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*

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

PURPOSE: To evaluate plasma pentraxin 3 (PTX3) in patients with retinal vein occlusion (RVO), and investigate the possibility of its role as a predictive biomarker. METHODS: Nested case-control study. The study included 57 patients with RVO and 45 age- and gender-matched subjects without RVO as controls. Plasma PTX3 and C-reactive protein concentration were measured in both groups a posteriori from frozen samples by using an enzyme-linked immunosorbent assay kit. RESULTS: The measured PTX3 value for the RVO group was 1,508 +/- 1,183 pg/mL (mean +/- standard deviation) and 833 +/- 422 pg/mL for the controls (p < 0.001). There was no significant difference in PTX3 levels between patients with central retinal vein occlusion and branched retinal vein occlusion (1,468 +/- 1,300 vs. 1,533 +/- 1,121 pg/mL; p = 0.818). CONCLUSIONS: Our data seems to support the role of chronic inflammation and ischemia in the development of RVO. It is possible that PTX3 can be used as a diagnostic biomarker of RVO.
Acute-Phase Proteins/metabolism ; Adult ; Aged ; Aged, 80 and over ; Biomarkers/*blood ; C-Reactive Protein/*metabolism ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Retinal Vein Occlusion/*blood/diagnosis ; Serum Amyloid P-Component/*metabolism

Psoriasis is a life-long chronic relapsing dermatosis that shows waxing and waning of disease despite of a lot of conventional treatment. Severe psoriasis, usually defined by a psoriasis area and severity index (PASI) score of more than 10 and an area of involved skin of more than 10%, is a typical indication for biologic therapy. TNF-alpha inhibitors (etanercept, infliximab, and adalimumab) and an IL-12/23 inhibitor (ustekinumab) are the major biologics currently available for psoriasis. After the introduction of biologic treatment, many patients with severe psoriasis experience dramatic improvement of their disease without many side effects and are able to maintain a long-term remission period. Long-term follow up of the side effects of currently available biologics reveals no increase in adverse events compared with non-psoriatic individuals. However, the high cost of psoriasis biologics is a major remaining hurdle for the prescription of these agents to patients with severe psoriasis.
Adalimumab ; Biological Products* ; Biological Therapy ; Etanercept ; Follow-Up Studies ; Humans ; Infliximab ; Prescriptions ; Psoriasis* ; Skin ; Skin Diseases ; Tumor Necrosis Factor-alpha ; Ustekinumab

OBJECTIVE: This study examines the effects of tumor necrosis factor (TNF) blockade on markers of bone metabolism in peripheral blood from active rheumatoid arthritis (RA) patients. METHODS: Eighteen patients (16 women, 2 men) aged 50 years (range 37-63 years), with persistently active RA (mean disease duration 7 years) were studied. Most took methotrexate (mean dose 12.5 mg) and all except one received corticosteroid (mean dose 5.7 mg). Four were treated with etanercept, eight received adalimumab and six received infliximab. Before and six months after taking TNF blockers, blood was sampled to obtain peripheral blood mononuclear cells (PBMCs), and serum bone turnover markers and acute phase reactants were measured. PBMCs were seeded and cultured to produce osteoblastic lineage cells and osteoclasts. RESULTS: The formation of calcified nodules by osteoblastic lineage cells from PBMC increased from 205.7±196.3 µmol/well at the baseline to 752.5±671.9 µmol/well after TNF blockade (p<0.024). The serum levels of bone formation markers, including bone specific alkaline phosphatase and osteocalcin also increased. The number of circulating osteoclasts and area of bone resorption pits made by osteoclasts were reduced after TNF blockade. CONCLUSION: The activity of circulating osteoblastic lineage cells increased after TNF blockade, whereas peripheral osteoclastogenesis tended to be suppressed. This is the first study of cultured human peripheral osteoblastic lineage cells in RA patients. Given that peripheral bone formation is difficult to study using radiologic methods, culture of these cells may provide a new modality for studying bone metabolism in RA.
Acute-Phase Proteins ; Adalimumab ; Alkaline Phosphatase ; Arthritis, Rheumatoid ; Biological Therapy ; Bone Remodeling ; Bone Resorption ; Etanercept ; Female ; Humans ; Infliximab ; Metabolism ; Methotrexate ; Osteoblasts* ; Osteocalcin ; Osteoclasts* ; Osteogenesis ; Tumor Necrosis Factor-alpha*

Advanced knowledges of cellular and molecular biology led to the development of therapies of rheumatoid arthritis (RA). The introduction of biologic agents into clinical practice has had a profound effect on the current management of RA. These agents can rapidly enhance functional status and inhibit the progression of joint damage from the disease. Tumor necrosis factor (TNF) inhibitors are the representative biologic agents for the treatment of RA. Their clinical efficacy and safety were revealed through many clinical trails. Novel TNF inhibitors and other biologic agents for the treatment of RA are developing continuously. Promising biologic agents such as TNF inhibitors have become an important part of treatment armamentarium for RA, although they have some side effects and problems to be solved. These agents may contribute to achieve the sustained remission and eventually cure of RA. Currently available TNF inhibitors in Korea include etanercept, infliximab and adalimumab. This review article introduces past, present, and future of the TNF inhibitors and suggests guidelines for the proper use of them on RA.
Arthritis, Rheumatoid* ; Biological Factors ; Joints ; Korea ; Molecular Biology ; Tumor Necrosis Factor-alpha* ; Adalimumab ; Infliximab ; Etanercept