scholarly journals The efficacy and safety of tacrolimus suppositories in patients with localized ulcerative colitis

2020 ◽  
Author(s):  
Shizuma Omote ◽  
Tatsuya Toyokawa ◽  
Ryohei Sumii ◽  
Akira Nakanishi ◽  
Yuka Kadowaki ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Blood Concentration ◽  
Efficacy And Safety ◽  
Monitoring Methods ◽  
Once Daily ◽  
Mayo Score ◽  
Amino Salicylic Acid ◽  
One Year ◽  
Dose Change

Abstract Background Tacrolimus is a calcineurin inhibitor used for the treatment of 5-Amino-salicylic acid (5-ASA) and systematic corticosteroid refractory ulcerative colitis. However, systemic administration of tacrolimus could lead to many adverse events. Therefore, we used tacrolimus suppositories as a local therapeutic agent and examined its efficacy and safety with strict blood concentration monitoring. Methods Sixteen patients with ulcerative colitis were administered a 0.5-mg tacrolimus suppository once daily. In cases with an insufficient clinical effect, additional amounts, at an increment of 0.5 mg of tacrolimus, were administered. The blood concentration was measured two weeks after the start of treatment or any dose change and every four weeks thereafter. Results The partial Mayo score was 5.31 before the start of treatment, and it decreased significantly after 2 (2.56, P = 0.001), 4 (1.53, P < 0.001), and 8 (1.47, P = < 0.001) weeks of treatment. The median duration of tacrolimus treatment was 24 (range 2–96) weeks, and 6 patients were treated continuously for more than one year after the pMayo score improved. No exacerbation of adverse events during the treatment regimen was observed. The effects and safety of tacrolimus suppositories were verified with strict blood concentration monitoring. Conclusions Our findings suggest that the application of tacrolimus suppositories is safe and effective in the treatment of patients with ulcerative colitis.

scholarly journals P323 Efficacy and safety of tofacitinib treatment for one year in Japanese patients with Ulcerative Colitis in a specialized Inflammatory Bowel Disease center

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S348-S348
Author(s):  
K Kojima ◽  
K Yokoyama ◽  
K Kaku ◽  
Y Takashima ◽  
T Sato ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Herpes Zoster ◽  
Adverse Events ◽  
Rectal Bleeding ◽  
Bowel Disease ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Inflammatory Bowel ◽  
One Year

Abstract Background Few reports of the real-world efficacy and safety of tofacitinib (TFB) in Asians are available, and potential predictors of the response to therapy are unclear. We investigated the efficacy and safety profiles of TFB treatment for one year in patients with active Ulcerative Colitis (UC) in our specialized Inflammatory Bowel Disease center. Methods This study included 111 patients who received TFB between May 2018 and February 2020. We assessed disease activity using the partial Mayo Score (pMS). Clinical remission was defined as pMS ≤2, with no subscore &gt;1 and a rectal bleeding subscore of 0. Clinical response was defined as a decrease in pMS of ≥2 points from baseline with an accompanying decrease in the rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of ≤1 point. Results Mean patient age was 35 years (interquartile range [IQR]: 28-47), 60 (59.4%) were men, and mean disease duration was 4.8 years (IQR:1.5-10). The pMS was 6 (IQR:4-7) and C-reactive protein was 0.30 mg/dl (IQR: 0.1-1.0). At baseline, 63 (62.4%) patients received an anti-TNFα agent, 11 (10.9%) received vedolizumab, and 7 (6.9%) received both. Clinical response and clinical remission were, respectively, 66.3% (67/101) and 50.5% (51/101) at week 8, and 47.1% (40/85) and 43.5% (37/85) at week 48. The cumulative remission rate was 61.7% at 1 year and 51.7% at 2 years, and tended to be better in the ≥2 anti-TNFα agents failure group than in the 1 anti-TNFα agent failure and bio-naïve groups (P=0.10). Cumulative colectomy-free survival was 91.9% at 1 year and 89.1% at 2 years. Cumulative drug-free survival in the non-remission group at week 8 was 30.9% at 1 year and 30.9% at 2 years, significantly lower than in the remission-achieving group at week 8 (P&lt;0.01). Baseline pMS was significantly lower in responders vs non-responders at week 8 (odds ratio, 0.61; 95% confidence interval, 0.45-0.82). Relapse occurred in 45.7% of patients after tapering TFB, and 85.7% of patients with re-increased TFB responded by week 4. Herpes zoster occurred in 6 unvaccinated patients (46±16 years old). There were no specific features regarding age, TFB dosage, duration of administration, or lymphocyte count in these patients. No thrombotic adverse events occurred, even though 54.1% patients continued treatment with 10 mg twice daily at week 48. Conclusion TFB was more effective in low-activity UC patients and its efficacy was not affected by previous treatment with anti-TNF agents. Most patients in the remission groups at week 8 could continue TFB for one year without severe adverse events, although careful monitoring for herpes zoster is necessary. The risk of thrombotic adverse events might be lower in Japanese UC patients.

scholarly journals OP33 Oral ritlecitinib and brepocitinib in patients with Moderate to Severe Active Ulcerative Colitis: Data from the VIBRATO umbrella study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S030-S031
Author(s):  
W Sandborn ◽  
S Danese ◽  
J Leszczyszyn ◽  
J Romatowski ◽  
E Altintas ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Rectal Bleeding ◽  
Active Ulcerative Colitis ◽  
Efficacy And Safety ◽  
Dose Response Relationship ◽  
Once Daily ◽  
Mayo Score ◽  
Adult Participants ◽  
Respective Treatment ◽  
To Receive

Abstract Background The efficacy and safety of oral ritlecitinib (JAK3/TEC inhibitor) and brepocitinib (TYK2/JAK1 inhibitor) were assessed in a 32-week Phase 2b induction-maintenance umbrella study (VIBRATO) in participants with moderate to severe active ulcerative colitis who had inadequate or loss of response, or intolerance to corticosteroids, immunosuppressants, or biologic therapies. We report efficacy and safety results from the 8-week induction period of the VIBRATO study. Methods Adult participants with Total Mayo Score ≥6 and centrally-read Mayo endoscopic subscore ≥1 were randomised to receive oral ritlecitinib 20, 70, or 200 mg; brepocitinib 10, 30, or 60 mg; or placebo once-daily (QD) for 8 weeks. Participants then continued in their respective treatment cohorts to receive ritlecitinib 50 mg or brepocitinib 30 mg QD for 24 weeks. The proportions of patients who achieved remission (Total Mayo Score ≤2; no individual subscore &gt;1; rectal bleeding subscore 0), modified remission (Modified Mayo Score: Total Mayo without Physician’s Global Assessment; stool frequency subscore ≤1; rectal bleeding subscore 0; endoscopic subscore ≤1), or endoscopic improvement (Mayo endoscopic subscore ≤1) were analysed. Results 319 participants were randomised: baseline mean (standard deviation [SD]) age 40.3 (13.8) years; mean (SD) Total Mayo Score 9.0 (1.5); and median (range) disease duration 4.8 (0.24, 36.5) years. Ritlecitinib and brepocitinib were generally safe and well tolerated. At Week 8, a dose–response relationship was observed across all efficacy endpoints for ritlecitinib and brepocitinib. The proportions of participants achieving remission were significantly higher (P&lt;0.05) with ritlecitinib 70 and 200 mg and brepocitinib 30 and 60 mg vs placebo (Figure 1). The proportions of participants achieving endoscopic improvement and modified remission were significantly higher in all ritlecitinib and brepocitinib groups vs placebo (Figures 2 and 3). Conclusion Ritlecitinib 70 and 200 mg QD and brepocitinib 30 and 60 mg QD demonstrated significant improvement in remission, modified remission, and endoscopic improvement in participants with moderate to severe active ulcerative colitis.

scholarly journals DOP01 Efficacy and safety of the IL-6 trans-signalling inhibitor olamkicept: a phase 2 randomized, placebo-controlled trial in moderately to severely active Ulcerative Colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S041-S042
Author(s):  
B Chen ◽  
S Zhang ◽  
B Wang ◽  
H Chen ◽  
Y Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Clinical Response ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Active Ulcerative Colitis ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Mayo Score

Abstract Background Total inhibition of IL-6 or its receptor represents a potent anti-inflammatory therapy with considerable side effects. Selective targeting IL-6 trans-signalling may have safety advantages that differentiates it from current pan-IL-6 inhibitors. We evaluated the efficacy and safety of olamkicept, a soluble gp130-Fc fusion protein that binds to the IL-6 and soluble IL-6 receptor complex, as induction therapy for active ulcerative colitis (UC). Methods This multi-national, randomized, double-blind, placebo-controlled phase 2 trial (NCT03235752) enrolled patients with active UC (full Mayo score ≥5, rectal bleeding (RB) score ≥1, endoscopy score (ES) ≥2) with an inadequate response to at least conventional therapy, in a 1:1:1 ratio to receive either placebo, olamkicept 300 mg or 600 mg biweekly for 12 weeks. Primary efficacy endpoint was clinical response (decrease in Mayo score from baseline ≥3 and ≥30%, including RB ≤1 or RB decrease ≥1) at week 12. Secondary endpoints were mucosal healing (ES 0 or 1) and clinical remission (Mayo score ≤2, with no subscore &gt;1 and RB=0). The efficacy endpoints were analysed by logistic regression. All p-values were 2-sided without adjustment for multiplicity. Results Of 91 treated patients (30 in placebo, 31 in olamkicept 300 mg group and 30 in 600 mg group), 88 patients (29:30:29) were evaluable for efficacy. Baseline disease and demographic characteristics were similar among the groups (Table 1). Most patients (94.5%) were bio-naïve. The percentage of patients achieving clinical response at week 12 was significantly greater for olamkicept 600 mg than placebo (58.6% vs 34.5%, P=0.032). Clinical remission at week 12 occurred in 0% (placebo), 6.7% (olamkicept 300 mg) and 20.7% (olamkicept 600 mg, P&lt;0.001) of patients. Mucosal healing at week 12 occurred in 3.4%, 10% and 34.5% (P&lt;0.001) of patients, respectively (Figure 1). Incidence of treatment emergent adverse events (TEAEs) was similar across the groups. The most common TEAEs included upper respiratory tract infection, increased AST levels, and increased urine bilirubin levels, which were mild to moderate and mostly transient. Serious adverse events (SAEs) were reported in 6.7%, 3.2% and 3.3% of patients, respectively. There were no deaths, or other severe AEs associated with current IL-6 inhibitors, such as perforations, severe infections, neutropenia or thrombocytopenia. Conclusion Biweekly 600 mg olamkicept induction therapy demonstrated clinical efficacy with respect to achieving clinical response, clinical remission and mucosal healing in patients with active UC. Olamkicept was well tolerated with a favourable safety profile. The positive results of this phase 2 study support further development of olamkicept in IBD.

scholarly journals 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

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.

scholarly journals Once-Daily MMX Mesalamine in the Management of Ulcerative colitis

2011 ◽  
Vol 4 ◽  
pp. CGast.S4276
Author(s):  
Wojciech Blonski ◽  
Anna M. Buchner ◽  
Gary R. Lichtenstein
Keyword(s):  
Ulcerative Colitis ◽  
Maintenance Treatment ◽  
Review Article ◽  
Active Ulcerative Colitis ◽  
Efficacy And Safety ◽  
Entire Colon ◽  
Once Daily ◽  
Gradual Release

Mesalamine (5-ASA) has been the mainstay therapy of mild to moderate active ulcerative colitis both as an induction and maintenance treatment. Multimatrix system (MMX) 5-ASA is a recently developed formulation of 5-ASA allowing for slow and gradual release of 5-ASA throughout the entire colon. This review article discusses the structure, pharmacokinetics, efficacy and safety of this new 5-ASA formulation.

scholarly journals Efficacy and Safety of Deracoxib for the Control of Postoperative Pain and Inflammation Associated with Dental Surgery in Dogs

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Stephen E. Bienhoff ◽  
Eric S. Smith ◽  
Linda M. Roycroft ◽  
Elizabeth S. Roberts ◽  
Larry D. Baker
Keyword(s):  
Postoperative Pain ◽  
Adverse Events ◽  
Treatment Response ◽  
Pain Scale ◽  
Efficacy And Safety ◽  
Dental Surgery ◽  
Once Daily ◽  
To Receive

The efficacy and safety of deracoxib administered at 1-2 mg/kg/day for 3 days was assessed for the control of postoperative pain and inflammation associated with dental surgery in dogs. Client-owned dogs scheduled for dental extractions were premedicated with butorphanol and randomly assigned to receive either deracoxib (n=31) or placebo (n=31) preoperatively and again once daily for 2 additional days. Dogs were evaluated prior to and after surgery using a modified Glasgow Composite Pain Scale (mGCPS). Dogs could be rescued at any time if they scored ≥4 on the mGCPS or in cases of obvious discomfort. Rescued dogs were considered treatment failures for determining treatment response and were removed from the study. Of the 62 dogs enrolled, 57 were usable for the efficacy analyses and all were assessed for safety. Four of 27 deracoxib-treated dogs (14.8%) were rescued compared to 20 of 30 placebo dogs (66.7%) (P=0.0006). Deracoxib-treated dogs also had numerically lower mGCPS scores. Eight of 31 deracoxib dogs (26%) had adverse events reported compared to 6 of 31 placebo dogs (19%). Results indicate perioperative administration of deracoxib to dogs at 1-2 mg/kg/day for 3 days significantly improves analgesia after dental surgery.

scholarly journals Pharmacokinetics and Safety of Caspofungin in Older Infants and Toddlers

2008 ◽  
Vol 53 (4) ◽  
pp. 1450-1456 ◽  
Author(s):  
Michael Neely ◽  
Hasan S. Jafri ◽  
Nita Seibel ◽  
Katherine Knapp ◽  
Peter C. Adamson ◽  
...  
Keyword(s):  
Adverse Events ◽  
Peak Concentration ◽  
High Performance ◽  
Geometric Mean ◽  
Area Under The Curve ◽  
Efficacy And Safety ◽  
Infants And Toddlers ◽  
Dosing Regimen ◽  
Elimination Phase ◽  
Once Daily

ABSTRACT Although information about the efficacy and safety experience with caspofungin at 50 mg/m2 daily is available for children and adolescents, the dosing regimen in infants and toddlers 3 to 24 months of age has yet to be established. We studied the pharmacokinetics and safety of caspofungin at 50 mg/m2 once daily in nine patients 10 to 22 months (median, 13 months) of age with fever and neutropenia who received caspofungin once daily for 2 to 21 (mean, 9.3) days. Plasma caspofungin concentrations were measured by high-performance liquid chromatography assay on days 1 and 4. On day 4, the area under the curve from 0 to 24 h (AUC0-24) was 130.3 μg-h/ml, the peak concentration (C 1) was 17.2 μg/ml, and the trough concentration (C 24) was 1.6 μg/ml. The day 4 geometric mean ratios (GMRs) and 90% confidence interval (CI) for these parameters in infants/toddlers relative to adults were 1.26 (1.06, 1.50), 1.83 (1.57, 2.14), and 0.81 (0.64, 1.04), respectively. Relative to children (2 to 11 years of age), the day 4 GMRs (and 90% CI) were 1.13 (0.89, 1.44), 1.10 (0.85, 1.42), and 1.12 (0.72, 1.76), respectively. The harmonic mean elimination phase t 1/2 in infants/toddlers (8.8 h) was reduced ∼33% relative to adults (13.0 h) but was similar to that in children (8.2 h). Clinical adverse events occurred in seven patients (78%); none were considered drug related. Laboratory adverse events occurred in five patients (56%) and were considered drug related in three (33%). There were no infusion-related events or discontinuations due to toxicity. Caspofungin at 50 mg/m2 daily was well tolerated in infants and toddlers; the AUC and caspofungin C 24 were generally comparable to those in adults receiving caspofungin at 50 mg daily.

scholarly journals One-year investigator-blind randomized multicenter trial comparing asacol 2.4 g once daily with 800 mg three times daily for maintenance of remission in ulcerative colitis

2012 ◽  
Vol 18 (10) ◽  
pp. 1885-1893 ◽  
Author(s):  
Barney A. Hawthorne ◽  
Rachel Stenson ◽  
David Gillespie ◽  
Edwin T. Swarbrick ◽  
Anjan Dhar ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Multicenter Trial ◽  
Once Daily ◽  
Maintenance Of Remission ◽  
One Year

scholarly journals The Diagnostic Usefulness of Circulating Profile of Extracellular Matrix Components: Sulfated Glycosaminoglycans (sGAG), Hyaluronan (HA) and Extracellular Part of Syndecan-1 (sCD138) in Patients with Crohn’s Disease and Ulcerative Colitis

2021 ◽  
Vol 10 (8) ◽  
pp. 1722
Author(s):  
Alicja Derkacz ◽  
Paweł Olczyk ◽  
Agnieszka Jura-Półtorak ◽  
Krystyna Olczyk ◽  
Katarzyna Komosinska-Vassev
Keyword(s):  
Ulcerative Colitis ◽  
Extracellular Matrix ◽  
Ecm Remodeling ◽  
Mayo Score ◽  
Extracellular Matrix Components ◽  
Adalimumab Therapy ◽  
Bowel Diseases ◽  
Diagnostic Usefulness ◽  
Quantitative Changes ◽  
One Year

The described research focused on the diagnostic usefulness of sulfated glycosaminoglycans (sGAG), hyaluronan (HA), and extracellular part of syndecan-1 (sCD138) as new markers related to extracellular matrix (ECM) remodeling in the intestine during the two most common forms of inflammatory bowel diseases (IBD), i.e., ulcerative colitis (UC) and Crohn’ disease (CD). Inflammatory markers belonging to ECM components were assessed in serum of patients with IBD using an immunoenzymatic method (HA and sCD138) and a method based on the reaction with dimethylmethylene blue (sulfated GAG). Measurements were carried out twice: at baseline and after one year of therapy with prednisone (patients with CD) or adalimumab (patients with UC). No quantitative changes were observed in serum sGAG, HA, and sCD138 concentrations between patients newly diagnosed with CD and the healthy group. In the case of patients with UC, the parameter which significantly differentiated healthy subjects and patients with IBD before biological therapy was HA. Significant correlation between serum HA level and inflammation activity, expressed as Mayo score, was also observed in patients with UC. Moreover, the obtained results have confirmed that steroid therapy with prednisone significantly influenced the circulating profile of all examined ECM components (sGAG, HA, and sCD138), whereas adalimumab therapy in patients with UC led to a significant change in only circulating sGAG levels. Moreover, the significant differences in serum HA levels between patients with UC and CD indicate that quantification of circulating HA may be useful in the differential diagnosis of CD and UC.

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