Anti-tumor Necrosis Factor Biologics Research Articles

A192 EFFICACY OF USTEKINUMAB IN SMALL BOWEL STRICTURES OF FIBROSTENOTIC CROHN'S DISEASE AS ASSESSED BY INTESTINAL ULTRASOUND

Abstract Background Small bowel Crohn’s disease (CD) strictures can lead to debilitating obstructive symptoms and the deterioration of quality of life. Imaging modalities such as intestinal ultrasound (IUS) are invaluable in the diagnosis of strictures. The use of IUS in CD is rapidly growing, is cost-effective, easily repeatable, and similar in accuracy to magnetic resonance enterography. Evidence for medical management of fibrostenotic CD has been limited to anti-tumor necrosis factor biologics. Studies on the efficacy of other biologic therapies for strictures such as ustekinumab, a p40/interleukin 12 and 23 inhibitor, are lacking. Purpose The objective of this study was to evaluate the efficacy of ustekinumab in the treatment of small bowel strictures on IUS. Method This retrospective cohort study evaluated the IUS changes of terminal ileal (TI) CD strictures at baseline and 12 months following ustekinumab initiation from 2016 to 2020 at a single tertiary care center. Strictures identified were defined as 1) increased bowel wall thickness (BWT) > 3mm, 2) narrowed luminal apposition, and 3) presence of pre-stenotic dilation (PSD) or the inability to pass the colonoscope through the narrowed area. Changes in sonographic parameters (BWT, luminal size, PSD, length, hyperemia, inflammatory fat, dysfunctional peristalsis) were recorded at baseline prior to initiation of ustekinumab and compared 12 months after treatment. Differences from baseline to 12 months were paired within-person and statistical analysis was performed using paired T-tests for continuous variables and McNemar’s test for categorical variables. Result(s) Of the 18 patients identified, 55% (n = 10) were male, median age was 49 years (Q1-Q3: 33-63 years) at initial scan, with median CD duration of 10 years (Q1-Q3: 8-20 years). The majority of TI strictures were surgically naïve (67%, n = 12). Between pre- and 12-month post ustekinumab therapy scans, there was significant improvement in BWT [8.2 mm vs 7.2 mm, p = 0.048], however there was no significant difference in the presence of peri-enteric inflammatory fat (p = 0.10), mean stricture length (17.7 vs 21.7 cm, p = 0.18), and mean stricture lumen diameter (3.3 mm vs 2.7 mm, p = 0.44) (Table 1). There was also no significant difference in the presence of stricture-associated peri-enteric fat (89% vs 67%, p = 0.10), stricture-associated hyperemia (83% vs 89%, p = 0.65) or dysfunctional peristalsis (50% vs 61%, p = 0.41) (Table 1). Image Conclusion(s) Our study is the first to report the efficacy of ustekinumab in small bowel CD strictures using IUS at baseline and 12 months. This study shows that although ustekinumab leads to improvement in overall sonographic appearance of bowel thickness, it does not improve luminal narrowing nor PSD, two hallmark criteria of fibrostenosis. More extensive studies with larger sample sizes evaluating ustekinumab, or combination therapies, are required to identify their role in stricturing CD. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Utilization of Antitumor Necrosis Factor Biologics in Very Early Onset Inflammatory Bowel Disease: A Multicenter Retrospective Cohort Study From North America.

Research on the utilization and effectiveness of antitumor necrosis factor (TNF) biologics in children with very early onset inflammatory bowel disease (VEOIBD) is urgently needed. Here we describe anti-TNF use and durability in a multicenter cohort. We performed a retrospective cohort study of patients diagnosed with VEOIBD (<6 years) between 2008 and 2013 at 25 North American centers. We performed chart abstraction at diagnosis and 1, 3, and 5 years after diagnosis. We examined the rate of initiation and durability of infliximab and adalimumab and evaluated associations between treatment durability and the following covariates with multivariate Cox proportional hazard regression: age at diagnosis, sex, disease duration, disease classification, and presence of combined immunomodulatory treatment versus monotherapy. Of 294 children with VEOIBD, 120 initiated treatment with anti-TNF therapy and 101 had follow-up data recorded [50% Crohn disease (CD), 31% ulcerative colitis (UC), and 19% IBD unclassified (IBD-U)]. The cumulative probability of anti-TNF treatment was 15% at 1 year, 30% at 3 years, and 45% at 5 years from diagnosis; 56 (55%) were treated between 0 and 6 years old. Anti-TNF durability was 90% at 1 year, 75% at 3 years, and 55% at 5 years. The most common reason for discontinuation of anti-TNF were loss of response in 24 (57%) children. Children with UC/IBD-U had lower durability than those with CD (hazard ratio [HR] 0.17; 95% confidence interval [CI], 0.06-0.51; P = 0.001). Utilization and durability of anti-TNF in VEOIBD is relatively high and comparable with older children. Having Crohn disease (compared with UC/IBD-U) is associated with greater durability.

P512 Vedolizumab is effective in the prevention and treatment of postoperative recurrence in patients with Crohn′s disease

Abstract Background Vedolizumab (VDZ), an anti-integrin monoclonal antibody has demonstrated its efficacy in inducing and maintaining response in patients with luminal Crohn`s disease (CD). Postoperative recurrence (POR) affects over half of the patients with CD and currently, majority of these patients undergo surgery due to primary or secondary failure of anti-tumor necrosis factor (antiTNF) biologics. Thus, data on efficacy of other agents in this setting are needed. Considering the slow onset of action of VDZ together with its favorable safety profile in older and co-morbid patients, VDZ would represent a good candidate for preventing and treating POR but the data on its efficacy in this specific clinical situation are scarce. Therefore, the aim of this study was to evaluate the efficacy of VDZ in preventing and treating of Crohn`s disease postoperative recurrence. Methods In this retrospective single-center cohort study, we included all patients with CD treated with VDZ between May 2015 and August 2020. Patients who started with VDZ immediately postoperatively or continued from the pre-operative period (prevention of POR) or patients who started VDZ because of clinical or endoscopic POR (treatment of POR) with a minimal follow-up of one year were eligible for further analysis. The effect of VDZ was determined by Harvey-Bradshaw Index ≤ 4 in case of prevention of POR, or as any decrease of 3 or more points in case of treatment of POR. Endoscopic response was evaluated by Rutgeerts` score as any decrease of the score. All patients underwent the colonoscopy at 6 months postoperatively and further follow-up colonoscopy one year after treatment adjustment. Results In the defined period, a total of 54 patients with Crohn`s disease were treated with VDZ. Of these 54 patients, sixteen (11 women; median age 57 years, range 25–75) receive VDZ for prevention (6) or treatment (10) of postoperative recurrence. Six patients received first-line VDZ due to high risk profile for systemic biologics (age and/or co-morbidities), the remaining ten patients all had previously failed at least one anti-tumor necrosis factor biologic agent. During the median follow-up of 24 months (range 12 to 70), thirteen patients (81%) had clinical response or achieved remission, eleven (69%) had endoscopic response. Three patients with no response had to change the treatment to another biologic. Out thirteen responders, seven (54%) necessitated intensification of dosing regimen to every 4 or 6 weeks in order to achieve clinical and/or endoscopic response. Conclusion Vedolizumab is effective in preventing and treating of Crohn`s disease postoperative recurrence in a difficult-to-treat population of patients.

Biologic therapy for Crohn's disease over the last 3 decades.

BACKGROUNDDespite the overload of publications on Crohn’s disease (CD), no comprehensive analysis of biologic therapy for CD has been reported.AIMTo determine knowledge gaps and identify areas of interest of biologic therapy for CD.METHODSThe top 100 highest-cited original articles were identified from January 1991 to December 2020 in the Clarivate Analytics Web of Science Core Collection database. We conducted a bibliometric analysis of biologic therapy for CD based on total citations, summarized the bibliographic information of the articles related to CD biologic therapy, and explored the research hotspots.RESULTSThe top 100 highest-cited original articles were identified with total citations ranging from 307 to 2978. The 2000s (Period II, n = 66) yielded the most influential original articles and saw the most dramatic growth. Among the top 10 countries, including 8 European countries and 2 North American countries, the United States (n = 37) and Belgium (n = 20) contributed the most publications. Among the top 10 institutions, the University Hospital Gasthuisberg in Belgium (n = 23), the University of Chicago in the United States (n = 20), and the Mayo Clinic in the United States (n = 17) published the most papers. Regarding authors, Rutgeerts P in Belgium (n = 32), Sandborn WJ in the United States (n = 23), and Feagan BG in Canada (n = 18) published the highest number of studies. The cooperation relationships between the United States and Europe were most frequent. Gastroenterology (impact factor = 22.682) published the most articles on biologic therapy for CD (n = 32) with 17654 total citations. Anti-tumor necrosis factor biologics and monoclonal antibodies were the most studied topics.CONCLUSIONThe bibliometric analysis emphasized the key contributions to the development of the specialized field. These data would provide useful research insights into biologic therapy for CD for clinicians and researchers.

Effect of listing strategies on utilization of antitumor necrosis factor biologics infliximab and etanercept: a cross-sectional analysis from Ontario, Canada

BACKGROUND: Use of costly biologic drugs for the treatment of chronic inflammatory diseases has increased significantly in recent years. However, biosimilar drugs offer an opportunity to ensure health system sustainability with robust uptake. OBJECTIVE: To study the effect of formulary listing strategies on the use of infliximab and etanercept innovator and biosimilar biologics. METHODS: This is a cross-sectional study of individuals in Ontario, Canada, dispensed a biologic prescription for infliximab or etanercept through Ontario's public drug program between January 1, 2010, and June 30, 2019. Quarterly utilization and costs were forecasted using Holt-Winters' exponential smoothing models to the second quarter (Q2) of 2022. Secondary analyses explored utilization for rheumatic conditions (RC) and inflammatory bowel disease (IBD). RESULTS: From Q1 2010 to Q2 2019, infliximab and etanercept users increased by 75.7% (n = 4,073 to 7,158), with a forecasted increase of 13.7% (n = 8,142; 95% CI = 7,438-8,847) by Q2 2022. Biosimilar users represented 13.8% (n = 539 of 3,905) of total infliximab users in Q2 2019, although this differed by indication with 6.9% for IBD (n = 187 of 2,712) and 26.6% for RC (n = 203 of 764). Etanercept biosimilar users represented 20.2% (n = 659 of 3,256) of total etanercept users for RC in Q2 2019. Biologics expenditures increased 109.7% during the study, amounting to $49.9 million in Q2 2019. CONCLUSIONS: Despite differing reimbursement restrictions between innovator infliximab and etanercept biologics, the uptake of their biosimilars was low and not noticeably different in the treatment of RC. Dynamic policy strategies are needed to improve the uptake of biosimilars, particularly for IBD. DISCLOSURES: Funding for this study was contributed by the Ontario Ministry of Health. The authors have no conflicts of interest to disclose.

Comparative Analysis of 3-Year Persistence With Vedolizumab Compared With Antibodies Against Tumor Necrosis Factor-Alpha in Patients With Inflammatory Bowel Disease in Germany: Retrospective Analysis of a Large Prescription Database.

The goal of the study was to compare persistence with vedolizumab versus adalimumab, golimumab, and infliximab in biologics-naïve patients with inflammatory bowel disease treated in gastroenterological practices and outpatient clinics in Germany. Patients aged 18 or older who had initiated a biological therapy (vedolizumab, infliximab, adalimumab, or golimumab) were included in the present study. Prescriptions between July 2014 and March 2017 of the respective biological drug emerging from gastroenterological practices or outpatient clinics in Germany were retrieved from the longitudinal prescription (LRx) database. Patients treated with vedolizumab were matched with patients treated with infliximab, adalimumab, or golimumab on the basis of age, gender, medication before biologic therapy, and index year. The primary outcome variable of the study was the rate of persistence with vedolizumab compared with antitumor necrosis factor biologics (infliximab, adalimumab, and golimumab) within 3 years of the first prescription in outpatient settings. Kaplan-Meier analysis was performed in 15,984 patients naïve to biologics revealing the statistically lower risk of discontinuation for vedolizumab compared with adalimumab, golimumab, or infliximab. In matched-pairs analyses, within 3 years after the first prescription, 39.5% of 2076 patients were persistent to vedolizumab compared with 33.5% of matched patients persistent to adalimumab (P<0.001). 37.6% of 716 patients were persistent to vedolizumab compared with 24.7% of matched patients persistent to golimumab (P<0.001). 35.7% of 2055 patients were persistent to vedolizumab compared with 30.2% of matched patients persistent to infliximab (P=0.119). Vedolizumab was associated with a significantly lower risk of therapy discontinuation compared with adalimumab [hazard ratio (HR)=0.86; 95% confidence interval (CI), 0.81-0.93] and golimumab (HR=0.60; 95% CI, 0.54-0.67), respectively; the vedolizumab risk of therapy discontinuation was numerically lower than infliximab but statistical significance was not achieved (HR=0.93; 95% CI, 0.85-1.02). In biologics-naïve IBD patients treated in outpatient settings in Germany, matched-pair analyses showed that vedolizumab was associated with significantly improved drug persistence compared with adalimumab or golimumab, whereas numerical improvement was shown in comparison with infliximab.

5-Aminosalicylic acid intolerance is associated with a risk of adverse clinical outcomes and dysbiosis in patients with ulcerative colitis.

Background/Aims5-Aminosalicylic acid (ASA) causes intolerance reactions in some patients. This study was performed to examine the prognosis of patients with ulcerative colitis (UC) and 5-ASA intolerance, and to evaluate the potential interaction between 5-ASA intolerance and the intestinal microbiota.MethodsWe performed a retrospective cohort study of patients with UC who visited participating hospitals. The primary endpoint was to compare the incidence of hospitalization within 12 months between the 5-ASA intolerance group and the 5-ASA tolerance group. The secondary endpoint was to compare the risk of adverse clinical outcomes after the start of biologics between the 2 groups. We also assessed the correlation between 5-ASA intolerance and microbial change in an independently recruited cohort of patients with UC.ResultsOf 793 patients, 59 (7.4%) were assigned to the 5-ASA intolerance group and 734 (92.5%) were assigned to the 5-ASA tolerance group. The admission rate and incidence of corticosteroid use were significantly higher in the intolerance than tolerance group (P< 0.001). In 108 patients undergoing treatment with anti-tumor necrosis factor biologics, 5-ASA intolerance increased the incidence of additional induction therapy after starting biologics (P< 0.001). The 5-ASA intolerance group had a greater abundance of bacteria in the genera Faecalibacterium, Streptococcus, and Clostridium than the 5-ASA tolerance group (P< 0.05).ConclusionsIn patients with UC, 5-ASA intolerance is associated with a risk of adverse clinical outcomes and dysbiosis. Bacterial therapeutic optimization of 5-ASA administration may be important for improving the prognosis of patients with UC.

Positive pharmacokinetic effect of azathioprine co-medication on infliximab trough levels is dose-dependent

BackgroundThiopurines seem to have positive effect on the pharmacokinetics of anti-tumor necrosis factor biologics. It has been suggested that a reduced dose of thiopurines is sufficient to achieve this synergism. AimsTo assess the differences of infliximab (IFX) trough levels according to the dose of concomitantly used azathioprine (AZA). Patients & methodsAll IBD patients treated with IFX (Remicade®) in two IBD centres between November 2015 and April 2017 were eligible. Infliximab trough levels were assessed by ELISA (Ridascreen®, R-Biopharm). The differences in IFX trough levels according to AZA dose were analyzed statistically. ResultsIn total, 125 patients were included, 42 pts (33.6%) on infliximab monotherapy, 83 pts (66.4%) using combined immune suppression.The respective median IFX levels according to AZA dose were as follows: group 1 (no concomitant AZA) 2.83 μg/ml (range 0–12); group 2 (AZA dose less than 1 mg/kg) 4.91 μg/ml (range 0.09–15.36); group 3 (AZA dose 1 < 2 mg/kg) 5.67 (range 0.16–16.97); group 4 (AZA dose above 2 mg/kg) 7.53 μg/ml (range 1.15–8.73). The differences in IFX trough levels between the respective groups according to AZA dose were statistically significant (p = 0.0159). ConclusionThe positive effect of azathioprine on infliximab levels seems to be dependent on the dose of concomitantly used azathioprine.

P060 COMBINATION THERAPY WITH TNF-INHIBITORS AND IMMUNOMODULATORS ARE ASSOCIATED WITH SHORTER DURATION TO FIRST SERIOUS INFECTION – THE DEVELOP EXPERIENCE

DEVELOP is a multicenter, international, prospective, observational registry of the long-term safety and clinical status of 6070 pediatric patients (pts) with inflammatory bowel disease (IBD) diagnosed prior to 18 years of age who were treated with anti-tumor necrosis factor biologics (aTNF) and/or other medical therapies for IBD. Our aim was to assess the risk factors that lead to first serious infection (SI): an infection requiring hospitalization and/or IV therapy. Physicians participating in the registry prescribe IBD treatments based on their usual clinical practice and standards of care. Pts are categorized into cohorts according to their IBD medication exposure representing prevalent or incident exposure. The registry started enrollment in 2007 and completed enrollment in 2017. After the initial enrollment visit, data are obtained by the registry physician or designee every 6 months. SI data includes infections that occurred within 91 days of exposure to aTNF relative to non-biologics. The most recent available data cut (June 30 2018) includes 33586 patient years (PY) of follow up in the registry. The analysis of the stepwise Cox regression model for time to first SI among aTNF only pts relative to the non-biologics cohort included 3,566 Crohn’s disease (CD) pts who had at least 1 post-baseline follow-up visit, complete baseline covariate data, and complete disease severity data at event. Covariates that were significantly associated with a shorter duration of time to first SI within 91 days of aTNF exposure (Table 1) included: PCDAI Score (Moderate to Severe vs. Inactive) monotherapy with corticosteroids (CS) combination therapy with aTNF and immunomodulators (IMM), Hospitalization in the year prior to enrollment monotherapy with aTNF, PCDAI Score (Mild vs. Inactive) Female gender Time since IBD was diagnosed The analysis of the stepwise Cox regression model included 1063 ulcerative colitis (UC) pts who also had at least 1 post-baseline follow-up visit, complete baseline covariate data, and complete disease severity data at event. The covariates that were significantly associated with shorter duration of time to first SI (Table 2) included: Monotherapy with CS Monotherapy with aTNF Hospitalization in the year prior to enrollment Partial Mayo Score (Mild vs. Inactive) Combination therapy with aTNF and IMM In CD pts, combination therapy with aTNF/IMM, monotherapy with aTNF or CS, disease severity, recent hospitalization, gender, length of diagnosis and geographic region were all significantly associated with shorter duration of time to first SI. In UC pts, only monotherapy with aTNF or CS, combination therapy with aTNF and IMM, disease severity and recent hospitalization were significantly associated with shorter duration of time to first SI.

02 NEW ONSET AUTOIMMUNE DISORDERS, PRIMARILY PSORIASIS, IN ANTI-TNF BIOLOGIC EXPOSED PEDIATRIC PATIENTS – THE DEVELOP EXPERIENCE

DEVELOP is a multicenter, prospective, observational registry of the long-term safety and clinical outcomes of 6070 pediatric patients with inflammatory bowel disease (IBD; Crohn’s disease, ulcerative colitis, or indeterminate colitis) treated with anti-tumor necrosis factor biologics (aTNF) and/or other medical therapies for IBD as part of routine clinical care. DEVELOP has sites in the United States, Canada and the European Union (EU). Our aim was to characterize the incidence of new autoimmune disorders in a pediatric IBD population exposed to aTNF compared to a population exposed only to non-biologics. Physicians participating in the registry prescribe IBD treatments based on their usual clinical practice and standards of care. Patients are categorized into cohorts according to their prevalent or incident medication exposure, including patients receiving therapy prior to enrollment and/or during registry follow-up. The most recent available data cut (June 30 2018) includes 21083 patient-years (PY) of follow up in the aTNF cohort and 11277 PY in the non-biologics cohort. Investigators record all new autoimmune disorders in the study database during biannual visits. Among all IBD patients, the incidence of all new autoimmune disorders was statistically significantly greater in the aTNF cohort (0.99 events/100 PY) than the nonbiologics cohort (0.27 events/100 PY) (Table 1). These results were driven by new-onset psoriasis (0.58 events/100 PY), the most frequently reported new autoimmune disorder in the aTNF cohort compared to 0.02 new psoriasis events/100 PY in the non-biologics cohort. The incidence of serious new autoimmune disorders was low in both the aTNF cohort (0.20 events/100 PY) and the non-biologics cohort (0.07 events/100 PY). In the aTNF cohort, serious new autoimmune disorders by preferred term that occurred more than once included the following: Psoriasis (0.06 events per 100 PY, n=12 events), Sclerosing Cholangitis (0.02 events per 100 PY, n=4) Lupus-like syndrome (0.02 events per 100 PY, n=4) Optic neuritis (0.01 events per 100 PY, n=3), Autoimmune hepatitis (0.01 events per 100 PY, n=3) In the non-biologics cohort, there were no reports of serious adverse events of psoriasis, optic neuritis, or lupus-like syndrome, one report (0.01 events/100 PY) each of serious autoimmune hepatitis and juvenile idiopathic arthritis and two cases of sclerosing cholangitis (0.02 events/100 PY). New autoimmune disorders were noted approximately once every 100 patient years in the aTNF cohort and were significantly more common compared to the non-biologic cohort. New serious autoimmune disorders in the aTNF cohort were uncommon, with only 0.20 new events per 100 PY. New autoimmune disorders do arise in aTNF treated pediatric IBD patients but overall are uncommon and not serious.

02 NEW ONSET AUTOIMMUNE DISORDERS, PRIMARILY PSORIASIS, IN ANTI-TNF BIOLOGIC EXPOSED PEDIATRIC PATIENTS – THE DEVELOP EXPERIENCE

DEVELOP is a multicenter, prospective, observational registry of the long-term safety and clinical outcomes of 6070 pediatric patients with inflammatory bowel disease (IBD; Crohn’s disease, ulcerative colitis, or indeterminate colitis) treated with anti-tumor necrosis factor biologics (aTNF) and/or other medical therapies for IBD as part of routine clinical care. DEVELOP has sites in the United States, Canada and the European Union (EU). Our aim was to characterize the incidence of new autoimmune disorders in a pediatric IBD population exposed to aTNF compared to a population exposed only to non-biologics. Physicians participating in the registry prescribe IBD treatments based on their usual clinical practice and standards of care. Patients are categorized into cohorts according to their prevalent or incident medication exposure, including patients receiving therapy prior to enrollment and/or during registry follow-up. The most recent available data cut (June 30 2018) includes 21083 patient-years (PY) of follow up in the aTNF cohort and 11277 PY in the non-biologics cohort. Investigators record all new autoimmune disorders in the study database during biannual visits. Among all IBD patients, the incidence of all new autoimmune disorders was statistically significantly greater in the aTNF cohort (0.99 events/100 PY) than the nonbiologics cohort (0.27 events/100 PY) (Table 1). These results were driven by new-onset psoriasis (0.58 events/100 PY), the most frequently reported new autoimmune disorder in the aTNF cohort compared to 0.02 new psoriasis events/100 PY in the non-biologics cohort. The incidence of serious new autoimmune disorders was low in both the aTNF cohort (0.20 events/100 PY) and the non-biologics cohort (0.07 events/100 PY). In the aTNF cohort, serious new autoimmune disorders by preferred term that occurred more than once included the following:Psoriasis (0.06 events per 100 PY, n=12 events),Sclerosing Cholangitis (0.02 events per 100 PY, n=4)Lupus-like syndrome (0.02 events per 100 PY, n=4)Optic neuritis (0.01 events per 100 PY, n=3),Autoimmune hepatitis (0.01 events per 100 PY, n=3) In the non-biologics cohort, there were no reports of serious adverse events of psoriasis, optic neuritis, or lupus-like syndrome, one report (0.01 events/100 PY) each of serious autoimmune hepatitis and juvenile idiopathic arthritis and two cases of sclerosing cholangitis (0.02 events/100 PY). New autoimmune disorders were noted approximately once every 100 patient years in the aTNF cohort and were significantly more common compared to the non-biologic cohort. New serious autoimmune disorders in the aTNF cohort were uncommon, with only 0.20 new events per 100 PY. New autoimmune disorders do arise in aTNF treated pediatric IBD patients but overall are uncommon and not serious.

Neuroimmunology and rheumatology: overlap and differential diagnoses

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are chronic inflammatory diseases of the central nervous system (CNS). They may cause inflammation in the brain, spinal cord and optic nerve. Both conditions must be differentiated from CNS manifestations of other systemic autoimmune diseases such as systemic lupus erythematosus (SLE), Sjögren's syndrome, autoinflammtory diseases and sarcoidosis, since amongst others myelitis and optic nerve inflammation may also occur in these conditions. Nevertheless, coexistence of MS or NMOSD with rheumatic disorders such as SLE or Sjögren's syndrome has also been reported especially in NMOSD. Since the therapeutic approach is different it is important to determine aclear diagnosis. In addition some drugs used in rheumatic disease such as anti-tumor necrosis factor biologics may induce inflammatory disease of the CNS and should be avoided in MS. An interdisciplinary approach between neuroimmunology and rheumatology is important for optimal care and treatment in such patients.

Excessive Weight Gain Is Associated with an Increased Risk for Pouch Failure in Patients with Restorative Proctocolectomy

The aim was to evaluate the impact of weight gain on pouch outcomes after ileostomy closure. Consecutive inflammatory bowel disease patients with ileal pouches followed up at our subspecialty Pouch Center from 2002 to 2011 were studied. The association of excessive weight gain (defined as a 15% increase the index weight) with pouch outcomes were evaluated using univariate and multivariate analyses. A total of 846 patients met inclusion criteria, with 470 (55.6%) being men. The mean age at the diagnosis of inflammatory bowel disease and at pouch surgery was 27.2 ± 11.9 years and 37.8 ± 12.8 years, respectively. Patients with weight gain more likely had mechanical or surgical complications of the pouch (18.4% versus 12.3%, P = 0.049), Crohn's disease of the pouch (30.6% versus 18.5%, P = 0.001), Pouch Center visits (2.0 [1.0-4.0] versus 2.0 [1.0-3.0], P = 0.008), and postoperative pouch-related hospitalization (21.1% versus 10.6%, P < 0.001). After a median follow-up of 9.0 (interquartile range = 4.0-14.0) years, 68 patients (8.0%) developed pouch failure. In the multivariate analysis, excessive weight gain was an independent risk factor for pouch failure with a hazard ratio of 1.69 (95% confidence interval = 1.01-2.84, P = 0.048) after adjusting for preoperative or postoperative use of anti-tumor necrosis factor biologics, postoperative use of immunosuppressants, Crohn's disease of the pouch, mechanical or surgical complications of the pouch, and postoperative pouch-associated hospitalization. Excessive weight gain after closure of the ileostomy is associated with worse pouch outcomes in patients with inflammatory bowel disease. Appropriate weight control may help improve pouch retention.

Immunosuppressive Therapy Does Not Increase Operative Morbidity in Patients With Crohn’s Disease

The aim of this study was to examine the impact of immunosuppressive therapy on the morbidity of intestinal surgery in patients with Crohn's disease. An increasing number of immunomodulating agents are being used in the treatment of Crohn's disease. The effect of these medications on surgical morbidity is controversial. We performed a retrospective review of our prospectively maintained database of patients with Crohn's disease who underwent intestinal surgery between June 1999 and May 2010. The effect of perioperative immunomodulation on postoperative outcomes, specifically anastomotic complications, was evaluated. Predictors of postoperative morbidity among demographic and surgical variables were identified. Length of hospitalization and rate of hospital readmission were compared between groups. Comparisons were made using Student t test and Fisher exact test. One hundred ninety-six intestinal procedures were performed. One hundred twenty-seven (64.8%) of these were performed among patients who received perioperative immunomodulation. Forty-six (23.5%) procedures were in patients who received >1 immunomodulating medication perioperatively. Complications occurred in 45 (23.0%) cases. There were 20 (10.2%) anastomotic complications, including 8 (4.1%) intra-abdominal abscesses, 8 (4.1%) anastomotic leaks, and 4 (2%) enterocutaneous fistulas. Preoperative treatment with steroids (P=0.21), 6-MP (P=0.10), and anti-tumor necrosis factor biologics (P=1.0) was not associated with increased postoperative anastomotic complications. Combination immunosuppressive therapy also did not increase morbidity (P=0.39). In our series, single agent and combination immunosuppressive therapy given around the time of intestinal surgery did not increase the incidence of surgical complications in patients with Crohn's disease.

SAT0100 Bone marrow OEDEMA is more associated with rapid radiographic progression than synovitis or bone erosion by using low field MRI in bio-naïve rheumatoid arthritis patients treated with adalimumab and methotrexate combination therapy

BackgroundRapid radiographic progression (RRP) has occurred in some rheumatoid arthritis (RA) patients regardless of any type of biological therapy. However, early diagnosis of RRP is still unknown.ObjectivesThe aim of this...

Endoscopic Features Associated with Ileal Pouch Failure

Endoscopic features as predictors in pouch failure have not been studied. A well-constructed J-pouch typically has an "owl's eye" appearance in the proximal pouch body. We hypothesized that loss of the owl's eyes is associated with a high risk for pouch failure. The aim of this study was to evaluate the association between the distorted endoscopic appearance of owl's eyes and pouch failure. A total of 711 available pouch endoscopic images from 426 J-pouch patients were reviewed and scored blindly. A scoring system was generated for distorted owl's eyes. Multivariable analyses were performed to assess the link between the endoscopic feature or other variables and pouch failure. A total of 37 patients (8.7%) developed pouch failure, with a median of 5.0 (interquartile range, 2.0-11.0) years of follow-up. Multivariable analyses showed that 2 or more "beak" abnormalities were associated with failure rates of 33.3%, 44.4%, and 72.2% by 5, 10, and 15 years of ileal pouch-anal anastomosis, respectively (hazard ratio = 3.7; 95% confidence interval, 1.5-9.0). In addition, diagnosis of Crohn's disease or surgical complications, the postoperative use of anti-tumor necrosis factor biologics, and a high cuff endoscopy inflammation score had statistically significant hazard ratios of 3.2, 5.8, and 1.5 for pouch failure, respectively. Distorted appearance of "beak" portion of owl's eyes along with Crohn's disease of the pouch or surgery-related complications, postoperative use of biologics, and persistent cuffitis were the risk factors associated with pouch failure. The assessment of endoscopic owl's eye structure may provide an additional clue to predict pouch outcome.

Maximizing early treatment with biologics in patients with rheumatoid arthritis: the ultimate breakthrough in joints preservation

Rheumatoid arthritis (RA) is a chronic, systemic, progressive inflammatory disease that, if left untreated, can lead to irreversible joint damage and serious disability. In Central and Eastern Europe, RA treatment varies widely, partly due to economic factors, restrictive treatment guidelines, and access to practicing rheumatologists. The recent treatment paradigm shift of treating to target in RA with early, aggressive therapy has proven to be a successful strategy for achieving optimal clinical outcomes. Several clinical studies demonstrate that utilizing this strategy with anti-tumor necrosis factor biologics leads to improved clinical, radiographic, and functional outcomes. Patient education is also a critical component of the treating to target strategy, and the patient's version of the treat-to-target recommendations is an important tool for successful implementation. This review discusses the evidence for the treat-to-target approach and describes areas to improve the disparity of treatment between patients in Western European compared with Central and Eastern European countries.

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Switching to the anti-interleukin-6 receptor antibody tocilizumab in rheumatoid arthritis patients refractory to antitumor necrosis factor biologics

We evaluated the short-term effects of the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) in six patients with rheumatoid arthritis (RA) who had been refractory to tumor necrosis factor (TNF) antagonist therapy. All subjects were considered to be secondary nonresponders to TNF antagonists as decided by each physician. The Disease Activity Score of 28 Joints (DAS28) appeared to improve slowly by TCZ compared with TNF antagonist therapy, but significantly decreased at 24 weeks. One patient achieved DAS28 remission [DAS28–erythrocyte sedimentation rate (ESR) <2.60, and 5 of 6 patients showed good or moderate clinical response. The change in the clinical Disease Activity Index was similar to that of the DAS28–ESR. The serum level of matrix metalloproteinase-3 (MMP-3), a marker for synovial overgrowth, also significantly decreased after the treatment (518 ± 567 at baseline, 141 ± 90 ng/ml at 24 weeks, p < 0.05). One patient discontinued TCZ because of tuberculous peritonitis. Although physicians need to watch for infectious adverse events, these data indicate that TCZ is effective for treating RA patients refractory to TNF antagonists.

Switching to the anti-interleukin-6 receptor antibody tocilizumab in rheumatoid arthritis patients refractory to antitumor necrosis factor biologics

We evaluated the short-term effects of the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) in six patients with rheumatoid arthritis (RA) who had been refractory to tumor necrosis factor (TNF) antagonist therapy. All subjects were considered to be secondary nonresponders to TNF antagonists as decided by each physician. The Disease Activity Score of 28 Joints (DAS28) appeared to improve slowly by TCZ compared with TNF antagonist therapy, but significantly decreased at 24 weeks. One patient achieved DAS28 remission [DAS28-erythrocyte sedimentation rate (ESR) <2.60, and 5 of 6 patients showed good or moderate clinical response. The change in the clinical Disease Activity Index was similar to that of the DAS28-ESR. The serum level of matrix metalloproteinase-3 (MMP-3), a marker for synovial overgrowth, also significantly decreased after the treatment (518 +/- 567 at baseline, 141 +/- 90 ng/ml at 24 weeks, p < 0.05). One patient discontinued TCZ because of tuberculous peritonitis. Although physicians need to watch for infectious adverse events, these data indicate that TCZ is effective for treating RA patients refractory to TNF antagonists.