Background There is limited data on advanced therapy outcomes in second-line vs. first-line advanced treatment of patients with ulcerative colitis (UC) and Crohn's disease (CD). Methods We conducted a retrospective health claims study of patients with UC and CD in Germany. We analyzed claims data from 2014 to 2021, and compared therapy persistence and dose escalation in first- (1L) and second-line (2L) advanced therapy. Our analysis included the approved therapies adalimumab (ADA), infliximab (IFX), ustekinumab (UST) and vedolizumab (VDZ) for both UC and CD patients and golimumab (GOL) and tofacitinib (TOF) for UC patients. Results 2,948 patients were included in the study and initiated 1L advanced therapy. Of these, 823 patients started a 2L advanced therapy. Time on treatment was generally shorter in 2L compared to 1L: In UC patients, persistence rates at 2 years ranged from 52.5% to 71.9% for 1L, and from 40.1% to 69.1% for 2L. In CD patients, persistence rates ranged from 66.6% to 86.6% for 1L, and from 59.9% to 74.3% for 2L. We observed more frequent dose escalations in 2L than in 1L for all advanced therapies except GOL in UC patients. Conclusions Our study indicates that advanced therapies have shorter persistence and require higher doses when used as 2L treatment compared to 1L treatment. Future studies on reliable response predictors in patients with UC or CD receiving advanced treatments are likely to improve the selection of more efficacious 1L therapy.

Pyoderma gangrenosum (PG) is a rare but challenging extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), affecting 6–48% of IBD patients. This retrospective study analyzes affected patients and evaluates therapeutic strategies for both IBD remission and PG resolution. A multicenter retrospective analysis was conducted on patients with IBD and PG in 8 tertiary centers in Germany and Austria. Demographic data, prior therapies, surgeries, treatment of PG were collected, and treatment responses assessed. The cohort included 50 patients (median age: 43 years; 68% female). Crohn’s disease (CD) was present in 58%, ulcerative colitis (UC) in 42%. Fifty percent of patients had prior surgery, 68% having an intestinal stoma. 48% were experienced to biologic therapy, predominantly anti-TNF therapy (83%). PG mainly affected the lower extremities (52%) and peristomal areas (24%). Systemic steroids were used in 52% of patients and led to PG resolution in only 12%. Anti-TNF therapy was the main approach, used in 68% of patients, with resolution achieved in 80%. Calcineurin inhibitors were given to 26% of patients and induced resolution in 38%. Three of six non-responders were successfully switched to infliximab. Overall PG resolution was achieved in 80%, correlating with IBD remission in 78%. The median time to PG resolution was five months. Anti-TNF therapy was an effective treatment for PG in IBD patients, even in those with prior non-response to calcineurin inhibitors. Systemic steroids showed low response rates. PG healing mostly aligned with IBD remission, underlining the need for tailored long-term therapy.

Pyoderma gangrenosum (PG) is a rare but challenging extraintestinal manifestation (EIM) of inflammatory bowel diseases (IBD), affecting 6%–48% of IBD patients. This retrospective study analyzed affected patients and evaluated therapeutic strategies for both IBD remission and PG resolution. A multicenter retrospective analysis was conducted on patients with IBD and PG in eight tertiary IBD centers. Demographic data, prior therapies, surgeries, and treatment of PG were collected retrospectively, and treatment responses were assessed. The cohort included 50 patients (median age: 43 years; 68% female). Crohn’s disease was present in 58% and ulcerative colitis in 42%. Fifty percent of patients had prior surgery, 68% had an intestinal stoma in their medical history. 48% were experienced with biologic therapy, predominantly anti-tumor necrosis factor (TNF) therapy (83%). PG mainly affected the lower extremities (52%) and peristomal areas (24%). Systemic steroids were used in 52% (26/50) and led to PG resolution in only 11.5% (3/26). Anti-TNF therapy was the main approach, used in 68% (34/50) of patients, with resolution achieved in 80% (27/34). Calcineurin inhibitors were given to 26% (13/50) of patients and induced resolution in 38% (5/13). Three of six non-responders were successfully switched to infliximab. Overall, PG resolution was achieved in 80% (40/50), correlating with IBD remission in 78% (31/40) of these patients. The median time to PG resolution was 4 months. Anti-TNF therapy was an effective treatment for PG in IBD patients, even in those with prior nonresponse to calcineurin inhibitors. Systemic steroids showed low response rates. PG healing mostly aligned with IBD remission, underlining the need for tailored long-term therapy.

BACKGROUND:The prospective RUN-CD registry investigates the effectiveness of ustekinumab (UST) and other biologics in Crohn's disease (CD) across Germany. Based on data from the registry, this study presents the maintenance phase results of a 12-month real-world-evidence (RWE) comparison of CD patients initiating new biologic therapies with UST or anti-TNF. METHODS:After excluding patients using biologics other than UST and anti-TNF and those with missing outcomes, the final sample consisted of 618 CD patients. Clinical remission (CR), defined as a Harvey-Bradshaw Index (HBI) ≤4, was the prespecified endpoint at 12 months. Switching to another biologic therapy was considered an outcome failure. Propensity score adjustment was used to reduce the effect of confounders. RESULTS:The study included 343 CD patients treated with UST and 264 treated with anti-TNF. Over 12 months, the frequency of therapy switches was significantly higher for infliximab (28%) compared with UST (17%) and adalimumab (17%) (P =.045). There was no significant difference in CR rates at 12 months between the UST and anti-TNF groups (65.8% vs 60.0%, P =.262). However, in week-16 responders, CR rates at 12 months were significantly higher with UST (77.6%) versus anti-TNF (65.4%) (P =.041). The change in EQ-VAS (QoL) scores between UST and anti-TNF showed a 5.1-point difference favoring UST (P =.002). CONCLUSIONS:In this 12-month RWE comparison, overall CR rates were similar between UST and anti-TNF. However, among week-16 responders, CR rates were significantly higher with UST. Additionally, UST was associated with a significantly greater improvement in QoL compared with anti-TNF.

Abstract Background JAK inhibitors (JAKi) can induce and maintain remission in inflammatory bowel disease (IBD). Around 5% of IBD patients develop primary sclerosing cholangitis (PSC). Given the potential involvement of JAK/STAT signaling in PSC pathogenesis, JAKi may have a role in modulating IBD-related PSC. We aim to explore the course of PSC in IBD-PSC patients on JAKi for IBD. Methods Following a call-for-cases via ECCO CONFER (Round 10), we retrospectively collected baseline and outcome data for both PSC and IBD, before and after JAKi treatment, including laboratory tests, imaging and endoscopic findings, histopathology and adverse effects. The data were analyzed both descriptively and comparatively. A p-value of less than 0.05 was considered statistically significant. Results We collected data from 58 patients (53 ulcerative colitis), with a median of disease duration of 5.5 (IQR 2-9) years (Table 1). The median age at PSC diagnosis was 26 (18.25-40.5) years. Each patient had been treated with a median of 2.5 different types of drugs before starting JAKi; 57% received tofacitinib, 26% upadacitinib, 17% filgotinib. At the time of data analysis, the median time of JAKi exposure was 32 (15.75-69) weeks and we will refer to that median time of exposure when analysing each data related to JAKi exposure. At baseline, alkaline phosphatase (ALP) was elevated in 71% of patients (median, 292 U/L, 185-471). After JAKi exposure, ALP dropped to a median of 203.5 U/L (138.7-394.5), p=0.0004. Among this specific group, 30% of subjects reached normal ALP values. Gamma-glutamyl transferase (GGT) was elevated in 80% of patients (350 U/L, 164-552) and dropped to a median value of 127 U/L (95-270), p=0.0055; 13% of this specific group reached normal values of GGT after JAKi exposure. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were high in 58% and 50% of patients, respectively; following JAKi exposure, the median value of both went down significantly. After a median time of 32 weeks of JAKi treatment, 39,6% of patients had to change therapy: 23% due to primary non-response, 62% due to lack of response, 15% underwent colectomy. Patients who had to change therapy were divided into: switch group, treated with additional 40 (36-46) weeks with a different JAKi; swap group, swapped to biologic for additional 27 (24-40) weeks. Better control of liver biomarkers was observed in the switch group (Figure 1). Conclusion Treatment with JAKi can positively impact liver inflammation in terms of cholestasis and cytolysis indexes in patients with PSC and concomitant IBD. References Schregel I, Ramos GP, Ioannou S, Culver E, Färkkilä M, Schramm C; International PSC Study Group. Evaluation of Tofacitinib in Primary Sclerosing Cholangitis and Associated Colitis: A Multicenter, Retrospective Study. Clin Gastroenterol Hepatol. 2023;21(13):3448-3450.e3. doi: 10.1016/j.cgh.2023.01.014. Khrom M, Long M, Dube S, Robbins L, Botwin GJ, Yang S, Mengesha E, Li D, Naito T, Bonthala NN, Ha C, Melmed G, Rabizadeh S, Syal G, Vasiliauskas E, Ziring D, Brant SR, Cho J, Duerr RH, Rioux J, Schumm P, Silverberg M, Ananthakrishnan AN, Faubion WA, Jabri B, Lira SA, Newberry RD, Sandler RS, Xavier RJ, Kugathasan S, Hercules D, Targan SR, RB Sartor, Haritunians T, McGovern DPB. Comprehensive association analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease. Gastroenterology. 2024;167(2):315-332. doi: 10.1053/j.gastro.2024.02.026. Dold L, Kalthoff S, Frank L, Zhou T, Esser P, Lutz P, Strassburg CP, Spengler U, Langhans B. STAT Activation in Regulatory CD4 (+) T Cells of Patients with Primary Sclerosis Cholangitis. Immune Inflamm Dis. 2024;12(4):e1248. doi: 10.1002/iid3.1248.

There is limited data on inflammatory bowel disease advanced therapy sequences. Therefore, we examined real-world advanced therapy sequences to compare persistence, healthcare use and costs in first-line advanced therapy. Evaluable patient characteristics, treatments, sequences, and outcomes were extracted from the WIG2 claims benchmark database and observed from 2014 to 2021. Therapeutic effectiveness (persistence without discontinuation or inadequate response), healthcare resource utilization, and associated costs were analyzed. Advanced treatment group differences were adjusted by inverse probability weighting. Two thousand nine hundred forty-eight patients with Crohn’s disease or ulcerative colitis initiated at least one of the following advanced therapies during the study period: adalimumab (1,260), golimumab (111), infliximab (1,035), tofacitinib (17), ustekinumab (138) or vedolizumab (387). In patients with ulcerative colitis, vedolizumab as first-line advanced therapy demonstrated superior effectiveness in persistence without inadequate response over three years compared to infliximab (p < 0.05). Patients taking infliximab or ustekinumab had higher disease-related costs than those taking adalimumab, golimumab, tofacitinib or vedolizumab. In Crohn’s disease patients, first-line treatment with adalimumab (p < 0.001), ustekinumab (p < 0.001) and vedolizumab (p < 0.017), showed superior persistence over 3 years compared to infliximab, and time to inadequate response was longer in patients taking adalimumab and vedolizumab (p < 0.001). Disease-specific treatment costs were lower in patients receiving adalimumab or vedolizumab as first-line advanced therapy. Compared to infliximab, patients treated with ustekinumab had significantly higher costs. Anti-TNF agents were most frequently used in first-line advanced therapy; however, vedolizumab appeared to be a preferred choice in terms of persistence and cost measures over three years from the start of treatment.

If a complete optical colonoscopy (OC) cannot be performed, an alternative diagnostic method should be considered.The aim of this retrospective chart review study was to investigate the surgical and interventional endoscopic implications of CT colonography (CTC) after fully intended but aborted OC.302 patients with CTC after an incomplete OC were compared to sex-matched controls who underwent a complete OC by the same examiner in the same year. The most common indications were preventive colonoscopy (29.1%) and pathological iFOBT (9.6%). The most common reasons for OC discontinuation were suspected adhesions (n=64) and a long sigmoid colon ± non-inflammatory diverticula (n=59). OC discontinuation was most prevalent in the sigmoid colon (n=149, 49.3%). Adenoma detection rates in patients undergoing preventive colonoscopy were 9.6 and 26.9 per cent in the CTC and the control groups, respectively (p<0.01). A total of 384 extracolonic CT findings were identified in 197 patients (65.2%) including 373 benign (97.1%) and 11 potentially malignant findings (2.9%). However, only two of these could be confirmed histologically.In our cohort, CTC revealed only a small number of (pre-)malignant (extra-)intestinal findings. Therefore, we recommend a limited use of CTC, depending on the indication and the local findings that led to the discontinuation of OC.

BACKGROUND & AIMS:Microscopic colitis (MC) is a leading cause of chronic diarrhea, particularly in older adults. Although many patients respond to budesonide, refractory and dependent cases pose major therapeutic challenges. Although the off-label use of advanced inflammatory bowel disease therapies is expanding, robust real-world data remain scarce. METHODS:Through the ECCO CONFER network, we conducted a multinational, retrospective study in patients with MC treated with biologics or small molecules following budesonide failure or intolerance. We systematically analyzed clinical outcomes, treatment durability, and predictors of therapeutic success. RESULTS:Among 229 treatment cycles in 142 patients, anti-tumor necrosis factor (TNF) agents were most frequently initiated (55.9%), followed by vedolizumab (28.8%) and Janus kinase (JAK) inhibitors (9.2%). Short-term clinical response and remission rates were highest with JAK inhibitors (95.2% and 81.0%, respectively), significantly outperforming anti-TNFs, vedolizumab, and ustekinumab (P < .01). Long-term drug persistence mirrored these findings: JAK inhibitors demonstrated a markedly lower discontinuation rate (23.8%) compared with other agents (56.3%; odds ratio, 5.07; 95% confidence interval, 1.52-16.9; P = .008). Multivariate analysis confirmed drug class as the only independent predictor of therapy continuation. Despite advanced therapies, 4.2% of patients ultimately required surgical intervention. CONCLUSIONS:This real-world study demonstrates the promising short- and long-term effectiveness of advanced therapies-particularly JAK inhibitors-in budesonide-refractory and budesonide-dependent MC. These findings pave the way for dedicated prospective trials and highlight evolving therapeutic strategies in MC.

Despite the wide range of medical and interventional therapy options available, some patients with Crohn’s disease (CD) need an ileostomy or colostomy. The aim of this study was to identify clinical, surgical and drug-related predictors of successful stoma reversal in CD patients. A retrospective medical record analysis of surgical department logs, hospital discharge letters and patient reports from outpatient departments was performed for all CD patients who underwent a first ostomy surgery. Our study analysed a total of 149 patients (76 women, 73 men, median age at first stoma of 34 years after a median CD duration of 9 years), with a median follow-up of 78.4 (IQR 88.6) months after first ostomy surgery. Of these patients, 73 (49

Abstract Background Microscopic colitis (MC) is a chronic inflammatory condition of the colon, resulting in an impaired quality of life due to debilitating watery diarrhea. First-line therapy consists of budesonide, though a subset of patients is refractory or becomes budesonide- dependent. Evidence for the efficacy of biologicals or small molecules in MC is sparse and limited to small case series. Hence, we aimed to generate more real-life efficacy data. Methods This retrospective series was collected as part of the CONFER project by ECCO and supported by the European Microscopic Colitis Group (EMCG). Cases of MC patients treated with advanced therapies were included through a standardised collection form. Clinical response was defined as a 50% reduction in stool frequency (SF); clinical remission was defined according to the Hjortswang criteria as < 3 stools/day or < 1 watery stool/day. Results Ninety-nine patients were identified (Table 1), of whom all but one were previously treated with budesonide. Reasons for budesonide discontinuation included primary non-response (PNR, 16.3%), refractory disease (34.7%), budesonide dependency (38.8%), or adverse events (AE, 10.2%). In total, 165 treatment cycles with advanced therapy (47 IFX, 40 ADA, 47 VDZ, 10 UST, 14 JAK inhibitors, 7 other) were reported. First-line advanced therapies included mainly anti-TNF (76.8%) and VDZ (20.2%) (Figure 1A). Patients were exposed to anti-TNF therapy for a median of 1.4 [0.5-3.1] years, with a significant drop in SF after induction (p<0.001), resulting in 50.0% clinical remission (Figure 1B). However, 63.0% ultimately discontinued anti-TNF therapy, mainly due to PNR (37.9%), loss-of-response (LOR, 36.2%) or AE (20.7%). VDZ induced 46.8% clinical remission, reflected in a significant drop in SF (p<0.001). Though, a 59.6% discontinuation rate was observed after a median 0.6 [0.3-1.3] years, mainly due to PNR (63.0%) and LOR (22.2%). Similarly, for UST a 40.0% clinical remission rate was accompanied by 60.0% therapy withdrawal, primarily due to PNR (83.3%). In contrast, JAK inhibition resulted in 78.6% clinical remission, with a substantial drop in SF (p=0.002) and 21.4% discontinuation rate after a median exposure of 0.6 [0.3-1.6] years. Conclusion Almost all advanced therapies are used in budesonide refractory or dependent MC, with anti-TNF agents the most often used first-line options. However, anti-TNF discontinuation is frequent due to lack/loss of efficacy. VDZ and UST could be alternatives, but also have a substantial discontinuation rate. In this retrospective series, the small number (n=14) of JAK inhibitor treated patients had the highest remission rate, suggesting further research on the role of JAK inhibitors in MC.

Schlüsselwörter chronisch-entzündliche Darmerkrankungen - CED - Diagnose - Therapie - Remission - Remissionserhaltung

Abstract Background Integrating systematic monitoring of patient-reported outcomes (PROs) with clinical information may enhance disease management and improve patient outcomes. Vedolizumab (VDZ) is approved for treating patients with ulcerative colitis (UC) and Crohn’s disease (CD). The German, multicentre, prospective, non-interventional LISTEN II study evaluates patient characteristics and effectiveness of VDZ treatment in real-world clinical practice, focusing on PROs. Methods Adult UC or CD patients, who either initiate VDZ intravenously (IV) or switch from IV maintenance to subcutaneous (SC) formulation, are enrolled. Data on patient characteristics, modalities of VDZ use and disease activity are recorded quarterly over one year. PROs are recorded via weekly questionnaires in app (ePRO). Sustained ePRO use was defined as proportion of patients reporting at least one PRO for ≥80% of available questionnaires. Interim data up to 9 months follow-up are presented. Results Data of 299 UC and 174 CD patients (51% and 59% female, respectively) with a mean age of 40 years were analysed. VDZ treatment was newly initiated IV (start) in 259 UC and 151 CD patients and switched from IV to SC application (switch) by 40 UC and 23 CD patients at baseline. Total mean pMayo score decreased in UC start-patients from 5.0 to 1.7 and from 1.1 to 0.8 in switch-patients. In CD start-patients HBI score decreased from 5.5 to 2.5 and from 3.1 to 2.3 in switch-patients. The ePRO was initially utilized by 226 UC and 124 CD patients (51% and 61% female, 57% and 52% sustained ePRO users, respectively) with a mean age of 39 years; 86% were start- and 14% switch-patients. Disease activity at baseline was comparable to the overall population, showing a total mean pMayo score of 4.5 for UC and a HBI of 5.3 for CD patients. Most UC (82%) and CD patients (88%) used a patient support program for the first time. ePRO use declined to approx. 40% usage within the second quarter and to 30% during further follow-up. Overall, mean symptom scores reported via the ePRO declined during the 9-month follow-up period. The most notable improvements (baseline to month 9) were reported for the symptom impact on work productivity (from 3.9 to 1.7 points) in UC patients and for sick leave (from 1.3 to 0.4 points) in CD patients (Table). For most PROs reduction in symptom scores was apparent within the first week of ePRO-use (Figure). Conclusion LISTEN II real-world data confirm VDZ effectiveness in UC and CD patients, with reduction in disease activity in IV starters and maintained effectiveness in IV-to-SC switchers. Both UC and CD patients reported sustained symptom improvement under VDZ treatment, with scores indicating improvement within the first week of ePRO-use.

Introduction: Long-term sequelae following acute SARS-CoV-2 infection appear to be common in patients with inflammatory bowel diseases (IBDs). Methods: We examined the frequency and characteristics of post-COVID-symptoms in patients with IBD (IBD-COVID), comparing them to two control cohorts: infected household members of the IBD-COVID patients without IBD (CONT-COVID) and IBD patients without SARS-COV-2 infection (IBD-no-COVID). A questionnaire for the retrospective documentation of possible post-COVID-19 symptoms was distributed to patients and controls from eight referral centers. Results: The 319 IBD-COVID, 108 CONT-COVID, and the 221 IBD-no-COVID patients were similar in terms of sex, age, and comorbidities. The occurrence and duration of fatigue in the IBD-COVID cohort correlated with IBD activity. Other complaints such as reduced cognitive performance (p < 0.05) and sleeping disorders (p < 0.05) were even more common in IBD-COVID patients. Persistent hematochezia (p < 0.001), abdominal pain (p < 0.005), diarrhea (p < 0.0001), and anal problems (p < 0.01) were more often in the IBD-COVID patients than in the CONT-COVID cohort. Furthermore, typical IBD-associated symptoms persist for a longer period after an infection. Frequency of post-COVID complaints is higher in IBD patients compared to controls. After infection, the number of outpatient consultations increased in IBD-COVID patients (7.8% vs. 10.9%, p = 0.008). Conclusion: Fatigue, cognitive impairment, and sleep disturbances are more prevalent among IBD-COVID than CONT-COVID patients. Furthermore, typical IBD-associated symptoms persist for a longer period after an infection. Frequency of post-COVID complaints is higher in IBD patients compared to controls. Tight control of IBD activity could be a suitable tool to avoid post-COVID problems.

BACKGROUND AND AIMS:Data regarding the effectiveness and safety of Janus kinase [JAK] inhibitors and sphingosine-1-phosphate [S1P] receptor modulators in antibiotic refractory chronic pouchitis [CARP] are lacking.METHODS:This ECCO-CONFER project retrospectively collected data for JAK inhibitor or S1P receptor modulator treatments for CARP with at least 3 months of follow-up. The outcomes included corticosteroid- and antibiotic-free clinical response and remission at 3 and 12 months, and trends in modified pouchitis disease activity index [mPDAI], endoscopic PDAI, C-reactive protein, and calprotectin.RESULTS:Seventeen treatments in 15 patients were evaluated. Previous pouchitis treatments included infliximab [5/15], adalimumab [4/15], vedolizumab [9/15], and ustekinumab [5/15]. Pooling data on JAK inhibitors [eight tofacitinib, one filgotinib, and six upadacitinib] after 3 months [T3], steroid- and antibiotic-free clinical response was achieved in 53.3% [8/15], and steroid- and antibiotic-free clinical remission was achieved in 40% [6/15]. Of the patients with at least 12 months of follow-up, steroid- and antibiotic-free clinical response was achieved in 50% [3/6] and remission in one patient [16.7%], endoscopic response in 50% [3/6], and endoscopic remission in 50% [3/6]. Of the two ozanimod treatments at T3, steroid- and antibiotic-free clinical response was achieved in one patient, without remission; both discontinued ozanimod before T12. No side effects were reported.CONCLUSIONS:Small molecules may represent a suitable option for CARP refractory to multiple biologics, deserving further investigation.

Abstract Background Data regarding effectiveness and safety of JAK inhibitors and S1P receptor modulators in chronic antibiotic refractory pouchitis (CARP) are lacking. This ECCO-CONFER project collected cases of CARP treated with JAK inhibitors or S1P receptor modulators. Methods This retrospective multicentre study collected cases across Europe through the ECCO-CONFER project, including patients with ulcerative colitis (UC) diagnosis who underwent proctocolectomy with ileal pouch anal anastomosis (IPAA), treated with JAK inhibitors or S1P receptor modulators for CARP and at least three months of follow up. Main outcomes were steroid and antibiotics-free clinical response at three months (T3) for each drug, defined as clinical part of modified Pouchitis Disease Activity Index (mPDAI) reduction by ≥1 points, steroid and antibiotics-free clinical response at 1 year (T12) assessment, defined as mPDAI reduction by ≥2 points, steroid and antibiotics-free clinical remission (mPDAI=0) at T3 and T12, endoscopic response at T12 (improvement in PDAI Endoscopic Inflammation subscore reaching <3) and endoscopic remission at T12 (endoscopic PDAI ≤1). Non-response imputation was applied. Results Seventeen treatments with small molecules of CARP in 15 patients were collected from nine centres in seven countries. Eight patients were treated with tofacitinib; steroid and antibiotics-free clinical response at T3 was achieved in six patients (75%) and steroid and antibiotics-free clinical remission was achieved in five patients (62.5%). One patient discontinued tofacitinib for loss of response after eight months. Of the patients with at least 12 months of follow-up, steroid and antibiotics-free clinical response was achieved in 50.0% of patients, steroid and antibiotics-free clinical remission in one patient (16.7%), endoscopic response in 50.0% and endoscopic remission in 50.0%. One patient was treated with filgotinib, neither steroid and antibiotics-free clinical response nor steroid and antibiotics-free clinical remission were achieved. Six treatments with upadacitinib were collected: at T3 steroid and antibiotics-free clinical response was achieved in 33.3% and steroid and antibiotics-free clinical remission was achieved in 16.7% of cases. Two cases were treated with ozanimod. At T3 steroid and antibiotics-free clinical response was achieved in one patient (50.0%) and steroid and antibiotics-free clinical remission was not achieved. No side effects were reported. Baseline characteristics and results are summarized respectively in figure 1 and table 2. Conclusion In a multiple biologic-refractory population, small molecules might be a suitable treatment option for CARP. Based on current limited data, the use of JAK inhibitors should be further investigated.

Abstract Background The number of advanced therapies (ADT) approved for the treatment (Tx) of inflammatory bowel disease (IBD) in is increasing, however, yet no guidance on optimal sequencing of treatments is available in Germany (and elsewhere). This study aims to investigate applied Tx sequences of ADT in claims data based on real-world setting across Germany in patients (pts) with IBD. Methods A retrospective healthcare claims data analysis was conducted using claims data from approx. 4.5 Mio pts within German statutory health insurance, including pts diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) from 2014 to 2021. Pts were followed up for at least 6 months after the first prescription of ADT (index date) if not deceased. A pre-index period of at least 12 months was applied to only include pts naïve to ADT. The study assessed Tx sequences and time to next treatment (TTNT) among other parameters. Data was not adjusted to disease severity and only descriptively reflects real world Tx patterns within the database. Results The database included 15.041/18.361 pts with CD/UC. Pts with CD/UC starting ADT between 2014 to 2021 received either Adalimumab (ADA: 923/337), Infliximab (IFX: 616/419), Ustekinumab (UST: 113/25) or Vedolizumab (VDZ: 139/248). In an analysis of ADT sequences and TTNT defined as start of first line (1L) Tx to start of second line (2L) Tx we found that during the observation period the majority of pts (71.4%) have not switched to 2L Tx yet. In 1L, ADA was observed as the preferred Tx in CD pts (51.5%) followed by IFX (34.4%), VDZ (7.8%) and UST (6.3%), in UC pts IFX (40.7%) was mostly prescribed as 1L followed by ADA (32.8%), VDZ (24.1%) and UST (2.4%). The proportion (%) of pts not switched to 2L Tx within one year for CD/UC were: ADA (83.6/70.3), IFX (79.0/73.1), UST (93.5/96.0) and VDZ (85.4/86.6). Within three years proportions of pts not switched to 2L Tx changed for CD/UC: ADA (68.1/54.5), IFX (57.8/56.8), UST (82.5/72.0) and VDZ (72.7/73.0) (table1). For pts who had a switch to a different ADT, the switch occurred within one year in over 50% of all pts. Most Tx switches (45.8%) were observed in pts who received IFX as 1L Tx, both in the UC and CD population. The majority of CD pts that received 2L Tx were switched to UST (35.7%), while in UC, a high proportion of pts were switched to VDZ (44.3%). Further Tx pathways and proportions of switches are summarized in Figure 1. Conclusion The study found that most IBD pts started ADT with ADA or IFX, but unadjusted time on 1L data may suggest a trend towards superior TTNT of VDZ and UST in UC and CD. Data should be interpreted carefully, as pts for >1L are limited and UST and VDZ were approved during the study period.

BACKGROUND The aim of this observational, real-world evidence, modified intention-to-treat (mITT) study based on prospectively collected data from the VEDOIBD registry was to compare the effectiveness of vedolizumab (VEDO) vs antitumor necrosis factor (anti-TNF) in biologic-naïve Crohn's disease (CD) patients. METHODS Between 2017 and 2020, 557 CD patients starting therapy with VEDO or anti-TNF were consecutively enrolled in 45 IBD centers across Germany. Per study protocol, the analysis excluded biologic-experienced patients and those with a missing Harvey-Bradshaw Index score, resulting in a final sample of 327 biologic-naïve CD patients. Clinical remission was measured using the Harvey-Bradshaw Index at the end of induction therapy and after 1 and 2 years. Switching to a different therapy was considered an outcome failure. Propensity score adjustment with inverse probability of treatment weighting was used to correct for confounding. RESULTS The effectiveness of both VEDO (n = 86) and anti-TNF (n = 241) was remarkably high for induction treatment, but VEDO performed significantly less well than anti-TNF (clinical remission: 56.3% vs 73.9%, P < .05). In contrast, clinical remission after 2 years was significantly better for VEDO compared with anti-TNF (74.2% vs 44.7%; P < .05; odds ratio, 0.45; 95% CI, 0.22-0.94). Remarkably, only 17% of patients switched from VEDO to another biologic vs 44% who received anti-TNF. CONCLUSIONS The results of this prospective, 2-year, real-world evidence study suggest that the choice of VEDO led to higher remission rates after 2 years compared with anti-TNF. This could support the role of VEDO as a first-line biologic therapy in CD.