Anti-TNF-α agents for refractory intestinal Behcet's disease: case series and meta-analysis.
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ABSTRACT:
SUBMITTER: Zhan S
PROVIDER: S-EPMC9445467 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
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Anti-TNF-α agents for refractory intestinal Behçet's disease: case series and meta-analysis.
Zhan Shukai S Liu Caiguang C Li Na N Li Tong T Tian Zhenyi Z Zhao Min M Wu Dongxuan D Chen Minhu M Zeng Zhirong Z Zhuang Xiaojun X
Therapeutic advances in gastroenterology 20220903
<h4>Background</h4>Behçet's disease (BD) is a relapsing systemic immune disorder, and intestinal BD is a significant cause of mortality in patients with BD. Conventional therapeutic strategies for intestinal BD showed unsatisfactory outcomes, especially in those patients with refractory subtypes. In recent years, biologic agents have exhibited promising results in this field. While the sample sizes of existing studies were limited, the results were heterogeneous.<h4>Objectives</h4>This study aim ...[more]
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Project description:PurposeIntestinal Behcet's disease (BD) is a systemic autoimmune disease for which treatment options are limited. As a prospective therapeutic strategy for intestinal BD, anti-tumor necrosis factor-alpha (anti-TNF-α) agents have received increasing attention. In this study, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of anti-TNF-α agents for patients with intestinal BD.Materials and methodsWe searched PubMed, Embase, and Cochrane Library databases up to July 1, 2021 and articles that met the eligibility criteria were further assessed. Pooled rates were synthesized by a randomized effects model using Stata software.ResultsEleven clinical trials covering 671 patients with intestinal BD were included. According to compositive data, the pooled rate for remission was 39% [95% confidence interval (CI) 26-52] in patients receiving anti-TNF-α agents. Intestinal symptoms were cured in 70% (95% CI 53-84) of the patients, and the rate for endoscopic healing was 65% (95% CI 52-78). Corticosteroid discontinuation was achieved in 43% (95% CI 28-58) of the patients, and the dose reduction of corticosteroid was 20.43 mg (95% CI 13.4-27.46). There were 239 adverse events and 80 serious adverse events during follow-up.ConclusionOur study indicated that anti-TNF-α agents may serve as an effective treatment with acceptable safety for patients with intestinal BD. However, more robust evidence from randomized controlled trials is urgently needed to assess the long-term efficacy and safety of anti-TNF-α agents for those patients.
| S-EPMC8819411 | biostudies-literature
Project description:BackgroundBehçet's disease (BD) is a recurrent multisystem inflammatory disease. Anti-tumor necrosis factor (TNF) α agents have been used to treat patients with intestinal BD with severe disease activity or those who are resistant to conventional treatments; however, the long-term efficacy of anti-TNFα agents in intestinal BD remains unclear. In the present study, we investigated the clinical outcomes and predictors of discontinuation of anti-TNFα agents in patients with intestinal BD.MethodsWe reviewed the medical records of patients with intestinal BD who received first-line anti-TNFα agents between January 2009 and June 2020. The primary outcome was the percentage of patients who continued anti-TNFα therapy for 48 weeks. Secondary outcomes included the percentage of patients who achieved marked improvement, complete remission, and mucosal healing, as well as predictors of discontinuation of anti-TNFα agents.ResultsA total of 29 patients were included in the study. Twenty-two (75.9%) patients continued anti-TNFα therapy for 48 weeks. The percentage of patients who achieved marked improvement, complete remission, and mucosal healing at week 48 was 48.3%, 37.9%, and 48.3%, respectively. At week 96, 11 (37.9%) patients achieved marked improvement, complete remission, and mucosal healing. A higher C-reactive protein level (CRP; ≥ 1 mg/dL) at baseline was a predictor of discontinuation of anti-TNFα agents.ConclusionsThe 48-week continuation rate of anti-TNFα agents was 75.9% in bio-naïve patients with intestinal BD. However, a higher baseline CRP level (≥ 1 mg/dL) was associated with discontinuation of anti-TNFα agents.
| S-EPMC8962253 | biostudies-literature
Project description:ObjectiveThe aim of this study was to evaluate the effectiveness and safety of low-dose interferon alpha-2a (IFNα2a) in Behçet's syndrome (BS) patients with refractory vascular/cardiac or neurological involvement.MethodsIn this retrospective cohort study, we consecutively included 25 BS patients with refractory vascular/cardiac (n = 16) or neurological involvement (n = 9) who received IFNα2a treatment in our center between June 2018 and September 2021. The low-dose IFNα2a (3 million IU, every other day) was used as an add-on treatment with the continuation of glucocorticoids (GCs) and immunosuppressants.ResultsIn total, 25 patients (20 males, 5 females) with a mean age of 31.92 ± 9.25 years were included. IFNα2a was administered for BS patients with refractory vascular/cardiac involvement (n = 16) and neurological involvement (n = 9). Before the initiation of IFNα2a, patients had insufficient response or intolerance to conventional therapies. After a median follow-up of 23 [interquartile range (IQR), 11-30] months, all patients achieved clinical improvement. The Behçet's disease Current Activity Form (BDCAF) score improved significantly (5 versus 0, median, p < 0.0001). BS Overall Damage Index (BODI) and vasculitis damage index (VDI) remain stable (p > 0.05). Decrease in erythrocyte sedimentation rate [ESR; 24 (IQR, 12-43.5) versus 5 (IQR, 2.75-10.5) mm/h, p = 0.0001] and C-reactive protein [CRP; 6.64 (IQR, 3.67-19.82) versus 1.24 (IQR, 0.24-3.12) mg/liter, p < 0.005] was achieved effectively. The median GCs dosage tapered from 26.25 (IQR, 11.88-41.25) to 10.00 (IQR, 7.50-10.63) mg/d, p < 0.0001. Immunosuppressants were also reduced in number (p < 0.005). No serious adverse events were observed during follow-up.ConclusionOur study suggests that low-dose IFNα2a, combined with GCs and immunosuppressants, is well-tolerated and effective for BS patients with refractory vascular/cardiac or neurological involvement and has a steroid- and immunosuppressant-sparing effect.
| S-EPMC9340357 | biostudies-literature
Project description:Rheumatoid arthritis (RA) has been associated with endothelial dysfunction, a pathophysiological feature of atherosclerosis. Our aim was to determine whether TNF-α blockade has a beneficial effect on endothelial function in RA. We performed a systematic review with meta-analysis to evaluate the effect of anti-TNF-α agents on endothelial function in RA patients. MedLine, Cochrane CENTRAL and SCOPUS were searched up to March 2016. Inclusion criteria were: 1) randomised controlled trial (RCT), quasi-RCT, before-after cohort study; 2) including RA patients; 3) treatment with anti-TNF-α medications; 4) evaluating the change from baseline in endothelial function. The search strategy retrieved 180 records, of which 20 studies were included in the systematic review. Pooled analysis using a random-effects model demonstrated a significant improvement in endothelial function following anti-TNF-α treatment (SDM 0.987, 95%CI [0.64-1.33], p < 0.0001). Generalisation of the results of the meta-analysis may be limited due to the presence of heterogeneity (I2 = 82.65%, p < 0.001) and evidence of possible publication bias. Meta-regression showed that endothelial function measurement technique was a significant contributor to heterogeneity. In conclusion, although limited by the methodological quality of the included studies, our meta-analysis suggests that anti-TNF-α treatment may improve endothelial function in RA patients.
| S-EPMC5509678 | biostudies-literature
Project description:Background and aimImmune checkpoint inhibitor (ICI) colitis is an increasingly common problem encountered as the use of checkpoint inhibitors (CPIs) grows in the management of cancers. Corticosteroids and tumour necrosis factor (TNF)-alpha inhibitors are widely recommended in the management of ICI colitis; however, the experience is limited when patients are refractory. Different authors have reported success with vedolizumab, mycophenolate, and cyclosporine. This case series describes our experience with calcineurin inhibitors in the management of corticosteroid and anti-TNF-alpha refractory ICI colitis.MethodsData from electronic medical records were identified and reviewed retrospectively from a cohort of patients treated at a single oncology center. All patients who were identified between March 2018 and May 2020 with ICI colitis refractory to treatment with infliximab and corticosteroids were included.ResultsThere were 11 patients who developed ICI colitis after receiving CPIs for advanced melanoma and required rescue therapy with either cyclosporine or tacrolimus after treatment failure of infliximab. Median age was 53 (±8.48) years, with nine patients (81%) receiving combination Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) / programmed cell death protein 1 (PD-1) immunotherapy. Median time after first CPI infusion to ICI colitis was 4.43 (±19.53) weeks. The median time from onset of symptoms to commencement of rescue therapy with calcineurin inhibitors was 70 days (±66.06). Eight of the 11 patients (72.7%) responded to calcineurin inhibition. In patients who responded, calcineurin inhibitors were continued for a median of 54 (±28.96) days.ConclusionThe calcineurin inhibitors cyclosporine and tacrolimus appear to be a safe and effective option for the management of patients with infliximab-refractory ICI colitis. The therapeutic benefit is observed rapidly, and adverse effects appear to be limited with close monitoring.
| S-EPMC8114988 | biostudies-literature
Project description:Intestinal Behçet's disease is a rare, immune-mediated chronic intestinal inflammatory disease; therefore, clinical trials to optimize the management and treatment of patients are scarce. Moreover, intestinal Behçet's disease is difficult to treat and often requires surgery because of the failure of conventional medical treatment. Administration of anti-tumor necrosis factor-α, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal Behçet's disease and inflammatory bowel diseases has been accumulating. Here, we review updated data on current experiences and outcomes after the administration of anti-tumor necrosis factor-α for the treatment of intestinal Behçet's disease. In addition to infliximab and adalimumab, which are the most commonly used agents, we describe agents such as golimumab, etanercept, and certolizumab pegol, which have recently been shown to be effective in refractory intestinal Behçet's disease. This review also discusses safety issues associated with anti-tumor necrosis factor-α, including vulnerability to infections and malignancy.
| S-EPMC6254627 | biostudies-literature
Project description:The largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn's disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium_animalis, and Muribaculaceae-previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy.
| S-EPMC9162754 | biostudies-literature
Project description:Background: Ustekinumab is used off-label in pediatric Crohn's disease refractory to anti-tumor necrosis factor. Data on optimal dosing, target trough levels, and potential benefit of therapeutic drug monitoring in children treated with ustekinumab are limited. Materials and Methods: We describe a series of six adolescents who consented to be treated with ustekinumab. We measured their trough levels, C-reactive protein, and fecal calprotectin before every administration. Results: Standard adult dosing was effective to achieve biochemical remission (fecal calprotectin < 250 mg/kg) in one patient and clinical remission (resolution of symptoms) in another. The other four patients failed to respond on standard dosing and underwent intravenous re-induction and interval shortening to increase ustekinumab trough levels. This resulted in biochemical remission in one patient and clinical remission in another, suggesting an exposure-response relationship. The remaining two patients had no therapeutic benefit, and ustekinumab was discontinued. Conclusion: In this report, we show that ustekinumab can induce remission in pediatric patients with anti-tumor necrosis factor refractory Crohn's disease. It is worth escalating the dose before abandoning the drug as ineffective. Prospective studies in children are needed to determine long-term efficacy of ustekinumab, usefulness of therapeutic drug monitoring strategies, and, if applicable, optimal target trough levels.
| S-EPMC10561290 | biostudies-literature
Project description: Not available
| S-EPMC4432417 | biostudies-literature
Project description:Crohn's Disease (CD) is a chronic inflammatory disease of the intestinal tract. We performed a whole-genome transcriptional analysis using colonic biopsies from CD patients before and after anti-TNF-α therapy. Involved colonic samples from Crohn's disease patients and healthy colonic samples from non-inflammatory controls were collected for RNA extraction and hybridization on Affymetrix microarrays. Inclusion criteria for CD patients were: age between 18 and 70, diagnosis of CD established at least 4 months before inclusion and exclusion of concomitant infection. Active disease was defined by endoscopic and clinical score: endoscopic active disease was defined as a CD endoscopic index of severity (CDEIS) of 5 or more and the presence of large ulcers (> 0.5 cm diameter) in at least one of the explored segments. Clinical activity was defined as a CD activity index (CDAI) above 150. Finally, a total of 39 biopsies were analyzed: 17 healthy controls, 10 active CD without anti-TNF therapy, 5 active CD with anti-TNF therapy (non-responders) and 7 inactive CD with anti-TNF therapy (responders).
2014-04-08 | E-GEOD-52746 | biostudies-arrayexpress