Concerns and Side Effects of Azathioprine During Adalimumab Induction and Maintenance Therapy for Japanese Patients With Crohn’s Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]

2019 ◽  
Vol 13 (9) ◽  
pp. 1097-1104 ◽  
Author(s):  
Tadakazu Hisamatsu ◽  
Takayuki Matsumoto ◽  
Kenji Watanabe ◽  
Hiroshi Nakase ◽  
Satoshi Motoya ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Side Effects ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Multivariable Analysis ◽  
Dropout Rate ◽  
Rank Test ◽  
Combination Group ◽  
Monotherapy Group ◽  
Significant Difference

Abstract Background Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn’s disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. Methods In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. Results There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher’s exact test, p <0.001]. Kaplan–Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. Conclusions Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

scholarly journals P718 Combination therapy of adalimumab with an immunomodulator is not more effective than adalimumab monotherapy in children with Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S578-S579
Author(s):  
M Matar ◽  
R Shamir ◽  
D Turner ◽  
E Broide ◽  
B Weiss ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Clinical Remission ◽  
Controlled Trial ◽  
Combination Group ◽  
Therapeutic Drug ◽  
Monotherapy Group ◽  
Serious Adverse Events ◽  
Significant Difference

Abstract Background The PAILOT trial was a randomised controlled trial aimed to evaluate proactive vs. reactive therapeutic drug monitoring in children with Crohn’s disease (CD) treated with adalimumab. Our aim, in this post-hoc analysis of the PAILOT trial, was to assess the efficacy and safety of adalimumab combination treatment in comparison to monotherapy at week 72 after adalimumab induction. Methods Participants were children 6–17 years old, biologic naïve, with moderate-to-severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline, maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit patients were assessed for disease index, serum biomarkers, faecal calprotectin, adalimumab trough concentration and anti-adalimumab antibodies. Results Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period there was no significant difference in the rates of sustained corticosteroid free clinical remission (25/34, 73% vs. 28/44, 63%; p = 0.35), and sustained composite outcome of clinical remission, CRP≤0.5 mg/dl and calprotectin≤150 µgr/gr (10/34, 29% vs. 14/44, 32%; p = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive sub-groups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but numerically higher in the monotherapy group. Conclusion Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD.

Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

2020 ◽  
Vol 15 (3) ◽  
pp. 216-233 ◽  
Author(s):  
Maliha Naseer ◽  
Shiva Poola ◽  
Syed Ali ◽  
Sami Samiullah ◽  
Veysel Tahan
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Bowel Disease ◽  
Relapse Prevention ◽  
Remission Induction ◽  
Inflammatory Bowel

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Difference ◽  
The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

scholarly journals Anastomotic Ulcers After Ileocolic Resection for Crohn’s Disease Are Common and Predict Recurrence

2019 ◽  
Vol 26 (7) ◽  
pp. 1050-1058 ◽  
Author(s):  
Robert P Hirten ◽  
Ryan C Ungaro ◽  
Daniel Castaneda ◽  
Sarah Lopatin ◽  
Bruce E Sands ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Multivariable Analysis ◽  
Disease Recurrence ◽  
Ileocolic Resection ◽  
Anastomotic Ulcer ◽  
Endoscopic Recurrence ◽  
Academic Center ◽  
Endoscopic Remission ◽  
The Impact

Abstract Background Crohn’s disease recurrence after ileocolic resection is common and graded with the Rutgeerts score. There is controversy whether anastomotic ulcers represent disease recurrence and should be included in the grading system. The aim of this study was to determine the impact of anastomotic ulcers on Crohn’s disease recurrence in patients with prior ileocolic resections. Secondary aims included defining the prevalence of anastomotic ulcers, risk factors for development, and their natural history. Methods We conducted a retrospective cohort study of patients undergoing an ileocolic resection between 2008 and 2017 at a large academic center, with a postoperative colonoscopy assessing the neoterminal ileum and ileocolic anastomosis. The primary outcome was disease recurrence defined as endoscopic recurrence (&gt;5 ulcers in the neoterminal ileum) or need for another ileocolic resection among patients with or without an anastomotic ulcer in endoscopic remission. Results One hundred eighty-two subjects with Crohn’s disease and an ileocolic resection were included. Anastomotic ulcers were present in 95 (52.2%) subjects. No factors were associated with anastomotic ulcer development. One hundred eleven patients were in endoscopic remission on the first postoperative colonoscopy. On multivariable analysis, anastomotic ulcers were associated with disease recurrence (adjusted hazard ratio [aHR] 3.64; 95% CI, 1.21–10.95; P = 0.02). Sixty-six subjects with anastomotic ulcers underwent a second colonoscopy, with 31 patients (79.5%) having persistent ulcers independent of medication escalation. Conclusion Anastomotic ulcers occur in over half of Crohn’s disease patients after ileocolic resection. No factors are associated with their development. They are associated with Crohn’s disease recurrence and are persistent.

Anxiety and Depression in Patients with Abdominal Bloating

1993 ◽  
Vol 38 (7) ◽  
pp. 475-479 ◽  
Author(s):  
Ji-Yung Song ◽  
Harold Merskey ◽  
Stephen Sullivan ◽  
Sam Noh
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Sex Education ◽  
Depression Scale ◽  
Normal Subjects ◽  
Anxiety And Depression ◽  
Childhood Experience ◽  
Personality Variables ◽  
Abdominal Bloating ◽  
Significant Difference

Eighteen patients with a syndrome of abdominal bloating and discomfort were examined to explore the relationship between their symptoms and their emotional problems. They were compared with 33 patients with Crohn's disease and 38 normal, healthy volunteers. Using the Hospital Anxiety and Depression Scale, patients with bloating were found to resemble patients with Crohn's disease. Both groups showed increased anxiety and depression. After controlling for age, sex, education, occupation, personality variables and childhood experience, there was a trend towards more anxiety in the bloating group compared with normal subjects and a significant difference for depression. These characteristics appear to be related to the effects of the illness or to selection, but not to personality or childhood experience. Although psychiatric problems are common among patients with abdominal bloating and pain who stay in touch with a clinic, they are not the primary cause of the disorder.

Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn’s disease

2005 ◽  
Vol 3 (2) ◽  
pp. 113-121 ◽  
Author(s):  
Erik J. Schoon ◽  
Simona Bollani ◽  
Peter R. Mills ◽  
Eran Israeli ◽  
Dieter Felsenberg ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Crohn’S Disease ◽  
Side Effects ◽  
Crohn's Disease ◽  
Bone Mineral ◽  
Mineral Density

scholarly journals Target Hemoglobin May Be Achieved with Intravenous Iron Alone in Anemic Patients with Cardiorenal Syndrome: An Observational Study

2015 ◽  
Vol 5 (4) ◽  
pp. 246-253 ◽  
Author(s):  
Eyal Ben-Assa ◽  
Yacov Shacham ◽  
Moshe Shashar ◽  
Eran Leshem-Rubinow ◽  
Amir Gal-Oz ◽  
...  
Keyword(s):  
Platelet Count ◽  
Adverse Effects ◽  
Observational Study ◽  
Treatment Strategy ◽  
Intravenous Iron ◽  
Cardiorenal Syndrome ◽  
Combination Group ◽  
Iron Treatment ◽  
Significant Difference ◽  
Iv Iron

Background: The treatment of anemia in patients with cardiorenal syndrome (CRS) is based mainly on intravenous (IV) iron therapy and/or erythropoiesis-stimulating agents (ESAs). There are concerns about the safety of ESAs due to a potentially higher risk for stroke and malignancy. Objective: We aimed to explore whether IV iron alone is sufficient to improve anemia in CRS patients and to define the predictors of treatment response. Methods: We retrospectively analyzed data of 81 CRS patient treated for anemia at our clinic. All patients received IV iron for 6 weeks. A subset of patients was additionally given subcutaneous ESAs. The end point was the improvement from baseline in hemoglobin (Hb) and ferritin levels at week 7. Results: We retrieved the files of 81 patients; 34 received IV iron alone and 47 were given IV iron and ESAs (the combination group). The Hb levels significantly increased in both groups (in the IV iron alone group: 10.6 ± 1.1 to 11.9 ±1.1 g/dl, p < 0.001; in the combination group: 10.2 ± 0.9 to 12.4 ± 1.3 g/dl, p < 0.001), but more pronouncedly in the combination group (2.17 vs. 1.24 g/dl; p = 0.001). The platelet count decreased significantly in the IV iron alone group but was unchanged in the combination group. Eighty percent of patients attained a Hb target of 11 g/dl, with no significant difference between the two groups (73.5 vs. 85.1%; p = 0.197). Low baseline Hb was the only predictor of a favorable outcome to treatment. Conclusion: Our observational study suggests that IV iron treatment without ESAs may substantially raise the Hb level to ≥11 g/dl in CRS patients. This treatment strategy may reduce the use of ESAs and hence its potential adverse effects.

scholarly journals The Effect of Systemic Methotrexate and Cyclosporine Combination Therapy inPsoriasis Vulgaris Patients in Bandung, Indonesia

2021 ◽  
Vol 33 (3) ◽  
pp. 200
Author(s):  
Oki Suwarsa ◽  
Fatima Aulia Khairani ◽  
Syawalika Ulya Isneny ◽  
Erda Avriyanti ◽  
Hartati Purbo Dharmadji ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Side Effects ◽  
Adverse Effects ◽  
Combination Therapy ◽  
Combination Treatment ◽  
Psoriasis Vulgaris ◽  
Severity Index ◽  
Dermatology Clinic ◽  
Significant Difference ◽  
Pasi Score

Background: Methotrexate (MTX) and cyclosporine have been used as effective systemic mono-therapy for psoriasis. Several factors are considered to switch monotherapy to combination therapy because monotherapy is no longer effective and has higher side effects. Hence,clinicians have avoided systemic therapy combinations due to its toxicity. However, some studies showed that this combination therapy could be usedeffectively for psoriasis patients. Purpose: This study aimed to analyze the efficacy and adverse effects of systemic MTX and cyclosporine combination therapy in Indonesian psoriasis vulgaris patients. Methods: The retrospective study assessed the effectiveness of 3 monthsmono-therapyand combination therapy of systemic MTX and cyclosporine in psoriasisvulgaris patients from 2016–2017 in Dermatology Clinic, Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia. Result: Psoriasis area and severity index (PASI) score 90 were achieved in the group MTX (50%) and cyclosporine group (50%), while none in the combination group.However, eight patients (50%) in group MTX and cyclosporine reached the primary endpoint of PASI 50. One patient in cyclosporine group had adverse effects on kidney profiles. Nonetheless, other patients had no biochemical changes. But, there was no significant difference in the change of PASI between each group (p=0.102). Conclusion: We propose that combination therapy of MTX and cyclosporine is relatively safe and efficacious in treating Indonesian psoriasis vulgaris patients. This combination treatment isas effective as MTX or cyclosporinemono-therapy.

scholarly journals The Comparison of Hypomethylating Agents (HMA) Monotherapy with HMA Combined with Intensive Chemotherapy for Intermediate / High-Risk MDS or AML

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3903-3903
Author(s):  
Jiang Ji ◽  
Zhao Wang ◽  
Bing Han
Keyword(s):  
High Risk ◽  
Combination Therapy ◽  
Death Rate ◽  
Therapy Group ◽  
Meta Analysis ◽  
Combination Group ◽  
Combination Therapy Group ◽  
Hypomethylating Agents ◽  
Monotherapy Group ◽  
Significant Difference

Introduction: Hypomethylating agents (HMA) azacitidine and decitabine were the first-line therapy for intermediate/ higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients unsuitable for hematopoietic cell transplantation (HSCT). HMA combined with chemotherapy was recently used to achieve for a better outcome. However, few studies were carried out to compare the HMA monotherapy to the HMA and chemotherapy combination therapy. This meta-analysis aimed to compare the efficacy, survival benefit and safety of HMA monotherapy and combination therapy (with chemotherapy) in patients with intermediate/high-risk MDS or AML. Methods: Related articles published between January 2009 and April 2019 were selected and patients were separated as monotherapy group and combination group for meta-analysis. To further eliminate the potential influence of differences in patients' baseline characteristic between the two groups, subgroups with similar patients' baseline characteristics were selected for further analysis. Complete response (CR) rate, overall response (ORR) rate, 1-year overall survival (OS) rate, 1-month death rate and the proportion of adverse event (AE) were pooled and compared. Results: 13 RCT or cohort studies with 997 patients (790 in monotherapy group, 207 in HMA combination group) were selected for meta-analysis. For the pooled data, there was no significant difference in sex and cytogenetic risk between the 2 groups, but the age of combination therapy group was significantly younger than that of the monotherapy group (61.3±13.2 year-old vs 67.7±10.2 year-old, p=0.000). The CR and ORR rate were significantly higher in combination therapy group (53% vs 17%, p=0.000 for CR and 67% vs 44%, p=0.000 for ORR). However, the 1-year OS (56% for combination therapy vs 51% for HMA monotherapy group, p=0.282) and 1-month death rate (5% for combination therapy vs 4% for HMA monotherapy group, p=0.965) were similar between the two groups. The incidence of CTCAE grade 3-4 infection and bleeding were significantly higher (infection: 50% for combination therapy vs 25.7% for monotherapy group, p=0.003; bleeding: 27.5%% for combination therapy vs 7.8% for monotherapy group, p=0.004) in combination group. In subgroup analysis, 117 and 179 patients were included in combination group and HMA monotherapy group, respectively. There was no significant difference in age (69.5±4.6 vs 69.0±6.8 years old, p=0.451) and proportion of favorable/intermediate cytogenetic risk (62% vs 71%, p=0.114) between the two groups, but a significantly lower proportion of male was found in combination therapy group (57% vs 74%, p=0.003). Although combination group had a higher CR rate (49% vs 17%, p=0.000), it had similar ORR rate (58% vs 49%, p=0.140) to monotherapy group. Meanwhile, combination therapy came with higher 1-month death rate (12% vs 3%, p=0.008) and lower 1-year OS (54% vs 68%, p=0.013) compared with monotherapy group. Conclusions: HMA combined with chemotherapy could increase CR rate in all patients and ORR rate in younger patients, but could not improve OS. For patients with similar older age, combination therapy could result in higher 1-month death rate and less 1-year OS. Disclosures No relevant conflicts of interest to declare.

scholarly journals P652 Underweight patients with Crohn’s disease and without vitamin D supplementation are at high risk of vitamin D deficiency

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S536-S537
Author(s):  
D Vranesic Bender ◽  
V Domislović ◽  
M Brinar ◽  
D Ljubas Kelečić ◽  
I Karas ◽  
...  
Keyword(s):  
Vitamin D ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Vitamin D Deficiency ◽  
Vitamin D Supplementation ◽  
Lower Range ◽  
Total Study Population ◽  
Vitamin D Levels ◽  
Significant Difference ◽  
Underweight Patients

Abstract Background Vitamin D deficiency is frequently present in inflammatory bowel disease (IBD) with a higher incidence in Crohn’s disease (CD) than in ulcerative colitis (UC). Given the involvement of the alimentary tract, many factors can contribute to vitamin D deficiency. The aim of the study was to investigate the association of vitamin D deficiency according to body mass index (BMI) in adult patients with IBD. Methods A cross-sectional study was conducted on a cohort of 152 IBD patients, 68.1% (n = 104) CD and 31.9% (n = 48) UC. The mean age of the total study population was 37.3±11.8 years and 57.3% (n = 87) were male. All patients were adult, Caucasian and without vitamin D supplementation. Patients were recruited during one year period. Results Out of all IBD patients, 60.5% (n = 92) had vitamin D deficiency, 32.2%, (n = 49) insufficiency and 7.2% (n = 11) sufficiency. According to BMI categories there were 12.5% (n = 19) obese patients, 27.6% (n = 42) overweight, 51.3% (n = 78) with normal body weight, and 8.6% (n = 13) underweight. There was a significant difference in vitamin D levels according to different BMI categories in terms of underweight patients having the lowest vitamin D levels; underweight 29.84±11.94 mmol/l, normal 46 ± 20.7 mmol/l, overweight 48±20.1 mmol/l, obese 51±15.3 mmol/l. In addition, there was a significant correlation of vitamin D levels and BMI values (Rho = 0.212, 95% CI 0.069–0.345, p = 0.004), which was more clearly observed in the lower range of BMI values (Figure 1). Male underweight patients had lower levels of vitamin D compared with female patients (26.6 ± 9 vs. 34.7 ± 5.6, p &lt; 0.05). Both patients with CD and UC had significant positive correlation of vitamin D levels and BMI values (UC Rho=0.40, 95% CI 0.16–0.59, p = 0.001, UC Rho = 0.27, 95% CI 0.01–0.05, p = 0.044). However, when comparing vitamin D levels according to phenotype, a significant difference in vitamin D levels was observed in underweight CD (28.4 ± 11.1) comparing to underweight UC patients (40.6 ± 10.6), p &lt; 0.05. In logistic regression analysis, CD phenotype was risk factor for vitamin D deficiency (OR 2.18 95% CI 1.01–4.72, β = 1.22, p = 0.04). Conclusion Our results on untreated IBD patients show a high proportion of vitamin D deficiency both in CD and UC, and significant correlation of vitamin D levels and BMI values, especially in the lower range of BMI values. Moreover, underweight CD patients have lower vitamin D levels comparing to UC. This suggests the need for regular vitamin D monitoring and supplementation especially in IBD patients at risk.

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