohn's disease on the basis of a combination of histology, endoscopic appearance, clinical symptoms and blood parameters. Histology was diagnostic of Crohn's disease in 8% and supportive of it in 15%. In 12%, an alternative diagnosis was made, of whom two patients were diagnosed with small bowel malignancy on histology.After a median follow-up period of 27 months, the actual prevalence for a new diagnosis of Crohn's disease in our study was 38%. CONCLUSION: DBE has a useful place in clarifying the diagnosis in patients with suspected Crohn's disease. Although histology can be nondiagnostic, the combination of the macroscopic appearance with clinical correlation is useful in the diagnosis and management.

Evaluation of pharmacokinetics and pharmacodynamics and clinical efficacy of certolizumab pegol for Crohn's disease.

INTRODUCTION: TNF-α antagonists have transformed the treatment of patients with Crohn's disease (CD). Certolizumab pegol (CZP) is the third TNF-α antagonist to be approved for use in the United States but is not currently approved in Europe. AREAS COVERED: This review evaluates the pharmacokinetics, pharmacodynamics and efficacy of CZP in CD. Safety, immunogenicity and its use in pregnancy have also been assessed. A literature search was conducted using Pub Med (2004 - 2014) for the terms 'Crohn's disease' and 'certolizumab pegol' or 'certolizumab' or 'cimzia'. Additional studies were identified from other sources including citation. EXPERT OPINION: As a Fab' fragment, CZP is effective in binding TNF-α, but does not cause Fc-mediated effects. PEGylation has improved its pharmacokinetic profile and allowed for an increased half-life of 2 weeks. Benefit for inducing response (an improvement in symptoms) and maintenance of remission has been shown. However, the benefit is less clear for the more stringent end-points of inducing remission and mucosal healing. There may be an advantage from the PEGylated formulation of CZP in terms of reduced injection-site reactions, reduced placental transfer in pregnancy and as a treatment option in patients who are unable to tolerate infliximab.