Tacrolimus induces short-term but not long-term clinical response in inflammatory bowel disease

2020 ◽  
Vol 51 (9) ◽  
pp. 870-879 ◽  
Author(s):  
Iago Rodríguez-Lago ◽  
Jesús Castro-Poceiro ◽  
Agnès Fernández-Clotet ◽  
Francisco Mesonero ◽  
Antonio López-Sanromán ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Response ◽  
Bowel Disease ◽  
Short Term ◽  
Inflammatory Bowel

Short‐term and long‐term outcomes of indigo naturalis treatment for inflammatory bowel disease

2019 ◽  
Vol 35 (3) ◽  
pp. 412-417 ◽  
Author(s):  
Yuichi Matsuno ◽  
Atsushi Hirano ◽  
Takehiro Torisu ◽  
Yasuharu Okamoto ◽  
Yuta Fuyuno ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Long Term Outcomes ◽  
Short Term ◽  
Indigo Naturalis ◽  
Inflammatory Bowel

scholarly journals P292 Effect of drug therapy on the lipid profiles of patient with Inflammatory Bowel Disease: a systematic review and meta-analysis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S322-S323
Author(s):  
J A M Sleutjes ◽  
J E Roeters van Lennep ◽  
E Boersma ◽  
A C de Vries ◽  
C J van der Woude
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Random Effect ◽  
Random Effect Model ◽  
Lipid Levels ◽  
Short Term ◽  
Cvd Risk ◽  
Drug Classes ◽  
Inflammatory Bowel

Abstract Background Increases of lipid levels associated with inflammatory bowel disease (IBD) medication have been previously reported. However, it is unknown whether this effect is similar for all IBD drug classes. Methods We performed a systematic literature search of randomized controlled trials and observational cohort studies of IBD treatment with corticosteroids, anti TNFα agents and tofacitinib that assessed total cholesterol (TC) before and after short-term (≤8 week) and long-term (≥12 week) treatment. Data of 11 studies (1,663 IBD patients) were pooled using a random effect model with as primary outcome TC levels. Lipid changes were reported as mean difference on the log2-scale (MDlog2) with 95% CI. The effect of patient and disease characteristics on TC changes were analyzed in 6 studies with individual patient data of 1,211 patients. Results A significant increase in TC was observed after treatment with corticosteroids, anti TNFα agents and tofacitinib (short-term +0.370, +0.197 and +0.190; long-term: +0.452, +0.068 and +0.162, respectively). (Figure 1) After correcting for age, sex, BMI and CRP, increases of TC levels after start of corticosteroids and tofacitinib treatment were higher (short-term: +0.293 and +0.161; long-term: +0.090 and +0.127, respectively) as compared to anti TNFα agents (short-term: -0.059, long-term: +0.041). (Figure 2) Conclusion Changes in lipid levels differ between IBD drug classes. TC levels increase was strongest for corticosteroids followed by tofacitinib but not observed for anti TNFα agents. Whether TC change associated with IBD treatment has effect on CVD risk requires further study.

scholarly journals P695 Vedolizumab induction and maintenance though levels and long-term clinical and biochemical status in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S563-S564
Author(s):  
A Gutiérrez Casbas ◽  
L Sempere Robles ◽  
R Muñoz Pérez ◽  
A Rodríguez Angulo ◽  
S Climent ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Response ◽  
Bowel Disease ◽  
Induction Phase ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Significant Difference ◽  
Inflammatory Bowel ◽  
Biochemical Remission

Abstract Background Therapeutic drug monitoring (TDM) postinduction of vedolizumab (VDZ) could have relationship with long-term outcome of inflammatory bowel disease (IBD) patients. However, clinical utility of TDM during maintenance VDZ therapy remains unclear. To examine the association of induction and maintenance vedolizumab though levels (VTL) with clinical and biochemical long-term outcome in IBD patients. Methods We performed a retrospective cohort study, including all consecutive IBD patients of our centre on VDZ treatment who had VTL and anti-vedolizumab antibodies (AVA) measured during induction and maintenance therapy. All patients had received a minimum of 6 weeks therapy following standard induction (0, 2, 6 ± 10 week dosing. Clinical response and remission were defined by Partial Mayo Score (PMS, UC) or Harvey Bradshaw Index (HBI, CD) and were assessed at week 52.Biochemical remission was defined as CRP < 0.5 g/dl and faecal biomarker remission as faecal calprotectin (FC) < 250 µg/g. Measurement of VTL and AVA was performed by ELISA assays(Vedolizumab-TheraDiag(R) with a detection limit for VTL of 2 μg/ml and measurement range of 2–60 μg/ml. Results In total, 34 patients were included (55.9% UC; 44.1% CD, 50% women). Median age was 52.76(17–83) and mean disease duration was 8 ± 7.2 years. Median baseline HBI was 6(0–12) and PMS was 5(3–7). FC and CRP measured before first dose of VDZ were 1425 ± 1189 μg/g and 2.1 ± 2.4 mg/dl. A total of 14 patients (41.2%) were naïve for biologic therapy. Only three patients (8.8%) were receiving a concomitant immunomodulator. Clinical response to induction phase was reported in 76%. Clinical remission, clinical response, biochemical remission and faecal biomarker remission were present in 30% (9/29), 41.4% (12/29), 40.9% (9/22) and 35% (7/20), respectively, at week 52. Thirteen patients (13/26, 50%) needed dose escalation at week 52. Twenty-six patients (78.8%) were persistent in VDZ therapy at the end of the study. The median level of VDZ at weeks 6 and 24 were 16.13 ± 7.06 μg/ml and 9.6 ± 6.7 μg/ml. Comparing patients with and without clinical response or remission to VDZ at week 52 no significant difference in VTL was found at Week 6 (16.27 vs. 15.46 μg/ml, p = 0.8) and week 24 (7.6 vs. 12.7 μg/ml, p = 0.1). No difference was observed in VTL in patients in biochemical remission (week 6: 23.6 vs. 15.7 μg/ml, p = 0.2; week 24: 10.3 vs. 10.2 μg/ml, p = 0.9) or with faecal biomarker remission (week 6: week 6: 25.5 vs. 16.2 μg/ml, p = 0.1; week 24: 10.7 vs. 8.2 μg/ml, p = 0.6) at week 52. No patient developed antibodies. Conclusion In this real-world study of IBD patients receiving VDZ, early induction or maintenance VTL are not associated with long-term outcome.

scholarly journals Efficacy, safety and drug survival of thioguanine as maintenance treatment for inflammatory bowel disease: a retrospective multi-centre study in the United Kingdom

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ahmed B. Bayoumy ◽  
Elsa L. S. A. van Liere ◽  
Melek Simsek ◽  
Ben Warner ◽  
Aathavan Loganayagam ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
United Kingdom ◽  
Adverse Events ◽  
Clinical Response ◽  
Bowel Disease ◽  
Multi Centre Study ◽  
The United Kingdom ◽  
Inflammatory Bowel

Abstract Background Thioguanine (TG) is a thiopurine which has been used for patients with inflammatory bowel disease (IBD), who have failed azathioprine (AZA) or mercaptopurine (MP) due to adverse events or suboptimal response. Its widespread use has been hampered due to concerns about nodular regenerative hyperplasia (NRH) of the liver. The aim of this study was to investigate the long-term efficacy and safety of low-dose TG therapy in IBD patients failing AZA and MP. Methods A retrospective multicentre study was performed in IBD patients who failed prior treatment with conventional thiopurines with or without following immunomodulation (thiopurine-allopurinol, biologicals, methotrexate, tacrolimus) and were subsequently treated with TG as rescue monotherapy between 2003 and 2019 at three hospitals in the United Kingdom. Clinical response, adverse events, laboratory results, imaging and liver biopsies were retrospectively collected. Results A total of 193 patients (57% female and 64% Crohn’s disease) were included, with a median daily TG dose of 20 mg (range: 20–40 mg), a median treatment duration of 23 months (IQR 10–47) and a median follow-up of 36 months (IQR 22–53). The clinical response rate at 12 months was 65 and 54% remained on TG until the end of follow-up. Adverse events consisted primarily of elevated liver tests (6%), myelotoxicity (7%) and rash (5%). NRH was histologically diagnosed in two patients and two other patients (1%) developed non-cirrhotic portal hypertension. The median 6-TGN and TPMT levels were 953 pmol/8 × 105 RBC (IQR 145–1761) and 47 mu/L (IQR 34.5–96). Conclusions Long-term follow-up suggests that TG can be an effective and well-tolerated therapy in more than half of difficult-to-treat and multi-therapy failing IBD patients. Findings of this study indicate that TG can be used safely and the occurrence of hepatotoxicity was low. The incidence rate of NRH was within the background incidence.

Antibodies to Human Recombinant Lipocortin-L in Inflammatory Bowel Disease

1993 ◽  
Vol 84 (4) ◽  
pp. 381-386 ◽  
Author(s):  
T. R. J. Stevens ◽  
S. F. Smith ◽  
D. S. Rampton
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Clinical Response ◽  
Corticosteroid Therapy ◽  
Bowel Disease ◽  
Corticosteroid Withdrawal ◽  
Inflammatory Bowel ◽  
Antibody Levels

1. Corticosteroid drugs are widely employed for the treatment of active inflammatory bowel disease. Not all patients receiving corticosteroid treatment, however, respond satisfactorily, their disease either remaining active in spite of continued treatment, or relapsing upon corticosteroid withdrawal. Raised levels of autoantibodies to lipocortin-I, a corticosteroid-inducible protein with anti-inflammatory activity in vitro, in patients receiving chronic oral corticosteroid therapy have been associated with poor clinical response in rheumatoid arthritis. 2. To determine whether a similar mechanism is responsible for the variable clinical response to corticosteroids in inflammatory bowel disease, we have measured circulating lipocortin-I antibody levels in sera from affected patients and related them to disease activity, treatment and subsequent outcome. 3. IgM, but not IgG, lipocortin-I antibody levels were elevated in patients with ulcerative colitis and Crohn's disease compared with healthy control subjects. In patients with Crohn's disease not taking corticosteroids, IgM lipocortin-I antibody levels were directly related to disease activity scored clinically. 4. IgM lipocortin-I antibody levels were higher in patients receiving sulphasalazine or no treatment and in patients receiving corticosteroids who responded to treatment within 2 months (steroid responders) than in those patients undergoing long-term corticosteroid therapy because of continued disease activity or repeated relapse on corticosteroid withdrawal (steroid non-responders). 5. The high levels of IgM lipocortin-I antibodies in patients with inflammatory bowel disease not taking corticosteroids provides further evidence of disturbed immunity in inflammatory bowel disease. The low levels of IgM lipocortin-I antibody in patients undergoing long-term corticosteroid therapy (steroid nonresponders) contrasts with previous findings in patients with rheumatoid arthritis and might reflect corticosteroid-induced antibody suppression and/or depressed production of endogenous lipocortin-I antigen.

scholarly journals COMPARISON AND EVALUATION OF TACROLIMUS VS STEROID THERAPY IN THE TREATMENT OF INFLAMMATORY BOWEL DISEASE IN ACTIVE PHASE

2021 ◽  
Vol 9 (02) ◽  
pp. 644-654
Author(s):  
Zeba Samreen ◽  
◽  
Minhaj Sultana ◽  
Mohd Shanawazuddin ◽  
Tahoora Zainab ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Remission Rate ◽  
Active Phase ◽  
Initial Therapy ◽  
Efficacy And Safety ◽  
Short Term ◽  
Inflammatory Bowel

Background:-The aim of the study is to compare and evaluate the efficacy and safety of short-term outcomes of tacrolimus in inflammatory bowel disease (IBD) patients who were not concomitantly receiving other immunosuppressive therapies by carrying out an observational prospective study of tacrolimus (TAC) v/s corticosteroid (CS) therapy in the treatment of IBD in active phase, to prevent patient from long term use of CS by reducing the incidence rate of flare. To use TAC as a step-up approach in IBD by early induction of remission and maintain it for longer period which reduces re-hospitalization and surgery rate hence improving quality of life. Method And Material:-The study was conducted in gastroenterology department, Princess Esra hospital, Hyd. 50 patients were enrolled based on our inclusion and exclusion criteria, allocated in 2 groups receiving CS and TAC respectively for 10 days. Follow-ups were done and at the end of 2 months, again a colonoscopy was performed to assess the effectiveness of the treatment. Results:-At an initial therapy of 2 months, clinical remissions were observed in most of the patients of both the groups. After six months of treatment, TAC showed 100% remission rate while 20% patients on CS have shown flare. Conclusion:- prolongs period of remission, and prevents the long-term use of CS thereby preventing its complications proving step-up to be a better approach towards the management of IBD. This study concludes that the efficacy and safety profile of TAC was overall favorable, and the doses were well tolerated by most of the patients.

Novel Targets For Therapeutic Intervention in Inflammatory Bowel Disease. What is the Best Way to Assess the Safety Profile of a Drug?

2019 ◽  
Vol 25 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Clara Yzet ◽  
Stacy S. Tse ◽  
Maia Kayal ◽  
Robert Hirten ◽  
Jean-Frédéric Colombel
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Evaluation Process ◽  
Population Based ◽  
Stage Of Development ◽  
Remission Rates ◽  
Safety Parameters ◽  
Post Marketing ◽  
Inflammatory Bowel

The emergence of biologic therapies has revolutionized the management of inflammatory bowel disease (IBD) by halting disease progression, increasing remission rates and improving long-term clinical outcomes. Despite these well-described benefits, many patients are reluctant to commence therapy due to drug safety concerns. Adverse events can be detected at each stage of drug development and during the post-marketing period. In this article, we review how to best assess the safety parameters of new IBD medications, from the earliest stage of development to population-based registries, with a focus on the special populations often excluded from the evaluation process.

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