INWENDIGE ZIEKTEN

CENTRUM INWENDIGE ZIEKTEN

ARTIKELS

ABSTRACT 1

Adverse effects of bevacizumab in metastatic colorectal cancer: a case report and literature review.

Willems E, George C, D'Hondt M, et al. Acta Gastro-enterologica Belgica, 2019, 82(2), 322-325

Het abstract is terug te vinden op pagina 4.

ABSTRACT 2

How dyspepsia led to the diagnosis of Morbus Crohn.

Maertens A, Persyn D, Van Moerkercke W, et al. Acta Clinica Belgica, 2019, Online ahead of print, 1-3

OBJECTIVE It is well known that Crohn's disease can involve the stomach. However, most often this upper gastrointestinal tract involvement is asymptomatic. Typically, there is involvement of the small intestine with the typical associated symptoms of Crohn's disease: abdominal cramps, diarrhoea and weight loss.

MATERIALS/METHODS We report a case of a young woman with complaints of dyspepsia since 2 months.

RESULTS Gastroscopy revealed severe aphthous pangastritis with biopsies showing a focal active and chronic gastritis with presence of granulomas. We therefore performed a coloscopy showing an aphthous terminal ileum. The pathologic report indicated granulomatous reaction concordant with a slightly active, mildly chronic terminal ileitis typical for Crohn's disease.

CONCLUSION The incidence of upper gastrointestinal tract involvement of Crohn's disease is still underestimated, partially due to the asymptomatic nature in two thirds of patients. IBD gastritis should always be included in the differential diagnosis of gastritis, considering the increased risk of a more severe disease course and complications. ABSTRACT 3

Whipple's disease in a man of North African descent : case report and brief review of the literature.

Lenfant M, Alaerts H, Van Moerkercke W, et al. Acta Gastro-enterologica Belgica, 2019, 82(1), 83-86

OBJECTIVE A 62-year-old man of North African descent presented with weight loss in the past year and diarrhea for three weeks. His medical history included erosive rheumatoid arthritis, treated with methotrexate and adalimumab. Histological examination of a duodenal biopsy showed foamy macrophages in the lamina propria, with PAS-positive cytoplasmatic inclusions. These findings are compatible with Whipple's disease, a rare chronic infectious disease caused by Tropheryma whipplei, an opportunistic bacterium. It is typically seen in middle-aged Caucasian men and the immunocompromised host. The classical presentation of Whipple's disease consists of intermittent migratory arthralgia, followed by intestinal symptoms which typically occur six to seven years later.

MATERIALS/METHODS The clinical image can be very variable, and this complicates the diagnostic process. PAS-staining and PCR are the diagnostic cornerstones.

RESULTS In our case, treatment consisted of a prolonged cure of antibiotics: intravenous ceftriaxone for two weeks, followed by an oral maintenance therapy of doxycycline and hydroxychloroquine for at least one year.

CONCLUSION A therapeutic dilemma arose as continued anti-TNF blockade was necessary to maintain remission of the rheumatoid arthritis. Lifelong follow-up is necessary because relapse is possible.

ABSTRACT 4

A toothpick a day, keeps the doctor away?

Depoorter L, Billiet T, Van Moerkercke W, et al. Acta Gastro-enterologica Belgica, 2019, 82(1), 97-98

OBJECTIVE A toothpick is a dreaded offender when ingested, as it is risky to cause impaction, obstruction or perforation of the

gut. When ingestion of a toothpick leads to one of these complications, it clinically mimics an acute abdomen. Often the patient doesn't recall the ingestion, leading to misdiagnosis as inflammatory bowel disease, appendicitis/diverticulitis, etc. We describe the case of a 50-year old woman presenting to the emergency department with right lower abdominal pain.

CONCLUSION CT-scan showed an obstruction without clear underlying cause. The hypothesis of obstruction due to intestinal adhesions without strangulation was assumed and non-operative management lead to recovery and dismissal of the patient. However, she presented 3 weeks later with identical complaints, this time showing a terminal ileitis on CT-scan. Surprisingly, a toothpick perforating the terminal ileum was found during endoscopy and could by removed. A clinician should think of foreign body ingestion when patients present with an acute abdomen with no clear underlying pathology.

ABSTRACT 5

Long-term clinical effectiveness of ustekinumab in patients with Crohn's disease who failed biologic therapies: a national cohort study.

Liefferinckx C, Verstockt B, Van Moerkercke W, et al. Journal of Crohn’s Colitis, 2019, 13(11), 1401-1409

INTRODUCTION/BACKGROUND Ustekinumab [UST] was recently approved in Europe for the treatment of moderate to severe Crohn's disease [CD]. Long-term real-world data are currently scarce for CD patients previously exposed to several biologics.

MATERIALS/METHODS This is an observational, national, retrospective multicentre study. Patients received intravenous UST ~6 mg/kg at baseline, with 90 mg subcutaneously thereafter every 8 weeks. Response and remission rates were assessed at Weeks 8, 16, and 52.

RESULTS Data from 152 patients were analysed. All patients were exposed to at least one anti-TNFα agent, with 69.7% were exposed to even two anti-TNFα and vedolizumab. After 1 year, 42.1% and 25.7% of patients had experienced clinical response and clinical remission, respectively, and 38.8% and 24.3% had achieved steroid-free clinical response and remission, respectively; 38.8% of patients discontinued therapy during the 12 months of follow-up. Colonic location was predictive of clinical response at 1 year, and low body mass index [BMI] at baseline was a negative predictor of clinical remission. Resolution of arthralgia was associated with clinical response over time. De novo arthralgia was reported by 17.9% of patients at Week 8 and 13.5% of patients at Week 52. No impact of UST on arthralgia was observed in patients with concomitant ankylosing spondylitis [n = 17]. Others adverse events were reported in 7.2% of patients.

CONCLUSION This real-world cohort study confirms the effectiveness of UST in CD patients previously exposed to several biologics. Ustekinumab was well tolerated with respect to adverse events.

ABSTRACT 6

Standardized approach to idiopathic retroperitoneal fibrosis: a comprehensive review of the literature.

Roussel E, Callemeyn J, Van Moerkercke W, et al. Acta Clinica Belgica, 2019, Online ahead of print, 1-6

INTRODUCTION/BACKGROUND Idiopathic retroperitoneal fibrosis (iRPF) is a rare fibro-inflammatory disease, characterized by inflammation of the abdominal aorta and its surrounding structures. The exact pathophysiology remains unclear. Diagnosis is often troublesome due to the non-specific and highly variable clinical presentation. Standardized treatment protocols are lacking.

OBJECTIVE This article presents a review on iRPF, addressing clinical and diagnostic modalities as well as its pathophysiology and the possible inclusion within the IgG4-related disease (IgG4-RD) spectrum. Finally, a diagnostic-therapeutic algorithm for a standardized approach to iRPF is proposed.

MATERIALS/METHODS The PubMed Internet database was searched. Articles were selected based on the relevance of abstract, article type and impact of the journal.

RESULTS iRPF and IgG4-RD share a common autoimmune aetiology. Diagnostics are multimodal and based on imaging. Ruling out malignancy should be of primary concern. Complications are mostly of renal or vascular origin due to compres-

sion of retroperitoneal structures. Corticosteroids remain the first-line treatment regimen and are mostly successful, but evidence supporting alternative immunosuppressive and anti-inflammatory treatments is growing. Long-term therapy, as well as follow-up, is paramount in this chronic and often relapsing disease.

ABSTRACT 7

Uveitis as a window to diagnosis of sarcoidosis - case report and review of the literature.

Dhont S, Leys M, Van Moerkercke W, Alaerts H, et al. Acta Clinica Belgica, 2019, May 5, 1-5

CONCLUSION Sarcoidosis is a multisystem disease of unclear etiology with a variable clinical profile characterized by the presence of non-caseating granuloma in involved organs. The diagnosis is often challenging and based on clinical, radiological and anatomopathological data. Sarcoidosis can be benign and self-limiting, but some cases may follow a chronic, progressive course and result in severe morbidity. The disease has a predilection for the lungs and thoracic lymph nodes but can involve nearly any part of the body, possible more commonly in areas with contact to the external environment, such as the eyes and the skin. This paper is based on a case in which a recurrent uveitis led to the diagnosis of an underlying sarcoidosis.

ABSTRACT 8

Polypectomy of a colonic mucosubmucosal elongated polyp.

Persyn D, Moubax K, Van Moerkercke W, Alaerts H, et al. Gastrointestinal endoscopy, 2019, 90(4), 693-694

INTRODUCTION/BACKGROUND A 53-year-old man was referred to our department after a positive fecal immunochemical test result. He had no symptoms or signs of iron deficiency anemia. Colonoscopy showed a large elongated polyp in the descending colon. An endoloop-assisted polypectomy was performed after placement of 2 hemostatic clips. The resected specimen (8 × 3 × 0.7 cm) was covered with normal mucosa. Histopathologic examination showed normal mucosa without dysplasia or inflammation (H&E, orig. mag. × 40). The diagnosis of a colonic mucosubmucosal elongated polyp (CMSEP) was made. ABSTRACT 9

Impact of first-line infliximab on the pharmacokinetics of second-line vedolizumab in inflammatory bowel diseases.

Liefferinckx C, Verstockt B, Van Moerkercke W, et al. United European Gastroenterology Journal, 2019, 7(6), 750–758

INTRODUCTION/BACKGROUND Very little is known about the impact of the wash-out period on the pharmacokinetics of a second-line biologic.

OBJECTIVE The objective of this article is to explore the impact of two different wash-out periods on the pharmacokinetics of vedolizumab and infliximab.

MATERIALS/METHODS Patients switching from infliximab to vedolizumab were retrospectively identified. The population was divided into two groups according to wash-out period: <6 weeks or >6 weeks. Vedolizumab and infliximab trough levels (TLs) were determined and correlated with clinical and biological outcomes.

RESULTS A total of 71 inflammatory bowel disease patients were included. At week 6, in patients previously treated with infliximab, median vedolizumab TLs were 21.9 µg/ml and 24.9 µg/ml for the <6 weeks and >6 weeks wash-out period, respectively (p = 0.31), whereas median residual infliximab TLs were 0.5 µg/ml and 0 µg/ml (p = 0.034). The rate of treatment discontinuation was similar (p = 0.64), and the infectious events were six and two for the <6 weeks and >6 weeks wash-out period, respectively (p = 0.12) by week 30.

CONCLUSION This study suggests clinicians may not need to be concerned about the impact of wash-out period on the pharmacokinetics of the second-line biologic when switching infliximab to vedolizumab. More data are required on the impact of wash-out period on safety.

ABSTRACT 10

Unexplained fever in a young man with Crohn's disease: a case report and review of literature.

Deroo L, Elewaut A, Van Moerkercke W, et al. Acta Clinica Belgica, 2019, Online ahead of print, 1-5

RESULTS A 23-year-old man with a known history of Crohn's disease (CD), who underwent an ileocaecal resection for localized disease activity three months ago, suffered from persistent fever with chills since 10 days. Despite the empirical antibiotic therapy that was started, his fever remained. A computed tomography (CT) angiography of the thorax and abdomen revealed a thrombosis of the iliacal veins bilateral and a pulmonary embolism (PE) in the right lower lobe with adjacent infiltrate. Venous thromboembolism (VTE) can be a life-threatening extraintestinal manifestation of inflammatory bowel disease (IBD). The risk that IBD patients develop a VTE is three times higher in comparison with healthy controls. They have a higher risk of recurrence and a higher mortality ratio. The pathogenesis of VTE in IBD is complex and until now not fully understood. More awareness should be raised, given the fact that it can be prevented by appropriate thromboprophylaxis.

ABSTRACT 11

Ruminococcus gnavus bacteremia, an uncommon presentation of a common member of the human gut microbiota: case report and literature review.

Lefever S, Van Moerkercke W, D'Hondt M, Pampols M, De

Bel A, Boudewijns M, et al. Acta Clinica Belgica, 2019, Dec 74(6), 435-438

Het abstract is terug te vinden op pagina 7.

ABSTRACT 12

Beclomethasone dipropionate in microscopic colitis: Results of an exploratory open-label multicentre study (COLCO).

Corte T, Janssens E, Van Moerkercke W, et al. United European Gastroenterololgy Journal, 2019, 7(9), 1183-1188

INTRODUCTION/BACKGROUND Budesonide has been proven to be an effective treatment for microscopic colitis (MC). However, the two current commercially available preparations are released in the ileum. Beclomethasone dipropionate (Clipper®) is a synthetic corticosteroid with topical colonic release. OBJECTIVE This study aimed to explore whether an open-label treatment with beclomethasone dipropionate is an effective treatment for MC.

MATERIALS/METHODS Prospectively collected data of 30 patients from six centres were retrospectively analysed. All patients had a confirmed diagnosis of idiopathic MC (lymphocytic and collagenous colitis) and were symptomatic (i.e. ≥ 21 loose stools over a seven-day period). Treatment consisted of 10 mg beclomethasone daily for four weeks, followed by 5 mg daily for another four weeks. The primary end point was the proportion of patients in remission (i.e. a mean of < 3 stools/day and a mean of <1 watery stool per day) after an eight-week treatment period. Secondary end points were the proportion of patients responding to therapy at weeks 4 and 8, remission at weeks 4 and 12 and relapse at week 12. Reported adverse events were collected.

RESULTS Overall, at week 8, remission was achieved in 70%, and 77% of patients were responding to treatment. After four weeks of treatment, 80% were responding, and 67% were in remission. Four weeks after stopping treatment, 60% were still in remission.

CONCLUSION This open-label study suggests that an eight-week course of beclomethasone could be a promising and relatively safe treatment for MC. A randomised controlled study is warranted.

ABSTRACT 13

Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study.

Moens A, Van der Woude CJ, Van Moerkercke W, et al. Alimentary Pharmacology & Therapeutics, 2020, 51(1), 129-138

INTRODUCTION/BACKGROUND Women with inflammatory bowel diseases (IBD) often receive biologicals during pregnancy to maintain disease remission. Data on outcome of vedolizumab-exposed pregnancies (VDZE) are sparse.

OBJECTIVE To assess pregnancy and child outcomes of VDZE pregnancies and to compare these results to anti-TNF exposed (TNFE) or both immunomodulatory and biologic unexposed (CON IBD) pregnancies.

MATERIALS/METHODS A retrospective multicentre case-control observational study was performed.

RESULTS VDZE group included 79 pregnancies in 73 IBD women. The TNFE and CON IBD group included 186 pregnancies (162 live births) in 164 IBD women and 184 pregnancies (163 live births) in 155 IBD women, respectively. At conception, cases more often had active disease ([VDZE: 36% vs TNFE: 17%, P = .002] and [VDZE: 36% vs CON IBD: 24%, P = .063]). No significant difference in miscarriage rates were found between groups (VDZE and TNFE: 16% vs 13%, P = .567; VDZE and CON IBD: 16% vs 10%, P = .216). In live-born infants, median gestational age and birthweight were similar between groups. Median Apgar score at birth was numerically equal. Prematurity was similar in the VDZE group compared to the control groups, even when correcting for disease activity during pregnancy. The frequency of congenital anomalies was comparable between groups as were the percentages of breastfed babies. During the first year of life, no malignancies were reported and infants' infection risk did not significantly differ between groups.

CONCLUSION No new safety signal was detected in VDZE pregnancies although larger, prospective studies are required for cofirmation.

ABSTRACT 14

Terminale ileïtis met een scherp kantje.

Persyn D, D’heygere F, Moubax K Tijdschrift voor Geneeskunde, 2019, 75(4), 286-287

INTRODUCTION/BACKGROUND A 35-year-old Caucasian male was admitted because of right iliac fossa pain. Blood analysis showed a C-reactive protein of 42.9 mg/l. A contrast-enhanced CT scan of the abdomen revealed terminal ileitis. Surprisingly, a toothpick entrapped in the terminal ileum was found during the endoscopy and was successfully removed. ABSTRACT 15

Golimumab dried blood spot analysis (GOUDA): a prospective trial showing excellent correlation with venepuncture samples and more detailed pharmacokinetic information.

Van Moerkercke W, Detrez I, Schops G, et al. The American Association of Pharmaceutical scientists (AAPS) Journal, 2019 21(1), 10. doi: 10.1208/s12248-0180282-x.

INTRODUCTION Development of a dried blood spot (DBS) method for golimumab will facilitate sample collection in a study setting and will give a more complete insight in the total drug exposure (area under the curve, AUC). We established a DBS method and assessed its robustness, user-friendliness and clinical usefulness in 10 patients with ulcerative colitis during golimumab induction and maintenance regimens. DBS was obtained through spotting of golimumab spiked in whole citrated blood to a filter paper. Several extraction conditions were evaluated and the selected extraction condition analytically validated. In a clinical setting, DBS and serum samples were taken simultaneously through intensive sampling regimens and a conversion factor was determined. Golimumab concentrations were measured using an in-house-developed ELISA and a CEmarked ELISA kit. User-friendliness was evaluated using a questionnaire. Mucosal healing was evaluated at week 14. A total of 79 matched pairs of serum and DBS sample golimumab concentrations revealed an overall conversion factor of 3.9. DBS golimumab concentrations after conversion correlated strongly with serum golimumab concentrations (ICC = 0.984). During induction, no linear correlation was found between golimumab trough concentration (TC) and AUC (R2 = 0.29). Multiple peaks emerged during drug absorption. Patients who achieved mucosal healing appeared to have less fluctuating TC and a constant AUC over time. Nine out of 10 patients reported DBS sampling as user-friendly. The GOUDA study showed that DBS sampling is a robust and patient-friendly alternative to venous blood collection. DBS sampling may provide better insights into golimumab absorption and exposure.

PRESENTATIES / CONGRESSEN

ABSTRACT 1

Effectiveness and safety of Vedolizumab maintenance therapy for Inflammatory Bowel Disease: findings from a Belgian registry.

European Crohn’s and Colitis Organisation (ECCO) / Belgian Week of Gastroenterology (BWGE) D’Heygere F, Louis E, Muls V, et al. March 2019, Copenhagen, Denmark

INTRODUCTION/BACKGROUND Clinical trials have demonstrated the efficacy and safety of vedolizumab (VDZ) as maintenance therapy for Crohn’s disease (CD) and ulcerative colitis (UC). This report presents outcome data for VDZ maintenance therapy in real life practice in Belgium.

MATERIALS/METHODS The Belgium VDZ Registry includes 202 VDZtreated adult patients from 19 Belgian centres. Inclusion criteria were ongoing VDZ therapy started 15+ days prior to recruitment and patient not in a clinical trial or VDZ PASS study. This interim analysis presents safety data for the all 202 registry participants, and clinical remission rates on the subset of 156 participants with at least one 6monthly investigator update on clinical management and outcomes. Clinical remission was defined as HarveyBradshaw Index <5 or partial Mayo Score < 3 with no subscore >1. Patients who discontinued VDZ were considered not in remission from that point forwards. An imputation analysis was included to account for missing disease activity scores, where a missing activity score was assumed not in remission, thereby giving a minimum imputation estimate.

RESULTS The characteristics of the 202 participants were 52% female, 66% had CD, predominantly ileal or ileocolonic CD, and 34% had UC, predominantly leftsided UC. Median age at onset of IBD was 28 years, and median duration of IBD prior to starting VDZ was 10 years. t recruitment, median length of ongoing VDZ therapy was 11 months, and 63% of UC and 60% of CD patients were in remission. Median duration of followup in the outcomes subset was 11 months (range 418 months). Clinical remission rates are shown below. The corresponding rates of corticosteroidfree clinical remission were 3040% for both CD and UC. All reported serious adverse events (SAEs) and nonserious AEs were considered unrelated to VDZ therapy. 34 patients (16.8%) had a SAE, the most frequent being worsening of CD/UC (4.0%) and small intestine obstruction (1.5%). 80 patients (39.6%) had a nonserious AE, the most frequent being constipation (2.5%), gastroenteritis (2.0%), nasopharyngitis (2.0%), and upper respiratory tract infection (2%). There were no reports of hepatic injury, infusionrelated reactions, hypersensitivity or opportunistic infection.

CONCLUSION These real life data collected from 19 gastroenterology centres across Belgium demonstrate sustained clinical benefit with up to 36 months of VDZ maintenance therapy in everyday clinical practice.