Postoperative complications and waiting time for surgical intervention after radiologically guided drainage of intra-abdominal abscess in patients with Crohn's disease.

BACKGROUND: In patients with active Crohn's disease (CD), treatment of intra-abdominal abscess usually comprises antibiotics and radiologically guided percutaneous drainage (PD) preceding surgery. The aim of this study was to investigate the risk of postoperative complications and identify the optimal time interval for surgical intervention after PD. METHODS: A multicentre, international, retrospective cohort study was carried out. Details of patients with diagnosis of CD who underwent ultrasonography- or CT-guided PD were retrieved from hospital records using international classification of disease (ICD-10) diagnosis code for CD combined with procedure code for PD. Clinical variables were retrieved and the following outcomes were measured: 30-day postoperative overall complications, intra-abdominal septic complications, unplanned intraoperative adverse events, surgical-site infections, sepsis and pathological postoperative ileus, in addition to abscess recurrence. Patients were categorized into three groups according to the length of the interval from PD to surgery (1-14 days, 15-30 days and more than 30 days) for comparison of outcomes. RESULTS: The cohort comprised 335 CD patients with PD followed by surgery. Median age was 33 (i.q.r. 24-44) years, 152 (45.4 per cent) were females, and median disease duration was 9 (i.q.r. 3.6-15) years. Overall, the 30-day postoperative complications rate was 32.2 per cent and the mortality rate was 1.5 per cent. After adjustment for co-variables, older age (odds ratio 1.03 (95 per cent c.i. 1.01 to 1.06), P < 0.012), residual abscess after PD (odds ratio 0.374 (95 per cent c.i. 0.19 to 0.74), P < 0.014), smoking (odds ratio 1.89 (95 per cent c.i. 1.01 to 3.53), P = 0.049) and low serum albumin concentration (odds ratio 0.921 (95 per cent c.i. 0.89 to 0.96), P < 0.001) were associated with higher rates of postoperative complications. A short waiting interval, less than 2 weeks after PD, was associated with a high incidence of abscess recurrence (odds ratio 0.59 (95 per cent c.i. 0.36 to 0.96), P = 0.042). CONCLUSION: Smoking, low serum albumin concentration and older age were significantly associated with postoperative complications. An interval of at least 2 weeks after successful PD correlated with reduced risk of abscess recurrence.

Inflammatory Bowel Disease [IBD] and Physical Activity: A Study on the Impact of Diagnosis on the Level of Exercise Amongst Patients With IBD.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] can impair patients' functional capacity with significant negative effects on their quality of life. Our aim was to determine the impact of IBD diagnosis on fitness levels and to assess the levels of engagement in physical activity and fatigue in IBD patient before and after diagnosis. METHODS: A prospective multi-centre cross-sectional study was performed. Patients diagnosed with IBD in the previous 18 months were recruited. Inclusion criteria included clinical remission and/or no treatment changes within the previous 6 months. Physical exercise levels were assessed by the Godin score and fatigue levels was assessed by the functional assessment of chronic illness therapy [FACIT] score. RESULTS: In total, 158 patients (100 Crohn's disease [CD]) were recruited. Mean age was 35.1 years (95% confidence interval [CI] ± 2.0). Gender distribution was approximately equal [51.3% male]. The Mean Harvey Bradshaw and Simple Clinical Colitis Activity indices were 2.25 [95% CI ± 0.40] and 1.64 [95% CI ± 0.49], respectively. The mean Godin score difference before and after IBD diagnosis was 6.94 [p = 0.002]. Patients with ulcerative colitis [UC] [41.8%] were more likely than patients with CD [23.0%] to reduce their exercise levels [p = 0.04]. FACIT scores were lower in patients who had experienced relapses [p = 0.012] and had severe disease [p = 0.011]. Approximately one-third of patients reduced their activity level following IBD diagnosis. CONCLUSIONS: Patients were significantly less physically active after a diagnosis of IBD and this was more apparent in UC. Identification of the risk factors associated with loss of fitness levels would help to address the reduced patient quality of life.

Safety, efficacy and pharmacokinetics of vedolizumab in patients with simultaneous exposure to an anti-tumour necrosis factor.

BACKGROUND: Data on combination-biologic treatment in (IBD) are still scant. AIM: To explore outcomes of patients co-exposed to anti-TNF and vedolizumab. METHODS: Patients starting vedolizumab having measurable anti-TNF levels after recently stopping adalimumab/infliximab ('VDZ-aTNF' group), were compared with control vedolizumab patients in a retrospective 1:2 matched case-control study. RESULTS: Seventy-five patients were included (25 VDZ-aTNF, 50 VDZ). Adverse events were experienced by 9/25 VDZ-aTNF compared to 13/50 VDZ patients (P = 0.4, follow-up 14 weeks in all). Week 14 clinical remission was attained in 10/25 (40%) of VDZ-aTNF patients versus 23/50 (46%) of VDZ patients (OR = 0.8, 95% CI 0.3-2.1, P = 0.6) and clinical response in 19/25 (76%) versus 39/50 (78%) respectively (OR = 0.9, 95% CI 0.3-2.7, P = 0.8). Corticosteroid-free remission and corticosteroid-free response were experienced by 30% and 54%, respectively, of the entire cohort, and were similar between the two groups. Vedolizumab drug concentrations at week 2, 6 and 14 were similar among VDZ-aTNF and VDZ patients (P > 0.5). Multi-variable analysis showed independent association of some vedolizumab drug-levels time-points with baseline albumin and weight, but not with anti-TNF co-exposure. In a prospective study of a separate cohort of patients starting infliximab (n = 12), the percentage of α4ß7+ memory T cells, slightly but nonsignificantly increased throughout weeks 0, 2 to 14 (26 ± 2.3%, 27.8 ± 2.9%, 29.5 ± 2.6% respectively, P = 0.06). CONCLUSIONS: Vedolizumab/anti-TNF co-exposure did not generate new safety signals during 14-weeks induction, nor did it reduce efficacy or alter vedolizumab pharmacokinetics. These observations may aid the design of future co-biologics trials and also suggest that a deliberate waiting-interval between anti-TNF cessation and subsequent vedolizumab initiation may not be warranted.

Early drug and anti-infliximab antibody levels for prediction of primary nonresponse to infliximab therapy.

BACKGROUND: Primary nonresponse, defined as lack of clinical benefit during the induction phase, occurs in up to 30% of IBD patients treated with infliximab. The mechanisms underlying primary nonresponse have not yet been clearly defined. AIM: To evaluate the association of early (week 2 and week 6) induction infliximab and anti-infliximab antibody levels with primary nonresponse. METHODS: A retrospective observational case-control study of inflammatory bowel disease patients treated with infliximab and followed at Sheba Medical Center between 2009 and 2016 was performed. Pre-infusion infliximab and antibodies to infliximab (ATI) levels were measured by our previously described drug-tolerant ELISA assay. RESULTS: Thirty-five primary nonresponders have been identified and matched with 105 primary responders (1:3 ratios). Both week 2 and week 6 infliximab levels were significantly lower among primary nonresponders compared to responders (week 2, 6: median level 7.2, 2.2 µg/mL vs 13.5, 9.5 µg/mL, P = .0019, P < .0001 respectively). Antibodies to infliximab appeared more frequently (either week 2 or 6, 68% vs 28% prevalence, P = .0004) and at higher levels in nonresponders compared to responders (week 2, 6: median ATI 7.3, 10.8 µg/mL-eq vs 3.8, 4.4 µg/mL-eq, P = .005, P = .008 respectively). Moreover, week 2 infliximab levels <6.8 µg/mL (AUC = 0.68, P = .002, sensitivity 50%, specificity 86%) and antibodies to infliximab levels >4.3 µg/mL-eq (AUC = 0.78, P = .0004, sensitivity 77%, specificity 71%) were predictive of primary nonresponse. Among the other clinical and demographic variables, higher baseline ulcerative colitis clinical score, infliximab monotherapy, prior adalimumab therapy and previous Crohn's disease-related surgeries were also associated with an increased risk of primary nonresponse. CONCLUSIONS: Infliximab levels below 6.8 µg/mL and antibodies to infliximab levels above 4.3 µg/mL-eq before the second infusion are associated with primary nonresponse, especially among Crohn's disease patients.

Pitfalls in diagnosing colon cancer on abdominal CT.

AIM: To assess the frequency of undetected colon cancer on conventional abdominal CT and to evaluate the imaging features that are characteristic of those cancers. MATERIALS AND METHODS: The present study included consecutive patients diagnosed with colorectal cancer at colonoscopy (2006-2015) who also underwent abdominal computed tomography (CT) performed for various reasons within a year prior to the colonoscopy. The frequency of undetected lesions was evaluated for the original CT interpretations ("original readers"). Two radiologists ("study readers"), blinded to the tumour location, independently performed interpretations oriented for colon cancer detection. The study readers analysed the imaging features of detected tumours (tumour shape, length, maximal wall thickness, free fluid, fat stranding, vascular engorgement, stenosis, and lymphadenopathy). Imaging features of the cancers undetected by the original readers were evaluated. RESULTS: The study included 127 patients. The original readers' frequency of undetected cancer was 25/127 (19.7%). Each study reader could not identify the cancer in 8/127 (6.3%) patients. Imaging features associated with undetected cancers by the original readers included the absence of fat stranding (p=0.007, p=0.003), absence of vascular engorgement (p<0.0001, p<0.0001) and absence of lymphadenopathy (p=0.005, p=0.004). Undetected tumours were shorter than those detected (original reader: 33.2±11.9 versus 51.4±18.2 mm; study reader: 32.5±9.6 versus 61.3±23.4 mm; p<0.001). CONCLUSION: Colon cancer is undetected in 20% of abdominal CT examinations in patients subsequently proven to have colon cancer at colonoscopy. The absence of fat stranding, vascular engorgement, or lymphadenopathy, and an average tumour length of 3.3 cm are contributing factors for failure of detection. Radiologists' training should emphasis these findings as it may improve cancer detection, and clinicians should be aware of the limitations of abdominal CT.

Diffusion-weighted imaging in quiescent Crohn's disease: correlation with inflammatory biomarkers and video capsule endoscopy.

AIM: To investigate the role of restricted diffusion in quiescent Crohn's disease (CD) patients and its association with inflammatory biomarkers and endoscopic disease. MATERIAL AND METHODS: Fifty-two quiescent CD patients prospectively underwent magnetic resonance enterography (MRE) and video capsule endoscopy (VCE) and were tested for the inflammatory biomarkers, faecal calprotectin (FCP) and C-reactive protein (CRP). Restricted diffusion in the distal ileum was qualitatively (absence/presence) and quantitatively (apparent diffusion coefficient [ADC]) assessed by two readers. The VCE-based Lewis score was calculated for the distal ileum. Restricted diffusion sensitivity and specificity for VCE ulcerations were assessed for patients with elevated (>100 µg/g) or normal (<100 µg/g) FCP. Receiver operating characteristic (ROC) curve was used to assess the ability of ADC to identify patients with concurrent VCE ulceration and elevated FCP. RESULTS: The sensitivity and specificity of restricted diffusion for patients with VCE ulceration were higher in patients with elevated FCP (reader 1: 71.4%, 80%, reader 2: 76.2%, 100%, respectively) compared to patients with normal FCP (reader 1: 46.2%, 61.5%; reader 2: 15.4%, 76.9%, respectively). The ADC had a high diagnostic accuracy for identifying patients that had concurrent VCE ulceration and elevated FCP (reader 1: AUC=0.819, reader 2: AUC=0.832). CONCLUSION: In quiescent CD patients, the presence of restricted diffusion is suggestive of an active inflammation, associated with elevated FCP. Thus, DWI may serve as a clinical tool in the follow-up of these patients, implying subclinical inflammatory flares.

Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab.

BACKGROUND: Anti-adalimumab antibodies (AAA) are associated with loss of clinical response (LOR). Addition of an immunomodulator has been shown to reverse immunogenicity and regain response with infliximab monotherapy. Similar data on adalimumab are lacking. AIM: To study the impact of immunomodulator addition on the emergence of AAA and LOR among adalimumab therapy patients. METHODS: The databases of three tertiary medical centres were reviewed to identify patients who developed AAA during adalimumab monotherapy with resultant LOR, and received an immunomodulator as a salvage combination therapy. All sera were prospectively analysed using previously described ELISA assays. Clinical response was determined using appropriate clinical scores. Elimination of AAA, designated as 'sero-reversal', elevation of drug levels and regained clinical response were the sought outcomes. RESULTS: Twenty-three patients (21 Crohn's disease, and 2 ulcerative colitis) developed AAA with subsequent LOR and were thereafter prescribed an immunomodulator as salvage therapy (thiopurine n = 14, methotrexate n = 9). Eleven patients (48%) underwent sero-reversal with gradual elimination of AAA, increase in drug trough levels and restoration of clinical response (median time to sero-reversal 5 months). In 12 patients (52%), immunogenicity and loss of response could not be reversed. There was no difference between responders and nonresponders in the type of immunomodulators used or baseline clinical characteristics. CONCLUSIONS: In almost half of inflammatory bowel disease patients developing anti-adalimumab antibodies and loss of response, established immunogenicity of adalimumab can be gradually reversed by the addition of immunomodulator therapy with restoration of a clinico-biological response. However, these observations need to be confirmed with larger studies.

Soluble Syndecan-1: A Novel Biomarker of Small Bowel Mucosal Damage in Children with Celiac Disease.

BACKGROUND: Syndecan-1 (SDC1) is essential for maintaining normal epithelial barrier. Shedding of SDC1 ectodomain, reflected by serum soluble syndecan-1 (SSDC1) levels, is regulated by inflammation. Increased intestinal permeability plays a central role in celiac disease (CD). The association between SSDC1 levels and mucosal damage in CD has not been evaluated. AIMS: To evaluate serum SSDC1 levels in children with CD and to determine its relationship with histological grading classified by modified Marsh criteria. METHODS: This is a cross-sectional, pilot study, in which serum SSDC1 was analyzed by ELISA in a cohort of 49 untreated children with CD and 15 children with nonspecific abdominal pain (AP). CD was diagnosed based on positive celiac serology and small intestinal biopsy. SSDC1 levels at the time of biopsy were correlated with Marsh grading. Controls were defined by AP, negative celiac serology, normal upper endoscopy, and small intestinal biopsies. RESULTS: SSDC1 levels were significantly higher in CD patients compared to AP controls (116.2 ± 161 vs. 41.3 ± 17.5 ng/ml, respectively, p < 0.01). SSDC1 levels were significantly higher in patients with Marsh 3c lesion compared to AP controls (170.6 ± 201 vs. 41.3 ± 17.5 ng/ml, respectively, p < 0.05). SSDC1 concentrations displayed a significant correlation with mucosal damage defined by Marsh (r = 0.39, p < 0.05). CONCLUSION: This is the first study demonstrating elevated levels of serum SSDC1 in children with CD. Our results suggest that SSDC1 is a potentially novel marker of intestinal mucosal damage in patients with CD. Its applicability as a surrogate biomarker in CD remains to be determined.

Induction infliximab levels among patients with acute severe ulcerative colitis compared with patients with moderately severe ulcerative colitis.

BACKGROUND: Infliximab is effective as salvage therapy for patients with steroid refractory acute severe ulcerative colitis (UC). Although current data suggest that the pharmacokinetics of infliximab are influenced by inflammatory burden in patients with acute severe UC, data comparing infliximab trough levels in patients with acute severe UC vs. moderately severe UC are scarce. AIM: To compare infliximab trough and anti-infliximab antibody levels at a standard fixed time-point during induction between patients with acute severe and moderately severe UC. METHODS: A multi-centre retrospective study comparing infliximab drug and antibody levels 14 days after the first infusion in hospitalised acute severe UC versus out-patients with moderately severe UC was performed. RESULTS: Sixteen acute severe UC patients, hospitalised between 2010-2015 and refractory to intravenous corticosteroids, were treated with infliximab 5 mg/kg salvage therapy. They were compared to 16 moderately severe UC out-patient controls. Mean infliximab trough levels at day 14 were significantly lower in patients with acute severe UC compared to moderately severe UC (7.15 ± 5.3 vs. 14.4 ± 11.2 µg/mL, P = 0.007). Seven patients (three acute severe and four moderate severe UC) were primary nonresponders to infliximab induction therapy. Infliximab level at day 14 did not differ between responders and nonresponders (9.8 ± 9 vs. 12.1 ± 10.6 µg/mL, respectively, P = N.S.). However, week 2 median antibody-to-infliximab levels were numerically higher among primary nonresponders (3.4 ± 5.7 vs. 1.2 ± 4 µg/mL-eq, respectively, P = 0.06). CONCLUSIONS: Infliximab trough levels at day 14 were lower in patients with acute severe UC compared to moderately severe UC, possibly due to a higher inflammatory burden and/or increased drug clearance. However, drug levels at day 14 were not lower among nonresponders compared with responders. Controlled trials are warranted to examine whether an a-priori-intensified infliximab induction protocol will lead to an improved outcome in acute severe UC.

Undetectable anti-TNF drug levels in patients with long-term remission predict successful drug withdrawal.

BACKGROUND: Low drug levels are associated with emerging loss of response to anti-TNF. However, this may not be the case in patients with long-term remission. AIM: To investigate the outcome of anti-TNF discontinuation in patients with long-term remission and incidental undetectable drug levels. METHODS: A retrospective cohort study examining the duration of relapse-free survival in IBD patients in remission who discontinued infliximab or adalimumab having undetectable drug levels. RESULTS: Forty eight patients who discontinued anti-TNF while in remission and had available drug levels were identified in two centres in France and Israel (infliximab-treated 35, adalimumab-13, Crohn's disease 30, ulcerative colitis 18, mean treatment duration of 22.7 ± 12.4 months). Endoscopy/MRE before stopping showed absence of active inflammation in 40/42 (95%) of evaluated patients, while inflammatory biomarkers (CRP and/or Calprotectin) were completely normal in only 31/48 (65%) of patients. During 12 months median follow-up, relapse occurred in 16/20 (80%) of patients who stopped anti-TNF while having measurable drug levels compared with 9/28 (32%) of patients who had undetectable drug levels (OR: 8.4, 95% CI: 2.2-32, P = 0.002). Relapse-free survival after anti-TNF cessation was significantly longer in patients with absent drug compared to those with detectable drug (P < 0.001, log rank test). On multivariate analysis, a patient's decision to stop therapy was weakly associated and abnormal inflammatory biomarkers and detectable drug levels were both strongly and independently associated with a higher risk of relapse after drug discontinuation. CONCLUSION: Incidental finding of undetectable anti-TNF drug levels in patients with stable long-term deep remission may identify a subset of patients whose clinical remission is no longer dependent on anti-TNF treatment.

Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn's disease.

BACKGROUND: Adalimumab is an effective treatment for Crohn's disease (CD). Anti-adalimumab antibodies (AAA) and low trough serum drug concentrations have been implicated as pre-disposing factors for treatment failure. AIMS: To assess adalimumab and AAA serum levels, and to examine their association and discriminatory ability with clinical response and serum C-reactive protein (CRP). METHODS: We performed a cross-sectional study using trough sera from adalimumab-treated CD patients. Demographical data, Montreal classification, treatment regimen and clinical status were recorded. Serum adalimumab, AAA and CRP were measured. Receiver operating characteristic analysis and a multivariate regression model were performed to find drug and antibody thresholds for predicting disease activity at time of serum sampling. RESULTS: One hundred and eighteen trough serum samples were included from 71 patients. High adalimumab trough serum concentration was associated with disease remission (Area Under Curve 0.748, P < 0.001). A cut-off drug level of 5.85 µg/mL yielded optimal sensitivity, specificity and positive likelihood ratio for remission prediction (68%, 70.6% and 2.3, respectively). AAA were inversely related with adalimumab drug levels (Spearman's r = -0.411, P < 0.001) and when subdivided into categorical values, positively related with disease activity (P < 0.001). High drug levels and stricturing vs. penetrating or inflammatory phenotype, but not AAA levels, independently predicted disease remission in a multivariate logistic regression model. CONCLUSIONS: Adalimumab drug levels were inversely related to disease activity. High levels of anti-adalimumab antibodies were positively associated with disease activity, but this association was mediated mostly by adalimumab drug levels.

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.

Thiopurine metabolite ratios for monitoring therapy in pediatric Crohn disease.

OBJECTIVES: Thiopurines (azathioprine, 6-mercaptopurine) are a mainstay of treatment in Crohn disease (CD). Monitoring intracellular metabolite (6-thioguanine nucleotides [6-TGN] and 6-methylmercaptopurine [6-MMP]) levels can help optimize therapeutic efficacy and minimize potential toxicity. Determination of 6-MMP/6-TGN ratios may provide additional useful information, such as the identification of individuals with excessive thiopurine methyltransferase activity and disadvantageous 6-MMP overproduction. These patients are at increased risk of therapeutic failure and hepatotoxicity. The aim of the study was to evaluate the correlation of 6-MMP/6-TGN ratios with therapeutic efficacy and risk of hepatotoxicity in CD. METHODS: The present study was a single-center cross-sectional study including pediatric patients with CD studied prospectively with clinical and laboratory assessments along with serial measurements of 6-MMP and 6-TGN. Clinical response was determined using established clinical indices. RESULTS: The study included 238 pediatric patients with CD with a total of 1648 evaluation points. The patients were in steroid-free remission at 59.1% of the evaluation points. 6-MMP/6-TGN ratios of 4 to 24 were protective against relapse (odds ratio [OR] 0.52, 95% confidence interval [CI] -0.39 to 0.69, P = 0.001). Hepatotoxicity was associated with high 6-MMP levels (>3919  pmol/8 × 10 red blood cell count: OR 7.65, 95% CI 3.7-15.9, P = 0.001) and high 6-MMP/6-TGN ratios (>24: OR 5.35, 95% CI -3.43 to 8.43, P = 0.001). CONCLUSIONS: We observed significant associations between 6-MMP/6-TGN ratios and clinical response, and risk of hepatotoxicity. Our results suggest that determination of thiopurine metabolite ratios is a valuable tool for identification of patients at increased risk of therapeutic failure and hepatotoxicity.

Prior varicella zoster virus exposure in IBD patients treated by anti-TNFs and other immunomodulators: implications for serological testing and vaccination guidelines.

BACKGROUND: Varicella zoster virus (VZV) is a severe and preventable infection in immunosuppressed IBD patients. ECCO guidelines recommend VZV immunisation in patients with negative VZV exposure history. The value of patient-reported VZV exposure history for prediction of seropositivity in IBD patients remains unknown. Moreover, data on VZV immunity in adult IBD patients or accuracy of VZV serological testing under immunomodulator treatment is sparse. AIMS: The primary aim was to determine the prevalence of seropositivity for VZV-IgG in immunomodulator-treated IBD patients. A secondary aim was to establish the value of patient-reported history of past VZV infection for prediction of immunity, to validate the current vaccination strategy. METHODS: History of VZV-related illness was accessed by epidemiological questionnaire, and serological testing for VZV-IgG was performed. Serum anti-TNF medications levels were measured when applicable. RESULTS: One hundred twenty one IBD (86% Crohn's disease, mean age 37 ± 12.8) patients were included in the study. Immunomodulator therapy was received by 87% (anti-TNFs- 71%) of the patients. Previous exposure to VZV was reported by 104 patients, and 97/104 (93%) were VZV-IgG seropositive. Seventeen patients, all seropositive, reported negative exposure history. The calculated positive and negative predictive values for the reported history of VZV exposure were 93% and 0% respectively. CONCLUSIONS: Negative history of VZV exposure is a poor predictor of seronegativity. History-positive patients may still be seronegative and exposed to VZV infection. We suggest serological testing of all IBD patients with subsequent immunisation of the seronegative patients before initiation of immunosuppressive therapy.

The decline of anti-drug antibody titres after discontinuation of anti-TNFs: implications for predicting re-induction outcome in IBD.

BACKGROUND: Anti-drug antibodies can be elicited by infliximab and adalimumab, but the rate of their decay after therapy is stopped is unknown. AIM: To investigate the decline of anti-drug antibody titre after anti-TNF cessation, and to evaluate the clinical utility of anti-drug antibody measurement before anti-TNF re-induction. METHODS: Inflammatory bowel disease (IBD) patients who stopped anti-TNF therapy and had measurable anti-drug antibodies were prospectively followed up by serial blood measurements of antibodies levels. The clinical outcome of a second cohort of patients who received re-induction by infliximab or adalimumab after a drug holiday >4 months was determined vis-à-vis their anti-drug antibodies status before re-induction. RESULTS: The first cohort included 22 patients with anti-drug antibodies who were prospectively followed up after cessation of anti-TNF. Sixteen had antibodies-to-infliximab (ATI) and six had antibodies-to-adalimumab (ATA). ATI titres declined within 12 months to below detection levels in 13/16 infliximab-treated patients, whereas ATA titres became undetectable in only 2/6 adalimumab-treated patients (P = 0.04). The second cohort comprised 27 patients who resumed anti-TNFs (24 infliximab, 3 adalimumab). Of these, 3/5 patients with measurable anti-drug antibodies before re-induction experienced severe hypersensitivity reaction and/or nonresponse mandating drug-discontinuation, compared to 11/22 patients who were re-induced without measurable anti-drug antibodies (OR = 1.5, 95% CI 0.2-11, P = 0.7). CONCLUSIONS: Antibodies to infliximab titres decline to undetectable levels within one year of cessation of infliximab in the majority of patients, whereas antibodies to adalimumab seem to persist longer after adalimumab discontinuation. Measuring antibodies to infliximab prior to infliximab re-induction is probably of little clinical utility, especially if more than a 12-month drug-holiday has elapsed.

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

BACKGROUND: Patients treated with infliximab for Crohn's disease (CD) frequently require intensified dosage due to loss of response. There are scant data regarding the efficacy of shortening the dosing interval to 6 weeks. AIM: We sought to investigate the efficacy of a once every 6 weeks' strategy compared with dose-doubling. METHODS: This work was a multicentre retrospective study of infliximab-treated CD patients who required dose escalation. The clinical outcome of patients treated by intensification to 5 mg/kg/6 weeks (6-week group) was compared with the outcome of patients whose infliximab was double-dosed (10 mg/kg/8 weeks or 5 mg/kg/4 weeks). RESULTS: Ninety-four patients (mean age: 29.8 years) were included in the study, 55 (59%) in the 6-week group and 39 (41%) in the double-dose group. Demographics and disease characteristics were similar between the two groups, although patients with re-emerging symptoms 5-7 weeks postinfusion were more likely to receive 5 mg/kg/6 weeks dosing (OR: 3.4, 95% CI: 1.4-8.8, P < 0.01). Early response to dose-intensification occurred in 69% of patients in the 6-week group and 67% in the double-dose group (P = N.S.). Regained response was maintained for 12 months in 40% compared with 29% of the patients respectively (P = N.S.). CONCLUSION: In CD patients who lost response to standard infliximab dose, especially when symptoms re-emerge 5-7 weeks postinfusion, shortening the dosing interval to 6 weeks appears to be at least as effective as doubling the dose to 10 mg/kg or halving the infusion intervals to once in 4 weeks.

[Retinopathy of prematurity--risk factors].

Retinopathy of prematurity (ROP) was first described by Terry in 1942. ROP is considered a multifactorial disease. Low gestational age, low birth weight and oxygen therapy are recognized as risk factors for this condition. Other risk factors including multigestational pregnancy, white race, sepsis, NEC, BPD, intraventricular hemorrhage, lung maturation, steroid treatment, blood transfusions and light exposure were identified by multiple studies. We aim to review these studies in order to identify the independent risk factors for the development of ROP. The reviewed studies confirm that low birth weight, low gestational age, prolonged oxygen treatment and blood transfusions are statistically significant risk factors for the development of ROP. The incidence of all stages of ROP is similar for Caucasian and black infants, although the occurrence of threshold ROP was found higher in the Caucasian group. No relationship was demonstrated between light exposure and the development of ROP. The studies reviewed show decreased frequency and severity of ROP in neonates of mothers who had received antenatal steroid therapy. The findings concerning the influence of postnatal steroid treatment on the incidence of ROP are controversial.