The Use of Biological Disease-modifying Antirheumatic Drugs for Inflammatory Arthritis in Korea: Results of a Korean Expert Consensus

Biological disease-modifying antirheumatic drugs (bDMARDs) are highly effective agents for the treatment of inflammatory arthritis; however, they also possess a potential risk for serious infection. Recently, with the rapid expansion of the bDMARDs market in Korea, reports of serious adverse events related to the agents have also increased, necessitating guidance for the use of bDMARDs. Current work entitled, “Expert Consensus for the Use of bDMARDs Drugs for Inflammatory Arthritis in Korea,” is the first to describe the appropriate use of bDMARDs in the management of inflammatory arthritis in Korea, with an aim to provide guidance for the local medical community to improve the quality of clinical care. Twelve consensus statements regarding the use of bDMARDs for the management of rheumatoid arthritis and ankylosing spondylitis were generated. In this review, we provide detailed guidance on bDMARDs use based on expert consensus, including who should prescribe, the role of education, indications for use, and monitoring strategies for safety.

Determination of diagnostic value (validity) leukocyte esterase (urine dipstick strip) in differentiating inflammatory arthritis from bacterial arthritis

Abstract Background: The current diagnostic cornerstone for septic arthritis contains gram stains, bacterial culture, and cell count with a differential of aspirated synovial fluid. Recently, a synovial leukocyte esterase (LE) test has been used for diagnosing septic arthritis. Since this test measures the esterase activity of leukocytes, there is always a dilemma for using this test in patients with inflammatory arthritis. Methods: We collected the synovial fluid specimens as part of the general diagnostic protocol for patients suspected of Juvenile Idiopathic Arthritis (JIA) or Septic Arthritis (SA). Each group included 34 patients. We compared the result of the synovial LE test with the result of the culture of each patient. Results: The mean ages of patients were 64.14 ± 31.27 and 50.88 ± 23.19 months in the JIA group and septic arthritis group, respectively. The LE test results were positive in 30 specimens, trace in 3 and negative in one in the first-time test and were positive in 31 specimens and trace in 3 in the second-time test, while it was negative in all patients with JIA. Hence, the sensitivity of the synovial LE test was 80.8%, the specificity, PPV, and NPV were 78.6, 70.0, 86.8% respectively based on a positive culture. Conclusion: The leukocyte esterase strip test can be used as a rapid, bedside method for diagnosing or excluding bacterial infections in different body fluids. The synovial LE test can be used as an accurate test to rapidly rule in or out an acute articular bacterial infection, even in patients with concurrent inflammatory arthritis.(AU)

Advanced Erosive Gout as a Cause of Fever of Unknown Origin / 가정의학회지

A 61-year-old man was referred to our hospital due to a 3-month history of fever of unknown origin, and with right knee and ankle joint pains. At another hospital, extensive investigations had produced negative results, including multiple sterile cultures of blood and joint fluids, and negative autoantibodies. His serum uric acid level was not elevated. However, after admission to our hospital, we performed right knee arthrocentesis, which revealed uric acid crystals. These findings, combined with the results of imaging tests, which showed joint degeneration, led to a diagnosis of advanced erosive gout. After receiving a therapeutic non-steroidal anti-inflammatory drug and a maintenance dose of colchicine for prophylaxis against recurrence, the patient's symptoms subsided and did not return. Advanced erosive gout should be considered a possible cause of fever of unknown origin and diagnostic arthrocentesis should be performed in patients with unexplained arthritis.

Effects and safety of intra-articular injection of recombinant human tumor necrosis factor-α receptor Ⅱ :IgG Fc fusion protein in patients with refractory knee effusion / 中国基层医药

Objective To evaluate the clinical efficacy and safety of the intra-articular injection of recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein (rhTNFR:Fc) in inflammatory arthritis patients with refractory knee effusion.Methods Ten inflammatory arthritis patients presented with refractory knee effusion after treatment of intra-articular steroid injection were involved.They received intra-articular injection rhTNFR:Fc (12.5mg twice weekly).The clinical efficacy and safety were assessed the first and second week after injection.Results At 1 week and 2 weeks,the total effective rate was 60％ and 70％ respectively.Patients and physicians global assessment score (visual analogue scale VAS 0-100mm),joint tenderness and movement pain scale (VAS) were significantly improved.Knee circumference was reduced as compared with baseline (all P ＜ 0.05).Conclusion Intra-artiular injection of rhTNFR:Fc in improving patients with refractory knee effusion is a worthwhile clinical treatment attempt.

The Safety and Effectiveness of Single and Repeat Dosing of Intra-Articular Anti-Tumour Necrosis Factor Treatment after Failure of Intra-Articular Steroids.

Objectives: To determine if intra-articular (ia) anti-tumour necrosis factor (TNF) yielded benefit in patients failing ia steroid injections and determine the safety and durability of single and repeated ia anti-TNF treatment in inflammatory arthritis. Methods: Patients with inflammatory arthritis having one or two active joints, and having failed previous ia steroids were injected with ia adalimumab or ia etanercept mixed with triamcinolone and lidocaine via a retrospective chart audit. Results: Twenty-six patients were followed: 18 received ia adalimumab, 12 received ia etanercept and 4 received both. Twenty-five knees, 17 ankles, 1 wrist and 1 PIP were injected of whom 6 had repeated injections to a joint. Nine were on concomitant systemic anti-TNF therapy. Fifteen had RA, 4 had a seronegativearthropathy, 3 had psoriatic arthritis, and 4 had other arthritis. When determining a response to ia anti-TNF for > 2 months in patients with sufficient follow up 13 of 18 receiving iaadalimumab and 6/7 with ia etanercept had benefit. There were no serious adverse events (SAEs) and only one AE in a wrist post ia adalimumab, with rebound inflammation after 6 weeks of marked relief. Two were able to cancel or postpone joint surgery(knee and ankle)and one cancelled an yttrium injection. Conclusions: There were no SAEs and prolonged benefit was found with ia anti-TNF and steroids and lidocaine compared to previous ia steroids with lidocaine in the majority (20/27). Although not approved for ia administration, ia anti-TNFs may be cost effective in persistent synovitis of one or two joints recalcitrant to ia steroids.

A Case of Inflammatory Arthritis in the Myelodysplastic Syndrome / 대한류마티스학회지

The myelodysplastic syndrome (MDS) is a heterogeneous group of refractory anemia resulting from a clonal abnormality in the pleuripotent stem cell. A variety of immunologic abnormalities have been reported in patients with MDS, and various rheumatic diseases, including rheumatoid arthritis, lupus, Sjogren? syndrome, vasculitis, have been reported in association with MDS. Inflammatory arthritis is a rare complication of MDS. Here we report a patient with refractory anemia with excess blasts with unusual manifestation of inflammatory arthritis, with a review of the literature.

Nitric Oxide(NO) in Inflammatory Arthritis / 대한내과학회지

OBJECTIVES:Nitric Oxide(NO) is a toxic, inorganic, gaseous free radical produced during the metabolism of L-Arginine by NO synthase(NOS). It has been implicated in a rapidly growing number of physiological and pathophysiological processes such as cytotoxic effects against microbes and tumor cells, blood vessel dilation and neurotransmitter. Recently there is growing evidence implicating NO in immune regulation, inflammation, autoimmunity, and arthritis. We performed this study to determine a role for nitric oxide in inflammatory arthritis especially rheumatoid arthritis(RA). METHODS: We measured (1) the concentrations of nitrite, a breakdown product of nitric oxide, in serum and synovial fluid from patients with RA and osteoarthritis(OA) and in the serum of controls (2) the concentrations of nitrite in the supernatant of cultured synovial tissue with RA and OA and (3) determined whether human chondrocytes and synoviocytes can synthesize nitric oxide and if so, how production is regulated by cytokines and antirheumatic drugs. RESULTS: 1) Serum nitrite concentrations in patients with RA and OA were higher than in controls. In both disease groups synovial fluid nitrite was higher than serum nitrite. Serum and synovial fluid nitrite concenrations in RA were higher than those in OA. However, those findings are not statistically significant. 2) Although these findings are not statistically significant, the concentration of nitrite in the supernatant of cultured synavial tissue with RA was higher than that in OA. 3) IL-1beta and TNF-alpah induced the biosynthesis of NO by chondrocytes and synoviocytes. IGF-1 and TGF-beta failed to provoke the production of NO. The biosynthesis of NO required an induction period of approximately 6 hours and was inhibited by L-NMMA and cycloheximide. Dexamethasone, indomethacin, gold sodium thiomalate and methotrexate had no effect on the induction of NO biosynthesis. CONCLUSION: These results suggest a role for nitric oxide as an inflommatory mediator in inflammatory arthritis.