1.Mechanism of action and exogenous supplementation of vitamin D in Crohn's disease.
Yu XIA ; Juan ZHOU ; Hong-Mei ZHAO ; Jie-Yu YOU
Chinese Journal of Contemporary Pediatrics 2023;25(8):870-876
Vitamin D can not only regulate calcium and phosphorus metabolism, but also exert an immunoregulatory effect. Vitamin D deficiency is common in patients with Crohn's disease (CD). Studies have shown that vitamin D is associated with CD and other autoimmune diseases and can improve the condition of patients with CD and promote their recovery by regulating intestinal immunity, repairing the intestinal mucosal barrier, inhibiting intestinal fibrosis, enhancing the response to infliximab, and regulating intestinal microbiota. Exogenous vitamin D supplementation can induce disease remission while increasing the serum level of vitamin D. However, only a few randomized, double-blind, and placebo-controlled trials have investigated the therapeutic effect of vitamin D in CD, and the optimal form of vitamin D supplementation, the specific dosage of vitamin D supplementation, and the optimal serum maintenance concentration of vitamin D remain to be clarified. This article mainly discusses the mechanism of action of vitamin D in CD and the beneficial effect of exogenous vitamin D supplementation on CD.
Humans
;
Calcium, Dietary
;
Crohn Disease/drug therapy*
;
Dietary Supplements
;
Infliximab
;
Vitamin D/therapeutic use*
2.Retrospective analysis of infliximab in the treatment of Kawasaki disease.
Li Ping XIE ; Lu ZHAO ; Chen CHU ; Lan HE ; Xue Cun LIANG ; Shu Na SUN ; Qu Ming ZHAO ; Feng WANG ; Yin Yin CAO ; Yi Xiang LIN ; Zi Qian ZENG ; Lin WU ; Guo Ying HUANG ; Fang LIU
Chinese Journal of Pediatrics 2022;60(1):14-19
Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.
Child
;
Coronary Aneurysm/etiology*
;
Female
;
Humans
;
Immunoglobulins, Intravenous/therapeutic use*
;
Infant
;
Infliximab/adverse effects*
;
Male
;
Mucocutaneous Lymph Node Syndrome/drug therapy*
;
Retrospective Studies
3.Association between drug trough concentration and disease outcome before infliximab maintenance treatment in children with Crohn's disease.
Xing DENG ; Yi YU ; Xin-Qiong WANG ; Jia LI ; Xu XU ; Chun-Di XU ; Yuan XIAO
Chinese Journal of Contemporary Pediatrics 2022;24(11):1246-1251
OBJECTIVES:
To study the association between infliximab trough level (IFX-TL) prior to maintenance treatment and disease outcome in children with Crohn's disease (CD).
METHODS:
A retrospective analysis was performed on 35 children with CD who received induction therapy with infliximab (IFX) and the measurement of IFX-TL before maintenance treatment from August 2018 to November 2021. Clinical data and laboratory markers at baseline and before maintenance treatment were collected, and the association between outcome and IFX-TL was analyzed.
RESULTS:
The clinical remission group, endoscopic remission group, and combined remission group had a significantly higher IFX-TL level than the corresponding non-remission groups (P<0.05), and there was no significant difference in the IFX-TL level between the biological remission and non-biological remission groups (P>0.05). The receiver operating characteristic (ROC) curve showed that IFX-TL had an area under the ROC curve of 0.959 (95%CI: 0.894-1) in predicting clinical remission, with a sensitivity of 90% and a specificity of 100% at the optimal cutoff value of 2.3 µg/mL (P<0.001).
CONCLUSIONS
Among children with CD receiving infliximab induction therapy, the children achieving clinical and endoscopic remission before maintenance treatment tend to have a higher level of IFX-TL. IFX-TL has a certain predictive value for clinical remission.
Child
;
Humans
;
Infliximab/therapeutic use*
;
Crohn Disease/drug therapy*
;
Gastrointestinal Agents/therapeutic use*
;
Retrospective Studies
;
C-Reactive Protein/analysis*
4.Comparative efficacy of secukinumab against adalimumab and infliximab in patients with moderate-to-severe plaque psoriasis.
Ran PAN ; Xiaolun WANG ; Min SHU ; Jaydeep DAS ; Manik KALRA ; Zhidong WANG
Chinese Medical Journal 2021;135(1):11-19
BACKGROUND:
Psoriasis is a common, chronic, immune-mediated inflammatory skin disease with increased epidermal proliferation. The objective of this review was to systematically identify the evidence and perform a network meta-analysis (NMA) to estimate the relative efficacy of secukinumab (SEC) against adalimumab (ADA) and infliximab (INF) for the treatment of moderate-to-severe plaque psoriasis.
METHODS:
A systematic literature review (SLR) was conducted according to a pre-specified protocol to identify relevant studies. Initially, the databases were searched from database inception till June 2013, and the SLR was updated in April 2020. The eligibility criteria included adult patients (≥18 years old) with moderate-to-severe plaque psoriasis, and the SLR included randomized controlled trials (RCTs). The comparators of interest were SEC, ADA, INF, and placebo (PLA), while outcomes of interest were Psoriasis Area and Severity Index (PASI) (50, 75, and 90) at weeks 12, 16, and 24. A Bayesian NMA for PASI was utilized with a framework that evaluated the probability of PASI responses in different categories of PASI thresholds within a single model.
RESULTS:
A total of 23 RCTs that assessed the efficacy of SEC, ADA, and INF in patients with moderate-to-severe plaque psoriasis were identified. At 12 weeks, SEC was associated with a significantly better response compared with PLA and ADA for PASI 75 and 90, while response results were comparable against INF. At 12 weeks, risk ratio (95% confidence interval) derived from NMA for SEC vs. ADA and INF for PASI 75 was 1.35 (1.19, 1.57) and 1.01 (0.90, 1.18), respectively. At the 16-week and 24-week time interval, SEC was significantly better than PLA, ADA, and INF for PASI 75 and 90.
CONCLUSION
Efficacy of SEC in the treatment of patient populations with moderate-to-severe plaque psoriasis is well demonstrated through NMA.
Adalimumab/therapeutic use*
;
Adolescent
;
Adult
;
Antibodies, Monoclonal, Humanized
;
Humans
;
Infliximab/therapeutic use*
;
Psoriasis/drug therapy*
;
Severity of Illness Index
;
Treatment Outcome
5.Neutrophil-lymphocyte ratio at 14th week predicts loss of response to 52-week infliximab therapy in patients with Crohn's disease.
Gao QIAN ; Dong HONGXIA ; L I JIN
Journal of Southern Medical University 2020;40(4):453-458
OBJECTIVE:
Loss of response (LOR) has become an important clinical problem in patients with Crohn's disease receiving infliximab (IFX) treatment. Neutrophil-lymphocyte ratio (NLR) has been shown to correlate with the activity of inflammatory bowel disease (IBD), and NLR at the 14th week of IFX therapy potentially allows the prediction of sustained response to IFX in Crohn's patients. The aim of this study was to explore whether NLR at the 14th week of IFX therapy could predict the occurrence of LOR to IFX in Crohn's patients.
METHODS:
Between January, 2012 and December, 2016, 54 patients with Crohn's disease underwent a 52-week treatment with IFX and successfully achieved response to the induction treatment in Zhongnan Hospital. We retrospectively examined their medical records and assessed the association between NLR at 14 weeks and LOR during IFX therapy.
RESULTS:
Of the 54 patients, 15 (27.8%) showed LOR to IFX during the follow-up. We noted a significant increase in NLR at 14 weeks in the patients with LOR as compared with the patients with sustained response to IFX[3.51 (2.9-6.25) 1.77 (1.23-2.56), =0.00]. Receiver-operating characteristic analysis showed that at the cut-off value of 2.75, NLR at 14 weeks was predictive of LOR within 52 weeks of IFX therapy with a sensitivity of 93.33% and a specificity of 84.62%, and the area under curve (AUC) of NLR was 0.903 (0.731-0.959). Univariate analysis revealed a significant correlation between relapse-free survival and the NLR at 14 weeks (=0.00). Multivariate analysis identified NLR at 14 weeks as an independent prognostic factor for LOR with a hazard ratio of 1.851 (95% :1.096-3.026, =0.021).
CONCLUSIONS
NLR at the 14th week during IFX therapy is a useful predictor for LOR in patients with Crohn's disease.
Crohn Disease
;
Gastrointestinal Agents
;
Humans
;
Infliximab
;
Lymphocytes
;
Neutrophils
;
Retrospective Studies
;
Treatment Outcome
6.Long-Term Efficacy of Anti-Tumor Necrosis Factor Agents in Pediatric Luminal Crohn's Disease: A Systematic Review of Real-World Evidence Studies
Hanna VAN RHEENEN ; Patrick Ferry VAN RHEENEN
Pediatric Gastroenterology, Hepatology & Nutrition 2020;23(2):121-131
PURPOSE: To determine the long-term efficacy of the anti-tumor necrosis factor (TNF) agents, infliximab (IFX) and adalimumab (ADA), in pediatric luminal Crohn's disease (CD) by performing a systematic literature review.METHODS: An electronic search was performed in Medline, Embase, and the Cochrane Library from inception to September 26, 2019. Eligible studies were cohort studies with observation periods that exceeded 1 year. Studies that reported time-to-event analyses were included. Events were defined as discontinuation of anti-TNF therapy for secondary loss of response. We extracted the probabilities of continuing anti-TNF therapy 1, 2, and 3 years after initiation.RESULTS: In total, 2,464 papers were screened, 94 were selected for full text review, and 13 studies (11 on IFX, 2 on ADA) met our eligibility criteria for inclusion. After 1 year, 83–97% of patients were still receiving IFX therapy. After 2 and 3 years the probability of continuing IFX therapy decreased to 67–91% and 61–85%, respectively. In total, 5 of the 11 studies subgrouped by concomitant medication consistently showed that the probabilities of continuing IFX therapy in patients with prolonged immunomodulator use were higher than those in patients on IFX monotherapy.CONCLUSION: This review of real-world evidence studies confirms the long-term therapeutic benefit of IFX therapy in diverse cohorts of children with luminal CD. Moreover, it supports the view that combination therapy with an immunomodulator prolongs the durability of IFX therapy in patients who previously failed to recover following first-line therapy. The limited number of time-to-event studies in patients on ADA prevented us from drawing definite conclusions about its long-term efficacy.
Adalimumab
;
Child
;
Cohort Studies
;
Crohn Disease
;
Humans
;
Infliximab
;
Necrosis
;
Pediatrics
;
Phenobarbital
;
Survival Analysis
;
Treatment Outcome
7.History and Future of Treatment for Acute Stage Kawasaki Disease
Masahiro ISHII ; Takasuke EBATO ; Hirihisa KATO
Korean Circulation Journal 2020;50(2):112-119
Kawasaki disease is a form of vasculitis, mainly in small and medium arteries of unknown origin, occurring frequently in childhood. It is the leading form of childhood-onset acquired heart disease in developed countries and leads to complications of coronary artery aneurysms in approximately 25% of cases if left untreated. Although more than half a century has passed since Professor Tomisaku Kawasaki's first report in 1957, the cause is not yet clear. Currently, intravenous immunoglobulin therapy has been established as the standard treatment for Kawasaki disease. Various treatment strategies are still being studied under the slogan, “Ending powerful inflammation in the acute phase as early as possible and minimizing the incidence of coronary artery lesions,” as the goal of acute phase treatments for Kawasaki disease. Currently, in addition to immunoglobulin therapy, steroid therapy, therapy using infliximab, biological products, suppression of elastase secretion inside and outside the neutrophils, inactivated ulinastatin therapy and cyclosporine therapy, plasma exchange, etc. are performed. This chapter outlines the history and transition of the acute phase treatment for Kawasaki disease.
Aneurysm
;
Arteries
;
Biological Products
;
Coronary Vessels
;
Cyclosporine
;
Developed Countries
;
Heart Diseases
;
Immunization, Passive
;
Incidence
;
Inflammation
;
Infliximab
;
Mucocutaneous Lymph Node Syndrome
;
Neutrophils
;
Pancreatic Elastase
;
Plasma Exchange
;
Prednisolone
;
Vasculitis
8.Comparison of Real-World Outcomes of Infliximab versus Adalimumab in Biologic-Naïve Korean Patients with Ulcerative Colitis: A Population-Based Study
Minkyung HAN ; Yoon Suk JUNG ; Jae Hee CHEON ; Sohee PARK
Yonsei Medical Journal 2020;61(1):48-55
infliximab (IFX) or adalimumab (ADA) in patients with ulcerative colitis (UC) are extremely limited, especially in the Asian population. We compared clinically important outcomes [colectomy, UC-related emergency room (ER) visits, UC-related hospitalizations, and need for corticosteroids] for these two biologics in biologic-naïve Korean patients with UC.MATERIALS AND METHODS: Using National Health Insurance claims, we collected data on patients who were diagnosed with UC and exposed to IFX or ADA between 2010 and 2016.RESULTS: A total of 862 new users of biologics were included, of whom 630 were treated with IFX and 232 were treated with ADA. Over a median follow-up of 1.8 years after starting biologic therapy, there were no significant differences in the risk of colectomy [adjusted hazard ratio (aHR), 1.87; 95% confidence interval (CI), 0.30–11.63], ER visits (aHR, 1.58; 95% CI, 0.79–3.16), hospitalizations (aHR, 0.83; 95% CI, 0.59–1.17), and corticosteroid use (aHR, 1.16; 95% CI, 0.76–1.78) between IFX and ADA users. These results were stable even when only patients who used biologics for ≥6 months were analyzed. Additionally, these results were unchanged in patients treated with biologic monotherapy or combination therapy with immunomodulators.CONCLUSION: In this nationwide population-based study, there was no significant difference in the risk of colectomy, ER visits, hospitalizations, and corticosteroid use between IFX and ADA users. Our findings indicate that IFX and ADA have comparable effectiveness in biologic-naïve Korean patients with UC.]]>
Adalimumab
;
Asian Continental Ancestry Group
;
Biological Products
;
Biological Therapy
;
Colectomy
;
Colitis, Ulcerative
;
Emergency Service, Hospital
;
Follow-Up Studies
;
Hospitalization
;
Humans
;
Immunologic Factors
;
Infliximab
;
National Health Programs
;
Ulcer
9.Long-term prognosis of Japanese patients with biologic-naïve Crohn’s disease treated with anti-tumor necrosis factor-α antibodies
Rintaro MOROI ; Katsuya ENDO ; Katsutoshi YAMAMOTO ; Takeo NAITO ; Motoyuki ONODERA ; Masatake KUROHA ; Yoshitake KANAZAWA ; Tomoya KIMURA ; Yoichi KAKUTA ; Atsushi MASAMUNE ; Yoshitaka KINOUCHI ; Tooru SHIMOSEGAWA
Intestinal Research 2019;17(1):94-106
BACKGROUND/AIMS: Few reports have described the long-term treatment outcomes of the anti-tumor necrosis factor-α antibody for Japanese Crohn’s disease (CD) patients. The aim of this study was to evaluate them and clarify the clinical factors that affect the long-term prognosis of the anti-tumor necrosis factor-α treatments. METHODS: This was a retrospective, observational, single-center cohort study. Japanese CD patients treated with either infliximab or adalimumab as a first-line therapy were analyzed. The cumulative retention rates of the biologics, relapse-free survival, and surgery-free survival were analyzed using Kaplan-Meier methods. The clinical factors associated with the long-term outcomes were estimated by both the log-rank test and Cox proportional hazard model. RESULTS: The cumulative retention rate was significantly higher in the group with a concomitant elemental diet of ≥900 kcal/day, baseline C-reactive protein (CRP) levels < 2.6 mg/dL, and baseline serum albumin levels ≥3.5 g/dL, respectively. The baseline serum albumin levels were also associated with both relapse-free and surgery-free survival. The lack of concomitant use of an elemental diet ≥900 kcal/day was identified as the only independent risk factor for the withdrawal of the biologics. CONCLUSIONS: Baseline CRP levels and serum albumin levels could affect the long-term outcomes in CD patients. Concomitant elemental diet of ≥900 kcal/day could have a positive influence on clinical treatment course.
Adalimumab
;
Antibodies
;
Asian Continental Ancestry Group
;
Biological Products
;
C-Reactive Protein
;
Cohort Studies
;
Crohn Disease
;
Food, Formulated
;
Humans
;
Infliximab
;
Necrosis
;
Prognosis
;
Proportional Hazards Models
;
Retrospective Studies
;
Risk Factors
;
Serum Albumin
10.Infliximab, Is It Really a New Horizon for the Treatment of Kawasaki Disease?
Korean Circulation Journal 2019;49(2):192-193
No abstract available.
Infliximab
;
Mucocutaneous Lymph Node Syndrome

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