Real-World Experience with Etanercept Therapy and the Switching Pattern among Korean Patients with Psoriasis after Withdrawal of Etanercept

( Chong Won Choi ),( Ji Su Lee ),( Da-ae Yu ),( Bo Ri Kim ),( Sang Woong Youn ) 대한피부과학회 2019 Annals of Dermatology Vol.31 No.1

Background: The efficacy and safety of etanercept in the treatment of psoriasis has been proven, and the drug was approved for the treatment of moderate to severe psoriasis. However, there have been few studies that have presented real-world data focused on concomitant treatment during etanercept treatment, and the switching pattern after discontinuation of etanercept. Objective: To reveal the real- world treatment pattern of etanercept-based psoriasis treatment and to investigate the switching pattern after withdrawal of etanercept. Methods: We enrolled 66 patients with psoriasis who were treated with etanercept. We collected data regarding the demographic characteristics of the patients, etanercept treatment schedules, and other treatments administered during the etanercept treatment period. We also investigated the treatment pattern after the discontinuation of etanercept with emphasis on the drug-free interval and the administered treatment modalities. Results: The mean treatment duration was 22.7±26.1 months and the mean number of etanercept injections was 21.5±27.9. Thirty-six patients were administered concomitant systemic medication or phototherapy. After discontinuation of etanercept, 54 patients were followed up and 34 of these patients were administered other systemic medication or phototherapy; phototherapy and cyclosporine was the most commonly administered treatment modality and 27.4% of treatments used biologics. Conclusion: The treatment schedule for etanercept was modified according to the severity of psoriasis and concomitant treatment was administered to improve the effectiveness of treatment in the patients enrolled in the study. We also found that most patients required other treatment modalities to control psoriasis during the period of etanercept treatment. (Ann Dermatol 31(1) 44∼50, 2019)

TNF-α-Inhibition Improves the Biocompatibility of Porous Polyethylene Implants In Vivo

Hussain Timon,Gellrich Donata,Siemer Svenja,Reichel Christoph A.,Eckrich Jonas,Dietrich Dimo,Knauer Shirley K.,Stauber Roland H.,Strieth Sebastian 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.2

Background: To improve the biocompatibility of porous polyethylene (PPE) implants and expand their application range for reconstructive surgery in poorly vascularized environments, implants were coated with tumor necrosis factor α (TNFα) inhibitor Etanercept. While approved for systemic application, local application of the drug is a novel experimental approach. Microvascular and mechanical integration as well as parameters of inflammation were analyzed in vivo. Methods: PPE implants were coated with Etanercept and extracellular matrix (ECM) components prior to implantation into dorsal skinfold chambers of C57BL/6 mice. Fluorescence microscopy analyses of angiogenesis and local inflammatory response were thrice performed in vivo over a period of 14 days to assess tissue integration and biocompatibility. Uncoated implants and ECM-coated implants served as controls. Results: TNFα inhibition with Etanercept led to a reduced local inflammatory response: leukocyte-endothelial cell adherence was significantly lowered compared to both control groups (n = 6/group) on days 3 and 14, where the lowest values were reached: 3573.88 leukocytes/mm-2 ± 880.16 (uncoated implants) vs. 3939.09 mm-2 ± 623.34 (Matrigel only) vs. 637.98 mm-2 + 176.85 (Matrigel and Etanercept). Implant-coating with Matrigel alone and Matrigel and Etanercept led to significantly higher vessel densities 7 and 14 days vs. 3 days after implantation and compared to uncoated implants. Mechanical implant integration as measured by dynamic breaking strength did not differ after 14 days. Conclusion: Our data show a reduced local inflammatory response to PPE implants after immunomodulatory coating with Etanercept in vivo, suggesting improved biocompatibility. Application of this tissue engineering approach is therefore warranted in models of a compromised host environment. Background: To improve the biocompatibility of porous polyethylene (PPE) implants and expand their application range for reconstructive surgery in poorly vascularized environments, implants were coated with tumor necrosis factor α (TNFα) inhibitor Etanercept. While approved for systemic application, local application of the drug is a novel experimental approach. Microvascular and mechanical integration as well as parameters of inflammation were analyzed in vivo. Methods: PPE implants were coated with Etanercept and extracellular matrix (ECM) components prior to implantation into dorsal skinfold chambers of C57BL/6 mice. Fluorescence microscopy analyses of angiogenesis and local inflammatory response were thrice performed in vivo over a period of 14 days to assess tissue integration and biocompatibility. Uncoated implants and ECM-coated implants served as controls. Results: TNFα inhibition with Etanercept led to a reduced local inflammatory response: leukocyte-endothelial cell adherence was significantly lowered compared to both control groups (n = 6/group) on days 3 and 14, where the lowest values were reached: 3573.88 leukocytes/mm-2 ± 880.16 (uncoated implants) vs. 3939.09 mm-2 ± 623.34 (Matrigel only) vs. 637.98 mm-2 + 176.85 (Matrigel and Etanercept). Implant-coating with Matrigel alone and Matrigel and Etanercept led to significantly higher vessel densities 7 and 14 days vs. 3 days after implantation and compared to uncoated implants. Mechanical implant integration as measured by dynamic breaking strength did not differ after 14 days. Conclusion: Our data show a reduced local inflammatory response to PPE implants after immunomodulatory coating with Etanercept in vivo, suggesting improved biocompatibility. Application of this tissue engineering approach is therefore warranted in models of a compromised host environment.

Methotrexate 치료를 받고 있는 활동성 류마티스 관절염 환자에서 etanercept의 유효성과 안전성에 관한 연구

최병렬,강태영,정청일,이혜순,엄완식,김태환,전재범,유대현,배상철 대한내과학회 2004 대한내과학회지 Vol.66 No.5

목적 : 류마티스 관절염을 앓고 있는 한국인 중에 기존 DMARDs로 치료 실패하였고, 고정용량의 MTX를 복용하고 있는 환자들에 있어서 etanercept의 유효성과 안전성을 평가하고자 하였다. 방법 : 기존 DMARDs로 치료 실패한 활동성 류마티스 관절염 환자 76명을 대상으로 하여 단일군, 공개시험을 하였다. 대상 환자들은 고정용량의 MTX를 복용하면서 etanercept 25 mg을 1주일에 두 번 피하 주사하였으며 12주간 투여하였다. 유효성은 ACR 20, ACR 50,조조강직 시간으로 평가하였고, 약제의 안전성은 이상반응 등으로 평가하였다. 결과 : 대상 환자는 총 76명으로 평균 연령은 45.2세, 남자 5명, 여자 71명이었다. 84.4%인 54명이 12주째에 ACR 20을 만족하였고, 53.1%인 34명이 12주째에 ACR 50을 만족하였다. 조조 강직 시간은 치료 전 203.3분에서 치료 12주째 42.6분을 평균 74.5% 호전되었다. 가장 흔한 이상반응은 주사부위 반응이었다. 이외에도 상기도 감염, 오심, 안면부종 등이 발생하였으나 심각한 부작용은 없었다. 결론 : etanercept는 효과적이고, 안전한 류마티스 관절염 치료 방법이며 특히 MTX치료에도 불구하고 활동성인 류마티스 관절염에 기대되는 치료라고 할 수 있다. Background : This study was performed to investigate the efficacy and safety of etanercept in active rheumatoid arthritis patients with stable dose of methotrexate in Korean. Methods : In a 12 week, single arm, open trial, we assigned 76 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs. Patients received twice-weekly subcutaneous injections of etanercept 25 ㎎ while containing to receive methotrexate at a stable dose of 7.5~25 ㎎ per week. The clinical response was defined as the percent improvement in disease activity according to the criteria of the American Collage of Rheumatology (ACR) at 12 weeks. Results : Etanrecept led to significant improvements in disease activity and was safe and well tolerated. At 12 week, 84.4% of the patients receiving 25 ㎎ of etanercept achieved a 20% ACR response, and 53.1% of those receiving etanercept achieved a 50% ACR response. The most common adverse event was injection-site reaction. Other advanse events were upper respiratory infection, nausea, and facial edema, but there were no serious adverse events associated with etanercept. Conclusion : In active rheumatoid arthritis patients, etanercept was safe, well tolerated, and provided rapid clinical improvements.

Etanercept와 저용량 Methotrexate의 병합요법으로 치료한 난치성 판상 건선

임희선 ( Hee Sun Lim ),윤숙정 ( Sook Jung Yun ),이지범 ( Jee Bum Lee ),김성진 ( Seong Jin Kim ),원영호 ( Young Ho Won ),이승철 ( Seung Chul Lee ) 대한피부과학회 2013 대한피부과학회지 Vol.51 No.6

Etanercept has been proven to be highly effective to moderate severe plaque psoriasis. Alternative biologics or combination therapies of etanercept with other systemic agents have been recommended to patients who are unable to be controlled by etanercept monotherapy. A 50-year-old woman, who did not respond to conventional therapy of psoriasis for 9 years, was treated with etanercept at a schedule of 50 mg doses per week. Psoriatic lesions were remarkably improved within two weeks after etanercept monotherapy, but skin lesions aggravated again 8 weeks after treatment. Then, she was treated with 50 mg etanercept in combination with 5 mg methotrexate per week. Psoriatic lesions were successfully controlled by the combination therapy for 6 weeks, followed by etanercept monotherapy without relapse for the past 13 months. We report the first Korean case of refractory psoriasis, which could be successfully controlled by combination therapy of etanercept with low doses of methotrexate.

Long Term Safety and Efficacy of Etanercept in Juvenile Idiopathic Arthritis in a Single Center

( Myung Hoon Bang ),( Kwang Nam Kim ) 대한류마티스학회 2019 대한류마티스학회지 Vol.26 No.3

Objective. Our aim was to investigate the long term safety and efficacy of etanercept in children with juvenile idiopathic arthritis (JIA). Methods. The study subjects were the 90 JIA patients treated with etanercept in the Department of Pediatrics, Hallym University Medical Center between January 2004 and December 2017. We retrospectively reviewed their medical records for age at diagnosis, duration of etanercept treatment, number of active joints, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and adverse events during treatment. Results. Among the 90 patients, 38 (42.0%) were male and 52 (58.0%) were female; 15 (16.7%) had systemic onset, 41 (45.6%) had extended oligoarticular, 14 (15.6%) had rheumatoid factor-positive polyarticular, 18 (20.0%) had rheumatoid factor-negative polyarticular, and 2 (2.1%) had enthesitis-related arthritis. The median age at the start of etanercept treatment was 9 years (range, 3∼18 years), and the median duration of etanercept treatment was 6 years (range, 0.5∼13 years). The median number of active joints decreased from 9 to 0 after 6 months of etanercept treatment. The median CRP and ESR were within normal range after 3 months of treatment. Six patients experienced recurrence, 9 switched to other medications and 3 discontinued etanercept. Of the 14 reported adverse events, 1 was serious, and there were no tuberculosis infections or malignancies. Conclusion. Long-term treatment with etanercept is efficacious and safe for children with JIA. However, those with the systemic onset subtype appear to have low drug survival rate compared to those with other types of JIA. (J Rheum Dis 2019;26:200-205)

Etanercept로 치료 중인 강직척추염 환자에서 임상적 효과 및 자기공명영상과 컴퓨터단층촬영술을 이용한 엉치엉덩관절염의 평가

정용근 ( Yong Geun Jeong ),이상용 ( Sang Yong Lee ),김현옥 ( Hyun Ok Kim ),김수경 ( Soo Kyoung Kim ),김재희 ( Jae Hee Kim ),류완희 ( Wan Hee Yoo ),이상일 ( Sang Il Lee ) 대한류마티스학회 2008 대한류마티스학회지 Vol.15 No.1

Objective: To assess the clinical effect and acute inflammatory and chronic bony changes of the sacroiliac (SI) joints as detected by magnetic resonance (MR) and computerized tomography (CT) imaging in patients with ankylosing spondylitis (AS) during treatment with etanercept. Methods: The all 16 patients with AS were treated with etanercept 25mg twice weekly subcutaneously and the clinical response was assessed by standardized parameters. Active inflammatory lesions and chronic bony changes of SI joints were assessed by the MR and CT images of the sacroiliac joints before and after treatment with etanercept. Results: The mean disease duration was 13.1±0.69 years and the mean duration of treatment was 14.9±4.86 weeks. The mean BASDAI and BASFI score decreased significantly after etanercept treatment. The regression of active inflammation of sacroiliac joint was seen only in a patient with early disease stage of AS (18 months). However, no significant changes in acute inflammatory and chronic bony changes of the SI joints were found on MR and CT images after treatment of etanercept. Conclusion: Etanercept treatment showed good clinical response. However, no decrease in acute inflammatory and chronic bony changes of the sacroiliac joints was shown on MR and CT images in the AS patients had long-standing disease. Thus, it is suggested that etanercept should be used in early disease stage to obtain the radiographic improvement of sacroiliac joints.

Etanercept 치료 중 발생한 류마티스성 결절

한우진 ( Woo Jin Han ),이종록 ( Jong Rok Lee ),윤규현 ( Kyu Hyun Yoon ),최효진 ( Hyo Jin Choi ),백한주 ( Han Joo Baek ) 대한류마티스학회 2008 대한류마티스학회지 Vol.15 No.3

Etanercept is a recombinant human tumor necrosis factor (TNF) receptor fusion protein, which inhibits the biological activity of TNF-α. The common side effects of TNF-α inhibitors are injection site reactions, infusion reactions and infection. Rheumatoid nodules are the most common extraarticular manifestation of rheumatoid arthritis. Drugs such as methotrexate were reported to be associated with rheumatoid nodules, but etanercept-related nodules were uncommonly observed. We report the new formation of cutaneous rheumatoid nodules in a 58-year-old man during anti-TNFα therapy with etanercept. He had 2-year history of seropositive rheumatoid arthritis, and been treated with methotrexate, hydroxychloroquine, sulfasalazine, prednisolone and nonsteroidal anti-inflammatory drugs before etanercept regimen. Rheumatoid nodules developed on the palmar surface of fingers 4 month after treatment of etanercept, although his disease activity was maintained low. One month later, we decided to stop etanercept because his nodulosis extended to elbow. Since then, he has been followed up without any progression of rheumatoid nodules or aggravation of arthritis.

A case of encephalitis in a juvenile rheumatoid arthritis patient treated with etanercept

권아름,박은정,김기환,김동수 대한소아청소년과학회 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.2

Tumor necrosis factor-α (TNF-α) is a major proinflammatory cytokine involved in the pathophysiology of juvenile rheumatoid arthritis. Etanercept is an effective inhibitor of TNF-α and has shown a beneficial effect in patients with JRA. However, the most important cause of concern related to etanercept administration is infection. We report a case of encephalitis in a JRA patient receiving long-term treatment with etanercept. The patient was a 4-year-old boy with refractory JRA, and he received etanercept subcutaneously at a dose of 0.4 mg kg-1 day-1 twice a week for 14 months, along with non-steroidal anti-inflammatory drugs, methotrexate, oral steroids, and sulfasalazine. The patient presented with sudden fever, headache, vomiting, a generalized tonic seizure, and changes in mental status. We suspected a central nervous system infection, and simultaneously administered antibiotics, an antiviral agent, and steroids. After 2 days of hospitalization, his mental function returned to normal, and he showed no further seizure-like movements. Brain magnetic resonance imaging scan of the patient showed a multifocal cortical lesion on both sides of the temporoparietooccipital lobe, which indicated encephalitis. Although we were unable to identify the causative organism of encephalitis, we think that the encephalitis may be attributed to infection, and the use of etanercept may have increased the risk of severe infection. Therefore, etanercept was discontinued and the patient recovered shortly after. To the best of our knowledge, this is the first case of encephalitis in a juvenile rheumatoid arthritis patient treated with etanercept.

소아에서 스테로이드 저항성 이식편대숙주병에 대한 Etanercept의 효과

한혜영,신지혜,김선영 대한혈액학회 2009 Blood Research Vol.44 No.4

Background: Etanercept is a recombinant human soluble tumor necrosis factor-alpha (TNF-α) receptor fusion protein that inhibits TNF-α, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in children with steroid-refractory acute GVHD (aGVHD) (n=5) and chronic GVHD (cGVHD) (n=3). Methods: Five males and 3 females were enrolled and their median age was 14.4 years (range, 2.1∼18.8). Etanercept 0.4 mg/kg per dose (maximum dose, 25 mg) was given subcutaneously twice weekly for 4 weeks followed by 0.4 mg/kg per dose (maximum dose, 25 mg) weekly for 4 weeks. At the time of initiation of etanercept, 5 patients had aGVHD grade III to IV (III=4, IV=1) and 3 patients had moderate to severe cGVHD (moderate=1, severe=2). Results: Overall, 6 of 8 patients (75%) responded to the treatment with etanercept, including 5 patients with aGVHD [n=3 complete response (CR), n=2 partial response (PR)] and 1 patient with cGVHD [n=1 PR, n=2 no response (NR)]. Clinical responses were most commonly seen in patients with refractory gut aGVHD. CMV reactivation occurred in 2 patients, bacterial infection in 1 patient, and fungal infection in 1 patient. Conclusion: Our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid refractory aGVHD, particularly in the setting of intestinal involvement.

류마티스 관절염 환자에서 HLA-DRB1의 유전적 변이와 Etanercept 치료 반응과의 연관성: 예비 연구

윤혜련 ( Hye Ryeon Yun ),강창수 ( Chang Soo Kang ),이경화 ( Kyung Wha Lee ),이혜순 ( Hye Soon Lee ),김태환 ( Tae Hwan Kim ),배상철 ( Sang Cheol Bae ) 대한류마티스학회 2006 대한류마티스학회지 Vol.13 No.1

Objective: To investigate the roles of genetic variation in the HLA-DRB1 as predictors of response to etanercept treatment in rheumatoid arthritis (RA) patients. Methods: Clinical responses of 66 patients treated with etanercept were determined according to the ACR criteria (ACR20 and 70). HLA-DRB1 typing and further subtyping of all alleles were performed by polymerase chain reaction, sequence-specific oligonucleotide probe hybridization, and direct DNA sequencing analysis. We tested whether genetic variation in the HLA-DRB1 influenced on the responses to 12 weeks of etanercept therapy. Univariate and multivariate analyses were performed to compare allele and genotype distribution between responders and nonresponders. Results: When allelic association with etanercept response was analyzed with ACR20 and ACR 70 criteria for shared epitope alleles (HLA-DRB1 *0101, *0401, *0404, *0405, *0410, *1001, and *1406 alleles) and protective alleles (HLA-DRB1*0701, *0802, *1301, *1302, *1403, and *1405 alleles), there was no association with etanercept efficacy. When ACR20 nonresponders were compared with ACR70 responders, there was no significant association. Next, we tested genotypic association for shared epitope carriage status. The presence of HLA-DRB1 alleles encoding the shared epitope (1 and 2 copies) was marginally associated with nonresponse effect for ACR 70 response (OR=0.27, 95% CI=0.08∼0.93, P=0.045). Conclusion: There was no influence of genetic variation in the HLA-DRB1 on the response to treatment of RA with etanercept.