P272 Tofacitinib as salvage therapy for patients hospitalized with refractory severe active ulcerative colitis: a GETAID multicenter prospective/retrospective cohort

Abstract Background Up to 25% of patients with ulcerative colitis (UC) will require hospitalization for severe flare. In UC patients admitted who have already experienced multiple drug failures, including steroids and anti-TNF agents, new quick-acting medical options are needed. Tofacitinib is effective in refractory UC and has a rapid mechanism of action. It could be considered in this setting. We aimed to evaluate the efficacy and safety of tofacitinib in patients hospitalized for an acute UC flare. Methods We conducted an observational and multicenter study with both retrospective and prospective collections in 14 GETAID tertiary IBD centers. The primary objective was to assess the survival without colectomy following tofacitinib initiation. We determined rates of clinical response, clinical remission, and clinical steroid-free remission at week 6 and week 14 and safety. Results Fifty-eight patients were included. All but one patient with active lupus were exposed to antiTNF. 50 (86.2%) patients have received infliximab and 18 (31%) to ciclosporin. Patients were previously exposed to a median of 2.5 lines of biologic treatment before tofacitinib.Median Lichtiger at inclusion was 11.5 (interquartile range IQR[9 - 13]), median CRP was 17 mg/l (IQR[6.5 - 67]) and total Mayo score was 10 (IQR[9.3 - 11]). Deep ulcerations were observed in 10 patients (17.2%).With a median follow-up of 6.5 months (IQR [2.9-12.4]), colectomy-free survival rates were estimated at 80.1% (95CI [70.1-91.4]) at 3 months and at 75.1% (95CI[64.1-88.1]) at 6 months. Rates of clinical response, clinical remission and clinical steroid-free remission were 60.3%, 46.6% and 37.9% at week 6 an, 48.1%, 37% and 35.2% at week 14, respectively. At the end of follow-up, 29 patients (50%) were still treated with tofacitinib. The survival without tofacitinib discontinuation was estimated at 82.8% (95CI[73.6-93.1), 67.8% (95CI[56.6-81.4]) and 46.2% (95CI[34.2-62.4]) at 1, 3, and 6 months (Figure 3).Regarding safety, no death was observed, three patients withdrew tofacitinib due to adverse events. Two herpes zosters occurred in patients aged over 60 years old. No thrombotic event occurred. Conclusion Tofacitinib appears as a promising option in patients hospitalized with a severe UC flare that needs further validation in prospective and controlled trials.

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Long-term, Real-life, Observational Study in Treating Outpatient Ulcerative Colitis with Golimumab

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld-3992 ◽

2021 ◽

Author(s):

Antonio Tursi ◽

Giammarco Mocci ◽

Walter Elisei ◽

Leonardo Allegretta ◽

Raffaele Colucci ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Clinical Remission ◽

Real Life ◽

Mucosal Healing ◽

Term Treatment ◽

Short Term Treatment ◽

Mayo Score

Background and Aims: Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy. Methods: A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up. Results: One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients. Conclusions: Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good.

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P663 Efficacy of tofacitinib in patients with ulcerative colitis after previous ineffective biological therapies

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.791 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S545-S546

Author(s):

M Rutka ◽

K Farkas ◽

D Pigniczki ◽

K Szántó ◽

B Anita ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Induction Therapy ◽

Dose Escalation ◽

Real Life ◽

Janus Kinase ◽

Inadequate Response ◽

Mayo Score ◽

Number Of Patients

Abstract Background Tofacitinib (TFC) is an oral, small-molecule Janus kinase inhibitor, which was recently approved for moderate to severe ulcerative colitis (UC). The aim of the current real-life study was to determine efficacy of TFC induction therapy regarding the clinical response and remission in patients with active UC. We evaluated short-term efficacy data in a Hungarian cohort with prior exposure to other biological agents such as anti-TNF drugs and vedolizumab. Methods In this single-centre retrospective study, patients with TFC introduction were included. Since January 2019, a total of 16 patients received an oral TFC induction therapy in a dose of 10 mg twice daily for 8 weeks. Endoscopic activity was evaluated by endoscopic Mayo (eMayo) score before the introduction of TFC and in case of an inadequate therapeutic response to the 5-mg-therapy to confirm therapeutic decision-making. Based on the evaluation of clinical symptoms and laboratory parameters, we either kept the dosage or reduced the dose to 5 mg according to local regulations. We also collected data from the 16. and 24. weeks of the therapy. Primary endpoints were a clinical response (as a reduction in partial Mayo Score [pMayo] by minimum 3 points) or remission (as a Mayo score of the maximum of 2 points and without blood in stool) at week 8. Results Sixteen patients had received the induction therapy (mean age: 36 years, 7 males and 9 females) in our centre. After 8 weeks, 12 (75%) patients responded to the TFC induction therapy and 6 (37.5%) of them were in remission. Four patients were primary non-responders (25%). Corticosteroid therapy (18 ± 7 mg) was required during the induction in 4 responder cases, which could be stepped down by week 8. As a continuous maintenance therapy, 4 patients have already reached the 16th week and 8 have completed the 24th week. By the end of the follow-up, 12 patients responded and 10 was in remission. During the observation period, 3 patients had to remain on 10 mg TFC dose, 6 patients required dose escalation from 5 mg to 10 mg and 5 mg was sufficient in case of only 3 patients after the introduction. Endoscopic activity showed a moderate decrease from 2.5 ± 0.5 eMayo score to 2 ± 1 (n = 7) until week 16. In respect the responder patients, CRP levels decreased from the mean of 7.23 to 5.02. No serious side-effects were observed during the follow-up. Conclusion After the 8-week TFC induction therapy, the response rate was high and only every fourth patients were non-responder. A low number of patients had adequate reactions to the 5 mg-therapy after the introduction, but TFC is effective with dose-escalation in respect of clinical response and remission in patients with UC, who have had an inadequate response to previous biological therapy.

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P668 Real-life comparison of different anti-TNF biologic therapies for ulcerative colitis treatment: A retrospective cohort study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.796 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S548-S549

Author(s):

B Barberio ◽

F Zingone ◽

R D’Incà ◽

C Marinelli ◽

M C Maccarone ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Clinical Remission ◽

Drug Exposure ◽

Real Life ◽

Intention To Treat ◽

Tnf Α ◽

Ulcerative Colitis Treatment ◽

Similar Good

Abstract Background Currently, ulcerative colitis (UC) can be treated with different anti-Tumor Necrosis Factor (TNF) drugs, which selection is mainly based on physician’s perspective. Indeed, head-to-head comparison studies evaluating the effectiveness and tolerability of anti-TNF drugs are lacking. The aim of this study was to compare the effectiveness and tolerability of anti-TNF-α drugs used in clinical practice in a cohort of patients with moderate to severe UC. Methods Retrospectively, 122 UC patients treated with Infliximab (IFX) Originator and Biosimilar, Adalimumab (ADA) and Golimumab (GOL) were included. We performed an intention to treat analysis to evaluate the clinical response, clinical remission, steroid-free clinical remission and endoscopy response according to the different time-points of the follow-up (ie. after induction, at 30 and 52 weeks). Baseline and post-induction predictor factors of these outcomes were evaluated using multivariate logistic regressions models. Data were analyzed using STATA11 software. Results Overall clinical response was 79.5% after induction, 79.5% at 30 weeks, 75.4% at 52 weeks, while the overall steroid-free clinical remission was 42.6%, 45.1%, 55.7%, respectively. After induction, a higher rate of treatment failure was observed in GOL group. Moreover, at the end of follow-up, lower rates of steroid-free clinical remission and clinical response were obtained by GOL (38.7% and 54.8% with p = 0.006 and p = 0.003, respectively). At week 52, endoscopic response was achieved by 46.5% of the population (IFX Originator: 46.7%; IFX Biosimilar: 40%; ADA: 51.6%; GOL: 22.6%; p = 0.003). Conclusion Among the different anti-TNF treatment, moderate-to-severe UC seems to respond better to IFX and ADA, whereas GOL seems to be less effective, despite a similar good safety profile. Current possibility of optimising also GOL will clarify whether these discrepancies are due to reduced drug exposure to GOL.

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MODERATE TO SEVERE ENDOSCOPIC INFLAMMATION IS FREQUENT AFTER ACHIEVING CLINICAL REMISSION IN PEDIATRIC ULCERATIVE COLITIS

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.031 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S13-S13

Author(s):

Chen Sarbagili-Shabat ◽

Dror Weiner ◽

Joram Wardi ◽

Lee Abramas ◽

Michal Yaakov ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Remission ◽

Residual Disease ◽

Activity Index ◽

Final Analysis ◽

Mucosal Healing ◽

Sustained Remission ◽

High Relapse Rate ◽

Mayo Score

Abstract Background Pediatric ulcerative colitis (UC) is characterized by low sustained remission rates and frequent extension of disease even if clinical remission is obtained with therapy. Moderate to severe endoscopic activity is a risk factor for relapse while evidence regarding early mucosal healing or persistence of inflammation after remission in children is not available. Our aim was to evaluate if persistence of significant inflammation is common and could explain the high relapse rate in pediatric UC. Methods Pediatric UC patients with clinical remission, defined as pediatric UC activity index (PUCAI) scores < 10, were prospectively assessed for mucosal healing by endoscopy 3–5 months after remission was documented. Mayo score was assessed for each segment by a blinded adult gastroenterologist using central reading. Symptomatic patients prior to sigmoidoscopy were excluded Sustained remission was assessed retrospectively at 18 months follow-up. Results Forty-six children were enrolled, 28 children in continuous clinical remission at time of sigmoidoscopy were included in the final analysis. Mayo 0 was present in 12/28 (42.86%), Mayo 1 in 2/28 (7.1%) and Mayo 2–3 in 14/28 (50.0%) endoscopies. Among 23/28 patients with follow-up through 18 months, remission was sustained in 2/11 (18.18%) of patients with Mayo 2 and 3 versus 6/12 (50.0%) with Mayo score 0–1. Conclusion Over 50% of children assessed for mucosal healing 3–5 months after clinical remission is obtained have residual disease activity, primarily moderate to severe inflammation which was associated with lower sustained remission. Early sigmoidoscopy after clinical remission for assessment of mucosal disease should be considered in pediatric UC.

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P588 Steroid sparing effect of adalimumab in cortisone–depended ulcerative colitis patients

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.709 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S539-S539

Author(s):

M Sina ◽

E Pengili ◽

X Pemaj ◽

D Osmanaj ◽

I Bibolli ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Remission ◽

Tertiary Hospital ◽

Average Dose ◽

Biologic Treatment ◽

Steroid Dose ◽

Steroid Dependent ◽

Sparing Effect ◽

Steroid Sparing

Abstract Background Corticosteroids are indicated for induction of remission in moderate to severe ulcerative colitis (UC) patients. However, due to their adverse effects associated with long-term use, steroids are not indicated as a maintenance therapy. The aim of this study was to assess the steroid sparing effect of adalimumab (ADA) in steroid-dependent UC patients. Methods This is a prospective study carried out at a tertiary hospital center in Albania from 2016–2020, including consecutive moderate-to-severe UC patients. All patients received biologic therapy with subcutaneous ADA 160/80mg at weeks 0/2 followed by 40mg every 2 weeks. We evaluated the steroid-sparing effect of ADA measuring the number of steroid–free patients and the average steroid dose at baseline before initiating biologic treatment and at week 8, 24, 52, 104, 156. Clinical remission was defined as total Mayo score ≤ 2 points. Results We enrolled 26 UC patients, mean age 47.3 ± 16.1 (24–85) years, 55.6% were females. The average disease duration before starting ADA was 7.3 ± 7.0 years (range 1–33); 44.4% had pancolitis and 55.6% left side colitis. 8(29.6%) patients were on combination therapy with azathioprine. 17/26 (65.4%) patients were taking prednisone at the time of the first ADA injection with an average dose of 17.7mg. The number of steroid-free patients at week 8, 24, 52, 104 and 156 was 12/26 (46.2%), 16/26 (61.5%), 15/21 (71.4%), 11/14 (78.6%), 8/9 (88.9%) respectively. At the end of the follow-up (week 156), the proportion of steroid free patient was significantly higher than at baseline [88.9% (8/9) vs 34.6% (7/26), p=0.005]. The reduction of the average dose of prednisone (8.8 mg, 4 mg, 6.8mg, 3.8mg and 3,8mg at week 8, 24, 52, 104 and 156 respectively), was also statistically significant (p<0.01). Clinical remission rates were 7.7% (2/26) at week 8, 47.6% (10/21) at week 52, 42.9% (6/14) at week 104 and 44.4 % (4/9) at week 156. Conclusion In our cohort, ADA administration to moderate–to severe UC significantly reduced the steroid dose and the proportion of patients taking cortisone during 3 years follow-up.

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OP24 Efficacy and safety of upadacitinib induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from the phase 3 U-ACHIEVE study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab075.023 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S022-S024

Author(s):

S Danese ◽

S Vermeire ◽

W Zhou ◽

A Pangan ◽

J Siffledeen ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Induction Therapy ◽

Clinical Remission ◽

Janus Kinase ◽

Phase 3 ◽

Mayo Score ◽

Significant Difference ◽

Endoscopic Remission ◽

Secondary Endpoints

Abstract Background An unmet therapeutic need remains in patients with ulcerative colitis (UC). U-ACHIEVE is one of two phase 3 induction trials evaluating the safety and efficacy of the selective Janus kinase–1 inhibitor upadacitinib (UPA) 45 mg once daily (QD) in adults with UC. Methods U-ACHIEVE is a multicentre, double-blind, placebo (PBO)–controlled trial (NCT02819635) that randomized patients with moderately to severely active UC 2:1 to UPA 45 mg QD or PBO for 8 weeks. Patients were stratified by response to biologic therapy (inadequate vs non–inadequate responder), baseline corticosteroid use (yes or no), and baseline adapted Mayo score (≤7 or >7). The primary endpoint was proportion of patients achieving clinical remission (per adapted Mayo Score) at week 8.Ranked secondary endpoints included endoscopic improvement, endoscopic remission, and clinical response per adapted Mayo Score at week 8; clinical response per partial adapted Mayo Score at week 2; and histologic-endoscopic mucosal improvement at week 8. Non-responder imputation incorporating multiple imputations for missing data due to COVID-19 are reported. Safety was assessed through week 8. Results 474 patients were randomized (UPA, n=319; PBO, n=155). Baseline characteristics were well balanced between groups (Table 1). A significantly higher proportion of patients receiving UPA (26.1%) vs PBO (4.8%) achieved clinical remission at week 8 (adjusted treatment difference [95% CI], 21.6% [15.8, 27.4]; P<0.001; Figure 1). For all ranked secondary endpoints, UPA was superior to PBO (P<0.001; Figure 1). A significant difference in clinical response favouring UPA vs PBO was seen as early as week 2 (60.1% vs 27.3%) and was sustained over 8 weeks (79.0% vs 41.6%; Figure 2). There were more serious adverse events (AEs), severe AEs, and AEs leading to study drug discontinuation with PBO (Table 2). The most common AEs were acne, creatine phosphokinase elevation, and nasopharyngitis with UPA and worsening of UC and anaemia with PBO. Incidence of serious infection was similar between UPA and PBO. Neutropenia and lymphopenia were reported more frequently with UPA vs PBO (Table 2).No adjudicated gastrointestinal perforation, major cardiovascular AEs, or thrombotic events and no active tuberculosis, malignancy, or deaths were reported. Conclusion In patients with moderately to severely active UC, UPA 45 mg QD induction therapy was superior to PBO in inducing clinical remission/response, and endoscopic remission/response over 8 weeks; responses were significant and rapid. UPA 45 mg QD was well tolerated; safety was comparable with the known safety profile of UPA, and no new safety signals were identified.

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P325 Real-World Effectiveness And Safety Of Ustekinumab In Patients With Ulcerative Colitis: A Multi-Centre Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.449 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S349-S350

Author(s):

D Parakkal ◽

A Johnson ◽

M Fenster ◽

G Ramos ◽

M Zulqarnain ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Real World ◽

Drug Level ◽

Previous Exposure ◽

Multi Centre Study ◽

Mayo Score ◽

Number Of Patients ◽

Endoscopic Remission

Abstract Background Pivotal trials have shown that ustekinumab (UST) is effective in ulcerative colitis (UC). However, the population included in these trials do not always represent the cohort of patients treated in the “real world”. In this study, we aimed to describe the effectiveness and safety of UST in a clinical cohort of patients with UC Methods We performed a multi-center cohort study and included patients with active UC starting UST. Variables collected included demographics, previous and current UC medications, disease activity (measured using partial and endoscopic Mayo score [PMS and EMS]) at 8 weeks, 6 months and end of follow-up. We also abstracted UST drug level and anti-UST antibodies (AUA), albumin and C-reactive protein levels. Primary outcomes were clinical response at week 8 defined as a reduction of 3 points in the PMS or PMS<2. Secondary outcomes were clinical remission defined as a PMS <2 and endoscopic remission defined as a MES ≤1, and the development of an adverse event (AE) attributed to UST. Results Ninety-five patients were included with a median age of 42 years (IQR:32-57) and 53 (56%) were female. Median follow-up was 5 months (IQR:2.2-7.4). Only 4 (4.3%) were naïve to biologics or tofacitinib and 62 (66%) had previous exposure to at least 2 other biologics. No variables were found to be associated with response at week 8 (Figure 2). Those patients who responded at week 8 had higher median albumin levels vs those who did not (median of 4.4 [IQR: 4.1-4.6] vs 4.1 g/dL [IQR:3.8-4.3]; p=0.02). There were no differences in baseline CRP levels (1mg/dL [IQR:0.6-2.8] vs 0.6 mg/dL [0.3-1.5]; p=0.06). Among the 33 patients who had follow-up endoscopic assessment, 7 (21.2%) had achieved endoscopic remission and 4 (12%) achieved histologic remission. Median UST level was 4.1 mcg/ml (IQR:2.5-5.1) and no patients had detectable AUA. Five patients underwent colectomy (5.3%). Only 6 patients (6.6%) presented with an AE (all minor that included, rash, headaches, arthralgias and infection). Conclusion In a population enriched with refractory UC, UST was well tolerated and induce response and remission in a significant number of patients. The rate of response was lower in obese patients and those with extensive colitis but was not associated with previous exposure to biologics and/or tofacitinib. Larger studies with a longer follow-up are warranted. Figure 1: Rates of clinical response and remission in patients with UC receiving ustekinumab Figure 2: Association between several baseline characteristics and response to ustekinumab in UC

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A232 EFFICACY OF TOFACITINIB FOR THE TREATMENT OF MODERATE-TO-SEVERE ULCERATIVE COLITIS: REAL-WORLD DATA

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.231 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 108-109

Author(s):

Y Xiao ◽

P L Lakatos ◽

R Bourdages ◽

A Bitton ◽

W Afif ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Clinical Remission ◽

Preliminary Analysis ◽

Kinase Inhibitor ◽

Significant Proportion ◽

Real Life ◽

Janus Kinase ◽

Severe Ulcerative Colitis ◽

Mayo Score

Abstract Background A significant proportion of patients with moderate to severe ulcerative colitis (UC) do not respond to therapy, which includes thiopurines, glucocorticoids, and antagonists to tumour necrosis factor-α and integrin. Tofacitinib, a Janus Kinase inhibitor, has emerged as an efficacious and safe treatment for moderate to severe ulcerative colitis. However, it is not known if this efficacy translates into real-life effectiveness in a regular clinical practice. Aims We aimed to assess the rate of clinical response and clinical remission at 3 and 6 months after tofacitinib initiation. Secondary endpoints included rate of biomarker normalization, corticosteroids-free clinical remission and severe infections. Methods We conducted a multi-center retrospective observational study of adult patients with active UC started on tofacitinib from January 1, 2015 to October 1, 2019 at the McGill University Health Center and Hotel-Dieu de Lévis. A positive clinical response was defined as a decrease of ≥3 in the partial Mayo score. Clinical remission was defined as partial Mayo score of ≤2. Biomarker normalization was defined as fecal calprotectin ≤250ug/g. Severe infection was defined as an infection requiring hospitalization. Results During the study period, 40 patients with UC were started on tofacitinib. Amongst the patients, 85% (n=34) had failed ≥1 biologic and 50% (n=20) had failed ≥3 biologics. At the time of this preliminary analysis, 38 patients had undergone 3 months of treatment and 30 patients had undergone 6 months of treatment. At 3 months, a clinical response was seen in 89.5% of patients (n=34) and clinical remission occurred in 63.2% (n=24). At 6 months, clinical response occurred in 73.3% of patients (n=22) and clinical remission was sustained in 53.33% (n=16). Biochemical normalization occurred in 29.0% (n=11) and 30.0% (n=9) at 3 and 6 months, respectively. Additionally, 63.2% (n=24) and 43.3% of patients (n=13) achieved steroid-free clinical remission at 3 and 6 months, respectively. In the interim, one patient developed a serious infection requiring discontinuation of drug. Conclusions Our preliminary analysis demonstrates that in a real-life setting, tofacitinib is an effective treatment for inducing clinical remission in refractory UC patients. Further data will be complied to better assess the efficacy over a longer follow up. Funding Agencies None

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Tofacitinib in Treatment-Refractory Moderate to Severe Ulcerative Colitis: Real-World Experience from a Retrospective Multicenter Observational Study

Journal of Clinical Medicine ◽

10.3390/jcm9072177 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2177

Author(s):

Peter Hoffmann ◽

Anna-Maria Globig ◽

Anne K. Thomann ◽

Maximilian Grigorian ◽

Johannes Krisam ◽

...

Keyword(s):

Ulcerative Colitis ◽

Adverse Events ◽

Clinical Response ◽

Real World ◽

Clinical Remission ◽

Safety Data ◽

Colon Perforation ◽

Severe Ulcerative Colitis ◽

Emergency Colectomy

(1) Background: Tofacitinib is approved in Europe for the treatment of adults with moderately to severely active ulcerative colitis since 2018. Real-world efficacy and safety data are currently scarce. (2) Methods: We performed a retrospective multicenter study at three German tertiary outpatient clinics for inflammatory bowel diseases and included all patients who started tofacitinib therapy between August 2018 and March 2020. The primary endpoint was a combined endpoint of steroid-free clinical remission, steroid-free clinical response, or clinical response at week 8. Secondary endpoints were biochemical response at week 8, as well as steroid-free clinical remission, steroid-free clinical response or clinical response at week 24, respectively, adverse events by week 24, and need for colectomy by the end of follow-up. (3) Results: Thirty-eight patients with moderate-to-severe ulcerative colitis were included. Eleven patients (28.9%) achieved steroid-free clinical remission at week 8. Fifty-three percent of the patients were primary non-responders at week 8. Three severe adverse events (pneumonia, hospitalization for aggravation of ulcerative colitis, emergency colectomy due to colon perforation), and 12 adverse events were documented by week 8 of therapy. By the end of follow-up, seven patients (18.4%) had undergone colectomy.

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P372 Effectiveness and safety of immunosuppressants for pouch disorders: results from the RESERVO Study of GETECCU

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.496 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S388-S390

Author(s):

F Mesonero Gismero ◽

Y Zabana ◽

A Fernández-Clotet ◽

E Leo ◽

B Caballol ◽

...

Keyword(s):

Ulcerative Colitis ◽

Adverse Events ◽

Clinical Response ◽

Clinical Remission ◽

Activity Index ◽

Disease Activity Index ◽

Multicentric Study ◽

Previous Diagnosis

Abstract Background Pouchitis and other inflammatory disorders of the pouch (IDP), such as Crohn′s-like disease of the pouch (CDP), are frequent in patients operated for a previous diagnosis of ulcerative colitis. Many different therapies have been used, but the effectiveness of immunosupresants (IMM) has been poorly explored in this setting. Our aim was to evaluate the use, efficacy and safety of IMM in patients with pouchitis or another IDP. Methods Retrospective and multicentric study of a Spanish cohort of pouch-carrying patients with previous diagnosis of ulcerative colitis, and subsequent diagnosis of IDP, following ECCO diagnostic criteria. Patients who used IMM to treat these conditions were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission, and non-response as no improvement or worsening symptoms. Endoscopic response was evaluated when possible using modified pouchitis disease activity index (PDAI) endoscopic subscore. Adverse events were collected. We used descriptive statistics. Results In the overall cohort of 338 patients with IDP, 93 (27%) were treated with IMM. Of those, 57% males, median age 40 (20-71) ys, and 72% non-smokers. Colectomy was performed at a median age of 31 (18-63) ys and IPD was diagnosed 25 (1-235) months after ileostomy closure. IMM used were thiopurines (n=86), methotrexate (n=4), cyclosporine (n=2) and tacrolimus (n=1). IMM were used as monotherapy in 66 (71%) cases and were indicated as treatment of pouchitis (n=60, 65%), CDP (n=32, 34.4%) and cuffitis (n=1, 1%). Effectiveness was evaluated only for thiopurine monotherapy (n=62). After a median follow-up of 23 (1-234) months, clinical remission was achieved in 31%, clinical response in 31% and non-response in 38% (Figure 1). There were no differences in effectiveness between pouchitis and CDP (63.9% vs 57.7%, p= 0.62). Endoscopic response was evaluated in 19 (30.6%) cases. After a median of 9 months of follow-up median PDAI endoscopic subscore dropped from 3 (range 2-4) to 1 (range 0-3), (Figure 2). Adverse events related with treatment appeared in 28 patients (45%). Thiopurines were discontinued in 39 cases (63%) due to failure (17), toxicity (16) and long remission (6 cases). Conclusion In our cohort, thiopurines were used in 27% of patients with IDP, with long-term benefit (remission or response) in around two-thirds of them. This therapy could be one more option to manage these disorders.

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