Overlap syndrome is defined as a disease entity that satisfies the classification criteria of at least two connective tissue diseases occurring concurrently or separately in a single patient. Here, we report a rare case of a 59-year-old woman with diffuse systemic sclerosis with lung involvement-rheumatoid arthritis overlap syndrome accompanied by cutaneous sarcoidosis. Although there is no consensus for the optimal treatment of overlap syndrome to date, this case of co-existing rheumatoid arthritis and systemic sclerosis with interstitial lung disease successfully responded to abatacept.
Abatacept ; Arthritis ; Arthritis, Rheumatoid ; Classification ; Connective Tissue Diseases ; Consensus ; Female ; Humans ; Lung ; Lung Diseases, Interstitial ; Middle Aged ; Sarcoidosis ; Scleroderma, Diffuse ; Scleroderma, Systemic

OBJECTIVETo explore the effects of blocking TCR-CD3 and B7-CD28 signals on immune function of mice with chronic GVHD by using TJU103 and CTLA4-Ig.

METHODSOn the basis of foregoing murine model of chronic GVHD, according to interference modes after infusion 6×10 spleen cells of donor mice, the recipients were divided into 5 groups: blank control, cGVHD, TJU103 interference, CTLA4-Ig interference and TJU103+CTLA4-Ig interference groups. The score of clinical manifestation and tissue histopathology were used to evaluate the effects of all the interferences on chronic GVHD.

RESULTSTJU103 and CTLA4-Ig could not influence the formation of the mouse chimera. The analysis of Kaplan survival curve of mice with chronic GVHD showed that the CTLA4-Ig and TJU103+CTLA4-Ig reduced the incidence of chronic GVHD, the TJU103 could delay the occurrence of chronic GVHD, but all the interference factors could not change the severity of chronic GVHD.

CONCLUSIONTJU103 can delay the onset time of chronic GVHD, and the CTLA4-Ig can reduce the incidences of cGVHD, the combining use of TJU103 and CTLA4-Ig can significantly reduce the incidence of chronic GVHD, but can not change the severity of chronic GVHD.

Abatacept ; Animals ; Antigen-Presenting Cells ; Antigens, CD ; Antigens, Differentiation ; CTLA-4 Antigen ; Chronic Disease ; Graft vs Host Disease ; prevention & control ; Immunoconjugates ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes

OBJECTIVE: Coexisting chronic hepatitis C can be problematic when treating rheumatoid arthritis (RA). This study examined the changes in the transaminase and viral load in hepatitis C virus (HCV)-infected RA patients after initiating biologic agents. METHODS: A multicenter retrospective study was conducted at 12 University Hospitals in Korea between November 2014 and November 2015, and 78 RA patients, who met the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for RA and were concomitantly infected with HCV, were identified. The baseline and longitudinal clinical data, changes in liver function, and viral RNA titers were evaluated. RESULTS: Seventeen (21.8%) patients were treated with biologic agents, including etanercept (n=8), adalimumab (n=8), infliximab (n=2), tocilizumab (n=2), abatacept (n=1), and golimumab (n=1) (median 1.5 patient-years). Four patients experienced marked increases in transaminase during treatment with adalimumab (n=2) and tocilizumab (n=2). Two patients (one using adalimumab, the other using tocilizumab) were treated with anti-viral agents and showed dramatic improvement in both the viral RNA and transaminase. One patient discontinued adalimumab due to the repeated elevated transaminase levels along with a twofold increase in the viral RNA titer, and the transaminase level subsequently normalized. No case of overt viral reactivation was identified. CONCLUSION: The data support that changes in transaminase and/or viral load associated with biologic agents in HCV-infected RA patients are possible. Therefore, the liver function and viral RNA titer should be followed regularly during biologic therapy.
Abatacept ; Adalimumab ; Antirheumatic Agents ; Arthritis, Rheumatoid* ; Biological Factors ; Biological Therapy* ; Classification ; Etanercept ; Hepacivirus ; Hepatitis C ; Hepatitis C, Chronic* ; Hepatitis, Chronic* ; Hospitals, University ; Humans ; Infliximab ; Korea ; Liver ; Retrospective Studies ; Rheumatic Diseases ; Rheumatology ; RNA, Viral ; Viral Load

A large proportion of patients with rheumatic disease have an immunocompromised status resulting from disease pathogenesis itself and/or several immunosuppressive drugs including biologics. These conditions are closely related to a higher risk of a variety of infectious diseases. Therefore, a few vaccinations for vaccine‐preventable pathogens should be considered in patients with rheumatic disease at the appropriate time. The quadrivalent inactivated influenza and pneumococcal vaccinations, including both 13‐valent conjugate and 23‐valent polysaccharide vaccines, are strongly recommended in all patients with rheumatic disease. The immunogenicity of influenza and pneumococcal vaccination have generally been demonstrated in patients with rheumatic disease on biologics except for rituximab and abatacept. Vaccines can be administered during therapy with tumor necrosis factor-α antagonists but may be more ideal during a stable or remission status without immunosuppressive therapy. In particular, vaccination should be done at least 6 months after an injection of rituximab as a B‐lymphocyte‐depleting biologic. Basically, all live-attenuated vaccines should be avoided in highly immunocompromised rheumatic disease patients. The vaccination for herpes zoster (HZ) can be taken carefully according to degree of immunosuppression because the currently available vaccine is only live‐attenuated. The newly developed subunit HZ vaccine is promising in immunocompromised patients with rheumatic disease.
Abatacept ; Biological Factors ; Biological Products* ; Communicable Diseases ; Herpes Zoster ; Humans ; Immunocompromised Host ; Immunosuppression ; Influenza, Human ; Necrosis ; Pneumococcal Infections ; Rheumatic Diseases* ; Rituximab ; Vaccination* ; Vaccines

German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma.
Abatacept ; Administration, Intranasal ; Allergens ; Antibodies ; Asthma ; Biological Products ; Blattellidae* ; Bronchi ; Collagen ; Cytoplasm ; Eosinophils ; Epithelium ; Family Characteristics ; Goblet Cells ; Inflammation* ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Lung ; Metaplasia ; Respiratory Hypersensitivity ; T-Lymphocytes ; T-Lymphocytes, Cytotoxic

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

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

This research was aimed to explore the effects of blocking B7/CD28 and CD40/CD154 co-stimulatory signals on engraftment of hematopoietic stem cell in the sensitized recipient so as to provide the experimental evidence for the treatment of sensitized recipient's immune rejection after clinical allogeneic hematopoietic stem cell transplantation (HSCT). The BALB/c mice were divided into 4 groups: (1)mice sensitized on 7 day before transplant; (2)mice were sensitized on 7 day before transplant, and injected CTLA4Ig+anti-CD154 applied; (3)normal mice injected by corresponding isotype control IgG of CTLA4Ig and anti-CD154; (4)normal blank control mice. Each group had 15 mice. On day 0, mice of each group were irradiated lethally 8 Gy by linear accelerator, and the bone marrow cells of C57BL/6 labeled by fluorescence staining were injected via the tail vein. The fluorescent cell level in peripheral blood and organ tissue at different time points were detected by flow cytometry (FCM) for homing assessment. Survival rates and hematopoietic reconstitution were also monitored and recorded. The results showed that application of CTLA4Ig anti-CD154 could promote implantation of allogeneic HSC in sensitized recipients, induce the immune tolerance, prolong their survival time and accelerate the hematopoietic reconstitution within 28 days, compared with the sensitized group. It is concluded that applying CTLA4Ig and anti-CD154 can enhance the engraftment of HSCT and induce immune tolerance in the sensitized recipient after allogeneic HSCT and accelerate the hematopoietic reconstitution.
Abatacept ; Animals ; B7 Antigens ; antagonists & inhibitors ; CD28 Antigens ; antagonists & inhibitors ; CD40 Antigens ; antagonists & inhibitors ; CD40 Ligand ; antagonists & inhibitors ; Graft Rejection ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Immune Tolerance ; Immunoconjugates ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Transplantation, Homologous