Pierre Ellul

Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response

Background: Intensifying infliximab therapy is often practiced in Crohns disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval‐halving compared with dose‐doubling. Methods: A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose‐doubling (10 mg/kg/8 weeks). Results: In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose‐doubling and 56 received interval‐halving strategy. Early response to dose‐escalation was experienced by 86/112 (77%) patients in the dose‐doubling group compared with 37/56 patients (66%) in the interval‐halving group (odds ratio [OR] 1.7, 95% confidence interval [CI] 0.8–3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50% of patients in the dose‐doubling group compared with 39% in the interval‐halving group (OR 1.5, 95% CI 0.8–2.9, P = 0.2). On multivariate analysis, predictors of long‐term response to escalation were a nonsmoking status, CD diagnosis between 16–40 years of age, and normal C‐reactive protein (CRP). Conclusions: Dose intensification leads to a sustained regained response in 47% of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose‐doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose‐doubling strategy may be preferable to the interval‐halving strategy. (Inflamm Bowel Dis 2012;)

The efficacy of shortening the dosing interval to once every six weeks in Crohn's patients losing response to maintenance dose of infliximab.

Aliment Pharmacol Ther 2011; 33: 349–357

H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy

Background Safety data are lacking on influenza vaccination in general and on A (H1N1)v vaccination in particular in patients with inflammatory bowel disease (IBD) receiving immmunomodulators and/or biological therapy. Aims and methods The authors conducted a multicentre observational cohort study to evaluate symptoms associated with influenza H1N1 adjuvanted (Pandemrix, Focetria, FluvalP) and non-adjuvanted (Celvapan) vaccines and to assess the risk of flare of IBD after vaccination. Patients with stable IBD treated with immunomodulators and/or biological therapy were recruited from November 2009 until March 2010 in 12 European countries. Harvey–Bradshaw Index and Partial Mayo Score were used to assess disease activity before and 4 weeks after vaccination in Crohns disease (CD) and ulcerative colitis (UC). Vaccination-related events up to 7 days after vaccination were recorded. Results Of 575 patients enrolled (407 CD, 159 UC and nine indeterminate colitis; 53.9% female; mean age 40.3 years, SD 13.9), local and systemic symptoms were reported by 34.6% and 15.5% of patients, respectively. The most common local and systemic reactions were pain in 32.8% and fatigue in 6.1% of subjects. Local symptoms were more common with adjuvanted (39.3%) than non-adjuvanted (3.9%) vaccines (p<0.0001), whereas rates of systemic symptoms were similar with both types (15.0% vs 18.4%, p=0.44). Among the adjuvanted group, Pandemrix more often induced local reactions than FluvalP and Focetria (51.2% vs 27.6% and 15.4%, p<0.0001). Solicited adverse events were not associated with any patient characteristics, specific immunomodulatory treatment, or biological therapy. Four weeks after vaccination, absence of flare was observed in 377 patients with CD (96.7%) and 151 with UC (95.6%). Conclusion Influenza A (H1N1)v vaccines are well tolerated in patients with IBD. Non-adjuvanted vaccines are associated with fewer local reactions. The risk of IBD flare is probably not increased after H1N1 vaccination.

Risk Factors for Osteoporosis in Crohnʼs Disease: Infliximab, Corticosteroids, Body Mass Index, and Age of Onset

Background:We analyzed the characteristics associated with increased risk of osteoporosis in patients with Crohns disease in Malta. Method:Eighty-three patients with histologically and endoscopically confirmed Crohns disease underwent a DEXA bone density scan and their phenotypic characteristics were analyzed. Results:There was a significant association between body mass index and bone mineral density (P = 0.004) and a significant difference in the T scores of patients according to age at diagnosis (Montreal Classification: P = 0.0006) with patients diagnosed <17 years (n = 13) having lower T scores than those diagnosed at older age groups (n = 70). There was a significant difference between the T scores of patients on infliximab (n = 33) and those not on biological therapy (n = 50, P = 0.0058). Patients with high cumulative corticosteroid doses (>10 mg/d for >3 mo, n = 18) had lower bone mineral densities than patients who received smaller corticosteroid doses (P = 0.013). There was however no significant difference in the T scores of patients according to disease location (P = 0.18), disease type (P = 0.64), gender (P = 0.30), and history of ileal resection (P = 0.68). There was also no significant correlation between disease duration and T scores (hip) (P = 0.61). Conclusions:Low body mass index, early disease onset, high corticosteroid doses and, anti–tumor necrosis factor &agr; therapy are associated with increased risk of osteoporosis. Lower T scores in patients on infliximab occur as patients receiving this therapy have more severe inflammation, which is associated with elevated osteoclastogenic factors, rather than as a side-effect of the anti–tumor necrosis factor-&agr; therapy.

Dose optimization is effective in ulcerative colitis patients losing response to infliximab: A collaborative multicentre retrospective study

BACKGROUND Subjects maintained on infliximab scheduled therapy for inflammatory bowel disease may require dose optimization due to secondary loss of response. There are limited data on infliximab dose optimization for ulcerative colitis. AIMS To investigate dose optimization in ulcerative colitis patients with secondary loss of response. METHODS This was a retrospective multicentre study. Primary outcome was rapid clinical response assessed at the next administration of infliximab after dose intensification. Secondary outcomes were rapid clinical remission, and clinical response, remission and colectomy rate by week 52. Doubling the dose (10mg/kg q8 weeks) vs. shortening the dose interval (5mg/kg every 6 or 4 weeks) were compared. RESULTS Forty-one patients from eight centres were enrolled (15 for double dose and 26 for interval shortening). Rapid response was achieved in 37/41 patients (90.2%), while 19/41 (46.3%) achieved rapid clinical remission. At week 52, 28/41 patients were maintained in clinical remission, but 4 (9.8%) underwent colectomy. No difference was found between the two optimization strategies. Subjects achieving rapid clinical response had a significantly higher colectomy-free rate at week 52 (p=0.002). CONCLUSION Dose optimization of infliximab was effective to restore clinical response or remission and to prevent colectomy in ulcerative colitis patients with secondary loss of response.

The effect of cigarette smoking on allergic conditions in Maltese children (ISAAC)

To cite this article: Montefort S, Ellul P, Montefort M, Caruana S, Grech V, Agius Muscat H. The effect of cigarette smoking on allergic conditions in Maltese children (ISAAC). Pediatric Allergy Immunology 2012: 23: 472–478.

Colonic tumour localization using an endoscope positioning device.

Background and study aim Although colonoscopy is reliable in identifying colorectal cancer (CRC), studies have demonstrated incorrect tumour localization in 21–34% of colonoscopies when compared with surgical localization. The aim of this study was to determine our accuracy in determining the position of CRCs detected at colonoscopy with the aid of the ScopeGuide endoscope positioning device. Patients and methods Cancers identified within the English National Bowel Cancer Screening Programme were studied. Retrospective analysis was undertaken of all patients diagnosed with CRC during the first screening round in Wolverhampton Bowel Cancer Screening Centre, England. ScopeGuide was used in all cases. Data from colonoscopy reports, computed tomography reports and surgical resection specimens were analysed. Results A total of 82 cancers were identified within the surgical resection specimen in 80 patients. Two proximal cancers were not identified at colonoscopy due to obstruction by the distal cancers. Colonoscopy with the aid of the endoscopy positioning device correctly identified the tumour location in 93.75% of cases in which the tumour could be reached endoscopically. Abdominopelvic computed tomography localized 82.5% of CRC. Conclusion The ScopeGuide endoscopy positioning device enables accurate localization of cancers at colonoscopy. Tattooing of suspected cancer remains to be a best practice for localization during laparoscopic resection. The use of the endoscopic-positioning device may, however, result in greater confidence for localization of polypectomy sites, which have not been tattooed, in cases when cancer was not suspected but found histologically.

Increasing prevalence of asthma, allergic rhinitis but not eczema in 5- to 8-yr-old Maltese children (ISAAC)

The International Study of Asthma and Allergies in Childhood (ISAAC) was the first worldwide study carried out with standardized questionnaires in order to create a reliable global map of childhood allergy. Phase 1 of the study was carried out in the Maltese Islands in 1994/95 while a similar study (phase 3) was repeated 7 yr later (2001/02). In this paper, the data obtained from 3816 5‐ to 8‐yr‐olds (80% response rate) in phase 3 were compared to that obtained from 3509 5‐ to 8‐yr‐olds (78.5% response rate) in phase 1 of the study in order to evaluate whether the problem of allergic conditions in Maltese schoolchildren was indeed changing. About 30.2% (phase 3) vs. 19.1% (phase 1) (p < 0.0001) of the participants were wheezers ‘ever’ while 14.8% vs. 8.8% (p < 0.0001) were current wheezers and 14.8% vs. 7.5% (p < 0.0001) were labelled as asthmatics. Of these wheezing children, 13.3% vs. 6.2% (p = 0.0002) had a wheezing episode severe enough to limit speech. Nasal problems were present in 28.8% of Maltese children in 2001 and in 23.4% in 1994 (p < 0.0001) and 24.4% vs. 20.7% (p < 0.0001) of all respondents persisted with these symptoms up to the year of answering the questionnaire. Hayfever had been diagnosed in 22.2% vs. 14.7% (p < 0.0001) of all the children. About 6.7% vs. 7.0% (p = 0.61) of respondents had an recurring itchy rash suggestive of eczema for at least 6 months of their lives and 5.4.% vs. 5.5% had it currently. In 1994, the prevalence of wheezing and eczema were slightly lower than the global mean, unlike the case of rhinitis, which in Malta was commoner than the world average, while in 2001 wheezing together with rhinitis surpassed the global mean as well. These results indicate a rising prevalence of wheezing and rhinitis but not eczema in Maltese children. Asthma seemed to be better controlled and all three allergic conditions more likely to be diagnosed.

A decrease in the prevalence and improved control of allergic conditions in 13- to 15-yr-old Maltese children (ISAAC)

To cite this article: Montefort S, Ellul P, Montefort M, Caruana S, Agius Muscat H. A decrease in the prevalence and improved control of allergic conditions in 13‐ to 15‐yr‐old Maltese children (ISAAC). Pediatr Allergy Immunol 2011; 22: e107–e111.

Capsule endoscopy in young patients with iron deficiency anaemia and negative bidirectional gastrointestinal endoscopy

Background Recent data imply young patients (age ≤50 years) undergoing small-bowel (SB) capsule endoscopy (CE) for iron deficiency anaemia (IDA) show higher diagnostic yield (DY) for sinister pathology. We aimed to investigate DY of CE in a large cohort of young IDA patients, and evaluate factors predicting significant SB pathology. Materials and methods This was a retrospective, multicentre study (2010–2015) in consecutive, young patients (≤50 years) from 18 centres/12 countries, with negative bidirectional gastrointestinal (GI) endoscopy undergoing SBCE for IDA. Exclusion criteria: previous/ongoing obscure-overt GI bleeding; age <19 or >50 years; comorbidities associated with IDA. Data retrieved: SBCE indications; prior investigations; medications; SBCE findings; final diagnosis. Clinical and laboratory data were analysed by multivariate logistic regression. Results Data on 389 young IDA patients were retrieved. In total, 169 (43.4%) were excluded due to incomplete clinical data; data from 220 (122F/98M; mean age 40.5 ± 8.6 years) patients were analysed. Some 71 patients had at least one clinically significant SBCE finding (DY: 32.3%). They were divided into two groups: neoplastic pathology (10/220; 4.5%), and non-neoplastic but clinically significant pathology (61/220; 27.7%). The most common significant but non-neoplastic pathologies were angioectasias (22/61) and Crohn’s disease (15/61). On multivariate analysis, weight loss and lower mean corpuscular volume(MCV) were associated with significant SB pathology (OR: 3.87; 95%CI: 1.3–11.3; p = 0.01; and OR: 0.96; 95%CI: 0.92–0.99; p = 0.03; respectively). Our model also demonstrates association between use of antiplatelets and significant SB pathology, although due to the small number of patients, definitive conclusions cannot be drawn. Conclusion In IDA patients ≤50 years with negative bidirectional GI endoscopy, overall DY of SBCE for clinically significant findings was 32.3%. Some 5% of our cohort was diagnosed with SB neoplasia; lower MCV or weight loss were associated with higher DY for SB pathology.