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

Since the late 1990s, based on scientific advancement and biotechnological improvement, many effective drugs such as leflunomide and biologic agents for rheumatoid arthritis (RA) have been developed. These include TNF-alpha inhibitors such as etanercept, infliximab, and adalimumab, a peripheral B-cell depleting agent such as rituximab, CTLA-4 Ig such as abatacept, and IL-1 receptor antagonist such as anakira. These new agents have provided good efficacy in the treatment of patents with severe or refractory rheumatoid arthritis and have provided retardation or prevention of radiographic progression or joint destruction despite some side effects such as tuberculosis, infection, malignancies. In this review, new therapeutic alternatives would be given, and chances for more improved outcomes in the care of patients with rheumatoid arthritis provided.
Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal, Murine-Derived ; Arthritis, Rheumatoid ; B-Lymphocytes ; Humans ; Immunoconjugates ; Immunoglobulin G ; Interleukin-1 ; Isoxazoles ; Joints ; Receptors, Tumor Necrosis Factor ; Tuberculosis ; Tumor Necrosis Factor-alpha ; Rituximab ; Abatacept ; Adalimumab ; Infliximab ; Etanercept

Rheumatoid arthritis (RA) is a common autoimmune disease of unknown etiology characterized by symmetric and erosive synovitis. The course of RA is usually chronic and progressive, so it can result destructive joint damages. Nonsteroidal anti-inflammatory drugs, disease modifying anti-rheumatic drugs (DM ARDs) and low-dose corticosteroid have been used for the treatments of RA. The importance of early usage of DMARDs are stressed recently, however, the effects of DMARDs on long-term prognosis is not convincing. Since 1998, several biologic agents were developed for RA and showed promising results. These agents include TNF-alpha blockers such as etanercept, infliximab, adalimumab, and IL-1 receptor antagonist such as anakinra. Clinical studies for rituximab, anti-IL-6 receptor monoclonal antibody, and CTLA4-Ig are underway. The biologic agents show rapid improvement in clinical and laboratory parameters and may prevent the erosions on Xray, but because of costs and unknown long-term side effects, we should be more careful for using these drugs.
Antirheumatic Agents ; Arthritis, Rheumatoid* ; Autoimmune Diseases ; Biological Factors ; Biological Therapy* ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1 ; Joints ; Prognosis ; Synovitis ; Tumor Necrosis Factor-alpha ; Abatacept ; Adalimumab ; Infliximab ; Rituximab ; Etanercept

Intestinal Behçet's disease is a rare, immune-mediated chronic intestinal inflammatory disease; therefore, clinical trials to optimize the management and treatment of patients are scarce. Moreover, intestinal Behçet's disease is difficult to treat and often requires surgery because of the failure of conventional medical treatment. Administration of anti-tumor necrosis factor–α, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal Behçet's disease and inflammatory bowel diseases has been accumulating. Here, we review updated data on current experiences and outcomes after the administration of anti-tumor necrosis factor–α for the treatment of intestinal Behçet's disease. In addition to infliximab and adalimumab, which are the most commonly used agents, we describe agents such as golimumab, etanercept, and certolizumab pegol, which have recently been shown to be effective in refractory intestinal Behçet's disease. This review also discusses safety issues associated with anti-tumor necrosis factor–α, including vulnerability to infections and malignancy.
Adalimumab ; Behcet Syndrome ; Certolizumab Pegol ; Etanercept ; Humans ; Inflammatory Bowel Diseases ; Infliximab ; Necrosis*

Targeted agents increase response rates and improved overall survival in treatment of metastatic gastrointestinal cancer. Therefore, physicians pay more attention to the role of targeted agents in treatment of local advanced gastrointestinal cancer. The clinical trials are ongoing to evaluate the efficacy of Trastuzumab in neoadjuvant treatment of local advanced gastric cancer with HER-2 gene over expression. Many studies reported Cetuximab plus chemotherapy as a conversion treatment improve R0 resection rates and prolonged overall survival of the patients with potentially resectable colorectal cancer liver metastasis with wild type KRAS gene status. A phase III( clinical trial is assessing the conversion efficacy of Bevacizumab in unresectable disease with KRAS gene mutation. Current evidence showed that neoadjuvant therapy of targeted agents did not prolong survival of patients with resectable liver metastasis. However, this is controversial. In neoadjuvant therapy of local advanced rectal cancer, Cetuximab did not improve the rates of pathological complete response in most of the phase II( trials. Furthermore, there are no phase III( trials to assess the role of Bevacizumab. Compared to chemotherapy alone for metastatic cancer, it is more important to evaluate the interaction and synergistic action of targeted agents, cytotoxic drugs, surgery and radiation, to make a scientific multidisciplinary model in comprehensive treatment of local advanced cancer.
Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Bevacizumab ; Cetuximab ; Gastrointestinal Neoplasms ; drug therapy ; Humans ; Liver Neoplasms ; Molecular Targeted Therapy ; Neoadjuvant Therapy ; Trastuzumab

The efficacy of anti-TNF-alpha antibodies including infliximab and adalimumab for refractory intestinal Behcet's disease has recently been demonstrated in a series of case reports. The efficacy of switching to a different kind of anti-TNF-alpha agent in the face of refractoriness to one kind of anti-TNF-alpha agent, a common practice of proven efficacy in rheumatoid arthritis, has yet not been reported for intestinal Behcet's disease. In the present study, we report a case of 52-year-old female patient with intestinal Behcet's disease, who lost initial good response to infliximab, and was refractory to subsequent administrations of adalimumab. Her recent relapse of intestinal lesions could be successfully treated with etanercept. This case suggests that switching to etanercept might be a reasonable therapeutic option in case of intestinal Behcet's disease with secondary non-response to anti-TNF-alpha antibodies that is most likely to be mediated by anti-drug antibody.
Antibodies ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Arthritis, Rheumatoid ; Female ; Humans ; Immunoglobulin G ; Receptors, Tumor Necrosis Factor ; Recurrence ; Adalimumab ; Infliximab ; Etanercept

No abstract available.
Antibodies, Anti-Idiotypic ; Antibodies, Monoclonal, Humanized ; Urticaria ; Omalizumab

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

BACKGROUNDThe development of new adjuvants for human use has been the focus of attention. This study's aim is to explore the possibility of using nanoparticle Ca nanoparticles (CA) as a vaccine adjuvant of anti-idiotypic antibody NP30 against schistosomiasis and its protective mechanisms.

METHODSNanoparticle CA-NP30 conjugate (CA-NP30) was fabricated. BALB/c mice were immunized actively with CA-NP30 to evaluate its effects of protective immunity on mice. The serum levels of specific IgG, IgG1 and IgG2a antibodies against NP30 and the concentrations of IFN-gamma and IL-4 in supernatant of splenocytes were determined via ELISA.

RESULTSNanoparticle CA could enhance significantly the protective immunity of NP30 against infection of Schistosoma japonicum and the worm reduction rose from 36.0% (NP30 alone) to 52.6%. The serum levels of specific IgG, IgG1 and IgG2a antibodies against NP30 increased remarkably, as compared with those of the group immunized with NP30 alone. The concentration of IFN-gamma in supernatant of splenocyte was drastically elevated [the groups immunized with CA-NP30 and NP30 alone were (493.80 +/- 400.74) pg/ml and (39.03 +/- 39.58) pg/ml, respectively], but the concentration of IL-4 showed no significant difference from that of NP30 alone [(27.94 +/- 9.84) pg/ml vs (27.28 +/- 14.44) pg/ml].

CONCLUSIONSNanoparticle CA could act as a vaccine adjuvant of anti-idiotypic antibody NP30 against schistosomiasis. The mechanism could be that CA-NP30 enhances humoral and cellular immune responses in mice.

Adjuvants, Immunologic ; Animals ; Antibodies, Anti-Idiotypic ; immunology ; Antibodies, Helminth ; immunology ; Mice ; Mice, Inbred BALB C ; Nanotechnology ; Schistosomiasis ; prevention & control ; Vaccines