P455 Tofacitinib Therapy is Effective for Arthralgias Associated with Active Inflammatory Bowel Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S450-S450
Author(s):  
A Silfen ◽  
N Cohen ◽  
C Traboulsi ◽  
T Rodriguez ◽  
J Steinberg ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Clinical Data ◽  
Gastrointestinal Disease ◽  
Activity Index ◽  
Gastrointestinal Symptoms ◽  
Janus Kinase ◽  
Induction Phase ◽  
Patient Reports ◽  
Joint Symptoms

Abstract Background Tofacitinib is an oral Janus kinase (JAK) inhibitor used to treat ulcerative colitis (UC). It is generally well tolerated and safe with mild to no side effects. Tofacitinib is FDA-approved for use in multiple inflammatory conditions such as rheumatoid arthritis, psoriasis and polyarticular course juvenile idiopathic arthritis as well as for ulcerative colitis (UC). Patients with UC often have extra-intestinal manifestations (EIMs) with up to 20% of patients having arthropathy. There are limited data describing the effect of tofacitinib therapy on EIMs in UC. The aim of this study is to determine whether tofacitinib therapy improves arthralgia in this patient population. Methods This retrospective study includes consecutive patients with active UC who initiated tofacitinib at our center since 2014 and remained on the therapy for at least 8 weeks. We reviewed electronic medical records to collect demographic and clinical data. Patients diagnosed with any EIM by the treating physician were included. Improvement in EIM symptoms was determined through patient reports or physician assessment. In the UC patients, a decrease in Simple Clinical Colitis Activity Index (SCCAI) of ≥ 3 was considered response and remission as a score of ≤ 2. In the CD patients, a 3-point reduction in Harvey Bradshaw index (HBI) was considered clinical response and a score of <5 remission. Results 112 patients were included in this cohort, with 36 (31 UC; 5 CD) having confirmed EIMs (32.1% of total). Basic demographic and clinical data are detailed in Table 1. 35 patients had peripheral arthralgia, 2 patients had primary sclerosing cholangitis (PSC) and 1 had pyoderma gangrenosum. 5 (13.9%) patients discontinued treatment during the induction phase due to lack of response. By 24 weeks, 26 (74.2%) out of 35 patients reported improvement in arthralgias, and 14 (40%) patients reporting resolution of joint symptoms. In terms of gastrointestinal disease activity, at week 24, 17/35 (48.6%) patients achieved clinical response and 11/35(31.4%) patients achieved clinical remission. There was no treatment effect noted on the other EIMs. Conclusion In our real world experience, treatment refractory IBD patients with peripheral arthralgia on tofacitinib showed significant improvement in joint symptoms, and this often paralleled improvement in gastrointestinal symptoms. This supports that tofacitinib is a suitable treatment for patients with IBD and concomitant peripheral arthralgia.

scholarly journals P416 Results of the first paediatric randomised controlled trial of faecal microbiota transplant for ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S379-S380
Author(s):  
N Pai ◽  
J Popov ◽  
L Hill ◽  
E Hartung ◽  
K Grzywacz ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Healthy Donor ◽  
Activity Index ◽  
Case Reports ◽  
Case Series ◽  
Faecal Microbiota ◽  
Open Label ◽  
Randomised Controlled

Abstract Background The role of faecal microbiota transplant (FMT) for the treatment of ulcerative colitis (UC) has been reported across 4 randomised-controlled trials (RCT) in adults. Promising data have emerged from small, open-label paediatric case series and case reports but a proper blinded, placebo-controlled RCT has not been described in children. We report results from the first multicentre RCT of FMT in paediatric UC patients, conducted over 36 months in Ontario and Quebec, Canada. Methods We enrolled 25 children, ages 4–17 years old with active UC across two tertiary IBD clinics. Patients had active inflammation and remained on stable doses of medication at entry. Blinded participants received enemas containing healthy donor stool (active) or normal saline (placebo), 2×/week for 6 weeks. Faecal calprotectin (fCal), C-reactive protein (CRP), and paediatric ulcerative colitis activity index (PUCAI) scores were compared between groups during intervention, and at four follow-up time points over 30 weeks. Donor and recipient stools were measured for 16s rRNA and metagenomics analyses. Results In intention-to-treat (ITT) analysis, FMT (n = 13) at 6 weeks was more likely to improve clinical response (OR 9.3, 95% CI [0.7, 122.6]), CRP (OR 4.7, 95% CI [0.8, 28.4]), and fCal (OR 13.3, 95% CI [1.1, 166.4]) from baseline compared with placebo (n = 12). FMT at 30 weeks was also more likely than placebo to improve clinical response, CRP, and fCal (Table 1). In ITT analysis of the open-label arm (n = 7), FMT at 6 weeks and 30 weeks decreased CRP (−42.9%, −28.6%), fCal (−28.6%, −42.9%), and PUCAI score (−14.3%, −42.9%) from baseline. Conclusion Serial FMT enemas containing healthy donor microbiota led to greater improvements in serum and stool inflammatory markers, and rates of clinical response, in paediatric patients with active UC compared with placebo. These improvements largely persisted beyond 6 months after final FMT treatment. This study offers the strongest preliminary evidence, from a blinded, placebo-controlled multicentre RCT for the role of FMT in the management of paediatric UC.

scholarly journals A Phase 2a, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of IBD98-M Delayed-Release Capsules to Induce Remission in Patients with Active and Mild to Moderate Ulcerative Colitis

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 523 ◽  
Author(s):  
Gionata Fiorino ◽  
Giacomo Carlo Sturniolo ◽  
Fabrizio Bossa ◽  
Andrea Cassinotti ◽  
Antonio Di Sabatino ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Activity Index ◽  
Controlled Trial ◽  
Disease Activity Index ◽  
Fecal Calprotectin ◽  
Summary Score ◽  
Double Blind ◽  
Release Formulation ◽  
Delayed Release

IBD98-M is a delayed-release formulation of mesalamine (mesalazine) and SH with a potential therapeutic role in ulcerative colitis (UC). A total of 51 patients with a modified Ulcerative Colitis Disease Activity Index (UCDAI) score of ≥4 and ≤10, and a modified UCDAI endoscopy subscore ≥1 were randomized for 6 weeks of double-blind treatment with IBD98 0.8 g/day or IBD 1.2 g/day or placebo. The efficacy and safety of IBD98-M in mild to moderate active UC were primarily evaluated. At week 6, 1 (5.9%), 2 (12.5%), and 2 (11.1%) patients receiving IBD98-M 0.8 g, IBD98-M 1.2 g, and placebo, respectively, (p > 0.999) achieved clinical remission. Higher clinical response was seen in IBD98-M 1.2 g (31.3%) versus placebo (16.7%) and endoscopic improvement in IBD98-M 0.8 g (29.4%) versus placebo (22.2%) was seen. Fecal calprotectin levels were reduced in IBD98-M groups versus placebo (p > 0.05). IBD98-M patients achieved significant improvement in physical health summary score component of the SF-36 (p = 0.01 and p = 0.03 respectively) compared to placebo. IBD98-M did not meet the primary end point but had higher clinical response (1.2 g/day) and endoscopic improvement (0.8 g/day) compared to placebo. The safety result shown that IBD98-M treatment was safe and well tolerated in this patient population. No new safety signals or unexpected safety findings were observed during the study. Further trials with different stratification and longer follow-up may be needed to evaluate the efficacy.

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

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.

scholarly journals 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

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.

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

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

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

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.

scholarly journals P662 Efficacy and safety of tofacitinib in patients with moderate-to-severe ulcerative colitis: A real-world retrospective study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S545-S545
Author(s):  
N Yoshimura ◽  
Soh Okano ◽  
Minako Sako ◽  
Masakazu Takazoe
Keyword(s):  
Ulcerative Colitis ◽  
Total Cholesterol ◽  
Clinical Response ◽  
Clinical Remission ◽  
Janus Kinase ◽  
Remission Induction ◽  
Efficacy And Safety ◽  
Response Level ◽  
Severe Ulcerative Colitis ◽  
Mayo Score

Abstract Background Tofacitinib is an orally active, small-molecule Janus kinase inhibitor, recently approved for the treatment of moderate to severe ulcerative colitis (UC) refractory to corticosteroid. However, currently, there is inadequate evidence for efficacy of Tofacitinib in UC patients. Therefore, our objective was to evaluate the efficacy and safety of Tofacitinib for inducing and maintaining remission in UC patients. Methods In a single-centre retrospective setting, 71 consecutive patients with UC who had failed to respond to corticosteroid or biologics were included. All patients had received 10mg Tofacitinib orally twice daily for at least 8 weeks as remission induction therapy and then, the responders received 5mg twice daily as maintenance therapy for up to 26 weeks. The clinical response and adverse events were evaluated at weeks 8 (induction) and 26 (maintenance). UC activity was assessed by the partial Mayo score. Clinical remission was defined as p-Mayo score ≤1 and the bleeding subscore = 0. Clinical response was defined as p-Mayo score ≤4 and a decrease of ≥3 points relative to baseline. Furthermore, the cumulative remission rates up to 26 weeks were determined by the Kaplan–Meier survival analysis. Results At week 8, 24 of 71 patients (33.8%) achieved clinical remission and 20 (28.2%) achieved response level. The mean p-Mayo score fell from 5.8 ± 1.1 at entry to 3.5 ± 2.3 at week 2 (p < 0.01) and 2.3 ± 1.9 at week 8 (P<0.01). The average total cholesterol increased from 180.8 ± 36.0 mg/dl at entry to 206.8±39.3 mg/dl (p < 0.01). In anti-tumour necrosis factor (TNF)-α or vedolizumab (VDZ) naïve subgroup (n = 14), 8 patients (57.1%) achieved response level, while in biologic failure subgroup (n = 57), 36 patients (63.2%) achieved response level. In single biologic failure subgroup (n = 27), 19 patients (70.4%), in double biologics failure subgroup, 14 of 24 patients (58.3%), and in 3 biologics failure subgroup, 3 of 6 patients (50.0%) achieved response level, showing a decrease in the efficacy of Tofacitinib in patients who had failed more than one biologic. Furthermore, of the 25 patients followed for 26 weeks, 23 (92.0%) sustained remission at week 16 and 19 (76.0%) at week 26. Herpes virus infection occurred in 4 patients. The increase in total cholesterol was observed in 68.8% of the patients. Conclusion Our retrospective efficacy assessment indicated that Tofacitinib was effective and safe for inducing and maintaining remission in corticosteroid refractory UC patients, regardless of biologic naïve or failure background. The efficacy of 10mg twice daily was rapid and observed within 2 weeks of starting the treatment.

scholarly journals DOP69 Ozanimod for induction treatment of Moderate-to-Severe Ulcerative Colitis: Results from a systematic literature review and network meta-analyses

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S103-S105
Author(s):  
K Eaton ◽  
C Duperrouzel ◽  
P Bhandari ◽  
S Craigie ◽  
A Bonner ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Literature Review ◽  
Clinical Response ◽  
Systematic Literature Review ◽  
Clinical Remission ◽  
Similar Efficacy ◽  
Induction Treatment ◽  
Induction Phase ◽  
Severe Ulcerative Colitis ◽  
Meta Analyses

Abstract Background Ozanimod (OZA) is an orally administered, selective sphingosine-1-phosphate receptor modulator that has been evaluated versus placebo (PBO) in the phase 3 True North trial in the treatment of adult patients with moderate-to-severe ulcerative colitis (UC). The objective of this study was to compare the relative efficacy of OZA versus other approved moderate-to-severe UC therapies via network meta-analyses (NMA). Methods A systematic literature review was conducted to identify randomised clinical trials published from Jan 1, 2000 to Oct 21, 2020 that evaluated biological therapies (infliximab [IFX], adalimumab [ADA], golimumab [GOL], vedolizumab [VEDO], and ustekinumab [UST]) or an oral small molecule (tofacitinib [TOF]) for adults with moderate-to-severe UC. Bayesian NMAs were performed to determine the comparative efficacy of these therapies based on clinical remission, clinical response, and endoscopic improvement in the induction phase (6 to 14 weeks). Three populations were considered: all patients (overall), first-line (biologic-naïve), or those with exposure to or failure of prior biologic therapy (biologic-experienced). All six comparator therapies were included in the overall and biologic-naive populations, whereas the biologic-experienced population included ADA, VEDO, UST, and TOF due to lack of biologic-experienced data for IFX and GOL. Results Twenty-two RCTs examining 10,269 patients in the induction phase were included (Figure 1). All therapies offered significant improvement over PBO across networks apart from ADA in the analysis of clinical remission and clinical response in the biologic-experienced population and ADA, VEDO, and OZA in the analysis of endoscopic improvement in the biologic-experienced population. In the overall and biologic-naïve populations, OZA offered similar efficacy to all other therapies across endpoints except for a significant improvement in endoscopic improvement over ADA (overall: OR 2.01, 95% CrI 1.14, 3.66 [Figure 2]; biologic-naïve: OR 2.13, 95% CrI 1.02, 4.50 [Figure 3]). OZA also offered similar efficacy to all other therapies across endpoints in the biologic-experienced population except for an improvement in clinical remission (OR 4.16, 95% CrI 1.55, 11.24) and clinical response (OR 3.11, 95% CrI 1.40, 7.08) over ADA (Figure 4). Conclusion This NMA suggests that OZA provides similar induction efficacy on clinical remission, clinical response, and endoscopic improvement versus other approved moderate-to-severe UC therapies regardless of prior biologic treatment status.

scholarly journals P512 Efficacy of tofacitinib for the treatment of moderate-to-severe ulcerative colitis: real-world data

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S444-S445
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 do not respond to therapy for moderate to severe ulcerative colitis (UC), including thiopurines, glucocorticoids, and antagonists to tumour necrosis factor-a and integrin. Tofacitinib, a Janus Kinase inhibitor, has emerged as an efficacious and safe treatment for moderate to severe ulcerative colitis. However, data on its real-life efficacy remains sparse. Methods We aimed to assess the rate of clinical response and clinical remission at 3 and 6 months after tofacitinib initiation. Secondary endpoints included the rate of biomarker normalisation, corticosteroids-free clinical remission and severe infections. We conducted a multi-centre 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 normalisation was defined as faecal calprotectin ≤250 μg/g. Severe infection was defined as an infection requiring hospitalisation. Results During the study period, 40 patients with UC were started on tofacitinib at 10 mg/kg twice a day. 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; 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 normalisation occurred in 29.0% (n = 11) and 30.0% (n = 9) at 3 and 6 months respectively. Additionally, 63.2% (n = 24) of patients and 43.3% (n = 13) of patients achieved steroid-free clinical remission at 3 and 6 months respectively. In the interim, one patient developed a serious infection requiring discontinuation of the drug. Conclusion 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.

scholarly journals P422 Tofacitinib induces clinical and endoscopic remission in biologic refractory ulcerative colitis patients: a real-world Belgian cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S384-S386 ◽  
Author(s):  
A Cremer ◽  
T Lobaton ◽  
S Vieujan ◽  
P Bossuyt ◽  
J F Rahier ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Rectal Bleeding ◽  
Real World ◽  
Stool Frequency ◽  
Janus Kinase ◽  
Short Term ◽  
Mayo Score ◽  
Endoscopic Remission

Abstract Background Tofacitinib, an oral small molecule Janus kinase inhibitor, has been approved in 2018 for the treatment of moderate to severe ulcerative colitis (UC) in Europe. We report on real-world short-term efficacy and safety data from a multicenter Belgium refractory cohort of UC patients with prior exposure to both anti-TNFα and vedolizumab. Methods This is an observational, national, retrospective multicentre study including all UC active patients started on tofacitinib (10 mg BID) from 25 centres in Belgium between November 2018 and August 2019. Prospectively collected data were retrospectively analysed according to intention to treat. Primary endpoints were clinical and endoscopic response and remission rates at weeks 8 and 16. Clinical response and remission were defined as a reduction in the Modified Clinical Mayo score (rectal bleeding, stool frequency) of ≥2 and ≤1, respectively. Endoscopic response and remission were defined as a reduction in Endoscopic Mayo score of ≥1 and ≤1, respectively. Complete endoscopic remission was defined as an Endoscopic Mayo score of 0. Descriptive statistics and Wilcoxon signed-rank test were calculated using Medcal 19.1. Results Demographic and baseline data of the 70 included patients are presented in Table 1. Of note is that nearly all patients were refractory to at least one anti-TNF and vedolizumab. Median follow-up was 16 weeks (IQR 13–26). Fifty-four per cent (38/70) of patients required prolonged induction at 10mg BID. Clinical evaluation was available in all patients at week 8 and 49 patients at week 16, while endoscopic data were available in 52 patients and 42 at weeks 8 and 16, respectively. Clinical response and remission, and endoscopic response and remission at weeks 8 and 16 are presented in Figures 1 and 2. Fifty per cent (21/42) of the patients under steroids at baseline could have stopped steroids at 16 weeks. Median baseline Modified Mayo score (rectal bleeding, stool frequency and endoscopy) decreased from 7 (IQR 5–8) to 4 (IQR 2–7) after 8 weeks (n = 49) (p < 0.0001), and down to 2 (IQR 1–5) at week 16 (n = 40) (p < 0.0001). Median CRP significantly decreased from baseline (5.3 mg/l, IQR [1.9–16.8]) to 1 mg/l at week 8 (IQR 0.5–6.2) (n = 49) (p = 0.003). Tofacitinib was well tolerated with only 1 reported case of single dermatome herpes zoster and no case of venous thromboembolism. Conclusion Tofacitinib very effectively induced short-term clinical and endoscopic response and remission even in a refractory cohort of patients with UC in a real-world clinical setting. During this short-term follow-up, tofacitinib was well tolerated with respect to adverse events.

Sign in / Sign up

Export Citation Format

Share Document