• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제20권4호
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• pp.236-243
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• 2017

Purpose: Studies on the efficacy of infliximab (IFX) in a large population of pediatric patients with Crohn's disease (CD) are limited, and prognostic factors are not well-known. The aim of this study was to evaluate outcomes of IFX in pediatric patients with CD and to identify factors associated with poor prognosis. Methods: We retrospectively analyzed medical data of 594 pediatric patients with CD between 1987 and 2013 in a tertiary center. Of these, 156 children treated with IFX were enrolled and were followed up for at least a year with intact data. Outcomes of induction and maintenance, classified as failure or clinical response, were evaluated on the tenth and 54th week of IFX therapy. Results: We treated 156 pediatric patients with CD with IFX, and the median duration of IFX therapy was 47 months. For IFX induction therapy, 134 (85.9%) patients experienced clinical response on the 10th week. Among the 134 patients who showed response to induction, 111 (82.8%) patients maintained the clinical response on the 54th week. In multivariate analysis, low hematocrit (p=0.046) at the time of IFX initiation was associated with the failure of IFX induction. For IFX maintenance therapy, longer duration from the initial diagnosis to IFX therapy (p=0.017) was associated with maintenance failure on the 54th week. Conclusion: We have shown the acceptable outcomes of IFX in a large cohort of pediatric CD patients in Korea. Hematocrit and early introduction of IFX may be prognostic factors for the outcomes of IFX.

• 한국임상약학회지
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• 제22권3호
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• pp.251-259
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• 2012

Ulcerative colitis (UC) is characterized by a life-long chronic course with remissions and exacerbations. Use of biological therapies may reduce or delay the surgical procedures in patients with UC. The aim of this study was to determine the impact of infliximab (IFX) use on the rate of remission, surgical interventions, and the effect on quality of life in patients with moderate to severe UC. Literature was searched for studies that investigated the efficacy of IFX on the rate of remission, colectomy and quality of life (QoL) between January 1990 and June 2012 at MEDLINE, January 1988 and June 2012 at EMbase and others. Eleven trials were included in the meta-analysis; divided into placebo controlled 8 trials and intravenous corticosteroid controlled group 3 trials. In comparison to placebo control groups, patients who received IFX had an odds ratio (OR) of 3.712 (95% CI: 2.714, 5.079) for the short-term clinical remission, and 3.053 (95% CI: 2.044, 4.559) for the rate of long-term remission. In colectomy rate and quality of life (QoL), odds ratio were 0.566(95% CI: 0.387, 0.827) and 0.658 (0.505, 0.811) respectively. Any adverse reactions including infections, infusion reaction, rash and arthralgia were equivalent in both groups. Compared with intravenous corticosteroid controlled group, patients who received IFX had lower remission rate with short-term odds ratio 0.227 (95% CI: 0.033, 1.556) and long-term odds ratio 1.054 (95% CI: 0.317, 3.502) respectively. However, statistical significance was not showed with both two analyses. The higher adverse drug reaction (ADR) rates were occurred in the corticosteroid controlled groups. 73.3% of patients treated corticosteroid reported Cushing-like syndrome with moon face. In conclusion, IFX does increase remission rate and decrease the rate of colectomy in patients with UC without elevating any adverse reactions significantly. IFX also improves QoL in moderate to severe UC patients. It would not exceed the efficacy of intravenous corticosteroid, whereas intravenous corticosteroid also reported high rate of adverse reactions.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권1호
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• pp.7-18
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• 2021

Purpose: The long-term efficacy and safety of infliximab (IFX) in children with ulcerative colitis (UC) have not been well-evaluated. Here, we reviewed the long-term durability and safety of IFX in our single center pediatric cohort with UC. Methods: This retrospective study included 20 children with UC who were administered IFX. Results: For induction, 5 mg/kg IFX was administered at weeks 0, 2, and 6, followed by every 8 weeks for maintenance. The dose and interval of IFX were adjusted depending on clinical decisions. Corticosteroid (CS)-free remission without dose escalation (DE) occurred in 30% and 25% of patients at weeks 30 and 54, respectively. Patients who achieved CS-free remission without DE at week 30 sustained long-term IFX treatment without colectomy. However, one-third of the patients discontinued IFX treatment because of a primary nonresponse, and one-third experienced secondary loss of response (sLOR). IFX durability was higher in patients administered IFX plus azathioprine for >6 months. Four of five patients with very early onset UC had a primary nonresponse. Infusion reactions (IRs) occurred in 10 patients, resulting in discontinuation of IFX in four of these patients. No severe opportunistic infections occurred, except in one patient who developed acute focal bacterial nephritis. Three patients developed psoriasis-like lesions. Conclusion: IFX is relatively safe and effective for children with UC. Clinical remission at week 30 was associated with long-term durability of colectomy-free IFX treatment. However, approximately two-thirds of the patients were unable to continue IFX therapy because of primary nonresponse, sLOR, IRs, and other side effects.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제23권2호
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• pp.121-131
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• 2020

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.

• Clinical and Experimental Pediatrics
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• 제53권11호
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• pp.936-941
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• 2010

The systematic approach to pharmacologic treatment is typically to begin with the safest, simplest, and most conservative measures. It has been realized that the more rapidly inflammation is under control, the less likely it is that there will be permanent sequelae. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of initial treatment for inflammation. In addition, the slow-acting antirheumatic drugs (SAARDs) and disease-modifying antirheumatic drugs (DMARDs) have efficacy of anti-inflammatory action in children with chronic arthritis. New therapeutic modalities for inflammation, such as etanercept and infliximab, promise even further improvements in the risk/benefit ratio of treatment. It is not typically possible at the onset of the disease to predict which children will recover and which will go on to have unremitting disease with lingering disability or enter adulthood with serious functional impairment. Therefore, the initial therapeutic approach must be vigorous in all children.

• Childhood Kidney Diseases
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• 제22권2호
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• pp.81-85
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• 2018

Amyloidosis is a rare disease that results from the deposition of extracellular protein in various body tissues, causing progressive organ dysfunction. Secondary renal amyloidosis is a rare but serious complication of chronic inflammatory bowel disease, particularly in patients with Crohn's disease or ulcerative colitis. We report a case of secondary renal amyloidosis in a pediatric patient who reported a 16-year history of "very early onset inflammatory bowel disease". Intensive treatment including repeated infliximab infusions improved clinical parameters of inflammatory bowel disease, although renal dysfunction showed progression. Amyloidosis should be considered in patients with IBD, particularly if they suffered disease progression.

• 한국임상약학회지
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• 제25권4호
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• pp.246-253
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• 2015

Background & Object: Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes ankylosis and deformation of axial joints. Since current medicine cannot cure the disease yet, alleviating pain and preventing deformation with medications are the main therapy for patients with AS. The key medications for these purposes include nonsteroidal anti-inflammatory drugs (NSAIDs), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) inhibitors. This study aims to analyze prescribing patterns of AS patients in South Korea. Method: National Patients Sample data compiled by the Health Insurance Review and Assessment Service from 2013 was analyzed. Patients with AS were identified with Korean Standard Classification of Diseases code-6, which was M45. The rates of prescription, discontinuation, and switching ingredients were calculated for each medication during 2013. Results: Total number of patients was 655, and most of them were male (n = 514, 78.5%). Of all age groups, the proportion of 30-40 year old patients was the greatest (35.1%). The most utilized drug class was NSAIDs (82.4%). Less than half of patients were prescribed $TNF-{\alpha}$ inhibitors (n = 212, 32.4%). Meloxicam, aceclofenac, and celecoxib were the most frequently prescribed NSAIDs. In case of $TNF-{\alpha}$ inhibitors, adalimumab, etanercept and infliximab were the top three most prescribed drugs. Although not recommended by the current practice guideline, significant proportions of patients were identified using disease modifying anti-rheumatic drugs (DMARDs). Conclusion: Considering the current practice guideline and previous studies about the efficacy, the use of DMARDs should be reduced and medical insurance term in South Korea should be re-examined.

• 한국임상약학회지
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• 제25권1호
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• pp.9-17
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• 2015

Background: Biologic disease-modifying antirheumatic drugs (bDMARDs) extend the treatment choices for rheumatoid arthritis patients with insufficient response or intolerance to conventional DMARDs (cDMARDs). These agents have considerable efficacy compared with conventional DMARDs, but only a few head-to-head comparisons among these agents have been performed. The objective of this systematic review and network meta-analysis (NMA) was to compare the relative efficacy of Certolizumab with conventional DMARD to licensed bDMARD with cDMARD therapy for patients who failed to prior cDMARD treatment under the condition of the reimbursement coverage criteria in Korea. Methods: A systematic review was conducted using MEDLINE and Cochrane library. Key endpoints were the American College of Rheumatology (ACR) responses of 20/50/70 at six months. Bayesian outcomes were calculated as median of treatment effect, probability of the best, Odds Ratio (OR) and probability that OR was greater than one. Results: Compared with other bDMARDs, Certolizumab were associated with higher or comparable ACR response rates; in ACR20, the OR (probability of OR>1) was 2.08 (92.6%) for Adalimumab, 1.86 (85.7%) for Etanercept, 1.89 (79.5%) for Golimumab, 2.36 (92.1%) for Infliximab, 1.79 (87.0%) for Abatacept, 1.74 (80.8%) for Rituximab and 1.82 (86.8%) for Tocilizaumab. In ACR50 and ACR70, the ORs did not present significant differences. Conclusion: Certolizaumab with cDMARD was more effective or comparable than other bDMARDs in patients who failed prior cDMARD treatment.

• Clinical and Experimental Pediatrics
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• 제59권8호
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• pp.328-334
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• 2016

Purpose: Although a significant number of reports on new therapeutic options for refractory Kawasaki disease (KD) such as steroid, infliximab, or repeated intravenous immunoglobulin (IVIG) are available, their effectiveness in reducing the prevalence of coronary artery lesions (CAL) remains controversial. This study aimed to define the clinical characteristics of patients with refractory KD and to assess the effects of adjuvant therapy on patient outcomes. Methods: We performed a retrospective study of 38 refractory KD patients from January 2012 to March 2015. We divided these patients into 2 groups: group 1 received more than 3 IVIG administration+steroid therapy, (n=7, 18.4%), and group 2 patients were unresponsive to initial IVIG and required steroid therapy or second IVIG (n=31, 81.6%). We compared the clinical manifestations, laboratory results, and echocardiographic findings between the groups and examined the clinical utility of additional therapies in both groups. Results: A significant difference was found in the total duration of fever between the groups ($13.0{\pm}4.04days$ in group 1 vs. $8.87{\pm}2.30days$ in group 2; P=0.035). At the end of the follow-up, all cases in group 1 showed suppressed CAL. In group 2, coronary artery aneurysm occurred in 2 patients (6.4%). All the patients treated with intravenous corticosteroids without additional IVIG developed CALs including coronary artery aneurysms. Conclusion: No statistical difference was found in the development of CAL between the groups. Prospective, randomized, clinical studies are needed to elucidate the effects of adjunctive therapy in refractory KD patients.

• Clinical and Experimental Pediatrics
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• 제64권2호
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• pp.68-75
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• 2021

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading worldwide since December 2019. Hundreds of cases of children and adolescents with Kawasaki disease (KD)-like hyperinflammatory illness have been reported in Europe and the United States during the peak of the COVID-19 pandemic with or without shock and cardiac dysfunction. These patients tested positive for the polymerase chain reaction or antibody test for SARS-CoV-2 or had a history of recent exposure to COVID-19. Clinicians managing such patients coined new terms for this new illness, such as COVID-19-associated hyperinflammatory response syndrome, pediatric inflammatory multisystem syndrome temporally associated with COVID-19, or COVID-19-associated multisystem inflammatory syndrome in children (MIS-C). The pathogenesis of MIS-C is unclear; however, it appears similar to that of cytokine storm syndrome. MIS-C shows clinical features similar to KD, but differences between them exist with respect to age, sex, and racial distributions and proportions of patients with shock or cardiac dysfunction. Recommended treatments for MIS-C include intravenous immunoglobulin, corticosteroids, and inotropic or vasopressor support. For refractory patients, monoclonal antibody to interleukin-6 receptor (tocilizumab), interleukin-1 receptor antagonist (anakinra), or monoclonal antibody to tumor necrosis factor (infliximab) may be recommended. Patients with coronary aneurysms require aspirin or anticoagulant therapy. The prognosis of MIS-C seemed favorable without sequelae in most patients despite a reported mortality rate of approximately 1.5%.