Prebiologic Era Research Articles

Clinical and laboratory features of juvenile idiopathic arthritis with wrist involvement: Results of a retrospective cohort study.

Previous studies in the pre-biological era showed an association of wrist inflammation in juvenile idiopathic arthritis (JIA) with progressive disease course, polyarticular involvement and failure of methotrexate treatment. To describe features of JIA, associated with wrist arthritis. Data from about 753 JIA patients were included in this retrospective cohort study. The clinical and laboratory features of patients with and without wrist involvement were analyzed. Wrist involvement was found in oligoarthritis (5.8%), RF(-)/RF(+) polyarthritis (44.9%/15.0%), enthesitis-related arthritis (17.7%), and systemic (58.6%) JIA categories. Unilateral wrist involvement was typical for oligoarthritis patients, bilateral involvement was either equal to that of unilateral involvement or was more frequent in other categories. Wrist arthritis was found to be associated with female sex, a low incidence of uveitis, and more indications of systemic inflammation, including elevated levels of C-reactive protein, erythrocyte sedimentation rate, and platelets, as well as involvement of the cervical spine, temporomandibular, shoulder, elbow, metacarpophalangeal, proximal interphalangeal, distal interphalangeal, hip, ankle, and tarsus arthritis. The number of patients with hip osteoarthritis and hip replacement was also higher. Wrist arthritis was associated with a lower probability of achieving remission [hazard ratio (HR) = 1.3 (95%CI: 1.0-1.7), P = 0.055], and a higher probability of being treated with biologics [HR = 1.7 (95%CI: 1.3-2.10, P = 0.00009)]. Wrist arthritis in JIA patients is a marker of a severe disease course, characterized by more intensive inflammation, unfavorable outcomes, and. requiring more intensive treatment with early administration of biologics. Close monitoring of wrist inflammation with ultrasound and MR assessment with early biological treatment might improve the outcomes.

Modern practical management of acute severe colitis.

Acute severe ulcerative colitis (ASUC) is one of life-threatening complications that occur in one-fifth of ulcerative colitis (UC) patients with significant morbidity and an estimated mortality rate up to 1%. There are no validated clinical scoring systems for ASUC. Intravenous corticosteroids remain the cornerstone for the management of ASUC patients However, one-third of patients are steroid refractory and require colectomy in the pre-biologic era or salvage therapy in the post-biologic era. The currently available predictors of non-response to steroids and salvages therapy are sub-optimal. Furthermore, there is a need for the development of clear outcome measures for ASUC patients. Although infliximab and cyclosporin are both effective as salvage therapy, they still carry a rate of treatment failure. Hence, there is an unmet need to explore alternative therapeutic options before colectomy particularly in prior infliximab-exposed patients. This may include the introduction of small molecules with rapid onset of action as a salvage or sequential therapy and the use of slow-onset other biological therapy after "bridging" with cyclosporine. In this article, we explore the current best evidence-based practice and detail the gaps in knowledge in the management of ASUC.

The long-term effect on surgery-free survival of biological compared to conventional therapy in Crohn’s disease in real world-data: a retrospective study

BackgroundThe introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term.This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn’s disease (CD) who were never with the surgical option.MethodsThis is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L’Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population.ResultsTwo hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01–8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69–6.44).ConclusionThis study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection.

The Impact of Biologic Therapies on Rate of Colectomy in Paediatric-onset Ulcerative Colitis - A Population-Based Cohort Study

AimBiologic therapies have been associated with reduced rate of colectomy in ulcerative colitis (UC) in adults, but data are limited in paediatric-onset UC. Our aim was to define the rate of colectomy in paediatric-onset UC, including post-transition into adult care, and to evaluate the impact of biologic therapies on rate of colectomy. MethodAll prevalent patients diagnosed with paediatric-onset UC in South-East Scotland were identified from a prospectively accrued database at our regional tertiary centre. Patients exposed to biologics or surgery were identified and further data collected from health records. Kaplan–Meier analysis was used to calculate cumulative risk of colectomy over time. Results145 prevalent patients were identified between 2000 and 2021. Median follow-up was 7.9 years (IQR 4.1–13.1). 23 patients (16 %) underwent a colectomy. 50/145 (34 %) patients received biologic therapy, and 13/23 (57 %) patients who underwent colectomy received biologics. The cumulative risk of colectomy across the whole cohort at 1, 5, and 10 years was 3 %, 13 % and 16 %, respectively. Patients exposed to biologics had a higher colectomy rate at 5 and 10 years (22 % and 34 %). Patients in the pre-biologic era (2000–2008) had non-significantly reduced time from diagnosis to colectomy (2.4 vs 3.7 years, p = 0.204). ConclusionWe have defined the 1-, 5-, and 10-year colectomy rate in a population-based cohort of Paediatric-onset UC patients. Patients who received biologic therapy had a significantly increased risk of colectomy. Increased severity of disease in these patients may account for the greater colectomy risk. Level of EvidenceLevel 1.

P27 A case of unilateral scleritis and biopsy proven retinal vasculitis in an elderly woman with rheumatoid arthritis and previous retinal detachment surgery with silicone oil band

P27 A case of unilateral scleritis and biopsy proven retinal vasculitis in an elderly woman with rheumatoid arthritis and previous retinal detachment surgery with silicone oil band

Treatment strategy changes for inflammatory bowel diseases in biologic era: results from a multicenter cohort in Japan, Far East 1000

Many molecular targeted agents, including biologics, have emerged for inflammatory bowel diseases (IBD), but their high prices have prevented their widespread use. This study aimed to reveal the changes in patient characteristics and the therapeutic strategies of IBD before and after the implementation of biologics in Japan, where the unique health insurance system allows patients with IBD and physicians to select drugs with minimum patient expenses. The analysis was performed using a prospective cohort, including IBD expert and nonexpert hospitals in Japan. In this study, patients were classified into two groups according to the year of diagnosis based on infliximab implementation as the prebiologic and biologic era groups. The characteristics of therapeutic strategies in both groups were evaluated using association analysis. This study analyzed 542 ulcerative colitis (UC) and 186 Crohn’s disease (CD). The biologic era included 53.3% of patients with UC and 76.2% with CD, respectively. The age of UC (33.9 years vs. 38.8 years, P < 0.001) or CD diagnosis (24.3 years vs. 31.9 years, P < 0.001) was significantly higher in the biologic era group. The association analysis of patients with multiple drug usage histories revealed that patients in the prebiologic era group selected anti-tumor necrosis factor (TNF)-α agents, whereas those in the biologic era group preferred biologic agents with different mechanisms other than anti-TNF-α. In conclusion, this study demonstrated that both patient characteristics and treatment preferences in IBD have changed before and after biologic implementation.

Clinically Established Temporomandibular Involvement in Adults With Juvenile Idiopathic Arthritis.

To study clinical variables defining temporomandibular function in adults with juvenile idiopathic arthritis (JIA) and healthy controls. In this cross-sectional study, the temporomandibular joint (TMJ) screening protocol, mandibular range of motion (MROM), and anterior maximum voluntary bite force (AMVBF) were compared between adults with JIA and healthy controls. Unadjusted and adjusted models with corrections for sex and disease duration were constructed for active maximum interincisal mouth opening (AMIO) and AMVBF. A total of 100 adults with JIA and 59 healthy adults were included in this study. In adults with JIA, 56% had clinically established TMJ involvement. AMIO was the MROM variable most reduced by TMJ involvement; AMIO was 8.8 mm (95% CI -11.40 to -6.12; P < 0.001) less in adults with JIA with TMJ involvement compared to JIA without TMJ involvement. No differences of AMIO were found between healthy adults and adults with JIA without TMJ involvement (-2.52, 95% CI -5.13 to 0.10; P = 0.06). Male sex was associated with a higher AMIO, and disease duration was associated with a decreased AMIO. Collinearity between the subtype prebiologic era and disease duration was found. AMVBF did not differ between adults with JIA and healthy adults. The high prevalence of clinically established TMJ involvement in adults with JIA indicates the need for awareness of TMJ problems in adults with JIA. TMJ involvement negatively influenced AMIO and should therefore be part of the TMJ screening in adults with JIA. AMVBF seems to have less utility for TMJ screening in adult populations.

Predictors of pouch failure: A tertiary care inflammatory bowel disease centre experience.

Rates of pouch failure after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) range from 5% to 18%. There is little consistency across studies regarding the factors associated with failure, and most include patients who underwent IPAA in the pre-biologic era. Our aim was to analyse a cohort of patients who underwent IPAA in the biologic era at a large-volume inflammatory bowel disease institution to better determine preoperative, perioperative and postoperative factors associated with pouch failure. A retrospective cohort analysis was performed with data from an institutional review board approved prospective database with ulcerative colitis or unclassified inflammatory bowel disease patients who underwent total proctocolectomy with IPAA at Mount Sinai Hospital between 2008 and 2017. Preoperative, perioperative and postoperative data were collected and univariate and multivariate analyses were performed to identify factors associated with increased risk of pouch failure. Out of 664 patients included in the study, pouch failure occurred in 41 (6.2%) patients, a median of 23.3 months after final surgical stage. Of these, 17 (41.4%) underwent pouch excision and 24 (58.5%) had diverting ileostomies. The most common indications for pouch failure were Crohn's disease like pouch inflammation (CDLPI) (n = 17, 41.5%), chronic pouchitis (n = 6, 14.6%), chronic cuffitis (n = 5, 12.2%) and anastomotic stricture (n = 4, 9.8%). On multivariate analysis, pre-colectomy biologic use (hazard ratio [HR] 2.25, 95% CI 1.09-4.67), CDLPI (HR 3.18, 95% CI 1.49-6.76) and pouch revision (HR 2.59, 95% CI 1.26-5.32) were significantly associated with pouch failure. Pouch failure was significantly associated with CDLPI, preoperative biologic use and pouch revision; however, reassuringly it was not associated with postoperative complications.

Scleritis in rheumatoid arthritis: Before and during biologic era.

Scleritis represents a severe extra-articular manifestation of rheumatoid arthritis (RA). Recent clinical observations suggest a decreasing incidence of scleritis in RA, attributed to improved treatment options. Our study reports on the incidence and clinical characteristics of scleritis in RA observed in the biological era and reflects on our results in a historical perspective. We performed a retrospective evaluation of all 1623 consecutive patients with RA diagnosed at the department of rheumatology between 2011 and 2021 at the Erasmus Medical Center to investigate the incidence of scleritis. We also reviewed clinical and laboratory data of all patients with scleritis and RA from the department of ophthalmology at our center. In addition, we reviewed the literature on this topic and discuss our results in view of changes over time. The incidence of scleritis within recent series of patients with a diagnosis of RA in our tertiary center was 0,25% in 10 years (4 out of 1623; 2011-2021).The cumulative incidence of scleritis in RA based on literature review from the pre-biologic era varied from 0.7% per 8 years to 0,8% per 30 years. Manifestations and complications of scleritis remained unchanged over time, with scleral necrosis developing in more than 80% of cases and mortality of RA patients with scleritis remained similar to pre-biologic era (30% in 9 years after the onset of scleritis). The RA patients with scleritis often exhibited autoantibodies (rheumatoid factor and/or anti-citrullinated protein antibody) and erosive disease. Although our recent series is characterized by a slightly lower incidence of scleritis in RA compared to the pre-biologic era, clinical presentation remained severe and similar to the pre-biologic era. Ophthalmologists and rheumatologists should be aware of scleritis as a severe extra-articular manifestation of RA.

P761 Negative Body Image in Inflammatory Bowel Disease persists despite Modern IBD care

Abstract Background Body image dissatisfaction (BID) is prevalent in patients with Inflammatory Bowel Disease (IBD). Historically female sex, previous IBD surgery, impaired QoL have been associated with negative body image. The introduction of biologic therapies and modern IBD care in Australia in 2007 has improved disease control and endoscopic outcomes, but it is unclear if body image has improved in parallel with this. We aimed to determine whether body image and QoL have improved amongst IBD patients with modern IBD car Methods Tertiary IBD service patients were offered inclusion in the study in 2006 by postal survey (pre-biologic era), and in 2021 by electronic survey (biologic era). Surveys included demographics and history of IBD surgery. In the pre-biologic era (PBE) body image dissatisfaction (BID) and QoL were assessed using a patient reported yes/no question, followed by an open question about how IBD or treatment has changed the way they view their body’s appearance. In the biologic era (BE) the validated modified Body Image Scale and Short Inflammatory Bowel Disease Questionnaire were used. Results The BE included 135 patients, 59% female, mean age 45.9. The PBE included 215 patients, 66% female and mean age 35.5. PBE had 40% reporting IBD surgery vs 36% in BE (P=0.489). BID was observed in 67% vs 39% of the PBE and BE respectively (p&amp;lt;0.01). In the PBE free text responses elicited themes of dissatisfaction with medication or steroid-related appearance changes (41%), bloating (30%), weight gain (28%), weight loss (12%), and specific appearance changes. The link between body image and QoL was mentioned by 33% of patients, with 8% specifically mentioning its impact on their mental health. Females were affected to a greater extent in both PBE (75% vs 52% p&amp;lt;0.01), and BE (50.5% versus 22% p&amp;lt;0.01). In the PBE patients with surgical intervention for IBD had higher rates of BID than those without surgery (81% vs 58%, p&amp;lt;0.01). This association between surgery and BID was not observed in the BE (47% vs 34.9%, p=0.168). In the PBE those with BID were significantly more likely to report impaired QoL(97% vs 71%, p&amp;lt;0.01). This association persisted with time with BE patients with BID also having higher rates of QoL impairment (85% vs 45% p&amp;lt;0.01). Conclusion Whilst the rate of BID has decreased with modern IBD treatment; it remains highly prevalent and is associated with impaired QoL. Whilst females remain disproportionately affected, the historically observed association between IBD surgery and impaired body image was not demonstrated in the BE. This may reflect improved surgical techniques and biologic down staging prior to surgery. However, body image remains an important Patient Reported Outcome in IBD and warrants further attention.

P240 Low surgery rates first year after diagnosis in Crohn’s disease; results from a large population-based inception cohort - the IBSEN III study

Abstract Background Surgery rates in Crohn’s disease (CD) have declined during recent years, in parallel with the introduction and increased use of biological treatment. The aim of this study was to describe the use of first-line biologic therapy and to estimate the intra-abdominal surgery rate during the first year after the CD diagnosis. Methods The Inflammatory Bowel Disease in South-Eastern Norway III (IBSEN III) study is a population-based inception cohort with a prospective follow-up of newly diagnosed inflammatory bowel disease patients from the South-Eastern Health Region of Norway included in the period 2017 to 2019. Five hundred and seven patients ≥18 years were diagnosed with CD and those attending the one-year follow-up visit were included in this study. Clinical data, including Montreal classification, were registered at time of diagnosis. At the one-year follow-up, use of biologic therapy and need for CD-related intra-abdominal surgery since diagnosis were registered. Kaplan-Meier plots estimated the cumulative incidence of first-line biologic therapy and intra-abdominal surgery. Results A total of 431/507 (85%) CD patients attended the one-year follow-up and were included, 54.8% female, median age 37 years (range 18-80). At diagnosis 218 (50.6%) presented with ileal disease location, 76 (17.6%) colonic and 137 (31.8%) ileocolonic disease location, while 11 (2.6%) also had upper gastrointestinal involvement. The majority, 351 (81.4%), had a non-stricturing non-penetrating disease behavior, 70 (16.2%) a stricturing and 10 (2.3%) a penetrating disease behavior, while 17 (3.9%) also had perianal disease. Within one year of follow-up, 165 (38.7%) received at least one biologic therapy (60.6% infliximab, 35.8% adalimumab and 3.6% vedolizumab). Seven patients (1.6%) underwent perianal surgery and 21 (4.9%) had intra-abdominal surgery within the first year. Three of these were diagnosed during their primary surgery. Time from diagnosis to start of first-line biologic therapy and first intra-abdominal surgery is shown in Figure 1 and Figure 2, respectively. Figure 1: Kaplan-Meier plot showing cumulative incidence of first-line biologic therapy. Figure 2: Kaplan-Meier plot showing cumulative incidence of Crohn's related intra-abdominal surgery. Conclusion In the IBSEN III cohort, the rate of intra-abdominal surgery during the first year of disease was low (4.9%) compared to a previous population-based study from the same geographic area during the pre-biologic era, the IBSEN study, where the surgery rate was reported as 15.9 %.1 We hypothesize that a large preponderance of patients presenting with milder phenotypes at diagnosis combined with high use of biologicals contribute to the low surgery rates.

P353 Ulcerative Colitis in the IBSEN III study: Frequent use of biologics and low colectomy rates first year of disease.

Abstract Background Biological therapy of ulcerative colitis (UC) has become more common in recent years, and colectomy rates have declined during the same period. The aim of this study was to describe the use of first-line biologic therapy and to estimate the colectomy rate in a population-based inception cohort during first year of disease. Methods Inflammatory Bowel Disease in South-Eastern Norway III (IBSEN III) is a population-based inception cohort with a prospective follow-up of newly diagnosed patients with inflammatory bowel disease from the South-Eastern Health Region of Norway, including from 2017 to 2019. In this project, we studied patients≥ 18 years with a verified UC diagnosis at baseline and at one-year follow-up. Baseline characteristics, use of biological therapy, and need for surgery during the first year after diagnosis were analysed. Kaplan-Meier plot was used to estimate the time to first-line biologic therapy. Results A total of 889 UC patients (45.9% female, median age 36 years (range 18-84), 6.2% smokers) were included in the study and met for one-year follow-up. Totally 129 (14.5%) patients started on biological therapy due to UC, during the first year of disease. Time from diagnosis to start of first-line biologic therapy is depicted in Figure 1 (Kaplan-Meier plot). In addition, four patients received biologics due to other indications than UC (not depicted in Figure 1). The colectomy rate at one-year follow-up was 0.9% (8/889). Figure 1: Cumulative incidence of biologic therapy. Conclusion In this population-based inception cohort, colectomy rates during first year of disease were low compared to a prior population-based study from the same geographic area in the pre-biologic era (the IBSEN study)1, while the proportion starting on biological therapy was higher than reported in comparable inception cohorts2.

P586 Surgical recurrence in Crohn’s Disease: Can we prevent it?

Abstract Background Crohn’s Disease (CD) is a chronic inflammatory disease primarily affecting the bowel. In the pre-biological era, approximately 40–50% of patients would undergo surgery within the first 2 decades after diagnosis, with a risk of postoperative recurrence up to 50% at 10 years. Although post-operative prophylaxis is recommended to prevent clinical and endoscopic recurrence, little is known about the factors associated with surgical recurrence. Methods Single-center, retrospective study including 992 patients with CD. Demographic and clinical data were retrieved from patients’ medical charts. Patients with 1 or more surgeries were selected for analysis, excluding perianal disease surgeries. Thiopurines and biologics were considered as prophylaxis for surgical recurrence only if initiated within the first year after surgery. A logistic regression analysis was performed to evaluate potential predictors of surgery recurrence. Results Three hundred and nine patients (31.1%) required at least one surgery during follow-up. Two hundred and twenty-four patients (72.5%) underwent a single surgery and 85 (27.5%) required two or more interventions. Patients with surgical recurrence were younger [31 (23–36) vs 34 years (24–44), p=0.009], and had lower rates of prophylaxis with thiopurines (23.5% vs 37.5%, p=0.013), and anti-tumor necrosis factor (TNF) agents (8.2% vs 22.3%, p=0.002) compared with patients without surgical recurrence. Multivariate analysis identified stricturing and penetrating phenotype as risk factor for surgical recurrence (OR 2.292 95%CI [1.500–3.502], p&amp;lt;0.001]). Likewise, older age (OR 0.949 95%CI [0.94–0.996], p=0.034), and prophylaxis with anti-TNFs (OR 0.309 95% [0.126–0.754], p=0.01) were protective factors against surgical recurrence. Twenty-five patients (29.4%) developed a second surgical recurrence. Patients with more than one surgical recurrence had lower utilization of thiopurines (16% vs 45%, p=0.009) and anti-TNFs (0% vs 26.7%, p=0.002). Conclusion Our findings suggest that postoperative prophylaxis with immunosuppressants, especially anti-TNFs, significantly reduces the risk of surgical recurrence. Postoperative prophylaxis should be implemented in high-risk patients, especially younger patients and those with a non-inflammatory phenotype.

P077 Incidence of Colonic Strictures - A Systematic Review and Meta-analysis.

Intestinal strictures are a complication of the inflammatory bowel diseases (IBD, including ulcerative colitis (UC) and Crohn's disease (CD)) that can lead to bowel obstruction and therapy failure. Intestinal strictures occurring after long-standing tissue damage and repair are more frequently reported in CD, but colonic strictures can occur in UC. However, there is a paucity of literature that comprehensively summarizes the available information regarding the incidence and etiology of colonic strictures in UC. The aim of this study was to perform a systematic review and meta-analysis of published reports on the incidence of colonic strictures in UC patients. Four independent reviewers performed a comprehensive review of all original articles describing the incidence of colonic strictures in UC published from inception to June 2021. Primary outcomes were (1) overall incidence of colonic strictures; (2) 10-year incidence of colonic strictures; and (3) incidence of colonic strictures containing high-grade dysplasia (HGD) or colorectal cancer (CRC). Subgroup analysis was performed to compare the outcomes between the pre-biologic era and post-biologic era. The meta-analysis was performed and the statistics were 2-tailed. Finally, probability of publication bias was assessed using funnel plots and with Egger's test. Eleven studies reporting on a total of --- patients with colonic strictures were included in the analysis after comprehensive search. This yielded a pooled colonic stricture incidence rate of 5.4% (95% confidence interval (CI) 3.7-7.8). The incidence rate of colonic strictures was lower in the post-biologic era compared to the pre-biologic era but the difference was not statistically significant (2.6% vs 6%; p = 0.14). The pooled 10-year colonic stricture rate was 3.2% (95% CI 1.5-6.8). The pooled 10-year incidence rate of colonic strictures was lower in the post-biologic era compared to the pre-biologic era but the difference was not statistically significant (1% vs 1.8%; p = 0.1). The pooled incidence of strictures with associated high-grade dysplasia (HGD) or colorectal cancer (CRC) was 21.9% (95% CI 12.2-36.5). The incidence rate of HGD or CRC in colonic strictures was higher in the post-biologic era compared to the pre-biologic era but the difference was not statistically significant (23.6% vs 20.4%; p = 0.79). This systematic review and meta-analysis on the incidence of colonic strictures in UC showed that the overall pooled incidence and 10-year incidence of colonic strictures in UC are low. There was a trend towards lower incidences of UC strictures in the post-biologic era, although the differences did not reach statistical significance. While the overall incidence of colonic strictures, in UC is low, a high proportion of colonic strictures are associated with HGD or CRC, even in the biologic era. Therefore, this study provides further support for importance of stricture biopsy and surgical evaluation for colectomy in the UC patient with colonic stricture.

A19 HEALTH CARE UTILIZATION DIFFERENCES BETWEEN FIRST NATIONS AND THE GENERAL POPULATION WITH INFLAMMATORY BOWEL DISEASE IN SASKATCHEWAN

Abstract Background Indigenous patients with inflammatory bowel disease (IBD) have expressed concerns about barriers to access IBD care. The limited evidence of IBD among Indigenous people highlights the need for studies evaluating access to IBD care in this population. Aims We aimed to compare health care utilization between First Nations (FNs) and individuals from the general population (GP) diagnosed with IBD in Saskatchewan (SK). Methods A population-based retrospective cohort study was conducted using administrative health databases of SK from 1998 to 2017 fiscal years. As a patient-oriented research initiative, outcomes of interest were chosen in collaboration with Indigenous patients and family advocates. A validated algorithm requiring multiple health care contacts was applied to identify incident IBD cases. The self-declared FN status variable was used to divide IBD cases between FNs and the general population (GP). To balance the groups, 1:5 age and sex matching was applied. Cox-proportional models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CI). Stratified analysis was completed for those diagnosed before and after 2008 (pre- and post-biologic eras). Results A matched cohort with 696 IBD incident cases was created (FN=116, GP=580). Comparing health care utilization of FNs and individuals from the GP with IBD, there were no statistically significant differences in outpatient gastroenterology visits (FNs=81.0%, GP=83.6%), colonoscopies (FNs=91.4%, GP=86.9%), and surgeries for IBD (FNs=31.0%, GP=33.5%). We observed differences in prescription claims for any medication for IBD (FNs=79.3%, GP=89.3%) and 5-aminosalicylic acid (5-ASA) claims (FNs=75.9%, GP=81.4%). The HRs adjusted by rural/urban residence and diagnostic type showed differences in prescription claims for any IBD medication (HR=0.52, 95%CI 0.41–0.65) and 5-ASA (HR=0.57, 95%CI 0.45–0.72). In the pre-biologic era, FNs had a lower risk of having a prescription claim for any IBD medication (HR=0.32, 95%CI 0.23–0.45) and 5-ASA (HR=0.33, 95%CI 0.24–0.47), respectively. These differences were not significant in the post-biologic era. Conclusions Our study identified an inverse association between FN status and having prescription medication claims for IBD in SK. We considered multiple confounding variables when evaluating this association but could not control by disease severity. Thus, this association might reflect a barrier to access IBD medications or that FNs with IBD might present a milder disease. Further studies should continue evaluating access to IBD care, medication use, and disease severity among FNs living with IBD. Funding Agencies Saskatchewan Centre for Patient-Oriented Research (SCPOR), Saskatchewan Health Research Foundation (SHRF), and College of Medicine, University of Saskatchewan.

Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults.

The treatment of inflammatory arthritis has been revolutionised by the introduction of biologic treatments. Many biologic agents are currently licensed for use in both paediatric and adult patients with inflammatory arthritis and contribute to improved disease outcomes compared with the pre-biologic era. However, immunogenicity to biologic agents, characterised by an immune reaction leading to the production of anti-drug antibodies (ADAs), can negatively impact the therapeutic efficacy of biologic drugs and induce side effects to treatment. This review explores for the first time the impact of immunogenicity against all licensed biologic treatments currently used in inflammatory arthritis across age, and will examine any significant differences between ADA prevalence, titres and timing of development, as well as ADA impact on therapeutic drug levels, clinical efficacy and side effects between paediatric and adult patients. In addition, we will investigate factors associated with differences in immunogenicity across biologic agents used in inflammatory arthritis, and their potential therapeutic implications.

21 NATURAL HISTORY OF COLECTOMY AMONG HOSPITALIZED PATIENTS WITH ULCERATIVE COLITIS IN THE CONTEMPORARY ERA OF BIOLOGICS

Abstract BACKGROUND Despite reducing mortality, the use of intravenous (IV) corticosteroids has not significantly reduced inpatient colectomy rates among hospitalized patients with ulcerative colitis (UC). Whether the occurrence of colectomy, estimated at 20–30% in this population in the prebiologic era, remains elevated is unknown. Methods A retrospective cohort study was conducted among health plan members of an integrated health care delivery organization that serves approximately 4.0 million members in urban, suburban, and semi-rural regions throughout Northern California. The study population consisted of 524 health plan members age &amp;gt;18 years of age with a 1) diagnosis of ulcerative colitis (ICD-9 code 556; ICD-10 code K51); 2) first hospitalization between 2009 and 2017 coded with ulcerative colitis as the primary cause for admission; 3) no prior hospitalizations for UC; 4) at least 1 year of continuous membership prior to the index hospitalization; 5) No dispensing of biologic therapy (infliximab, adalimumab, golimumab, vedolizumab) recorded prior to hospitalization; 6) No record of Clostridium difficile or cytomegalovirus infection during the hospitalization or 30 days prior. The primary outcome was the occurrence of colectomy during the index hospitalization and up to 12 months after hospitalization. Additional outcomes assessed were trends in colectomy over this time period and predictors for colectomy during the index hospitalization. Results A total of 5.3% of UC patients underwent colectomy during the index hospitalization (95%CI 3.3–7.3%) and 11.9% underwent colectomy within the first year after hospitalization (95% CI: 9.1–14.6%). Inpatient colectomy declined from 6.5% (95%CI: 2.5–10.6%) in 2009–2010 to 3.4% (95%CI: 3.3–7.3%) in 2015–2017. Colectomy in the first year after admission declined from 15.7% (95%CI 10.0–21.4%) in 2009–2011 to (10.1%; 95% CI: 5.4–14.7) in 2015–2017. A total of 16.3% of patients received infliximab in the hospital and 36.3% received within the first year of admission. In a multivariable model, the 2015–2017 cohort experienced a 64% reduction in inpatient colectomy compared to the 2009–2011 cohort (OR 0.36; 95%CI: 0.11–1.14, p=0.082) and a 54% reduction in colectomy in the first year (OR 0.46; 95%CI: 0.22–0.96, p=0.038). A prior study between 1998–2004 in this same population showed colectomy rates of 20% during the index hospitalization and 30% at 1 year. Conclusion Colectomy within the first year after hospital admission for UC has declined over time in the modern era of biologics with a magnitude of colectomy that is lower than the historical rate of 20–30%. Our data imply cause for optimism that the natural history of colectomy in acute severe UC may be different and modifiable in the modern biologic era compared to the past.

21 NATURAL HISTORY OF COLECTOMY AMONG HOSPITALIZED PATIENTS WITH ULCERATIVE COLITIS IN THE CONTEMPORARY ERA OF BIOLOGICS

Despite reducing mortality, the use of intravenous (IV) corticosteroids has not significantly reduced inpatient colectomy rates among hospitalized patients with ulcerative colitis (UC). Whether the occurrence of colectomy, estimated at 20-30% in this population in the prebiologic era, remains elevated is unknown.

P290 Long-term disease outcome of ulcerative colitis (UC) in South Ostrobothnia, Finland with a follow-up time of 25 years

Abstract Background Finland has one of the highest prevalence of inflammatory bowel disease (IBD), especially UC. There is scarce data about long-term disease outcome in UC in population-based cohorts. The aim was to evaluate the long-term clinical outcome of patients with UC in the region of South Ostrobothnia, a district in rural central western Finland with a population of about 190 000. Methods All patients treated with diagnosis of UC or IBDU (inflammatory bowel disease Unclassified) during years 1981–2000 were included in this study. Data were collected retrospectively from the patient registry of the Central Hospital of South Ostrobothnia until 1 August 2019. Results There were 589 patients with a median follow-up time of 25 years. Median age at the diagnosis was 34 years. 59% of patients were male, 93% had UC and 7% IBDU. According to Montreal classification 80% had extensive disease, 15% left-sided disease and 5% proctitis. Medical treatment used at any point during the disease is shown in Table 1. Twenty-two per cent of patients had colectomy. Of operated patients, (pan)proctocolectomy with ileostomy was performed to 50%, IPAA (ileal pouch anal anastomosis) to 40% and IRA (ileorectal anastomosis) to 3%. Median time from the diagnosis to surgery was 11 years; the risk of surgery is shown in Table 2. Twenty-six per cent of the operations were emergency surgeries. The mean age at the time of surgery was 49 years. The indications for colectomy are specified in Table 3. Cumulative risk of colorectal cancer (CRC) and biliary tract cancer was 3.2% and 1.7%, respectively. Twenty-eight per cent of patients died during follow-up, at the mean age of 72 years. The cause of death was recorded for 91/167 and the most common causes were cardiovascular disease and malignancy. Conclusion In this population-based cohort with surveillance of 25 years 22% patients with UC or IBDU were operated. Even after becoming available, biological medication is rarely used for UC patients diagnosed in the prebiologic era.

P561 The management of Crohn’s disease (CD) patients post ileocaecal resection: a multicentre, regional audit in Northern England

Abstract Background 70% of patients with Crohn’s disease (CD) require intestinal resection.1 Post-operative recurrence (POR) is common with 70% of patients requiring further surgery in the pre-biologic era.2 ECCO guidelines suggest identifying patients at risk of recurrence (disease phenotype, smoking, prior resection), the use of imidazole antibiotics following surgery and assessment for recurrence within 12 months. The ECCO guidelines recommend ileocolonoscopy, although alternative modalities can be used. The Rutgeerts score predicts POR and is recommended to establish the need for preventative treatment.3 The aim of this study was to undertake a region-wide audit of practice with regards to post-operative CD in the Northern region. Methods A regional, multicentre, retrospective audit was conducted by GRANT, a network of gastroenterology trainees in Northern England. Data collection was performed for CD patients who had an ileocaecal resection between 1/9/16 and 1/9/17. Patients with an end-ileostomy were excluded. Patients were identified using clinical coding and data collection sheets were completed. Results Seven of 9 Hospital Trusts returned data. The number of eligible patients was 38 with a mean age of 41 years. Seventy-six per cent (29/38) patients had at least one risk factor rendering them ‘high-risk’ for POR (Figure 1). Only 13% (5/38) of patients received imidazole antibiotics postoperatively and only 29% (11/38) had an ileocolonoscopy within 12 months. However, 32% (12/38) had an alternative assessment of POR, with calprotectin being the most popular. An escalation in treatment following assessment was required in 25% (9/38) of patients. Postoperatively, 40% (15/38) of patients had no maintenance therapy before POR assessment; 26% (10/38) continued on the same therapy as preoperatively and34% (13/38) had augmented pre-operative therapy. Conclusion The majority of patients in Northern England who have an ileocaecal resection for CD are high risk for recurrence and many patients are not being assessed. Endoscopic POR predates clinical POR [4] and, without monitoring, the opportunity to augment therapy and prevent clinical recurrence can be missed. In Northern England, less invasive disease monitoring is being used to assess for POR and this audit would suggest that these have a comparable rate of identifying a need to escalate maintenance therapy. A postoperative CD management bundle is being developed and will be implemented to assess whether this drives improvement.