Background: Faecal microbiota transplantation [FMT] shows some effcacy in treating patients with ulcerative colitis [UC], although variability has been observed among donors and treatment regimens.... Show moreBackground: Faecal microbiota transplantation [FMT] shows some effcacy in treating patients with ulcerative colitis [UC], although variability has been observed among donors and treatment regimens. We investigated the effect of FMT using rationally selected donors after pretreatment with budesonide or placebo in active UC. Methods: Patients ≥18 years old with mild to moderate active UC were randomly assigned to 3 weeks of budesonide [9 mg] or placebo followed by 4-weekly infusions of a donor faeces suspension. Two donors were selected based on microbiota composition, regulatory T cell induction and short-chain fatty acid production in mice. The primary endpoint was engraftment of donor microbiota after FMT. In addition, clinical effcacy was assessed. Results: In total, 24 patients were enrolled. Pretreatment with budesonide did not increase donor microbiota engraftment [p = 0.56] nor clinical response, and engraftment was not associated with clinical response. At week 14, 10/24 [42%] patients achieved [partial] remission. Remarkably, patients treated with FMT suspensions from one donor were associated with clinical response [80% of responders, p < 0.05] but had lower overall engraftment of donor microbiota. Furthermore, differences in the taxonomic composition of the donors and the engraftment of certain taxa were associated with clinical response. Conclusion: In this small study, pretreatment with budesonide did not signifcantly infuence engraftment or clinical response after FMT. However, clinical response appeared to be donor-dependent. Response to FMT may be related to transfer of specifc strains instead of overall engraftment, demonstrating the need to characterize mechanisms of actions of strains that maximize therapeutic beneft in UC. Show less
Straatmijer, T.; Akker-van Marle, M.E. van den; Ponsioen, C.Y.; Horst, D. van der; Scherpenzeel, M.P.M.; Duijvestein, M.; Meulen-de Jong, A.E. van der 2023
IntroductionSince the number of medical treatment options for Ulcerative Colitis (UC) has expanded over the last decades, patients and physicians face challenges regarding decisions about the... Show moreIntroductionSince the number of medical treatment options for Ulcerative Colitis (UC) has expanded over the last decades, patients and physicians face challenges regarding decisions about the medication options. We aimed to identify patients' preferences about their UC treatment options in the Netherlands. Furthermore, we assessed after how many failed treatment options, patients are willing to consider surgical treatment.MethodsWe conducted a web-based, multicenter, discrete choice experiment (DCE) among adult UC patients. Patients were repeatedly asked to choose between two hypothetical medicinal treatment options. The choice tasks were based on administration route, administration location, chance of symptom reduction (on short and long term) and chances on infection and other adverse events. Data were analyzed by using Hierarchical Bayes estimation.ResultsA total of 172 UC patients participated in the DCE. More than half were anti-TNF experienced (52.9%). The chance of symptom reduction after one year (relative importance (RI) 27.7 (95% CI 26.0-29.4)) was most important in choosing between medicinal treatments, followed by the chance of infection (RI 22.3 (21.4 - 23.3)) and chance of symptom reduction after eight weeks (RI 19.5 (18.3 - 20.6)). Considering surgical treatment, nineteen patients (14.3%) would not even consider surgery after failing eight treatment options without any new available therapies left. Nine patients would consider surgery before trying any treatment options.ConclusionWe found that symptom reduction after one year was the most important attribute in choosing between treatments in UC patients. These outcomes can help understand the trade-offs and preferences of UC patients. Show less
Background and AimsOur goals were to study frailty screening in association with hospitalization and decline in quality of life [QoL] and functional status in older patients with inflammatory bowel... Show moreBackground and AimsOur goals were to study frailty screening in association with hospitalization and decline in quality of life [QoL] and functional status in older patients with inflammatory bowel diseases [IBD].MethodsThis was a prospective multicentre cohort study in IBD patients ≥65 years old using frailty screening [G8 Questionnaire]. Outcomes were all-cause, acute, and IBD-related hospitalization, any infection, any malignancy, QoL [EQ5D-3L], and functional decline (Instrumental Activities of Daily Living [IADL]) during 18 months of follow-up. Confounders were age, IBD type, biochemical disease activity [C-reactive protein ≥10 mg/L and/or faecal calprotectin ≥250 µg/g], and comorbidity [Charlson Comorbidity Index].ResultsOf 405 patients, with a median age of 70 years, 196 [48%] were screened as being at risk for frailty. All-cause hospitalizations occurred 136 times in 96 patients [23.7%], and acute hospitalizations 103 times in 74 patients [18.3%]. Risk of frailty was not associated with all-cause (adjusted hazard ratio [aHR] 1.5, 95% confidence interval [CI] 0.9–2.4), but was associated with acute hospitalizations [aHR 2.2, 95% CI 1.3–3.8]. Infections occurred in 86 patients [21.2%] and these were not associated with frailty. A decline in QoL was experienced by 108 [30.6%] patients, and a decline in functional status by 46 patients [13.3%]. Frailty screening was associated with a decline in QoL (adjusted odds ratio [aOR] 2.1, 95% CI 1.3–3.6) and functional status [aOR 3.7, 95% CI 1.7–8.1].ConclusionsFrailty screening is associated with worse health outcomes in older patients with IBD. Further studies are needed to assess the feasibility and effectiveness of its implementation in routine care. Show less
Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammations of the digestive tract with increasing prevalence, yet they... Show moreInflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammations of the digestive tract with increasing prevalence, yet they have unknown origins or cure. CD and UC have similar symptoms but respond differently to surgery and medication. Current diagnostic tools often involve invasive procedures, while laboratory markers for patient stratification are lacking. Large glycomic studies of immunoglobulin G and total plasma glycosylation have shown biomarker potential in IBD and could help determine disease mechanisms and therapeutic treatment choice. Hitherto, the glycosylation signatures of plasma immunoglobulin A, an important immunoglobulin secreted into the intestinal mucin, have remained undetermined in the context of IBD. Our study investigated the associations of immunoglobulin A1 and A2 glycosylation with IBD in 442 IBD cases (188 CD and 254 UC) and 120 healthy controls by reversed-phase liquid chromatography electrospray-ionization mass spectrometry of tryptic glycopeptides. Differences of IgA O- and N-glycosylation (including galactosylation, bisection, sialylation, and antennarity) between patient groups were associated with the diseases, and these findings led to the construction of a statistical model to predict the disease group of the patients without the need of invasive procedures. This study expands the current knowledge about CD and UC and could help in the development of noninvasive biomarkers and better patient care. Show less
Background and AimsPrior studies on the effect of smoking on the risk of colitis-associated colorectal neoplasia (CRN) have reported conflicting results. We aimed to further elucidate the... Show moreBackground and AimsPrior studies on the effect of smoking on the risk of colitis-associated colorectal neoplasia (CRN) have reported conflicting results. We aimed to further elucidate the association between smoking, including possible dose-effects, and the development of colorectal neoplasia in patients with inflammatory bowel disease (IBD).MethodsWe performed a prospective multicenter cohort study including patients with colonic IBD enrolled in a surveillance program in four academic hospitals between 2011 and 2021. The effects of smoking status and pack-years at study entry on subsequent recurrent events of CRN (including indefinite, low- and high-grade dysplasia, and colorectal cancer [CRC]) were evaluated using uni- and multivariable Prentice, Williams, and Peterson total-time Cox proportional hazard models. Adjustment was performed for extensive disease, prior/index dysplasia, sex, age, first-degree relative with CRC, primary sclerosing cholangitis, and endoscopic inflammation.ResultsIn 501 of the enrolled 576 patients, at least one follow-up surveillance was performed after the study index (median follow-up 5 years). CRN occurred at least once in 105 patients. Ever smoking was not associated with recurrent CRN risk (adjusted hazard ratio [aHR] 1.04, 95% confidence interval [CI] 0.75–1.44), but an increasing number of pack-years was associated with an increased risk of recurrent CRN (aHR per 10 pack-years 1.17, 95% CI 1.03–1.32; p < 0.05). Separate analyses per IBD type did not reveal differences.ConclusionsThis study found that an increase in pack-years is associated with a higher risk of recurrent CRN in patients with IBD, independent of established CRN risk factors (NCT01464151). Show less
Frailty is increasingly recognized as an important concept in patients with Inflammatory Bowel Disease (IBD). The aim of this scoping review is to summarize the current literature on frailty in IBD... Show moreFrailty is increasingly recognized as an important concept in patients with Inflammatory Bowel Disease (IBD). The aim of this scoping review is to summarize the current literature on frailty in IBD. We will discuss the definition of frailty, frailty assessment methods, the prevalence of frailty, risk factors for frailty and the prognostic value of frailty in IBD. A scoping literature search was performed using the PubMed database. Frailty prevalence varied from 6% to 53.9%, depending on the population and frailty assessment method. Frailty was associated with a range of adverse outcomes, including an increased risk for all-cause hospitalization and readmission, mortality in non-surgical setting, IBD-related hospitalization and readmission. Therefore, frailty assessment should become integrated as part of routine clinical care for older patients with IBD. Show less
Barnhoorn, M.C.; Meulen-de Jong, A.E. van der; Schrama, E.C.L.M.; Plug, L.G.; Verspaget, H.W.; Fibbe, W.E.; ... ; Schepers, K. 2022
Locally applied mesenchymal stromal cells (MSCs) have the capacity to promote the healing of perianal fistulas in Crohn's disease (CD) and are under clinical development for the treatment of... Show moreLocally applied mesenchymal stromal cells (MSCs) have the capacity to promote the healing of perianal fistulas in Crohn's disease (CD) and are under clinical development for the treatment of proctitis in ulcerative colitis (UC). Despite these clinical advances, the mechanism of action of local MSC therapy in inflammatory bowel disease (IBD) is largely unknown. We hypothesized that the local cytokine environment in IBD patients affects the immunomodulatory properties of MSCs. To evaluate this, 11 cytokines were analyzed in inflamed tissues obtained from CD and UC patients. Based on the identified cytokine profiles 4 distinct cytokine mixtures that mimic various inflammatory IBD environments were established. Next, MSCs were cultured in the presence of either of these 4 cytokine mixtures after which the expression of immunomodulatory and tissue regenerative molecules and the capacity of MSCs to modulate T-cell proliferation and dendritic cell (DC) differentiation were assessed. Our data show that MSCs respond, in a cytokine-specific manner, by upregulation of immunomodulatory and tissue regenerative molecules, including cyclooxygenase-2, indoleamine 2,3-dioxygenase, and transforming growth factor-beta 1. Functional studies indicate that MSCs exposed to a cytokine profile mimicking one of the 2 UC cytokine milieus were less effective in inhibition of DC differentiation. In conclusion, our data indicate that cytokine mixes mimicking the local cytokine milieus of inflamed UC colonic or CD fistulas tissues can differentially affect the immunomodulatory and tissue regenerative characteristics of MSCs. These data support the hypothesis that the local intestinal cytokine milieu serves as a critical factor in the efficacy of local MSC treatment. Show less
Unen, V. van; Ouboter, L.F.; Li, N.; Schreurs, M.; Abdelaal, T.; Kooy-Winkelaar, Y.; ... ; Koning, F. 2022
Chronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the... Show moreChronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the role of all immune cell subsets simultaneously. Therefore, we aimed to identify immune cell types associated with inflammation in IBD using high-dimensional mass cytometry. We analyzed 188 intestinal biopsies and paired blood samples of newly-diagnosed, treatment-naive patients (n=42) and controls (n=26) in two independent cohorts. We applied mass cytometry (36-antibody panel) to resolve single cells and analyzed the data with unbiased Hierarchical-SNE. In addition, imaging-mass cytometry (IMC) was performed to reveal the spatial distribution of the immune subsets in the tissue. We identified 44 distinct immune subsets. Correlation network analysis identified a network of inflammation-associated subsets, including HLA-DR(+)CD38(+) EM CD4(+) T cells, T regulatory-like cells, PD1(+) EM CD8(+) T cells, neutrophils, CD27(+) TCR gamma delta cells and NK cells. All disease-associated subsets were validated in a second cohort. This network was abundant in a subset of patients, independent of IBD subtype, severity or intestinal location. Putative disease-associated CD4(+) T cells were detectable in blood. Finally, imaging-mass cytometry revealed the spatial colocalization of neutrophils, memory CD4(+) T cells and myeloid cells in the inflamed intestine. Our study indicates that a cellular network of both innate and adaptive immune cells colocalizes in inflamed biopsies from a subset of patients. These results contribute to dissecting disease heterogeneity and may guide the development of targeted therapeutics in IBD. Show less
West, R.; Russel, M.; Bodelier, A.; Kuijvenhoven, J.; Bruin, K.; Jansen, J.; ... ; Lubbinge, H. 2022
Background & Aims: The dose and duration of mesalazine treatment for ulcerative colitis (UC) is a potentially important determinant of effectiveness, with evidence suggesting that continuing... Show moreBackground & Aims: The dose and duration of mesalazine treatment for ulcerative colitis (UC) is a potentially important determinant of effectiveness, with evidence suggesting that continuing the induction dose for 6-12 months may improve outcomes; however, real-world data are lacking. We assessed mesalazine use in Dutch clinical practice, including how differences in dose and duration affected UC outcomes. Methods: Adults with mild-to-moderate UC who received oral prolonged-release mesalazine de novo or had a dose escalation for an active episode were followed for 12 months in this non-interventional study (ClinicalTrials.gov identifier: NCT02261636). The primary endpoint was time from start of treatment to dose reduction (TDR). Secondary endpoints included recurrence rate, adherence, and work productivity. Results: In total, 151 patients were enrolled, of whom 108 (71.5%) were newly diagnosed with UC. The majority (120; 79.5%) received a dose of >= 4 g/day. Nearly one-third (48; 31.8%) underwent dose reduction, with mean TDR being 8.3 months. Disease extent and endoscopic appearance did not influence duration of induction therapy, while TDR increased with higher baseline UCDAI scores. TDR was longer in patients without (mean 8.8 months) than with (4.1 months) recurrence, although not significantly (p=0.09). Patients on >= 4 g/day had a significantly lower chance of recurrence versus those on 2-<4 g/day (26.6% vs 62.5%, respectively; p=0.04). Longer treatment duration was associated with significantly reduced recurrence risk [hazard ratio >6 months vs 3-6 months: 0.19 (95%CI: 0.08-0.46); p<0.05], particularly for those on >= 4 g/day [0.15 (0.06-0.40) vs 0.26 (0.01-11.9) for 2-<4 g/day). Patients reported significantly increased work productivity, which was maintained throughout follow-up. Conclusions: Mesalazine was effective induction therapy, with treatment duration not meaningfully influenced by disease extent and endoscopic appearance at initiation. A higher induction dose of oral mesalazine (>= 4 g/day) and longer duration of treatment (>6 months) was associated with a lower recurrence risk. Show less
West, R.; Russel, M.; Bodelier, A.; Kuijvenhoven, J.; Bruin, K.; Jansen, J.; ... ; Lubbinge, H. 2022
Background and Aims: The dose and duration of mesalazine treatment for ulcerative colitis (UC) is a potentially important determinant of effectiveness, with evidence suggesting that continuing the... Show moreBackground and Aims: The dose and duration of mesalazine treatment for ulcerative colitis (UC) is a potentially important determinant of effectiveness, with evidence suggesting that continuing the induction dose for 6-12 months may improve outcomes; however, real-world data are lacking. We assessed mesalazine use in Dutch clinical practice, including how differences in dose and duration affected UC outcomes.Methods: Adults with mild-to-moderate UC who received oral prolonged-release mesalazine de novo or had a dose escalation for an active episode were followed for 12 months in this non-interventional study (ClinicalTrials.gov identifier: NCT02261636). The primary endpoint was time from start of treatment to dose reduction (TDR). Secondary endpoints included recurrence rate, adherence, and work productivity.Results: In total, 151 patients were enrolled, of whom 108 (71.5%) were newly diagnosed with UC. The majority (120; 79.5%) received a dose of ≥4 g/day. Nearly one-third (48; 31.8%) underwent dose reduction, with mean TDR being 8.3 months. Disease extent and endoscopic appearance did not influence duration of induction therapy, while TDR increased with higher baseline UCDAI scores. TDR was longer in patients without (mean 8.8 months) than with (4.1 months) recurrence, although not significantly (p=0.09). Patients on ≥4 g/day had a significantly lower chance of recurrence versus those on 2-<4 g/day (26.6% vs 62.5%, respectively; p=0.04). Longer treatment duration was associated with significantly reduced recurrence risk [hazard ratio >6 months vs 3-6 months: 0.19 (95%CI: 0.08-0.46); p<0.05], particularly for those on ≥4 g/day [0.15 (0.06-0.40) vs 0.26 (0.01-11.9) for 2-<4 g/day). Patients reported significantly increased work productivity, which was maintained throughout follow-up.Conclusions: Mesalazine was effective induction therapy, with treatment duration not meaningfully influenced by disease extent and endoscopic appearance at initiation. A higher induction dose of oral mesalazine (≥4 g/day) and longer duration of treatment (>6 months) was associated with a lower recurrence risk. Show less
West, R.; Russel, M.; Bodelier, A.; Kuijvenhoven, J.; Bruin, K.; Jansen, J.; ... ; Lubbinge, H. 2022
Background and Aims: The dose and duration of mesalazine treatment for ulcerative colitis (UC) is a potentially important determinant of effectiveness, with evidence suggesting that continuing the... Show moreBackground and Aims: The dose and duration of mesalazine treatment for ulcerative colitis (UC) is a potentially important determinant of effectiveness, with evidence suggesting that continuing the induction dose for 6-12 months may improve outcomes; however, real-world data are lacking. We assessed mesalazine use in Dutch clinical practice, including how differences in dose and duration affected UC outcomes.Methods: Adults with mild-to-moderate UC who received oral prolonged-release mesalazine de novo or had a dose escalation for an active episode were followed for 12 months in this non-interventional study (ClinicalTrials.gov identifier: NCT02261636). The primary endpoint was time from start of treatment to dose reduction (TDR). Secondary endpoints included recurrence rate, adherence, and work productivity.Results: In total, 151 patients were enrolled, of whom 108 (71.5%) were newly diagnosed with UC. The majority (120; 79.5%) received a dose of ≥4 g/day. Nearly one-third (48; 31.8%) underwent dose reduction, with mean TDR being 8.3 months. Disease extent and endoscopic appearance did not influence duration of induction therapy, while TDR increased with higher baseline UCDAI scores. TDR was longer in patients without (mean 8.8 months) than with (4.1 months) recurrence, although not significantly (p=0.09). Patients on ≥4 g/day had a significantly lower chance of recurrence versus those on 2-<4 g/day (26.6% vs 62.5%, respectively; p=0.04). Longer treatment duration was associated with significantly reduced recurrence risk [hazard ratio >6 months vs 3-6 months: 0.19 (95%CI: 0.08-0.46); p<0.05], particularly for those on ≥4 g/day [0.15 (0.06-0.40) vs 0.26 (0.01-11.9) for 2-<4 g/day). Patients reported significantly increased work productivity, which was maintained throughout follow-up.Conclusions: Mesalazine was effective induction therapy, with treatment duration not meaningfully influenced by disease extent and endoscopic appearance at initiation. A higher induction dose of oral mesalazine (≥4 g/day) and longer duration of treatment (>6 months) was associated with a lower recurrence risk. Show less
Background: Patients suffering from inflammatory bowel diseases (IBD) and treated with originator infliximab are increasingly being switched to biosimilars. Some patients, however, are "reverse... Show moreBackground: Patients suffering from inflammatory bowel diseases (IBD) and treated with originator infliximab are increasingly being switched to biosimilars. Some patients, however, are "reverse switched" to treatment with the originator. Here we assess the prevalence of reverse switching, including its indication and outcomes.Methods: In this retrospective multicenter cohort study, data on patients with IBD from 9 hospitals in the Netherlands were collected. All adult patients with IBD were included if they previously had been switched from originator infliximab to the biosimilar CT-P13 and had a follow-up time of at least 52 weeks after the initial switch. The reasons for reverse switching were categorized into worsening gastrointestinal symptoms, adverse effects, or loss of response to CT-P13. Drug persistence was analyzed through survival analyses.Results: A total of 758 patients with IBD were identified. Reverse switching was observed in 75 patients (9.9%). Patients with reverse switching were predominantly female (70.7%). Gastrointestinal symptoms (25.5%) and dermatological symptoms (21.8%) were the most commonly reported reasons for reverse switching. In 9 patients (12.0%), loss of response to CT-P13 was the reason for reverse switching. Improvement of reported symptoms was seen in 73.3% of patients after reverse switching and 7 out of 9 patients (77.8%) with loss of response regained response. Infliximab persistence was equal between patients who were reverse-switched and those who were maintained on CT-P13.Conclusions: Reverse switching occurred in 9.9% of patients, predominantly for biosimilar-attributed adverse effects. Switching back to originator infliximab seems effective in patients who experience adverse effects, worsening gastrointestinal symptoms, or loss of response after switching from originator infliximab to CT-P13. Show less
BackgroundTofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).AimTo evaluate effectiveness, safety and use of tofacitinib in daily practice.MethodsUC... Show moreBackgroundTofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).AimTo evaluate effectiveness, safety and use of tofacitinib in daily practice.MethodsUC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation.ResultsIn total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively.ConclusionTofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients. Show less
Background Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).Aim To evaluate effectiveness, safety and use of tofacitinib in daily practice.Methods UC... Show moreBackground Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).Aim To evaluate effectiveness, safety and use of tofacitinib in daily practice.Methods UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] <= 2), biochemical remission (faecal calprotectin level <= 250 mu g/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation.Results In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively.Conclusion Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients. Show less
