scholarly journals Effectiveness and Safety of Combining Tofacitinib with a Biologic in Patients with Refractory Inflammatory Bowel Diseases

2020 ◽  
Author(s):  
Quazim A. Alayo ◽  
Aava Khatiwada ◽  
Anish Patel ◽  
Maria Zulfiqar ◽  
Anas Gremida ◽  
...  
Keyword(s):  
Clinical Response ◽  
Clinical Remission ◽  
Clinical Symptoms ◽  
Therapeutic Option ◽  
Secondary Outcome ◽  
Physician Global Assessment ◽  
Radiographic Response ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Biologic Monotherapy

ABSTRACT AND KEY WORDSBackgroundOne therapeutic option with limited data among patients with active moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD) despite biologic monotherapy is using a combination of a biologic with Tofacitinib (TBT). Our aim was to examine the effectiveness and safety of TBT in this subset of patients.MethodsData of IBD patients at 2 referral centers on TBT were extracted. The primary outcome was clinical response (>50% reduction in symptoms) at week 8 and/or 16 determined by Physician Global Assessment. Secondary outcome was clinical remission (resolution of symptoms), corticosteroid-free clinical response and remission, normalization of CRP and endoscopic/radiographic response and remission. Adverse events (AEs) including any abnormal lipid profile or surgical complications were also assessed.ResultsThirty-five patients (25UC, 10CD) were included. Biologics combined with tofacitinib were vedolizumab (68.6%), ustekinumab (17.1%), and infliximab (14.3%) and the median follow-up duration was 4 months. A majority (57.2%) had failed at least two biologics prior to starting TBT. At weeks 8 and/or 16, 37.1% achieved clinical response with 5.7% in clinical remission. Among the 23 patients with endoscopically/radiographically active disease at baseline, 56.5% had endoscopic/radiographic response and 34.8% achieved remission. Three AEs occurred in 2 (5.7%) patients, with an IR of 20.5 (15.0–47.2)/100PYF. No VTE and herpes zoster was reported.ConclusionsTBT is effective at inducing endoscopic/radiographic response and a modest clinical response in UC and CD patients with active clinical symptoms despite prior biologic monotherapy. No new safety signals were detected beyond those reported with tofacitinib monotherapy.

scholarly journals Vedolizumab in patients with inflammatory bowel diseases of in real clinical practice

2020 ◽  
Vol 92 (2) ◽  
pp. 67-73
Author(s):  
M. V. Shapina ◽  
B. A. Nanaeva
Keyword(s):  
Clinical Practice ◽  
Clinical Response ◽  
Inflammatory Bowel Diseases ◽  
Clinical Remission ◽  
Line Therapy ◽  
Steroid Dependent ◽  
Endoscopic Remission ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Real Clinical Practice

Vedolizumab is currently the only selective biological drug for the treatment of inflammatory bowel diseases (IBD). Its effectiveness and safety has been shown in clinical trials. This article presents the experience of using vedolizumab in real clinical practice in patients with various forms of ulcerative colitis (UC) and Crohns disease (CD). Materials and methods.96 patients with IBD (62 with CD and 34 with UC) were prescribed therapy with vedolizumab at a dose of 300 mg intravenously at 0, 2, and 6 weeks, and further maintenance therapy was continued every 8 weeks. Most patients had prolonged inflammation (27 (79.4%) with total UC, 35 patients with CD (56.5%) had ileocolitis), resistance to therapy, including biological drugs (19 (55.9%) in patients with UC and 49 (79.0%) in patients with CD). The effectiveness of therapy was evaluated after 3 months (based on clinical response and clinical remission), 6 and 12 months (endoscopic response and endoscopic remission were additionally evaluated). Results.After 3 months, clinical remission was observed in 62.5% and 36.6%, respectively. After 6 months, these indicators were 66.7% and 61.0%, and after 12 months, 70.8% and 61.0%, respectively. After 6 months, endoscopic remission was observed in 50.0% of UC patients and 26.8% of CD patients. After 12 months, it reached 58.3% and 31.7%, respectively. The analysis showed greater efficacy in bio-naive patients with CD (steroid-free remission after 12 months 62.5%, endoscopic remission 37.5%), as well as patients with non-stricturizing non-penetrating CD (58%). In patients with UC, vedolizumab showed the same effectiveness both in bio-naive patients (70.0%) and as a second-line therapy (71.2%). It turned out to be more effective in patients with moderate UC (76.2%) and steroid-dependent UC (77.8%). Conclusions.Vedolizumab is effective in achieving clinical response and clinical remission, as well as endoscopic response and endoscopic remission in patients with UC and CD. Given the selective mechanism of action of the drug, it can be recommended as a first-line therapy.

scholarly journals Immunological Variables Associated With Clinical and Endoscopic Response to Vedolizumab in Patients With Inflammatory Bowel Diseases

2020 ◽  
Vol 14 (9) ◽  
pp. 1190-1201 ◽  
Author(s):  
Marina Coletta ◽  
Moira Paroni ◽  
Maria Francesca Alvisi ◽  
Matilde De Luca ◽  
Eliana Rulli ◽  
...  
Keyword(s):  
Clinical Response ◽  
Lamina Propria ◽  
Inflammatory Bowel Diseases ◽  
Peripheral Blood ◽  
Clinical Remission ◽  
Multivariable Analysis ◽  
Response To Treatment ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Baseline Levels

Abstract Background and Aims Vedolizumab [VDZ] is a monoclonal antibody directed against the α4β7 integrin heterodimer, approved for patients with inflammatory bowel diseases [IBD]. This study aimed at identifying immunological variables associated with response to vedolizumab in patients with ulcerative colitis [UC] and Crohn’s disease [CD]. Methods This is a phase IV explorative prospective interventional trial. IBD patients received open-label VDZ at Weeks 0, 2, 6, and 14. Patients with a clinical response at Week 14 were maintained with VDZ up to Week 54. At Weeks 0 and 14, their peripheral blood was obtained and endoscopy with biopsies was performed. The Week 14 clinical response and remission, Week 54 clinical remission, and Week 14 endoscopic response were evaluated as endpoints of the study. The expression of surface markers, chemokine receptors, and α4β7 heterodimer in peripheral blood and lamina propria lymphocytes was assessed by flow cytometry. A panel of soluble mediators was assessed in sera at baseline and at Week 14 by 45-plex. Results A total of 38 IBD patients [20 UC, 18 CD] were included in the study. At Week 14, the clinical response and remission rates were 87% and 66%, respectively. Higher baseline levels of circulating memory Th1 cells were strongly associated with clinical response at Week 14 [p = 0.0001], whereas reduced baseline levels of lamina propria memory Th17 and Th1/17 cells were associated with endoscopic response. Immunological clusters were found to be independently associated with vedolizumab outcomes at multivariable analysis. A panel of soluble markers, including IL17A, TNF, CXCL1, CCL19 for CD and G-CSF and IL7 for UC, associated with vedolizumab-induced Week 54 clinical remission. Conclusions The results of this exploratory study uncovered a panel of circulating and mucosal immunological variables associated with response to treatment with vedolizumab.

scholarly journals Sclerosing cholangitis and inflammatory bowel disease: which comes first?

2021 ◽  
Vol 66 (1) ◽  
pp. 39-46
Author(s):  
A. V. Nikitin ◽  
G. V. Volynets
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Sclerosing Cholangitis ◽  
Clinical Symptoms ◽  
Cross Reactivity ◽  
Formation Mechanisms ◽  
Malignant Neoplasms ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Sclerosing cholangitis is one of the most common hepatologic extraintestinal manifestations of inflammatory bowel disease. The article discusses the phenotype of the combination of sclerosing cholangitis and inflammatory bowel disease. The authors present their theories of the etiopathogenesis of sclerosing cholangitis in patients with inflammatory bowel disease, as well as some features of the phenotype of both mixed and monogenic forms of diseases.Sclerosing cholangitis in combination with inflammatory bowel disease is commonly associated with pancolitis, but the endoscopically visualized activity of inflammatory bowel diseases is significantly lower and clinical symptoms are less pronounced. The authors have established that the patients with the combination of sclerosing cholangitis and inflammatory bowel disease are at the increased risk of developing malignant neoplasms. The formation mechanisms of a combination of inflammatory bowel disease and sclerosing cholangitis remain poorly understood, although this pathology is influenced by lymphocytic cross-reactivity, aberrant recognition of microbiotic epitopes and intestinal microbiota imbalance. New biological agents aimed at correcting the interaction between the immune system and target organs may provide new ways of treatment for sclerosing cholangitis associated with inflammatory bowel disease.

scholarly journals Serum Interleukin-6 and -8 as Predictors of Response to Vedolizumab in Inflammatory Bowel Diseases

2020 ◽  
Vol 9 (5) ◽  
pp. 1323 ◽  
Author(s):  
Lorenzo Bertani ◽  
Gian Paolo Caviglia ◽  
Luca Antonioli ◽  
Rinaldo Pellicano ◽  
Sharmila Fagoonee ◽  
...  
Keyword(s):  
Clinical Response ◽  
Inflammatory Bowel Diseases ◽  
Area Under The Curve ◽  
Clinical Role ◽  
Faecal Calprotectin ◽  
Prediction Ability ◽  
Prospective Multicentre Study ◽  
Number Of Patients ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Vedolizumab, a monoclonal antibody directed against integrin α4β7, is an effective treatment for inflammatory bowel diseases. However, a significant number of patients do not achieve steroid-free clinical remission in the first year of treatment. An early identification of these patients is one of the most important challenges for clinicians and offers the possibility of therapeutic optimization in order to personalize biological therapy. The aim of our study was to test the prediction ability of interleukin (IL)-6 and -8 of clinical response after 12 months of therapy with vedolizumab (T2). We performed a prospective, multicentre study in patients affected by inflammatory bowel disease by analysing cytokines level before starting vedolizumab (T0) and after 10 weeks of therapy (T1). In the overall cohort (n = 54), IL-8 decrease > 2.6 pg/mL in the first 10 weeks of therapy was able to predict clinical response (area under the curve (AUC) = 0.70, sensitivity = 66%, specificity = 75%, p = 0.010), negative C-reactive protein (CRP) (AUC = 0.71, sensitivity = 64%, specificity = 80%, p = 0.009) and calprotectin < 250 mg/kg (AUC = 0.69, sensitivity = 64%, specificity = 78%, p = 0.030) after 44 weeks of therapy. In patients with ulcerative colitis (n = 40), baseline IL-8 values > 8.6 pg/mL and a decrease of IL-6 values > 0.4 pg/mL from T0 to T1 were significant and independent predictors of clinical response after 12 months of vedolizumab therapy (odds ratio (OR) = 6.96, 95% CI 1.27–38.22, p = 0.026 and OR = 7.29, 95% CI 1.42–37.50, p = 0.017, respectively). In patients with Crohn’s disease (n = 14), baseline IL-8 values > 8.6 pg/mL and baseline IL-6 values > 1.6 pg/mL allowed the identification of patients achieving negative CRP at T2 (AUC = 0.75, sensitivity = 74%, specificity = 76%, p < 0.001) and patients with faecal calprotectin values < 250 mg/kg at T2 (AUC = 0.71, sensitivity = 78%, specificity = 63%, p = 0.004). In conclusion, our study highlights a potential clinical role of serum cytokine levels for the prediction of clinical and biochemical steroid-free response in patients treated with vedolizumab.

scholarly journals P360 Safety and clinical efficacy of double switch from originator infliximab to biosimilars CT-P13 and SB2 in patients with inflammatory bowel diseases (SCESICS): A multicentre study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S342-S342
Author(s):  
S Mazza ◽  
A Fascì ◽  
V Casini ◽  
C Ricci ◽  
F Munari ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Inflammatory Bowel Diseases ◽  
Clinical Remission ◽  
Comparable Efficacy ◽  
Potential Cost ◽  
Safety And Efficacy ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Double Switch

Abstract Background Since infliximab (IFX) patent expiry in 2015, several IFX biosimilars have been licensed in EU for all indications, including inflammatory bowel diseases (IBD). IFX biosimilars currently available in Italy include CT-P13 and SB2, both of which demonstrated comparable efficacy, safety and immunogenicity with IFX originator in IBD patients. Safety and clinical efficacy of single switch from originator IFX to CT-P13 have also been confirmed in a prospective clinical trial. On the contrary, data regarding multiple therapeutic switching of IFX originator with CT-P13 and SB2 are currently lacking. Methods This study was aimed to evaluate the safety and efficacy of double switch from IFX originator to CT-P13 and subsequently to SB2 in patients with IBD. From November 2018 to May 2019, patients undergoing IFX double switch in 8 Centres in Lombardy were retrospectively analysed. The overall rate of IFX discontinuation, incidence and type of adverse events (AE) and proportion of patients on clinical remission over time were recorded. Data were compared with a control group of 66 IBD patients single switched from IFX originator to CT-P13. Results Fifty-two double-switched IBD patients were enrolled (63% M, mean age 41 years, 75% Crohn’s disease, 25% ulcerative colitis). Main indications for IFX therapy were moderate to severe disease (50%) and steroid-dependent disease (25%). The overall 24- and 48-week IFX discontinuation rates following second switch (CTP13-&gt;SB2) were 2% (95% CI 0–6%) and 14% (95% CI 3–25%), respectively. During a median follow-up of 40 weeks (18–48), 4 patients (12%) experienced a total of 6 AE (2 cutaneous, 2 infectious, 1 articular and 1 immunological), leading to IFX discontinuation in 3 cases (6%). No infusion reactions were observed. At week 24 following second switch, 49 (94%) patients were in clinical remission, the remaining 3 patients not being in remission already at the time of second switch. Only one patient lost response after week 24, 48 (92%) of patients being in clinical remission at the end of follow-up. No differences in IFX discontinuation, AE and clinical remission rates were found between double-switched and single-switched patients. No clinical parameters were found to predict safety and efficacy outcomes. Conclusion The study supports both safety and efficacy of the double switch from IFX originator to CT-P13 and SB2 in patients with IBD, and demonstrates its non-inferiority to a single switch strategy, with potential cost implications.

scholarly journals EXPERIENCE OF TOFACITINIB USING IN THERAPY OF ULCERATIVE COLITIS IN REAL CLINICAL PRACTICE

2019 ◽  
Vol 18 (4) ◽  
pp. 86-99
Author(s):  
E. A. Belousova ◽  
Вю I. Abdulganieva ◽  
O. P. Alekseeva ◽  
I. G. Bakulin ◽  
O. V. Vasilyeva ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Clinical Response ◽  
Clinical Improvement ◽  
Clinical Remission ◽  
Therapeutic Option ◽  
Mucosal Healing ◽  
Induction Treatment ◽  
Extraintestinal Manifestations ◽  
Biological Drugs ◽  
Real Clinical Practice

AIM: to demonstrate the first Russian experience with the use of tofaciminib (TOFA) for the treatment of moderate and severe UC in real clinical practice.PATIENTS AND METHODS: eighty-five patients with UC (aged 41.38±14.69 years, average disease duration 9.55±5.27 years, mild UC – 3.5%, moderate UC – 41.2%, severe – 52.9%, acute severe UC – 2.6%), resistant to corticosteroid therapy (36.5%) and biological agents (61.2%), were prescribed with TOFA at an induction dose of 10 mg 2 times a day, followed by a decrease in the dose to a maintenance dose (5 mg 2 times a day). Early clinical response, clinical and endoscopic remission, prevalence and dynamic of extraintestinal manifestations were assessed at 8 and 12 weeks of treatment, as well as safety and tolerability.RESULTS: Sixty-eight (80.0%) patients completed induction treatment with TOFA for 8 weeks, other patients continue to receive TOFA. A quick response within one week was detected in 41 (50.6%) patients, on average, on the 5th day of therapy. At the end of induction, 52 (76.5%) patients achieved clinical remission, 3 (4.4%) achieved a clinical response, 13 (19.1%) patients showed no positive changes. Of the 53 patients observed over 12 weeks, 41 (77.4%) had clinical remission, 6 (11.3%) had clinical improvement, and 6 (11.3%) patients had no response to the treatment. The changes of extraintestinal manifestations were positive: 55.2% of patients at week 8 and 77.8% of patients at week 12 showed clinical improvement, mainly in relation to the joint syndrome. One episode of herpes zoster infection, one case of anemia, were identified dur-ing 12 weeks of follow-up.CONCLUSION: TOFA in UC is effective in achieving a rapid clinical response, clinical remission and mucosal healing in patients who do not adequately respond to therapy with basic as well as biological drugs. Tofacitinib is an effective and safe therapeutic option for this challenging patient population.

scholarly journals P305 Effectiveness and Safety of Vedolizumab in Biologic-Naïve Patients: Real-World Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD)

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S333-S333
Author(s):  
F Macaluso ◽  
W Fries ◽  
S Renna ◽  
A Viola ◽  
M Muscianisi ◽  
...  
Keyword(s):  
Clinical Response ◽  
Real World ◽  
Primary Outcome ◽  
Real World Data ◽  
Mayo Score ◽  
Significant Difference ◽  
Bowel Diseases ◽  
Observational Cohort ◽  
Inflammatory Bowel

Abstract Background Biologic-naïve patients treated with Vedolizumab (VDZ) are largely underrepresented in real-world cohorts. We performed a multicentre, observational, cohort study on the effectiveness and safety of VDZ as treatment for Crohn’s disease (CD) and ulcerative colitis (UC) among biologic-naïve subjects. Methods Data of consecutive biologic-naïve patients with CD and UC treated with VDZ from July 2016 to December 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). The primary outcome was the clinical response at 14 and 52 weeks evaluated with Harvey Bradshaw Index in CD and partial Mayo score in UC. Results 172 consecutive patients (CD: n=88; UC: n=84; median age 66.0 years) were included, with a median follow-up of 58.8 weeks. After 14 weeks, a clinical response was reported in 68.2% of patients with CD and 67.9% of patients with UC treated with VDZ, including 45.5% patients in the CD group and 46.4% patients in the UC group who achieved steroid-free remission. After 52 weeks, a clinical response was reported in 77.4% of CD and in 73.8% of UC patients treated with VDZ, including 59.7% patients in the CD group and 60.7% patients in the UC group who achieved steroid-free remission. All differences between CD and UC were not statistically significant. Cox survival analysis showed no significant difference in the probability of treatment discontinuation between CD and UC patients (log-rank p=0.73). Conclusion This large, real-world, multicenter study demonstrated the effectiveness and safety of VDZ as a first-line biologic, showing high rates of clinical response and steroid-free remission at both induction and maintenance.

scholarly journals Mucosal Eosinophilia Is an Independent Predictor of Vedolizumab Efficacy in Inflammatory Bowel Diseases

2019 ◽  
Vol 26 (8) ◽  
pp. 1232-1238 ◽  
Author(s):  
Erin M Kim ◽  
Cara Randall ◽  
Renee Betancourt ◽  
Staci Keene ◽  
Amy Lilly ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Multivariable Analysis ◽  
Patient Characteristics ◽  
Predictors Of Response ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Negative Predictor ◽  
Colonic Biopsies

Abstract Background Peripheral and mucosal eosinophilia may be associated with more aggressive disease in inflammatory bowel disease (IBD) patients. Vedolizumab blocks T lymphocytes, eosinophil adhesion, and extravasation in the gastrointestinal tract. It is not known if mucosal eosinophilia is a predictor for the therapeutic efficacy of vedolizumab. Methods This was a retrospective cohort study of IBD patients with ileal or colonic biopsies who were off steroids before starting vedolizumab. Biopsies were rereviewed by pathologists, and mean eosinophil density was quantified. Patient characteristics and steroid-free clinical response 6 months after beginning vedolizumab were determined. Features were compared between nonresponders and responders, and multivariable logistic regression was performed to identify predictors of clinical response. Results Of 251 IBD patients starting vedolizumab therapy, 65 patients (48% Crohn’s disease, 52% ulcerative colitis) met inclusion criteria. All IBD patients not responding to vedolizumab were more likely to have a higher baseline mean eosinophil count (340 ± 156 vs 236 ± 124; P = 0.004), be previously exposed to an anti-TNF (96% vs 56%; P = 0.001), and be male (58% vs 28%; P = 0.02). Mean eosinophil counts were significantly increased in colonic biopsies in UC nonresponders (438 ± 149 vs 299 ± 145; P = 0.01). A similar trend was seen in CD nonresponders. On multivariable analysis, colonic eosinophil density and prior anti-TNF exposure—and the combination of both—were independent predictors of response. Conclusion In ulcerative colitis, colonic eosinophilia and prior anti-TNF exposure were independent predictors of 6-month clinical nonresponse to vedolizumab. Mucosal eosinophil density as a novel biomarker should be explored in larger patient cohorts. Aside from the previous anti-TNF exposure, eosinophil density in the colon of patients with UC is a negative predictor for a steroid-free long-term response to vedolizumab. The degree colonic eosinophilia may be a novel biomarker that should be further explored.

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