P678 Effect of accelerated infliximab induction on short-term outcomes of paediatric acute severe ulcerative colitis

Abstract Background Due to a higher inflammatory burden and a rapid clearance of infliximab (IFX) in Acute Severe ulcerative colitis (ASUC), the accelerated IFX induction may be considered (IFX up to 10 mg/kg per dose, at week 0, 1 and 4–5) in those patients who need to start second-line treatment. The aim of our study is to describe the short-term outcomes of ASUC pediatric patients who have received an accelerated IFX induction regimen in our Unit. Methods In a retrospective study we collected data from patients with ASUC who received treatment with accelerated IFX induction. We analyzed demographic, clinical and analytical data as well as treatment adverse events from medical records. The short-term outcomes (at the end of the induction and at 3 months) were analyzed based in the Paediatric Ulcerative Activity Index (PUCAI)) and analytical parameters (haemoglobin, C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and albumin. Results Six patients with ASUC who received accelerated IFX induction were included (5 male; median age at diagnosis 10.5 years (IQR: 2–15); mean time from diagnosis to ASUC flare: 1.8 years (IQR: 0–9 years)). At disease onset, 5/6 patients presented with pancolonic involvement (E4) with an average PUCAI of 55 points. At ASUC flare all of them presented pancolonic involvement with a PUCAI over 65 points, 50% of them had anaemia, 66.6% elevation of inflammatory markers (CRP and/or ESR) and 50% hypoalbuminemia. The patients received an accelerated IFX induction with IFX at 10 mg/kg at 0, 1 and 4 - 5 weeks without adverse events. After accelerated IFX induction regimen 5/6 patients showed clinical response and normalisation of laboratory tests (haemoglobin, inflammatory markers and albumin). One patient presented treatment failure needing surgery (colectomy rate 16.6%). At 3 months follow-up, no new patients needed colectomy. One patient had an infusional reaction and was changed to Vedolizumab treatment maintaining remission, the other 4 patients were maintained on IFX treatment (1 clinical remission, 3 mild clinical activity). The overall colectomy rate after accelerated IFX induction remained in 16,6%. Conclusion In our cohort of ASUC patients treated with an accelerated IFX induction regimen we observed an 83.3% free colectomy rate at short-term, being this regimen a valid therapeutic option to avoid surgery. Prospective and comparative studies are needed to determine the efficacy of this strategy in reducing the colectomy rate, both in the short-and long-term follow-up.

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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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Infliximab in severe ulcerative colitis: short-term results of different infusion regimens and long-term follow-up

Alimentary Pharmacology & Therapeutics ◽

10.1111/j.1365-2036.2007.03415.x ◽

2007 ◽

Vol 26 (5) ◽

pp. 747-756 ◽

Cited By ~ 115

Author(s):

A. KOHN ◽

M. DAPERNO ◽

A. ARMUZZI ◽

M. CAPPELLO ◽

L. BIANCONE ◽

...

Keyword(s):

Ulcerative Colitis ◽

Short Term ◽

Severe Ulcerative Colitis ◽

Long Term Follow Up

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Bone mineral density and explanatory factors in children and adults with juvenile dermatomyositis at long term follow-up; a cross sectional study

Pediatric Rheumatology ◽

10.1186/s12969-021-00543-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Henriette Schermacher Marstein ◽

Kristin Godang ◽

Berit Flatø ◽

Ivar Sjaastad ◽

Jens Bollerslev ◽

...

Keyword(s):

Bone Turnover ◽

Inflammatory Markers ◽

Juvenile Dermatomyositis ◽

Inflammatory Myopathy ◽

Disease Onset ◽

Whole Body ◽

Mineral Density ◽

Z Scores

Abstract Background Juvenile dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in children and adolescents. Both the disease and its treatment with glucocorticoids may negatively impact bone formation. In this study we compare BMD in patients (children/adolescence and adults) with long-standing JDM with matched controls; and in patients, explore how general/disease characteristics and bone turnover markers are associated with BMD. Methods JDM patients (n = 59) were examined median 16.8y (range 6.6–27.0y) after disease onset and compared with 59 age/sex-matched controls. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD of the whole body and lumbar spine (spine) in all participants, and of ultra-distal radius, forearm and total hip in participants ≥20y only. Markers of bone turnover were analysed, and associations with outcomes explored. Results Reduced BMD Z-scores (<−1SD) were found in 19 and 29% of patients and 7 and 9% of controls in whole body and spine, respectively (p-values < 0.05). BMD and BMD Z-scores for whole body and spine were lower in all patients and for < 20y compared with their respective controls. In participants ≥20y, only BMD and BMD Z-score of forearm were lower in the patients versus controls. In patients, BMD Z-scores for whole body and/or spine were found to correlate negatively with prednisolone use at follow-up (yes/no) (age < 20y), inflammatory markers (age ≥ 20y) and levels of interferon gamma-induced protein 10 (IP-10) (both age groups). In all patients, prednisolone use at follow-up (yes/no) and age ≥ 20y were independent correlates of lower BMD Z-scores for whole body and spine, respectively. Conclusion In long-term JDM, children have more impairment of BMD than adults in spine and whole-body. Associations with BMD were found for both prednisolone and inflammatory markers, and a novel association was discovered with the biomarker of JDM activity, IP-10.

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Evaluation of efficacy and comparative frequency of adverse events in patients with ulcerative colitis receiving the original infliximab and its biosimilar. One year of observation

Terapevticheskii arkhiv ◽

10.26442/00403660.2019.08.000331 ◽

2019 ◽

Vol 91 (8) ◽

pp. 41-46

Author(s):

O V Knyazev ◽

T V Shkurko ◽

A V Kagramanova ◽

A A Lishchinskaya ◽

M Yu Zvyaglova ◽

...

Keyword(s):

Ulcerative Colitis ◽

Adverse Events ◽

Real Life ◽

Fecal Calprotectin ◽

Biologic Drugs ◽

Real Life Data ◽

Bowel Diseases ◽

Significant Clinical Improvement ◽

One Year

Real - life data on the effectiveness and safety of biosimilar and biologic drugs licensed for treatment of inflammatory bowel diseases (IBD) is lacking. Aim. To investigate efficacy of original Infliximab (IFX) and its biosimilar in treating patients with ulcerative colitis (UC) and determine the frequency of adverse events during 1 year follow - up period. Materials and methods. Our cohort consisted of 98 ulcerative colitis patients, treated with original IFX and its biosimilar since December 2017 till December 2018 years. Original Infliximab was prescribed in 56 UC patients (57.1%) during 5 years and longer; 16 patients (16.3%) were switched to IFX biosimilar; 13 UC bio - naïve patients (13.3%) received original IFX, 29 (29.6%) patients - biosimilar IFX. In 14 patients (14.3%) original infliximab was rotated with biosimilar. We picked out 42 patients to assess efficacy of original IFX and biosimilar. Results and discussion. Twelve patients, received original IFX and 28 patients, treated with its biosimilar, showed significant clinical improvement by decreasing Mayo index from 9.7±0.4 and 10.2±0.2 points to 1.9±0.09 and 2.1±0.1 points, accordingly. Also we noticed positive change in laboratory markers - CRP decrease from 89.6±8.7 mg/l and 77.5±8.0 mg/l to 6.5±0.8 mg/l and 6.9±0.8 mg/l (p>0.05), albumin increase from 30.1±4.7 g/l and 29.6±3.6 g/l to 34.1±6.3 g/l and 32.8±5.9 g/l (p>0.05), increase of serum iron levels from 6.4±0.5 mcg/l and 7.1±0.65 mcg/l to 14.6±4.4 mcg/l and 15.9±5.1 mcg/l (p>0.05), hemoglobin increase from 104.7±9.8 g/l and 102.2±8.8 g/l till 124±11.3 g/l and 121±10.9 g/l (p>0.05), and fecal calprotectin decrease from 1680±134 mcg/g and 1720±126 mcg/g till 245.5±33.4 mcg/g and 230.5±29.8 mcg/g (p>0.05). During 1 year follow - up 12 UC patients, treated with original IFX and its biosimilar, developed adverse events. The majority of adverse events (n=8) were registered in patients, rotating administration of original IFX and its biosimilar. Conclusion. IFX biosimilar is effective as well as original IFX. Frequency of adverse events, occurred in patients, treated with original IFX, was comparable with adverse events frequency in patients, received biosimilar IFX. Frequency of adverse events was significantly higher in UC patients, rotating original IFX and its biosimilar.

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Long-term outcomes of acute severe ulcerative colitis in the rescue therapy era: A multicentre cohort study

United European Gastroenterology Journal ◽

10.1177/2050640620977405 ◽

2020 ◽

pp. 205064062097740

Author(s):

Stefano Festa ◽

Maria L Scribano ◽

Daniela Pugliese ◽

Cristina Bezzio ◽

Mariabeatrice Principi ◽

...

Keyword(s):

Ulcerative Colitis ◽

Tumour Necrosis ◽

Rescue Therapy ◽

Tumour Necrosis Factor Alpha ◽

Necrosis Factor Alpha ◽

Severe Ulcerative Colitis ◽

Factor Alpha ◽

Necrosis Factor

Background The long-term course of ulcerative colitis after a severe attack is poorly understood. Second-line rescue therapy with cyclosporine or infliximab is effective for reducing short-term colectomy but the impact in the long-term is controversial. Objective The purpose of this study was to evaluate the long-term course of acute severe ulcerative colitis patients who avoid early colectomy either because of response to steroids or rescue therapy. Methods This was a multicentre retrospective cohort study of adult patients with acute severe ulcerative colitis admitted to Italian inflammatory bowel disease referral centres from 2005–2017. All patients received intravenous steroids, and those who did not respond received either rescue therapy or colectomy. For patients who avoided early colectomy (within three months from the index attack), we recorded the date of colectomy, last follow-up visit or death. The primary end-point was long-term colectomy rate in patients avoiding early colectomy. Results From the included 372 patients with acute severe ulcerative colitis, 337 (90.6%) avoided early colectomy. From those, 60.5% were responsive to steroids and 39.5% to the rescue therapy. Median follow-up was 44 months (interquartile range, 21–85). Colectomy-free survival probability was 93.5%, 81.5% and 79.4% at one, three and five years, respectively. Colectomy risk was higher among rescue therapy users than in steroid-responders (log-rank test, p = 0.02). At multivariate analysis response to steroids was independently associated with a lower risk of long-term colectomy (adjusted odds ratio = 0.5; 95% confidence interval, 0.2–0.8), while previous exposure to anti-tumour necrosis factor alpha agents was associated with an increased risk (adjusted odds ratio = 3.0; 95% confidence interval, 1.5–5.7). Approximately 50% of patients required additional therapy or new hospitalization within five years due to a recurrent flare. Death occurred in three patients (0.9%). Conclusions Patients with acute severe ulcerative colitis avoiding early colectomy are at risk of long-term colectomy, especially if previously exposed to anti-tumour necrosis factor alpha agents or if rescue therapy during the acute attack was required because of steroid refractoriness.

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P445 Efficacy and safety of induction therapy with calcineurin inhibitors followed by maintenance therapy with vedolizumab in severe ulcerative colitis: a large patient cohort with long-term follow-up

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.574 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S401-S401

Author(s):

J OLLECH ◽

S Dwadasi ◽

I Normatov ◽

A Israel ◽

V Rai ◽

...

Keyword(s):

Ulcerative Colitis ◽

Maintenance Therapy ◽

Median Time ◽

Induction Therapy ◽

Calcineurin Inhibitor ◽

Calcineurin Inhibitors ◽

Free Survival ◽

Severe Ulcerative Colitis ◽

Steroid Refractory

Abstract Background The options for the medical management of patients with severe ulcerative colitis failing IV steroids are limited and include the calcineurin inhibitors cyclosporin or tacrolimus, especially in patients who had previously failed anti-TNF agents. Following induction therapy with a calcineurin inhibitor, transitioning to vedolizumab as maintenance therapy could be an option. We report on the largest cohort of patients successfully induced with calcineurin inhibitors who were then transitioned to vedolizumab maintenance therapy. Methods We performed a retrospective observational study of adult ulcerative colitis patients followed at the University of Chicago Inflammatory Bowel Disease Center. Patients with severe steroid-refractory ulcerative colitis were included if they received a calcineurin inhibitor (ciclosporin or tacrolimus) as induction therapy followed by maintenance therapy with vedolizumab between January 2014 and December 2018. Patients who had a follow-up of fewer than three months were excluded. The primary endpoint was colectomy-free survival. Secondary endpoints included survival without vedolizumab discontinuation as well as clinical, steroid-free and biochemical remission at week 14. Results A total of 71 patients (59% male) were treated with vedolizumab after induction therapy with calcineurin inhibitors for severe steroid-refractory colitis. Truelove and Witts criteria for Acute Severe Ulcerative Colitis were fulfilled in 77% of patients, and 97% of patients had moderate to severe endoscopic disease. Patients were followed for a median time of 25 months (IQR 16–36). Colectomy free survival rates from vedolizumab initiation were 67% at one year and 55% at two years (Figure 1, Panel A). At the end of induction with vedolizumab at week 14, 50% of patients were in clinical remission, and 62% of patients had a normal CRP. At one and two years following vedolizumab initiation, 43% and 28% of patients were still on vedolizumab, respectively (Figure 1, Panel B). Vedolizumab was dose escalated to infusions every four weeks in 44% of patients. The median time to dose escalation was 5.6 months (IQR 4.1–8.2). No serious adverse events were recorded in our patient cohort. Conclusion Transitioning to vedolizumab following induction of remission with calcineurin inhibitors is effective and safe. Such a treatment strategy should be considered in patients with severe steroid-refractory ulcerative colitis, especially in cases of previous anti-TNF failure.

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Incidence of Colectomy During Long-term Follow-up After Cyclosporine-Induced Remission of Severe Ulcerative Colitis

Clinical Gastroenterology and Hepatology ◽

10.1016/j.cgh.2006.04.001 ◽

2006 ◽

Vol 4 (6) ◽

pp. 760-765 ◽

Cited By ~ 197

Author(s):

David N. Moskovitz ◽

Gert Van Assche ◽

Benedikte Maenhout ◽

Joris Arts ◽

Marc Ferrante ◽

...

Keyword(s):

Ulcerative Colitis ◽

Severe Ulcerative Colitis ◽

Long Term Follow Up

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Tacrolimus or infliximab for severe ulcerative colitis: short-term and long-term data from a retrospective observational study

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2014-000021 ◽

2015 ◽

Vol 2 (1) ◽

pp. e000021 ◽

Cited By ~ 21

Author(s):

Naoki Minami ◽

Takuya Yoshino ◽

Minoru Matsuura ◽

Yorimitsu Koshikawa ◽

Satoshi Yamada ◽

...

Keyword(s):

Ulcerative Colitis ◽

Observational Study ◽

Retrospective Observational Study ◽

Short Term ◽

Severe Ulcerative Colitis ◽

Term Data

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Efficacy of tofacitinib as a «rescue therapy» in patients with severe ulcerative colitis

Koloproktologia ◽

10.33878/10.33878/2073-7556-2021-20-3-43-50 ◽

2021 ◽

Vol 20 (3) ◽

pp. 43-50

Author(s):

D. V. Podolskaya ◽

M. V. Shapina ◽

T. A. Baranova ◽

I. A. Tishaeva ◽

T. L. Alexandrov ◽

...

Keyword(s):

Ulcerative Colitis ◽

Rescue Therapy ◽

Clinical Manifestations ◽

Stool Frequency ◽

Line Treatment ◽

Second Line ◽

Severe Ulcerative Colitis ◽

Laboratory Changes ◽

Time Of Administration

AIM: to evaluate the effectiveness of tofacitinib as a second line treatment.PATIENTS AND METHODS: the study included 12 patients, 4 (33.34%) males and 8 (66.66%) females. The median age was 41 ± 5 years. All patients admitted to the hospital with a severe flare-up of ulcerative colitis, which was the inclusion criterion in this study. Clinical manifestations, laboratory parameters, and colonoscopy were done at the time of administration of tofacitinib, on days 3 and 7, and after 12 weeks.RESULTS: a fast clinical response on 3 day of treatment, reduction in stool frequency, decrease blood in stool was noted in 10 (83.3%) patients. After 7 days from the start of TFCS therapy, all patients showed a decrease from severe activity to mild activity, as well as a decrease in inflammatory blood markers and hemoglobin levels. During the follow-up for 12 weeks, 100% of patients showed positive clinical and laboratory changes. In 10 (83.4%) patients, remission or maintenance of negligible minimal activity was noted.CONCLUSION: the results obtained show that the use of TFTB in hormone-resistant patients can be effective as a second line of “rescue therapy”.

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P476 Effectiveness and safety of ustekinumab in ulcerative colitis: Real-world evidence from the ENEIDA registry

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.599 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S465-S466

Author(s):

M Chaparro ◽

A Garre ◽

M Iborra ◽

M Sierra ◽

M Barreiro-de Acosta ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Practice ◽

Elevated Serum ◽

Real Life ◽

Development Program ◽

Lower Probability ◽

Clinical Activity ◽

Mayo Score

Abstract Background The development program (UNIFI) has shown promising results of ustekinumab in ulcerative colitis (UC) treatment that should be confirmed in clinical practice. Aims Primary: to evaluate the durability of ustekinumab treatment in UC patients in clinical practice. Secondary: to assess the short-term response (at week 16) and the long-term effectiveness (at maximum follow-up) and to assess the safety of ustekinumab in clinical practice. Methods Patients included in the prospectively maintained ENEIDA registry who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score (PMS) >2] were included. Clinical activity and effectiveness were defined based on PMS. Results 95 patients were included (table 1). At week 16, 53% of patients had clinical response (including 35% of patients in remission) (figure 1). In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with clinical remission. Long-term remission is represented in figure 2. 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at week 16, 63% at week 56, and 59% at week 72 (figure 3); primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusion Ustekinumab is effective both in the short and the long-term in real-life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

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