No abstract available.
Arthritis, Rheumatoid ; Humans ; Immunoconjugates ; Abatacept

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 ; Female ; Follow-Up Studies ; Humans ; Immunoconjugates ; Korea ; Methotrexate ; Quality of Life ; Abatacept

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 ; Female ; Follow-Up Studies ; Humans ; Immunoconjugates ; Korea ; Methotrexate ; Quality of Life ; Abatacept

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* ; Arthritis, Rheumatoid* ; Humans ; Korea ; Odds Ratio ; Rheumatology ; Abatacept ; Adalimumab ; Infliximab ; Rituximab ; Etanercept

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 ; Adalimumab ; Antirheumatic Agents ; Arthritis, Rheumatoid* ; Biological Therapy ; Etanercept ; Herpes Zoster* ; Humans ; Incidence ; Infliximab ; Retrospective Studies ; Rituximab ; Seoul

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* ; Arthritis, Rheumatoid* ; Delivery of Health Care ; Health Care Costs ; Humans ; Injections, Subcutaneous* ; Outpatients ; Palliative Care ; Rheumatology ; Abatacept ; Adalimumab ; Etanercept

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 ; Calcineurin ; Graft Survival ; Humans ; Immunosuppression* ; Immunosuppressive Agents ; Kidney Transplantation* ; Kidney* ; Organ Transplantation ; Sirolimus ; Tacrolimus ; Thrombotic Microangiopathies* ; Transplants

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

BACKGROUND: Atopic asthma is characterized by activation of Th2-type T cells in the bronchial mucosa. Several reports have suggested an important role for costimulation through the CD28/CTLA4 (cytotoxic T lymphocyte-associated antigen 4)-B7 (CD80/CD86) pathway in allergen activation of T cells in animal models of allergen-induced asthma, because B7-CD28/ CTLA4 interaction can promote the differentiation and development of the Th2 lymphocyte subset. OBJECTIVE: In the present study, we intended to investigate a potential role of humanized CTLA4-Ig on the inhibition of T and B cell activation by blocking B7/CD28 interactions. METHOD: For this purpose we produced humanized CTLA4-Ig fusion protein by transfection to CHO cell and examined its inhibitory effects for activated T and B cell responses. We evaluated the inhibitory effect of MLR (mixed lymphocyte reaction) and con A-stimulated T cell proliferation. And we assayed wheather B cell was inhibited by stimulation of costimulatory signal in LPS-induced B cell response and PFC assay. RESULT: In vitro assay, humanized CTLA4-Ig fusion protein inhibited T cell-specific immune response in dose-dependent manner: CTLA4-Ig inhibited allogeneic stimulation in murine MLR, and the proliferation of T cell by the stimulation of Con A. But CTLA4-Ig did not inhibit directly the proliferative response of B cell by the stimulation of LPS. In addition, in vivo assay, CTLA4-Ig inhibited the production of antibody from B cell, which was presented by plaque-forming cell (PFC) assay. CONCLUSION: These findings suggest that humanized CTLA4-Ig is effective to inhibit the proliferation of activated T cell directly by blocking B7/CD28 costimulation. And humanized CTLA4-Ig influences antibody-producing capacity of B cell indirectly by regulating T cell.
Abatacept ; Animals ; Antibody Formation* ; Asthma ; Cell Proliferation ; CHO Cells ; Cricetinae ; Humans ; Lymphocyte Subsets ; Lymphocytes ; Models, Animal ; Mucous Membrane ; T-Lymphocytes ; Transfection

OBJECTIVETo study the protective role of Sertoli cell expressing FasL and CTLA-4Ig on allogeneic renal cell.

METHODSTesticular Sertoli cell and renal cell were prepared by digestion with enzymes. About 106 cells were injected into the subrenal capsule of allogeneic rats. 36 rats were divided into 3 groups: control group (10), co-transplantation group (16) and co-transplantation collaborated with CTLA-4Ig group (CTLA group, 10). Levels of serum IL-2 were tested on the 1st, 7th, 14th, 20th day after transplantation. The kidney was extracted on the 20th day. The survival of renal cells was determined by the Avidin Biotin Peroxidase Complex Technique (ABC); the brightness of grafts was measured by MD-20 image analysis system. Apoptosis within the grafts was observed with Terminal Deoxynucleotidyl Transferase-mediated X-dUTP Nick end Labeling (TUNEL) method.

RESULTSThe survival of renal cells in control group, co-transplantation group and CTLA group was 0, 14 and 10 respectively; The brightness values of co-transplantation group and CTLA group were 0.362 +/- 0.017 and 0.445 +/- 0.021, and the statistic differences between them were significant. Levels of serum IL-2 in CTLA group were lower compared with co-transplantation group, there being significant differences as well; Apoptosis of lymphocyte was observed within the grafts.

CONCLUSIONSSertoli cell and CTLA-4Ig have coordinative protective effect on allogeneic renal cell.

Abatacept ; Animals ; Antibodies ; Antigens, CD ; Antigens, Differentiation ; immunology ; CTLA-4 Antigen ; Immune Tolerance ; Immunoconjugates ; Kidney ; cytology ; Kidney Transplantation ; immunology ; Lymphokines ; Male ; Rats ; Rats, Wistar ; Sertoli Cells ; immunology