1.Long Term Safety and Efficacy of Abatacept in Patients with Rheumatoid Arthritis.
Journal of Rheumatic Diseases 2013;20(2):71-73
No abstract available.
Arthritis, Rheumatoid
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Humans
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Immunoconjugates
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Abatacept
2.Comparative Effectiveness of Biologic DMARDs in Rheumatoid Arthritis Patients with Inadequate Response to conventional DMARDs: Using a Bayesian Network Meta-analysis.
Sun Kyeong PARK ; Hye Lin KIM ; Min Young LEE ; Anna KIM ; Eui Kyung LEE
Korean Journal of Clinical Pharmacy 2015;25(1):9-17
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.
Antirheumatic Agents*
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Arthritis, Rheumatoid*
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Humans
;
Korea
;
Odds Ratio
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Rheumatology
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Abatacept
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Adalimumab
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Infliximab
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Rituximab
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Etanercept
3.Long-term Safety and Efficacy of Abatacept in Koreans with Rheumatoid Arthritis.
Seung Cheol SHIM ; Sung Hwan PARK ; Sang Cheol BAE ; Jung Yoon CHOE ; Yeong Wook SONG ; Pranab MITRA ; Chetan S KARYEKAR
Journal of Rheumatic Diseases 2013;20(1):30-39
OBJECTIVE: The safety and efficacy of intravenous (IV) abatacept in patients with active RA unresponsive to methotrexate have been demonstrated in short-term (ST) studies in global populations and a ST, Phase III study in a Korean patient population. Abatacept's long-term safety and efficacy profile has been established in open-label global studies with treatment up to 5 years. The objective of this study was to determine the long-term safety and efficacy of abatacept in patients with RA from the ST Korean study. METHODS: This was an open-label long-term extension (LTE) of a Phase III, multicenter, randomized, double-blind, placebo-controlled study in which Korean patients who had received IV abatacept or placebo in the ST trial (169 days) were given the option to receive open-label abatacept to Day 1485 with 84 days' follow-up (total 1,569 days, ~4 years). RESULTS: A total of 105 patients were enrolled in the LTE (86.7% female, median age 49.0 years). Abatacept was generally well tolerated. Adverse events were mostly mild or moderate and no new safety signals were identified. Improvement in disease activity (assessed by ACR response and DAS28 [CRP]), physical function (assessed by KHAQ-DI), and quality of life (assessed by SF-36 score) were maintained in patients initially treated with abatacept or observed in patients who had switched to abatacept after placebo in the ST study. CONCLUSION: Long-term treatment with IV abatacept over 1485 days was generally well tolerated in Korean patients with RA. Additionally, the efficacy profile from the ST study was maintained over the LTE.
Arthritis, Rheumatoid
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Female
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Follow-Up Studies
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Humans
;
Immunoconjugates
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Korea
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Methotrexate
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Quality of Life
;
Abatacept
4.Long-term Safety and Efficacy of Abatacept in Koreans with Rheumatoid Arthritis.
Seung Cheol SHIM ; Sung Hwan PARK ; Sang Cheol BAE ; Jung Yoon CHOE ; Yeong Wook SONG ; Pranab MITRA ; Chetan S KARYEKAR
Journal of Rheumatic Diseases 2013;20(1):30-39
OBJECTIVE: The safety and efficacy of intravenous (IV) abatacept in patients with active RA unresponsive to methotrexate have been demonstrated in short-term (ST) studies in global populations and a ST, Phase III study in a Korean patient population. Abatacept's long-term safety and efficacy profile has been established in open-label global studies with treatment up to 5 years. The objective of this study was to determine the long-term safety and efficacy of abatacept in patients with RA from the ST Korean study. METHODS: This was an open-label long-term extension (LTE) of a Phase III, multicenter, randomized, double-blind, placebo-controlled study in which Korean patients who had received IV abatacept or placebo in the ST trial (169 days) were given the option to receive open-label abatacept to Day 1485 with 84 days' follow-up (total 1,569 days, ~4 years). RESULTS: A total of 105 patients were enrolled in the LTE (86.7% female, median age 49.0 years). Abatacept was generally well tolerated. Adverse events were mostly mild or moderate and no new safety signals were identified. Improvement in disease activity (assessed by ACR response and DAS28 [CRP]), physical function (assessed by KHAQ-DI), and quality of life (assessed by SF-36 score) were maintained in patients initially treated with abatacept or observed in patients who had switched to abatacept after placebo in the ST study. CONCLUSION: Long-term treatment with IV abatacept over 1485 days was generally well tolerated in Korean patients with RA. Additionally, the efficacy profile from the ST study was maintained over the LTE.
Arthritis, Rheumatoid
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Female
;
Follow-Up Studies
;
Humans
;
Immunoconjugates
;
Korea
;
Methotrexate
;
Quality of Life
;
Abatacept
5.CTLA-4 gene A/G polymorphism associated with diabetes mellitus in Han Chinese.
Yun MA ; Xulei TANG ; Wei CHANG ; Lin GAO ; Maoxin LI ; Wenwei YAN
Chinese Medical Journal 2002;115(8):1248-1250
OBJECTIVETo investigate the association of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene A/G polymorphism with susceptibility to diabetes mellitus in Han Chinese.
METHODSAn A/G transition at position 49 of exon 1 was analyzed in 31 patients with type 1 diabetes, 31 patients with type 2 diabetes, and 36 controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis.
RESULTSA highly significant increase in the frequency of the G allele was seen in patients with type 1 diabetes compared with controls (66.1 % vs. 34.7%, respectively; P < 0.0005; OR = 3.670) . This reflected an increase in the GG genotype in patients (48.4% vs. 22.2%, respectively; P =0.025; OR =3.281) and a significant decrease in the AA genotype (16.1 % vs. 52.8%, respectively; P = 0.002). The allele frequencies of A and G in patients with type 2 diabetes were not significantly different from controls(A/G, 50.0/50.0% vs. 65.3/34.7%; P = not significant) . The distribution of genotype, however, differed significantly. This difference reflected an increase in the AG genotype in patients (54.8% vs.25.0%, respectively; P=0.012; OR=3.643) and a decrease in the AA genotype (22.6% vs. 52.8%, respectively; P=0.011).
CONCLUSIONSCTLA-4 49 AA is protective from diabetes mellitus, whereas, CTLA-4 49 G allele (both as homozygotes and as heterozygotes ) confers an increased risk of diabetes mellitus.
Abatacept ; Antigens, CD ; Antigens, Differentiation ; genetics ; CTLA-4 Antigen ; China ; ethnology ; Diabetes Mellitus ; genetics ; Humans ; Immunoconjugates ; Polymorphism, Genetic
6.Cost-Minimization Analysis of Biologic Disease-Modifying Antirheumatic Drugs Administered by Subcutaneous Injections in Patients with Rheumatoid Arthritis.
Seung Hoo PARK ; Min Young LEE ; Eui Kyung LEE
Korean Journal of Clinical Pharmacy 2016;26(1):59-69
BACKGROUND: The subcutaneous formulation of biologic disease-modifying antirheumatic drugs (DMARDs) was preferred due to favored self-administration and would be an economical treatment option for patients with rheumatoid arthritis. This study was to compare the economic impact of biologic DMARDs administered by subcutaneous injection in patients with rheumatoid arthritis who had inadequate response to conventional DMARDs. METHODS: The cost-minimization analysis was conducted to estimate the lifetime health care costs of treatment sequences with subcutaneous biologic DMARDs as first-line therapy from a health care system perspective. The Markov model was developed to represent the transitions through treatment sequences based on American College of Rheumatology response rate and discontinuation rate. The health care costs comprised the cost of medications, administration, dispensing, outpatient visits, test/diagnostic examination, palliative therapy and treatment of serious infection. All costs were expressed in 2016 Korean Won (KRW) and discounted at 5%. RESULTS: The mean lifetime health care cost per patient was lowest in the etanercept sequence, which was estimated at KRW 63,441,679. The incremental costs of the treatment sequence started with adalimumab, golimumab, abatacept, and tocilizumab were KRW 7,985,730, KRW 4,064,669, KRW 2,869,947, and KRW 4,282,833, respectively, relative to etanercept sequence. These differences in costs mainly were attributable to medication costs. One-way and probabilistic sensitivity analyses confirmed that etanercept represented the option with the lowest cost compared with comparators. CONCLUSION: This study found that etanercept is likely a cost-saving treatment option among subcutaneous biologic DMARDs in patients with rheumatoid arthritis.
Antirheumatic Agents*
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Arthritis, Rheumatoid*
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Delivery of Health Care
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Health Care Costs
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Humans
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Injections, Subcutaneous*
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Outpatients
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Palliative Care
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Rheumatology
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Abatacept
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Adalimumab
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Etanercept
7.Risk of Herpes Zoster in Patients with Rheumatoid Arthritis Undergoing Biologic Disease-Modifying Therapy.
Hyun Mi KWON ; Sang Jin LEE ; Ji Ae YANG ; Yunhee CHOI ; Jin Kyun PARK ; Eun Young LEE ; Yeong Wook SONG ; Eun Bong LEE
Journal of Rheumatic Diseases 2017;24(4):220-226
OBJECTIVE: Rheumatoid arthritis (RA) patients suffer from an increased risk of herpes zoster (HZ) partially due to immunosuppressant medications. This study investigated HZ in RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs), as compared with conventional DMARDs (cDMARDs). METHODS: This retrospective case series study assembled record information of 277 RA patients who received bDMARDs after failure of at least one cDMARDs at Seoul National University Hospital between August 2003 and February 2015. Following capture of baseline information and identification of HZ episodes, crude HZ incidence rates per 100 patient-years (95% confidence intervals) were calculated. RESULTS: For 718 treatment courses, 277 (38.6%) comprised cDMARDs, 66 (9.2%) infliximab, 175 (24.4%) etanercept, 95 (13.2%) adalimumab, 9 (1.3%) golimumab, 41 (5.7%) rituximab, 31 (4.3%) abatacept, and 24 (3.3%) tocilizumab. There were 37 HZ episodes, 16 during cDMARD treatment courses, and 21 accompanying bDMARDs, two with infliximab, eight with etanercept, five with adalimumab, and three each with rituximab and abatacept. The crude HZ incidence rate per 100 patient-years was 2.4 (1.4∼3.9) for cDMARDs, 2.2 (0.3∼7.9) for infliximab, 1.8 (0.8∼3.6) for etanercept, 3.7 (1.2∼8.4) for adalimumab, 3.9 (0.8∼11.0) for rituximab, and 8.5 (1.8∼23.1) for abatacept. CONCLUSION: We conclude that bDMARDs do not always increase the risk of HZs in RA patients, although HZ rates vary for different bDMARDs.
Abatacept
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Adalimumab
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Antirheumatic Agents
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Arthritis, Rheumatoid*
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Biological Therapy
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Etanercept
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Herpes Zoster*
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Humans
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Incidence
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Infliximab
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Retrospective Studies
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Rituximab
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Seoul
8.Overcome of Drug Induced Thrombotic Microangiopathy after Kidney Transplantation by Using Belatacept for Maintenance Immunosuppression.
Seong Han YUN ; Jin Ho LEE ; Joon Seok OH ; Seong Min KIM ; Yong Hun SIN ; Yong Jin KIM ; Joong Kyung KIM
The Journal of the Korean Society for Transplantation 2016;30(1):38-43
Thrombotic microangiopathy (TMA) is a serious complication of solid organ transplantation. Drug-induced TMA is typically caused by immunosuppressants, particularly calcineurin inhibitors. Withdrawing the causative drug can be one of the treatments for TMA. However, the more immunosuppressants are reduced, the more risk of rejection increases. Even if TMA is successfully resolved, the outcomes of patient and graft survival would be worse than expected. Therefore, it is necessary to maintain efficient and safe immunosuppression therapy. We report on a case of de novo TMA after kidney transplantation triggered by tacrolimus and reactivated by sirolimus. Belatacept, a novel CTLA4 Ig fusion protein, was administered for maintenance immunosuppressant with mycophenolate mofetil and prednisolon. The patient had excellent early graft outcome, and there have been no adverse events so far.
Abatacept
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Calcineurin
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Graft Survival
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Humans
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Immunosuppression*
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Immunosuppressive Agents
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Kidney Transplantation*
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Kidney*
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Organ Transplantation
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Sirolimus
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Tacrolimus
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Thrombotic Microangiopathies*
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Transplants
9.The role of CTLA4-Ig in a mouse model against allergic asthma.
Huanying WAN ; Min ZHOU ; Qing XU ; Shaoguang HUANG ; Weiwu DENG
Chinese Medical Journal 2003;116(3):462-464
OBJECTIVETo investigate CTLA4-Ig's potential role in therapy for allergic asthma by blocking B7/CD28 interactions with cytotoxic T lymphocyte antigen 4-Ig (CTLA4-Ig).
METHODSWe divided BALB/C mice into the three groups: Sham/Sham (control), ovalbumin (OVA)/OVA and mCTLA4-Ig. Blood, bronchoalveolar lavage, histology and determination of cytokines were performed 24 hours after airway challenge.
RESULTSIn the OVA/OVA group, the number of cells, the percentage of inflamed cells and the level of IL-4 in BALF were increased. Airways in our murine model for allergic asthma underwent pathological changes, which were significantly reduced after treatment with mCTLA4-Ig.
CONCLUSIONBlockage of co-stimulation with mCTLA4-Ig can inhibit allergy-specific response of T cells, and asthmatic response as well.
Abatacept ; Animals ; Asthma ; immunology ; pathology ; therapy ; Immunoconjugates ; therapeutic use ; Interleukin-4 ; blood ; Leukocyte Count ; Mice ; Mice, Inbred BALB C ; Trachea ; pathology
10.Construction of an adeno-associated virus vector expressing CTLA-4Ig and its expression in the transplanted liver allografts.
Shen LU ; Xue-hao WANG ; Guo-qiang LI ; Yun GAO ; Yue YU
Chinese Journal of Hepatology 2005;13(3):183-186
OBJECTIVESTo construct a recombinant adeno-associated virus vector pSNAV expressing CTLA-4Ig and to demonstrate its expression in transplanted liver allografts and to see if a long term inhibitive effect of CTLA-4Ig could be obtained though its use.
METHODSAfter AAVCTLA-4Ig and PUC18 were cut with BamHI, CTLA-4Ig cDNA was inserted into the plasmid PUC18 by T4DNA ligase and PUC18-CTLA-4Ig was constructed. The obtained PUC18-CTLA-4Ig and pSNAV cut with Kpn I and EcoR I, CTLA-4Ig cDNA was inserted into plasmid pSNAV to construct the recombinant vector pSNAV-CTLA-4Ig, which was transfected into BHK-21 packaging cells by lipofectine-mediated transfection. Then the BHK-21 cell line was infected with HSV1-rc to produce a large amount of pSNAV- CTLA-4Ig. The specificity of the expressed product was identified by digestion with BamHI, PCR and sequence determination. The titer of the virus was detected. The product was infused into rats liver allografts via portal vein and its expression in the transplanted livers was detected immunohistochemically.
RESULTSRecombinant adeno-associated virus vector pSNAV-CTLA-4Ig was generated and purified into 8.5 x 10(11)/ml. Agarose gel analysis of PCR products verified the presence of CTLA-4Ig. Digestion with BamHI and sequence determination confirmed that pSNAV-CTLA-4Ig was constructed. Expression of CTLA-4Ig in the transplanted livers was detected successfully.
CONCLUSIONPrepared pSNAV-CTLA-4Ig was constructed correctly and can express CTLA-4Ig effectively. Besides this, it can express CTLA-4Ig in rat liver allografts. It may be used in the study of transplant tolerance.
Abatacept ; Animals ; Dependovirus ; genetics ; metabolism ; Genetic Vectors ; Immunoconjugates ; genetics ; metabolism ; Liver Transplantation ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Transplantation, Homologous