OBJECTIVE: Our aim was to investigate the long term safety and efficacy of etanercept in children with juvenile idiopathic arthritis (JIA). METHODS: The study subjects were the 90 JIA patients treated with etanercept in the Department of Pediatrics, Hallym University Medical Center between January 2004 and December 2017. We retrospectively reviewed their medical records for age at diagnosis, duration of etanercept treatment, number of active joints, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and adverse events during treatment. RESULTS: Among the 90 patients, 38 (42.0%) were male and 52 (58.0%) were female; 15 (16.7%) had systemic onset, 41 (45.6%) had extended oligoarticular, 14 (15.6%) had rheumatoid factor-positive polyarticular, 18 (20.0%) had rheumatoid factor-negative polyarticular, and 2 (2.1%) had enthesitis-related arthritis. The median age at the start of etanercept treatment was 9 years (range, 3~18 years), and the median duration of etanercept treatment was 6 years (range, 0.5~13 years). The median number of active joints decreased from 9 to 0 after 6 months of etanercept treatment. The median CRP and ESR were within normal range after 3 months of treatment. Six patients experienced recurrence, 9 switched to other medications and 3 discontinued etanercept. Of the 14 reported adverse events, 1 was serious, and there were no tuberculosis infections or malignancies. CONCLUSION: Long-term treatment with etanercept is efficacious and safe for children with JIA. However, those with the systemic onset subtype appear to have low drug survival rate compared to those with other types of JIA.
Academic Medical Centers ; Arthritis ; Arthritis, Juvenile ; Blood Sedimentation ; C-Reactive Protein ; Child ; Diagnosis ; Etanercept ; Female ; Humans ; Joints ; Male ; Medical Records ; Pediatrics ; Recurrence ; Reference Values ; Retrospective Studies ; Survival Rate ; Tuberculosis

Pustulotic arthro-osteitis (PAO) is a rare chronic inflammatory disorder characterized by inflammatory osteitis of the sternoclavicular joint and palmoplantar pustulosis. Here, we report a case of PAO that was successfully treated with a TNF-α inhibitor. A 45-year-old man presented with a 3-month history of pustular eruption on the palms and soles. Physical examination showed multiple erythematous papulopustules on the palms, back, and left shin, accompanied by sternoclavicular joint swelling and tenderness. Skin biopsy showed intraepidermal pustules filled with neutrophils on the palm. Bone scintigraphy revealed increased uptake in the bilateral sternoclavicular and other axial joints. Based on these findings, we made the diagnosis of PAO. Even after 6-month treatment of oral steroids and cyclosporine, skin manifestations insufficiently improved, so etanercept therapy was started. Complete clearance of skin lesions and joint pain were achieved after 3 months of etanercept therapy.
Arthralgia ; Biopsy ; Cyclosporine ; Diagnosis ; Etanercept ; Humans ; Joints ; Middle Aged ; Neutrophils ; Osteitis ; Physical Examination ; Radionuclide Imaging ; Skin ; Skin Manifestations ; Sternoclavicular Joint ; Steroids

BACKGROUND: Currently, no generally accepted laboratory marker for monitorizing the disease activity and therapy response of psoriasis is known. OBJECTIVE: The aim of the study is to evaluate the effects of systemic therapies on C-reactive protein (CRP) and the neutrophil-lymphocyte ratio (NLR) in psoriasis. METHODS: One hundred patients with psoriasis treated with narrow band ultraviolet B, acitretin, cyclosporine, methotrexate, adalimumab, etanercept, and ustekinumab were prospectively evaluated. At baseline and at week 12, CRP, NLR, and Psoriasis Area and Severity Index (PASI) were evaluated. RESULTS: A statistically significant decrease was observed in PASI scores, CRP, and NLR values from the baseline to the 12-week visit (p=0.001, p=0.001, p=0.001, respectively). The reduction in PASI scores and NLR values was positively correlated (r=0.460, p=0.001). The comparisons between treatment groups revealed that the median decrease in NLR values was statistically higher in the adalimumab group than in the methotrexate group (p=0.007). And the median decrease in PASI scores was significantly higher in the adalimumab group compared with the methotrexate and acitretin therapy group (p=0.007, p=0.042, respectively). CONCLUSION: In the present study, systemic therapy of psoriasis was demonstrated to decrease the levels of CRP and NLR, which are known to be indicators of systemic inflammation and cardiovascular comorbidities.
Acitretin ; Adalimumab ; Biomarkers ; C-Reactive Protein ; Cardiovascular Diseases ; Comorbidity ; Cyclosporine ; Etanercept ; Humans ; Inflammation ; Methotrexate ; Prospective Studies ; Psoriasis ; Ustekinumab

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis), which are the main treatment for ankylosing spondylitis (AS), have been reported not only to reduce the incidence of anterior uveitis (AU) but also to induce it, and these effects differ among the various types of TNFis in clinical use. The present study investigated the effect of TNFis on uveitis by analyzing the long-term clinical course of AU in AS patients treated with TNFi therapy. METHODS: Patients treated with at least one TNFi between January 2007 and July 2017 were reviewed, and 54 patients with at least one episode of AU were included in this study. The TNFis included anti-TNF-α antibodies (adalimumab, infliximab, and golimumab), and a soluble TNF receptor molecule (etanercept). The effect of prevention of AU, the likelihood of new-onset uveitis after the initiation of TNFi therapy, and the effects of drug switching and dose escalation were assessed. RESULTS: The first uveitis flare was observed before TNFi therapy in 39 patients and after TNFi therapy in 15 patients. Anti-TNF-α antibodies were more efficacious in decreasing the recurrence of AU than etanercept. Among patients in which uveitis first occurred after beginning TNFi therapy, patients on etanercept tended to first develop AU less than 1 year after starting the drug, and their AS tended to be well-controlled at the time of uveitis flares. Patients with a uveitis flare before their medication was switched did not recur afterwards, and five of eight patients showed no relapse after dose escalation. CONCLUSION: TNFis have various effects on AU. TNFis, particularly anti-TNF-α antibodies, should be considered in patients with AS and frequent AU relapse. Additionally, clinicians should consider whether AU is due to an absence of a therapeutic response of AS to TNFi treatment or to TNFi treatment itself, and appropriate treatment changes should be made accordingly.
Adalimumab ; Antibodies ; Drug Substitution ; Etanercept ; Humans ; Incidence ; Infliximab ; Receptors, Tumor Necrosis Factor ; Recurrence ; Spondylitis, Ankylosing ; Tumor Necrosis Factor-alpha ; Uveitis ; Uveitis, Anterior

Ankylosing spondylitis (AS) can involve the eye, gastrointestinal system, cardiopulmonary system, skin, kidneys, and spinal and peripheral joints. It is rarely accompanied by immunoglobulin A (IgA) nephropathy. Although IgA is involved in both AS and IgA nephropathy, the relationship between these diseases remains unclear. We detected hematuria and proteinuria in a 32-year-old male patient with ankylosing spondylitis that remained stable for 4 years through treatment with etanercept, a tumor necrosis factor-α (TNF-α) inhibitor, and diagnosed IgA nephropathy through a renal biopsy. IgA nephropathy seems to be less commonly associated with AS disease activity or specific treatment such as TNF-α inhibitor use.
Adult ; Biopsy ; Etanercept* ; Glomerulonephritis, IGA* ; Hematuria ; Humans ; Immunoglobulin A* ; Joints ; Kidney ; Male ; Necrosis ; Proteinuria ; Skin ; Spondylitis, Ankylosing* ; Tumor Necrosis Factor-alpha

Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-α antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia (DRG) and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etanercept and in TNFR1/R2 DKO mice. Dry skin induced TNF-α expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-α/TNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be beneficial for chronic itch treatment.
Animals ; Chloroquine ; toxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Etanercept ; therapeutic use ; Ganglia, Spinal ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Pruritus ; chemically induced ; drug therapy ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Receptors, Tumor Necrosis Factor, Type I ; deficiency ; genetics ; Receptors, Tumor Necrosis Factor, Type II ; deficiency ; genetics ; Signal Transduction ; drug effects ; Skin ; drug effects ; metabolism ; Spinal Cord ; drug effects ; metabolism ; Thalidomide ; therapeutic use ; Time Factors ; Tumor Necrosis Factor-alpha ; adverse effects ; genetics ; metabolism ; p-Methoxy-N-methylphenethylamine ; toxicity

BACKGROUND/AIMS: To evaluate drug survival of the tumor necrosis factor α inhibitors (TNFi) and risk factors for the drug discontinuation in patients with ankylosing spondylitis (AS). METHODS: We retrospectively evaluated 487 AS patients at a single tertiary hospital. Among the TNFi users, drug survival and risk factors of TNFi discontinuation were investigated. RESULTS: Among 487 patients, 128 AS patients were treated with at least one TNFi. Patients who were treated with TNFi were younger at disease onset, had more peripheral manifestations, and had higher level of acute phase reactants and body mass index than those of TNFi non-users at baseline. Of 128 patients, 28 patients (21.9%) discontinued first TNFi therapy during the follow-up period of 65.1 ± 27.9 months. In the multivariable analysis, female (hazard ratio [HR], 6.08; 95% confidence interval [CI], 2.27 to 16.27; p = 0.003), hip involvement (HR, 2.52; 95% CI, 1.08 to 5.87; p = 0.033) and a high C-reactive protein (CRP; HR, 1.10; 95% CI, 1.00 to 1.21; p = 0.044) were risk factors for drug discontinuation. Etanercept showed better survival rate than infliximab. The main reason for discontinuation of TNFi was inefficacy. CONCLUSIONS: TNFi discontinuation rate of Korean patients with AS seems to be similar to those with the European patients. Female sex, hip involvement, CRP, and the type of TNFi were associated with TNFi discontinuation.
Acute-Phase Proteins ; Body Mass Index ; C-Reactive Protein ; Drug Users ; Etanercept ; Female ; Follow-Up Studies ; Hip ; Humans ; Infliximab ; Korea* ; Retrospective Studies ; Risk Factors ; Spondylitis, Ankylosing* ; Survival Rate ; Tertiary Care Centers ; Tumor Necrosis Factor-alpha*

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

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*

The development of cutaneous sarcoidosis as a paradoxical adverse event of tumor necrosis factor alpha (TNF-α) blockers has been reported in the literature; however, an erythrodermic form of cutaneous sarcoidosis during anti-TNF-α therapy has not yet been reported. Herein, we report the first case of an erythrodermic form of cutaneous sarcoidosis during anti-TNF-α therapy and review previous studies of cutaneous sarcoidosis. A 6-year-old Korean girl who had been suffering from juvenile rheumatoid arthritis presented with generalized erythematous skin eruption involving more than about 90% of her body surface area. After 14 months of etanercept treatment, the new erythematous skin eruption had developed and progressed into generalized erythroderma. Exclusion of suspected co-medication had been performed based on medication history. She had no other systemic symptoms, and ophthalmologic and neurologic examinations were normal. Histopathologic findings of the skin lesion revealed diffuse non-caseating granulomatous infiltrates composed of epithelioid histiocytes with sparse lymphocytes involving the entire dermis. Periodic-acid-Schiff and acid-fast stains were negative, and acid-fast bacilli was not detected by polymerase chain reaction of the skin biopsy. Based on clinicopathologic findings, she was diagnosed with etanercept-induced sarcoidal granuloma. After discontinuation of the suspected agent, the lesions spontaneously disappeared.
Arthritis, Juvenile* ; Biopsy ; Body Surface Area ; Child ; Coloring Agents ; Dermatitis, Exfoliative ; Dermis ; Etanercept ; Female ; Granuloma ; Histiocytes ; Humans ; Lymphocytes ; Neurologic Examination ; Polymerase Chain Reaction ; Sarcoidosis* ; Skin ; Tumor Necrosis Factor-alpha*