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

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”.

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

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”.

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

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.

scholarly journals DOP35 Ambulatory care management of 70 patients with Acute Severe Ulcerative Colitis in comparison to 700 inpatients: Insights from a multicentre UK cohort study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S073-S074
Author(s):  
K V Patel ◽  
J Segal ◽  
S Sebastian ◽  
S Subramanian ◽  
T Conley ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Ambulatory Care ◽  
Rescue Therapy ◽  
Corticosteroid Treatment ◽  
Inpatient Setting ◽  
Close Monitoring ◽  
Severe Ulcerative Colitis ◽  
Significant Difference ◽  
Secondary Outcomes

Abstract Background Acute severe ulcerative colitis (ASUC) traditionally requires inpatient hospital management for intravenous therapies and/or colectomy. Patients with ASUC can deteriorate rapidly and hence require close monitoring of vital signs correlated with clinical, biochemical and radiological investigations. Traditionally, patients are admitted to hospital to facilitate endoscopic assessment, exclude concomitant infective complications, monitor response to first-line corticosteroid treatment and determine the need for and timing of rescue therapy and/or colectomy. Ambulatory care pathways, which utilise outpatient monitoring and drug delivery, have been shown to deliver safe and effective treatment for conditions which have historically mandated hospitalisation e.g. pulmonary embolus. To date there are a paucity of data regarding the use of ambulatory pathways in ASUC cohorts. We used data from PROTECT, a UK multicentre observational COVID-19 i (IBD) study, to report the extent, safety and effectiveness of ASUC ambulatory pathways. Methods Adults (≥ 18 years old) meeting Truelove and Witts criteria between 01/01/2019- 01/06/2019 and 01/03/2020–30/06/2020 were recruited to PROTECT (Figure 1). We utilised demographic, disease phenotype, treatment outcomes and 3-month follow-up data. Primary outcome was rate of rescue therapy and/or colectomy. Secondary outcomes included corticosteroid response, response to rescue therapy, colectomy, mortality and hospital readmission within 3-months. We compared outcomes in 3 cohorts: i) patients treated entirely in inpatient setting; ambulatory patients subdivided into ii) patients hospitalised and subsequently discharged to ambulatory care; iii) patients managed as ambulatory from diagnosis . Results 38%(23/60) participating hospitals used ambulatory pathways. Of 770 eligible patients, 700(91%) patients received entirely inpatient care, 55(7%) patients were discharged to ambulatory pathways and 15(2%) patients were managed as ambulatory from diagnosis. The rate of rescue therapy and/or colectomy (49%[339/696] vs 41%[22/54] vs 67%[10/15], respectively, p=0.18) (figure 2) and secondary outcomes were similar among all three cohorts. After 3-months follow up from the index ASUC diagnosis there was no significant difference in either rate of UC flare, readmission to hospital with UC flare or colectomy between the cohorts. Conclusion In the largest description of ambulatory ASUC care to date, we report an emerging practice which challenges treatment paradigms. Our data suggest ambulatory ASUC treatment may be safe and effective in selected patients but further studies exploring clinical and cost effectiveness as well as patient and physician acceptability are needed.

PO57 ACTIVE SEVERE ULCERATIVE COLITIS (UC): WHICH SECOND-LINE OR RESCUE THERAPY?

2012 ◽  
Vol 44 ◽  
pp. S282
Author(s):  
D. Comito ◽  
A. Chiaro ◽  
R. Mallamace ◽  
S. Cardile ◽  
C. Romano
Keyword(s):  
Ulcerative Colitis ◽  
Rescue Therapy ◽  
Second Line ◽  
Severe Ulcerative Colitis

Outcomes of Chronic Myeloid Leukemia (CML) Patients Who Stopped Second Generation Tyrosine Kinase Inhibitors (2GTKIs) As Second Line Treatment. Results of the CML Spanish National Registry (RELMC)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3764-3764
Author(s):  
J Valentin Garcia-Gutierrez ◽  
Begoña Maestro ◽  
Luis Felipe Casado ◽  
Manuel Perez-Encinas ◽  
Isabel Massague ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Research Funding ◽  
Second Generation ◽  
Rescue Therapy ◽  
National Registry ◽  
Line Treatment ◽  
Second Line ◽  
Treatment Change ◽  
Third Line

Abstract Abstract 3764 Introduction: In CML-CP patients showing resistance or intolerance to imatinib, rescue therapy with second generation 2GTKIs produced nearly 50% of complete cytogenetic responses (CCyR). However, in the long term, a high percentage (roughly 70%) of patients abandoned the targeted treatment. The information about the outcome of patients treated in third line with TKI's is scarce, and come mostly form clinical trials. In these experiences CCyR were obtained in approximately 20%, and the duration of MCyR was around 18 months. Aims: To describe the evolution of patients who interrupted 2GTKI, given as 2nd line treatment, outside clinical trials. Patients and methods: In our registry, we have identified 105 patients treated with second generation TKI in second line out of 487 patients treated with imatinib as first TKI. Reasons for treatment change were failure in 53%, intolerant in 33% and suboptimal in 14%. Sokal risk indexes were 40%, 47% and 13% for low, intermediate and high risk, respectively. 33% of patients had received interferon prior to imatinib. Cummulative incidence of CCyR and major molecular responses (MMR) with a median follow up of 85.59 (8.93–130) months, were 65% and 49%. Fifty two (49%) withdrew treatment because of failure (22%), intolerance (18%), suboptimal response (7%) and exitus (8%). Results: A total of 31 patients started third-line therapy with a third TKI, representing 29% of patients who started second-line treatment and 78% of patients who discontinued the treatment. The reasons for starting the 3rd line treatment was failure in 55% and intolerance, in 44%. With a median follow up of 9 months, probabilities of achievement a complete hematological response (CHR) and CCR was 93% and 30%. These responses were influenced depending on the indication of treatment, with cummulative indidence of CCyR of 18% and 50% for resistant and intolerant patients, respectively (p = 0.031). The corresponding figures for transformation-free survival and overall survival were 61% vs 76, and 72% vs 88% for failure and intolerance settings, respectively. Conclusions: In this registry-based experience, outside clinical trials, 2GTKI have offered a substantial benefit to patients resistant or intolerant to Imatinib. However, the experience in 3rd line in patients resistant to 2GTKI in 2nd line, has been dismal, with less than 20% of CCyR. In this particular subgroup, BMT must be considered, and new experimental therapeutic schemes are necessary for those patients who are not suitable candidates for BMT. Disclosures: Casado: Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau. Steegmann:Pfizer: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau.

scholarly journals P466 Acute Severe Ulcerative Colitis in the modern era: biologic therapy-exposed patients and salvage therapy with intensified infliximab

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S457-S457
Author(s):  
K Fasoulas ◽  
K Soufleris ◽  
N Kafalis ◽  
P Kevrekidou ◽  
S Bouzoukas ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Medical Therapy ◽  
Salvage Therapy ◽  
Biologic Therapy ◽  
Rescue Therapy ◽  
Fecal Calprotectin ◽  
Disease Extent ◽  
Severe Ulcerative Colitis ◽  
Modern Era

Abstract Background Acute Severe Ulcerative Colitis (ASUC) is still associated with significant morbidity and risk of colectomy, almost 70 years since the landmark study of Truelove-Witts established steroid efficacy and 15 years since the Järnerot study introduced infliximab as an effective rescue therapy. It remains unclear if management of ASUC in the modern era (biologic-exposed patients and intensified infliximab regimens) leads to different outcomes. Methods A retrospective review of all recently hospitalized ASUC patients was performed. We aimed to compare rates of colectomy, response to steroids, and response to salvage infliximab in bio-naive and bio-exposed patients. Intensified infliximab was used as salvage therapy: 10 mg/kg infusions, aiming a trough level of at least 10 μg/ml at Week 10. We also tried to identify disease and patient related characteristics predictive of colectomy or response to medical therapy. Results 50 patients were included (male 66%, mean age: 47.4 years) and followed up for a mean of 24.2 months. 24 patients (48%) experienced ASUC while on biologic therapy: 11 on infliximab, 6 on vedolizumab, 5 on adalimumab, 2 on golimumab. Endoscopy showed deep ulcers at 23 patients (47%). Fecal calprotectin was > 1800 ng/ml in all patients. Half the patients (25) received rescue therapy with Infliximab due to steroid refractoriness. Eleven patients (22%) underwent colectomy, 2 (4%) of which during the index hospitalization. Although colectomy rates were similar among bio-naïve and bio-exposed (20% vs 25%, p:0.675), bio-exposed patients were more refractory to steroids (0dds Ratio:3.6 ;95% CI:1.01–13.2, p:0.047). Response to rescue infliximab was similar (Odds Ratio:0.45 ;95% CI:0.13–1.5, p:0.215), even in patients failing standard dosed infliximab. High CRP levels (4.89 mg/dl vs 2.64 mg/dl, p:0.014) and low albumin levels (3.4 g/dl vs 3.9 g/dl, p:0.013) were predictive of colectomy in contrast to endoscopic severity and disease extent. Conclusion ASUC remains a therapeutic challenge in the modern era, with considerable refractoriness to medical therapy and colectomy risk: 50% of our group of ASUC patients responded to steroids and 22% underwent colectomy within two years of follow-up. High inflammatory burden, depicted by high CRP values and hypoalbuminemia can predict need for colectomy. Bio-exposed patients were more refractory to steroids but they showed comparable response to intensified infliximab, so they can be managed in the same way, at least until therapy with small molecules proves more efficient by future studies.

scholarly journals Acute severe ulcerative colitis: management advice for internal medicine and emergency physicians

2021 ◽  
Author(s):  
Konstantina Rosiou ◽  
Christian Philipp Selinger
Keyword(s):  
Ulcerative Colitis ◽  
Rescue Therapy ◽  
Medical Emergency ◽  
Close Monitoring ◽  
Surgical Morbidity ◽  
Severe Ulcerative Colitis ◽  
General Management ◽  
Management Measures ◽  
Management Advice ◽  
Team Setting

AbstractAcute severe ulcerative colitis is a medical emergency that warrants in-patient management. This is best served within a multidisciplinary team setting in specialised centres or with expert consultation. Intravenous corticosteroids remain the cornerstone in the management of ASUC and should be initiated promptly, along with general management measures and close monitoring of patients. Unfortunately, one-third of patients will fail to respond to steroids. Response to intravenous corticosteroid therapy needs to be assessed on the third day and rescue therapies, including cyclosporine and infliximab, should be offered to patients not responding. Choice of rescue therapy depends on experience, drug availability and factors associated with each individual patient, such as comorbidities, previous medications or contra-indications to therapy. Patients who have not responded within 7 days to rescue therapy must be considered for surgery. Surgery is a treatment option in ASUC and should not be delayed in cases of failure of medical therapy, because such delays increase surgical morbidity and mortality. This review summarises the current management of acute severe ulcerative colitis and discusses potential future developments.

scholarly journals Tofacitinib: An Option for Acute Severe Ulcerative Colitis?

2021 ◽  
pp. 1-3
Author(s):  
Sara Santos ◽  
Verónica Gamelas ◽  
Rita Saraiva ◽  
Guilherme Simões ◽  
Joana Saiote ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Improvement ◽  
Rescue Therapy ◽  
New Drugs ◽  
Multiple Drug ◽  
Disease Course ◽  
Efficacy And Safety ◽  
Severe Ulcerative Colitis ◽  
Rapid Absorption

Tofacitinib has emerged as a new option for ulcerative colitis. Its rapid absorption, metabolism, and clinical improvement make it an interesting option for rescue therapy in acute severe ulcerative colitis (ASUC), a situation with limited therapeutic options in patients with a long-term disease course and multiple drug failure. The management of ASUC in this setting becomes challenging, underlying the need for new drugs and data on their efficacy and safety. We describe 2 cases of acute episodes in which tofacitinib was used as a rescue therapy.

scholarly journals Sequential Treatment of Metastatic Adenocarcinoma of the Pancreatic Duct with Liver Metastasis Following the NAPOLI-1 Study Protocol with nal-Irinotecan plus 5-FU in the Second Line

2020 ◽  
Vol 13 (1) ◽  
pp. 79-84
Author(s):  
Dilara Akhoundova Sanoyan ◽  
Cäcilia S. Reiner ◽  
Panagiota Papageorgiou ◽  
Alexander R. Siebenhüner
Keyword(s):  
Systemic Treatment ◽  
Sequential Treatment ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Curative Surgery ◽  
To Receive

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced or metastatic stage, when curative surgery is not recommended. Therefore, the prognosis is poor for this dismal disease, with only 1–2% of the patients reaching the 5-year survival follow-up. Current advances in systemic treatment with gemcitabine regimens, specifically polychemotherapy with gemcitabine plus nab-paclitaxel or other multidrug regimens such as FOLFIRINOX in the first line, have improved disease control over time. This higher efficacy of systemic treatment enables metastatic PDAC patients to receive second-line treatment more often nowadays. Currently, there is only one regimen for second-line treatment approved by the EMA, FDA, and Swissmedic, based on the phase III NAPOLI-1 study. In this case report, we present an outstanding response to sequential treatment with gemcitabine plus nab-paclitaxel followed by second-line treatment with nal-irinotecan plus 5-fluorouracil.

Sign in / Sign up

Export Citation Format

Share Document