Exabis Library

Sphingosine-1-phosphate (S1P) receptor modulators may be associated with bradycardia and atrioventricular conduction delays. A previous analysis demonstrated first-dose ozanimod had minimal effects on cardiac function, including in patients (pts) with a known history of cardiovascular disease. This analysis evaluated long-term cardiac safety following continuous ozanimod treatment from the phase 3 ulcerative colitis (UC) True North trial and multiple sclerosis (MS) 12-mo SUNBEAM and 24-mo RADIANCE trials. 

Ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg)–treated pts from True North and pooled SUNBEAM/RADIANCE trials were included. In True North, pts in Cohort 1 received double-blind ozanimod or placebo and pts in Cohort 2 received open-label ozanimod in the induction period; in the maintenance period, pts with clinical response to ozanimod at 10 weeks were rerandomized to double-blind ozanimod or placebo. In True North, ECGs were monitored at screening, day 1, wk-10, and wk-52; heart rate (HR) was monitored at every visit. In the MS trials, ECGs were monitored at screening, baseline, day 15, and end of treatment (EOT); HR was monitored similarly at the beginning, then every 3 mo until EOT. Cardiac-related treatment-emergent AEs (TEAEs) were reported.

In the UC trial, continuous ozanimod treatment was not associated with any clinically significant changes in HR or ECG. The incidence of cardiac-related TEAEs with ozanimod during induction in Cohorts 1 and 2 was low (Table). In maintenance, cardiac-related TEAEs were reported in 1.3% (3/230) of pts in the continuous ozanimod group (Table); incidence was numerically higher in ozanimod pts with (2 of 57 pts [3.5%]) versus without (1 of 173 pts [0.6%]) prior history of cardiovascular disease. Cardiac-related serious AEs (SAEs) were uncommon (angina pectoris, coronary artery stenosis, pericarditis in 1 patient each). In the pooled MS studies, no clinically significant HR or ECG changes were associated with chronic treatment up to mo 24. The incidence of cardiac-related TEAEs was low with ozanimod (Table); incidence was similar among pts with (6 of 171 pts [3.5%]) versus without (24 of 711 pts [3.4%]) prior history of cardiovascular disease. Two of 882 patients experienced cardiac-related SAEs resulting in hospitalization with ozanimod in the MS studies (asymptomatic sinus bradycardia [HR 44 bpm] and symptomatic supraventricular tachycardia).

Ozanimod had a manageable long-term cardiac safety profile with a low incidence of bradycardia and few serious long-term cardiac safety findings in the phase 3 UC and MS ozanimod trials.

Claire Liefferinckx discusses her work with the Belgian Inflammatory Bowel Disease research and development group (BIRD) to capture real-world outcomes of ustekinumab treatment for Crohn’s disease, using a large national cohort of patients with a history of significant previous biologic exposure.

The vast majority of patients with ulcerative colitis (UC) and Crohn’s disease (CD) who acquire coronavirus disease 2019 (COVID-19) survive the infection. Still, the long-term health consequences of COVID-19 are not well described in patients with underlying inflammatory bowel disease (IBD).

We conducted a population-based study investigating the outcomes of COVID-19 among patients with UC and CD in Denmark. The Danish COVID-19 IBD Database is an extensive population-based database which prospectively monitors the disease course of laboratory-confirmed COVID-19 among patients with UC and CD. Severe COVID-19 was defined as COVID-19 necessitating intensive care unit admission, ventilator use, or death, while adverse COVID-19 was defined as requirement of COVID-19 related hospitalization. Sequelae following COVID-19 were defined as symptoms that developed during or after an infection consistent with COVID-19, were present for more than 12 weeks, and were not attributable to alternative diagnoses.

The study included 319 patients with UC and 197 patients with CD from January 28^th, 2020, to April 1^st, 2021. Of these, a total of 137 (42.9%) and 85 (43.1%), respectively, participated in a subsequent investigation of post-COVID-19 sequelae after a median of 5.1 months (IQR 4.5-7.9) after infection (Table 1). An equal proportion of patients with UC (58 (42.3%)) and CD (39 (45.9%), p=0.60) reported persisting symptoms of COVID-19 for at least 12 weeks, consistent with the development of post-COVID-19 syndrome. The most common persisting patient-reported symptoms included fatigue (UC: 49 (35.8%), CD: 31 (36.5%), p=0.92), anosmia (UC: 37 (27.0%), CD: 25 (29.4%), p=0.70), ageusia (UC: 26 (19.0%), CD: 24 (28.2%), p=0.11), headache (UC: 19 (13.9%), CD: 16 (18.8%), p=0.32), dyspnea (UC: 19 (13.9%), CD: 16 (18.8%), p=0.32), and arthralgia (UC: 17 (12.4%), CD: 14 (16.5%), p=0.40) (Figure 1). Only discontinuation of immunosuppressive therapies for UC during COVID-19 (OR=1.50 (95% CI 1.07-10.22), p=0.01) and the severity of COVID-19 among patients with CD were independently associated with the long-term effects of COVID-19 (OR=2.76 (95% CI 1.05-3.90), p=0.04) (Tables 2-3).

This Danish population-based study found a high occurrence of patient-reported persisting symptoms following the acute phase of COVID-19 infection, which were associated with the discontinuation of immunosuppressive therapies for UC during COVID-19 and the severity of COVID-19 among patients with CD. These findings might have implications for planning the healthcare of patients with inflammatory bowel diseases in the post-COVID-19 era.

Very early-onset inflammatory bowel disease (VEOIBD) is diagnosed before the age of 6 years while infantile IBD occurs before the age of 2 years. We aimed to assess disease characteristics and long-term outcomes in these populations.

We conducted a retrospective longitudinal cohort study in 21 pediatric centers worldwide. Patients diagnosed with VEOIBD between the years 2008-2018 with at least 2 years of follow-up were included.

The cohort included 243 patients (52% males), with median follow-up of 5.8 (IQR 3.2-8.4) years. Median age at diagnosis was 3.3 (IQR 1.8-4.5) years, with 69 (28%) diagnosed before the age of 2 years. Disease was classified as Crohn’s disease (CD), ulcerative colitis (UC) and IBD-unclassified (IBDU) in 30%, 59% and 11%, respectively. In patients with UC or IBDU, 75% presented with pancolitis. In patients with CD, 62% presented with isolated colonic disease and 32% with ileo-colonic disease, while 19% had perianal involvement. Genetic testing was performed in 96 (40%) patients [40 (58%) <2 years, 56 (32%) 2-6 years, p=0.001], with monogenic diagnosis identified in 23% (33% and 16%, respectively, p=0.08). The most common findings were mutations in IL10-receptor (5 cases, 23%). Stricturing or penetrating disease was observed in 9 cases (4%).

First induction therapies were corticosteroids, 5-aminosalicylic acid (5ASA) and nutritional therapy in 53%, 30% and 11%, respectively. Corticosteroids were more common as first induction in infantile vs. non-infantile IBD (64% vs. 49% respectively, p=0.003). Maintenance therapies included deep immune-suppression (mainly biologics and corticosteroids) in 51%, immunomodulators in 27%, and non-immunosuppressive agents (5-ASA, nutritional therapy and antibiotics) in 22% of patients, with no significant differences between age groups.

Compared to patients diagnosed after 2 years of age, patients with infantile IBD presented with higher rates of IBDU, lower levels of hemoglobin and albumin and higher levels of CRP, lower weight (but not height) z-scores, had lower rates of response to first induction therapy and shorter time to hospitalization during follow-up (p<0.05 for all).

Colectomy was performed in 11% and diversion surgery in 4% of the cohort, with no significant differences between age groups. No malignancies and nor deaths were observed. At end of follow-up, 85% of patients were in corticosteroid free clinical remission.

Patients with VEOIBD, including infantile IBD, have fair long-term outcome with low rates of complications and surgical interventions. Nevertheless, patients with infantile IBD demonstrated more severe clinical features at presentation and a lower response to induction therapy.

In the UNIFI study of ustekinumab (UST) in ulcerative colitis (UC), patients who achieved histo-endoscopic mucosal healing (HEMH; ie, both histologic and endoscopic improvement of mucosa) after induction had higher clinical remission and corticosteroid-free clinical remission rates through 1 year than those who achieved either histologic or endoscopic improvement alone.¹ Here, we report the effect of achieving HEMH after induction on long-term symptomatic outcomes through 3 years.

Patients who were in clinical response after 8 wks of IV induction with UST 130mg or ~6mg/kg (wk 8 responders) were randomized to maintenance treatment with SC UST 90mg q12w or q8w on entry into maintenance. Those who were not in clinical response to the initial UST dose at wk8 but achieved response at wk16 after receiving a single SC dose of UST 90mg at wk8 (wk16 responders) entered maintenance receiving SC 90mg q8w. After 44 wks of maintenance treatment, patients were given the option to continue in the long-term extension. HEMH was defined as achieving both endoscopic improvement (Mayo endoscopy subscore ≤1) and histologic improvement (neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue; based on the Geboes score). Patients with insufficient data for histologic evaluation at the end of induction were excluded. Symptomatic remission was defined as a Mayo stool frequency subscore of 0 or 1 and a Mayo rectal bleeding subscore of 0.

Of the 438 patients who were wk8 or wk16 responders to UST induction and received UST maintenance, 116 (26.5%) achieved HEMH after induction, 30 (6.8%) achieved endoscopic improvement without histologic improvement (EI), and 106 (24.2%) achieved histologic improvement without endoscopic improvement (HI). Patients who achieved HEMH after induction had higher symptomatic remission and corticosteroid-free symptomatic remission rates at wks92 and 152 than those with EI or HI; the differences were statistically significantly greater at wk152, while they were only numerically greater  at wk92 (Table). The differences were primarily driven by patients with HEMH after induction being more likely to maintain symptomatic remission between wks92 and 152, than those with EI or HI alone. Symptomatic remission and corticosteroid-free remission rates decreased between wks92 and 152 in patients with EI or HI only.

Patients with UC who achieved HEMH after induction with UST were more likely to maintain symptomatic remission and corticosteroid-free symptomatic remission between 2 and 3 years of maintenance treatment than those who achieved EI or HI alone.

1. K Li, et al. Poster 1008. Presented at UEGW 2019. October 22, 2019. Barcelona, Spain.

The PISA-II trial showed that anti-TNF induction combined with surgical closure induces MRI healing more frequently than anti-TNF alone at 18 months follow-up (FU) and that this was associated with no recurrences at the time. The aim of this study was to compare long-term outcomes of both treatment arms.

In this FU study, data were collected from patients who participated in the PISA-II trial, a multicentre, international patient preference randomised controlled trial that compared anti-TNF induction combined with surgical closure to anti-TNF therapy alone as treatment for Crohn’s perianal fistulas. FU data were collected from the time of enrolment in the PISA-II trial until November 2021. Primary outcome was radiological healing at MRI and secondary outcomes included long-term clinical closure, recurrences, anti-TNF trough levels (suboptimal level was defined as infliximab <5.0ug/ml, adalimumab <5.9ug/ml), incontinence (improved, decreased or never had), and a decisional regret scale.

Long-term FU data were collected from 88 out of 94 patients included in the PISA-II trial, 35/38 in the surgical closure arm and 53/56 in the anti-TNF treatment arm. Median FU was 5 years (IQR 4-7). During long-term FU radiological healing occurred in significantly more patients in the surgical closure arm (40% vs 17%; P=0.018). Long-term clinical closure occurred in 71% in the surgical closure arm and in 60% in the anti-TNF treatment arm (P=0.533). Recurrences occurred in 20% in the surgical closure arm and in 36% in the anti-TNF treatment arm (P=0.111). One patient with radiological healing developed a recurrence (4.3%) vs 12/57 (21.1%) patients with clinical closure. Trough levels were available in 32/53 patients treated with anti-TNF. Around the time of recurrence a suboptimal anti-TNF serum trough level occurred in 6/10. In the surgical closure arm, 6 patients had more and 6 patients had less incontinence problems after treatment, comparable to the 5 patient in the anti-TNF treatment arm with more and 8 with less incontinence problems. All patients in the surgical closure arm who completed the questionnaire (strongly) agreed that undergoing surgery was the right decision and 79% of the patients in the anti-TNF arm (strongly) agreed, 14% neither agreed nor disagreed and 7% disagreed that anti-TNF treatment was the right decision.

This study further supports the previous finding that anti-TNF induction combined with surgical closure should be considered in patients with Crohn’s perianal fistulas as long-term outcomes are favourable. Interestingly, surgical closure does not seem to be correlated to decreased continence, and all patients agreed that surgery was the right decision.

The PISA-II trial showed that anti-TNF induction combined with surgical closure induces MRI healing more frequently than anti-TNF alone at 18 months follow-up (FU) and that this was associated with no recurrences at the time. The aim of this study was to compare long-term outcomes of both treatment arms.

In this FU study, data were collected from patients who participated in the PISA-II trial, a multicentre, international patient preference randomised controlled trial that compared anti-TNF induction combined with surgical closure to anti-TNF therapy alone as treatment for Crohn’s perianal fistulas. FU data were collected from the time of enrolment in the PISA-II trial until November 2021. Primary outcome was radiological healing at MRI and secondary outcomes included long-term clinical closure, recurrences, anti-TNF trough levels (suboptimal level was defined as infliximab <5.0ug/ml, adalimumab <5.9ug/ml), incontinence (improved, decreased or never had), and a decisional regret scale.

Long-term FU data were collected from 88 out of 94 patients included in the PISA-II trial, 35/38 in the surgical closure arm and 53/56 in the anti-TNF treatment arm. Median FU was 5 years (IQR 4-7). During long-term FU radiological healing occurred in significantly more patients in the surgical closure arm (40% vs 17%; P=0.018). Long-term clinical closure occurred in 71% in the surgical closure arm and in 60% in the anti-TNF treatment arm (P=0.533). Recurrences occurred in 20% in the surgical closure arm and in 36% in the anti-TNF treatment arm (P=0.111). One patient with radiological healing developed a recurrence (4.3%) vs 12/57 (21.1%) patients with clinical closure. Trough levels were available in 32/53 patients treated with anti-TNF. Around the time of recurrence a suboptimal anti-TNF serum trough level occurred in 6/10. In the surgical closure arm, 6 patients had more and 6 patients had less incontinence problems after treatment, comparable to the 5 patient in the anti-TNF treatment arm with more and 8 with less incontinence problems. All patients in the surgical closure arm who completed the questionnaire (strongly) agreed that undergoing surgery was the right decision and 79% of the patients in the anti-TNF arm (strongly) agreed, 14% neither agreed nor disagreed and 7% disagreed that anti-TNF treatment was the right decision.

This study further supports the previous finding that anti-TNF induction combined with surgical closure should be considered in patients with Crohn’s perianal fistulas as long-term outcomes are favourable. Interestingly, surgical closure does not seem to be correlated to decreased continence, and all patients agreed that surgery was the right decision.

Ustekinumab (UST), an anti-interleukin-12/23 antibody, has successfully been introduced in the treatment of IBD, mainly in patients failing anti-TNF-agents. The STOCUSTE study includes IBD patients treated with UST at four teaching hospitals in Stockholm to provide long-term follow-up data. Here, we report the outcome in Crohn’s disease over the first 12 months.

This retrospective study includes patients diagnosed with Crohn’s disease and treated with UST who were followed until withdrawal of treatment for any reason, or until end of study, July 31, 2021. Disease activity (Harvey-Bradshaw Index (HBI); Physician Global Assessment (PGA), laboratory parameters and drug persistence were assessed. The primary outcome was remission (HBI ≤4; PGA = 0) and response (decrease HBI ≥3; PGA ≥1 from baseline) at 3 and 12 months, respectively.

120 patients, 61 women (51%), with a median age of 27 (IQR 27) at start of UST were included. All patients had luminal disease and 19 (16%) also fistulizing disease. 109 (91%) had failed ≥1 and 59 (49%) ≥2 anti-TNF drugs. In addition, 50 patients (42%) failed vedolizumab. At inclusion, 106 (88%) had active disease; 40 (33%) were on corticosteroid treatment and 22 (18%) on thiopurines.

The persistence on UST was high, 93% at 3 months and 56% at 12 months. Of patients on UST at 3 months, 38% were in remission, and, at 12 months, 53%. An additional 26% were in response at 12 months. Of the 40 patients initially on corticosteroids, 17 (43%) and 28 (70%) had stopped steroids at 3 and 12 months, respectively. The median faecal calprotectin level declined from 272 (90-1763) at baseline to 75 (49-99) µg/g at 3 months (p<0.01). There was a slight decrease in CRP over 12 months, from 3 (2-12) to 1 (1-2) mg/l, together with increases in haemoglobin and serum albumin (n.s).

Withdrawal from treatment during the first 12 months was 44% (53/120), mainly due to persisting disease activity. Four patients were withdrawn due to adverse events, three needed bowel surgery, two had malignancy and one patient suffered from systemic infection.

In this group of difficult-to-treat patients with Crohn’s disease, UST was shown to be effective in the majority, with high drug persistence at 12 months in combination with a favorable safety profile.

Ozanimod was approved by the FDA to treat patients (pts) with moderately to severely active Ulcerative Colitis (UC) based on the results from the 52-week (wk) phase 3 True North (TN) study. We sought to evaluate long-term efficacy and safety of ozanimod.

We examined data from an interim analysis of pts in the TN parent study who entered the ongoing TN open-label extension (OLE). Pts entered the TN OLE from the phase 3 TN study if they were non-responders at the end of induction, lost response during maintenance, or completed maintenance treatment, or from the phase 2 Touchstone OLE if they remained at study closure and received once-daily oral ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg). Clinical remission, clinical response, endoscopic improvement, and corticosteroid (CS)-free remission were evaluated at Wks 46, 94, and 142 in the TN OLE for all pts who entered the OLE from the TN parent study, and in the subset of pts in clinical response at the OLE entry. The data were analysed in the intent-to-treat population using observed cases (OC), which used the number of pts remaining in the study at the corresponding time point, and non-responder imputation (NRI), which used the number of pts remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed. Treatment-emergent adverse events were evaluated from the pooled phase 2 and phase 3 UC studies.

A total of 823 pts from TN entered the TN OLE; as of the cut-off date (Sept 30, 2020), 64% completed Wk 46, 34% completed Wk 94, and 14% completed Wk 142 of the OLE. The most common reason for discontinuation was lack of efficacy (21%). Baseline demographics were similar as in the TN study. A total of 261 pts were in clinical response at the time of OLE entry. OC analyses showed that the percentage of pts achieving clinical remission, clinical response, endoscopic improvement, and CS-free remission was maintained over time (Table). Efficacy in the responders was higher compared to the total population and was comparable within the endpoints at Wks 46 and 94. Using the more conservative NRI analysis, the proportion of pts achieving each endpoint was lower than in the OC; however, after 94 wks of OLE treatment, 34% of all pts and 55% of the responders still maintained clinical response. No new safety signals were seen with longer-term ozanimod use in the 1158 pts in the pooled population.

UC pts from the phase 3 TN study demonstrated maintenance of response with long-term ozanimod treatment. These data reflect approximately 2 years of additional ozanimod treatment, with no new safety signals identified.

1. To understand different treatment options for perianal fistulas beyond TNF-antibodies
2. To have an overview over optimal treatment strategies in patients with perianal fistulas

Protein tyrosine phosphtase non-receptor type 23 (PTPN23) plays a critical role in regulating epidermal growth factor (EGF) receptor signaling and its loss has been associated with aberrant cell proliferation and promotes onset of epithelial cancers. However, the role of PTPN23 in the intestinal epithelium has not been investigated yet. Here, we investigated how PTPN23 deletion in intestinal epithelial cells (IEC) affects intestinal homeostasis.

To study the role of PTPN23 in the intestinal epithelium, we crossed mice with a LoxP flanked PTPN23 gene (PTPN23^fl/fl mice) to mice expressing the CreERT construct under the villin promoter (PTPN23-VilCreERT mice). PTPN23 was deleted in IEC in these mice by tamoxifen-injections on five consecutive days. PTPN23 ^fl/fl mice injected with tamoxifen served as control.

PTPN23 deletion in IEC resulted in drastic loss of weight starting around 10-14days after the first tamoxifen injection, eventually leading to death within 3-5 weeks due to severe wasting disease with severe diarrhea. Histology revealed massive hyper-proliferation of the colonic epithelium accompanied with elevated immune cell infiltration. In line with previous reports on the function of PTPN23, we observed highly elevated levels of EGF receptor, possibly accounting for the massive epithelial hyper-proliferation and aberrant water secretion/defective water resorption in these mice. Furthermore, we observed bacterial translocation to the spleen and the liver, indicating defective anti-bacterial defense in the intestinal epithelium of PTPN23-VilCreERT mice. In line with this, 16S sequencing revealed significant differences in the intestinal microbiome with an overgrowth of bacteria that have been reported to be heavily coated with IgA. PTPN23-VilCreERT mice showed reduced apical presence of the poly Ig receptor, a receptor that transports IgA from the lamina propria through IEC into the gut lumen. Notably, while serum IgA levels were normal, its levels in the stool were reduced, confirming defective transport of IgA into the gut lumen. In addition, autophagy was significantly reduced in PTPN23-VilCreERT mice when compared to their littermates. Of interest, antibiotic treatment was sufficient to prevent epithelial hyper-proliferation, diarrhea and death in PTPN23VilCreERT mice, indicating that this drastic phenotype was microbiota-dependent and likely the result of defects in bacterial handling.

Our results demonstrate that PTPN23 is indispensible for normal IEC function and its loss renders the intestinal epithelium unable to cope with invading bacteria. This uncovers a novel, so far unknown role of PTPN23 for regulating pathways involved in bacterial handling.

In a previous real-world study of long-term (up to 4 years) treatment with golimumab (GLM) in ulcerative colitis (UC), patients reported a low overall colectomy incidence (5.8%).¹ This analysis evaluates the incidence of colectomy among patients with moderate-to-severe active UC in the PURSUIT-maintenance (-M)² and long-term extension (-LTE)³ studies.

Eligible PURSUIT-M trial participants completed a 6-week GLM induction trial without requiring colectomy.^4,5 Responders to GLM induction were randomised 1:1:1 to GLM 50 mg, 100 mg, or placebo (PBO) maintenance for up to 1 year, administered every 4 weeks (q4w). Nonresponders to GLM or PBO induction received GLM 100 mg; responders to PBO induction received PBO (each administered q4w for up to 1 year). Participants experiencing loss of clinical response during maintenance were eligible for one treatment intensification (switch from PBO to GLM 100 mg, or GLM dose increase). Participants who completed PURSUIT-M were eligible to continue their treatment in the 3-year PURSUIT-LTE study. Colectomy (total or partial) was a prespecified outcome in PURSUIT-M; serious adverse event narratives and safety summaries were also examined for reports of colectomy (total or partial). For PURSUIT-LTE, serious adverse event narratives and safety summaries were examined for reports of colectomy (total or partial). The reasons for colectomy were not collected systematically in PURSUIT-M or -LTE.  Descriptive information on colectomies was assessed and reported.

A total of 60 (4.9%) colectomies were reported among the 1228 patients who enrolled in the 1-year PURSUIT-M study, including 672 participants who continued into the 3-year LTE study. The table shows the distribution of colectomies by study phase, induction responder status, initial treatment assignment, and treatment prior to colectomy. The colectomy rate during the 3-year extension was lower than that observed during the maintenance phase of the study [1.3% (9/672) compared to 4.2% (51/1228)].

Consistent with previously reported data, this retrospective evaluation of colectomy data from the PURSUIT-M and -LTE studies in patients with moderate-to-severe active UC demonstrated a low occurrence of colectomy with long-term (up to 4 years) GLM treatment. The limited number of colectomies observed in the LTE study occurred predominantly in patients with more severe disease at baseline (induction non-responders) who had been receiving GLM 100 mg. 

References:
1. Iborra M, et al. SciRep. 2020;10:17774
2. Sandborn WJ, et al. Gastroenterol. 2014;146:96–109
3. Reinisch W, et al. J Crohn's Col. 2018;12:1053–1066
4. Sandborn WJ, et al. Gastroenterol. 2014;146:85–95
5. Rutgeerts P, et al. Aliment Pharmacol Ther. 2015;42:504–514

In this real-world-evidence (RWE) study we aimed to analyse the persistence of biologic therapy in biologic-naïve ulcerative colitis (UC) patients and to compare 1-year effectiveness of vedolizumab (VDZ) and anti-TNF.

Between 2017 and 2020, 1200 consecutively enrolled biologic-naïve and biologic- experienced patients with UC and Crohn´s disease (CD) were prospectively included in the VEDO_IBD-Registry from 45 IBD-experienced centres across Germany. After exclusion of bio-experienced patients, CD and missing outcomes, the final sample consisted of 274 biologic-naïve UC-patients with 1-year follow-up data. Switchers of a drug were considered as treatment failure (modified intention-to-treat analysis; mITT) while switchers were excluded from per protocol analysis (PP). Clinical response modified (reduction of partial Mayo score (pMayo) from baseline to 1-year by >3 points or a reduction of at least 30% compared to baseline or reaching remission at 1-year) and (steroid-free) remission rates (pMayo ≤1 plus a bleeding subscore=0 (and no systemic use of steroids or budesonide at 1-year)) were predefined as outcomes. To reduce the effect of confounders, PS adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI).

158 VDZ and 116 anti-TNF (ADA: 27.6%, IFX: 57.8%, GOL: 14.7%) biologic-naïve UC-patients were included in this prospective RWE comparing the effectiveness of VDZ vs anti-TNF. Until week 52 significantly more patients switched to another biologic-drug in the anti-TNF group than in the VDZ group (40.5% vs 16.5%; p<0.001) (Fig. 1). In mITT, clinical response at 1-year was significantly higher in VDZ than in anti-TNF treated patients (61.7% vs. 40.3%; OR 2.39 (95% CI 1.39-4.10)). VDZ also tended to be superior to anti-TNF for (steroid-free) remission (Tab. 1; p=0.058 (p=0.051)). In the PP-analysis, VDZ showed numerically higher 1-year effectiveness, but this did not reach statistical significance (Tab. 1). Analysing week-14 induction phase responders (Tab. 2), VDZ had numerically higher effectiveness rates compared to anti-TNF but without significant difference.

The 1-year maintenance findings suggested, in line with our previous induction phase data, only moderate long-term effectiveness in both groups. However, besides the significant response data, VDZ showed numerically higher remission rates compared to anti-TNF though only borderline significant. The higher treatment persistence of VDZ vs anti-TNF, along with the higher effectiveness, may suggest VDZ as a first-line biologic therapy option in UC patients.