Deep ulcers are associated with increased C-reactive protein in active ulcerative colitis.

BACKGROUND: Increased C-reactive protein (CRP) is used to diagnose and predict response to treatment in acute severe ulcerative colitis (UC). AIMS: To investigate the connection between CRP elevation and deep ulcers in UC. METHODS: Patients with active UC were enrolled in a multicenter prospective cohort and a retrospective cohort of consecutive patients undergoing colectomy from 2012 to 2019. RESULTS: Forty-one (9 (22%) with deep ulcers) patients were included in the prospective cohort: 4/5 (80%) patients with CRP > 100 mg/L, 2/10 (20%) patients with CRP between 30 and 100 mg/L and 3/26 (12%) patients with CRP < 30 mg/L had deep ulcers (p = 0.006). In the retrospective cohort [46 patients (31 (67%) with deep ulcers)], 14/14 (100%) patients with CRP > 100 mg/L, 11/17 (65%) patients with CRP between 30 and 100 mg/l and 6/15 (40%) patients with CRP < 30 mg/L had deep ulcers (p = 0.001). Positive predictive value of CRP > 100 mg/l for presence of deep ulcers was 80% and 100% in both cohorts, respectively. CONCLUSIONS: CRP elevation is a robust surrogate marker for presence of deep ulcers in UC. Elevated CRP or presence of deep ulcers could influence the choice of medical therapy in acute severe UC.

Assessing adherence to objective disease monitoring and outcomes with adalimumab in a real-world IBD cohort.

BACKGROUND: Data suggests that tight objective monitoring may improve clinical outcomes in IBD. AIM: To assess the adherence to serial tight objective monitoring(clinical and biomarkers) and its effect on clinical outcomes. METHODS: We retrospectively reviewed the chart of 428 consecutive IBD patients started on adalimumab between January 1,2015-January 1,2019 [338 Crohn's disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms(assessed by Harvey-Bradshaw-Index,partial Mayo),C-Reactive Protein(CRP), and fecal calprotectin(FCAL) assessments were captured at treatment initiation and at 3,6,9, and12 months. Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method. RESULTS: Clinical evaluation was available in nearly all patients at 3(CD-UC:95-94%), 6(90-83%), 9(86-85%) and 12(96-89%) months. CRP testing frequency decreased in CD patients over time. Compliance to serial FCAL testing was low. Clinical remission at one-year was higher in patients adherent to early assessment visit at 3 months(p = 0.001 for CD and UC). Adherence to early follow-up resulted in earlier dose optimization in CD and UC patients(pLogrank=0.026 for UC & p = 0.09 for CD). Overall drug sustainability did not differ. CONCLUSION: Clinical & CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization, improved one-year clinical outcomes but did not change drug sustainability.

An unusual case of hamartomatous polyposis with malignancy complication in a patient with ulcerative colitis treated with golimumab.

We report an unusual case of hamartomatous polyposis with malignant complications in a patient with ulcerative colitis on golimumab and previous thiopurine therapy. This patient was evaluated for iron deficiency anemia and underwent hemicolectomy for extensive right-side predominant inflammatory pseudopolyps. Anemia persisted post-colectomy and subsequent gastroscopy showed a fungating polypoid lesion along with numerous carpet-like strawberry appearing polyps in the stomach extending from the gastro-esophageal junction to the distal part of the antrum, necessitating a gastrectomy. Histology showed extensive hamartomatous-like polyps with adenocarcinoma and nodal metastases. Presence of alopecia totalis and hamartomas in this patient raise the possibility of Cronkhite-Canada Syndrome although this may also represent an undescribed hamartomatous polyposis associated with ulcerative colitis. Even though thiopurine analogue and anti-tumor necrosis factor agents have not been associated with increased risk of solid tumors, immunosuppression in patients with extensive polyposis should be cautiously used due to the potential accelerated malignancy risk. This case also highlights the importance of performing additional imaging of the gastrointestinal tract, in inflammatory bowel disease patients with anemia, particularly if the severity is incongruent with disease activity.

Subcutaneous ustekinumab for the treatment of anti-TNF resistant Crohn's disease--the McGill experience.

BACKGROUND: Ustekinumab is a fully human IgG1κ monoclonal antibody that blocks the biologic activity of interleukin-12/23. Ustekinumab is approved for treatment of plaque psoriasis and has been shown to be effective for induction and maintenance of clinical response in anti-TNF resistant Crohn's disease (CD). The aim of the study was to describe the real-life experience with open-label use of ustekinumab in anti-TNF resistant CD patients. METHODS: A retrospective observational open-label study. Clinical response was defined by physician's global assessment combined with decision to continue therapy. The clinical response was evaluated at 3, 6, 12months and last follow-up. RESULTS: Thirty-eight patients were included in the study. Initial clinical response was achieved in 28/38 (73.7%) of the patients. Among the initial responders, 80% with follow-up data maintained their response for 6months. At 12months of follow-up, 88.9% of patients responding at 6months maintained their response. At the last follow-up (7.9±5.2 mo) 27/38 (71%) of the patients were responding, and 73.3% were able to discontinue corticosteroids. Dose escalation was required in 47.7% of the patients and was successful in 61.1% of them. SUMMARY: In this real-life cohort of severe anti-TNF resistant CD, an initial clinical response to subcutaneous ustekinumab was observed in 73.7% of the patients. The initial response was successfully maintained in the majority of patients for up to 12months. Subcutaneous ustekinumab is an effective therapeutic option in this challenging patient cohort. The optimal dosing and injection schedule remain to be established in future studies.

Review article: non-malignant haematological complications of anti-tumour necrosis factor alpha therapy.

BACKGROUND: Tumour necrosis factor-alpha (TNF-α) is an important mediator of the molecular cascade leading to chronic inflammation. TNF-α inhibitors have proven their safety and efficacy in the treatment of inflammatory diseases. AIM: To review the non-malignant haematological adverse events, such as thrombocytopaenia, neutropaenia, hypercoagulability, pancytopaenia and aplastic anaemia in patients receiving TNF-α inhibitors. METHODS: We reviewed the literature by searching MEDLINE and EMBASE databases as well as references of all retrieved articles for the following terms: anti-tumour necrosis factor, anti-TNF, infliximab, adalimumab, certolizumab, etanercept, haematological complications, thrombocytopaenia, neutropaenia, anaemia, bone marrow and thrombosis. RESULTS: Thombocytopaenia is a very rare phenomenon and was associated with no serious adverse events. However, transient neutropaenia developed in up to 16% of cases. Patients with a previous history of neutropaenia on other therapies or baseline neutrophil count <4 × 10(9) /L are at a particularly higher risk. The association between anti-TNF-α therapy and thrombosis is very nebulous due to the multitude of potential confounders. Only one case of primary eosinophilia has been reported with anti-TNF-α therapy. CONCLUSION: Regular monitoring of the white blood cell count at baseline and with each infusion is recommended for patients on anti-TNF-α. Further studies to elucidate their interaction with the immune system are warranted.