Comparative Efficacy and Safety of Febuxostat and Allopurinol in the Treatment of Hyperuricemia: A Bayesian Network Meta-analysis

( Gwan Gyu Song ),( Young Ho Lee ) 대한류마티스학회 2015 대한류마티스학회지 Vol.22 No.6

Objective. The aim of this study was to assess the relative urate-lowering efficacy and safety of febuxostat and allopurinol in hyperuricemic patients with or without gout. Methods. Randomized controlled trials (RCTs) examining the efficacy and safety of febuxostat compared to allopurinol or placebo in hyperuricemic patients with/without gout were included in this Bayesian network meta-analysis. Results. Eight RCTs including 4,099 patients met the inclusion criteria. The number of subjects achieving a serum urate (sUA) level <6.0 mg/dL was significantly higher in the febuxostat 120 mg and 80 mg groups than in the allopurinol (100 to 300 mg) group (odds ratio [OR] 7.17, 95% credible interval [CrI] 3.86 to 14.09; OR 3.49, 95% CrI 1.97 to 5.91, respectively). However, achievement of the target sUA level was comparable between febuxostat 40 mg and allopurinol. Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that febuxostat 120 mg had the highest probability of being the best treatment for achieving the target sUA (SUCRA=0.9973), followed by febuxostat 80 mg (SUCRA=0.752), febuxostat 40 mg (SUCRA=0.4289), allopurinol (SUCRA=0.3217), and placebo (SUCRA=0). In contrast, no significant difference in safety based on the number of withdrawals due to adverse events was observed among the 5 interventions. Conclusion. Febuxostat 80 mg and 120 mg were more efficacious than allopurinol (100 to 300 mg), and febuxostat 40 mg and allopurinol were comparable in urate-lowering efficacy. The safety of febuxostat at all doses was comparable with that of allopurinol. (J Rheum Dis 2015;22:356-365)

Causal Association between Bone Mineral Density and Osteoarthritis: A Mendelian Randomization Study

( Gwan Gyu Song ),( Young Ho Lee ) 대한류마티스학회 2019 대한류마티스학회지 Vol.26 No.2

Objective. To examine whether bone mineral density (BMD) is causally associated with osteoarthritis (OA). Methods. We performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighting (IVW), weighted median, and MR-Egger regression methods. We used publicly available summary statistics datasets of a genome-wide association study (GWAS) on femur neck (FN) BMD of individuals of European ancestry as the exposure and a GWAS for non-cancer illness code self-reported: OA from the individuals included in the UK Biobank as the outcome. Results. We selected 21 independent single- nucleotide polymorphisms with genome-wide significance (p<5.00E-08) from GWAS on FN BMD as the instrumental variables. The IVW method (beta=0.010, standard error [SE]=0.003, p=0.002) and the weighted median approach (beta=0.011, SE=0.004, p=0.006) yielded evidence of a causal association between FN BMD and OA. However, the MR-Egger analysis showed no causal association between FN BMD and OA (beta=0.005, SE=0.017, p=0.753). Since MR-Egger regression suffers from a lack of power and a susceptibility to weak instrument bias, the MR analysis results may support a causal association between FN BMD and OA. Conclusion. The results of MR analysis by IVW and weighted median, but not MR-Egger regression indicate that FN BMD is likely to be causally associated with an increased risk of OA incidence The current findings may provide an opportunity to elucidate the underlying mechanisms of the effects of BMD on the OA incidence. (J Rheum Dis 2019;26:104-110)

Efficacy and safety of tofacitinib for active rheumatoid arthritis with an inadequate response to methotrexate or disease-modifying antirheumatic drugs: a meta-analysis of randomized controlled trials

( Gwan Gyu Song ),( Sang Cheol Bae ),( Young Ho Lee ) 대한내과학회 2014 The Korean Journal of Internal Medicine Vol.29 No.5

Background/Aims: The aim of this study was to assess the efficacy and safety oftofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis(RA). Methods: A systematic review of randomized controlled trials (RCTs) that examinedthe efficacy and safety of tofacitinib in patients with active RA was performedusing the Medline, Embase, and Cochrane Controlled Trials Registerdatabases as well as manual searches. Results: Five RCTs, including three phase-II and two phase-III trials involving1,590 patients, met the inclusion criteria. The three phase-II RCTs included 452patients with RA (144 patients randomized to 5 mg of tofacitinib twice daily, 156patients randomized to 10 mg of tofacitinib twice daily, and 152 patients randomizedto placebo) who were included in this meta-analysis. The American Collegeof Rheumatology 20% response rate was significantly higher in the tofacitinib5- and 10-mg groups than in the control group (relative risk [RR], 2.445; 95% confidenceinterval [CI], 1.229 to 4.861; p = 0.011; and RR, 2.597; 95% CI, 1.514 to 4.455;p = 0.001, respectively). The safety outcomes did not differ between the tofacitinib5- and 10-mg groups and placebo groups with the exception of infection in thetofacitinib 10-mg group (RR, 2.133; 95% CI, 1.268 to 3.590; p = 0.004). The results oftwo phase-III trials (1,123 patients) confirmed the findings in the phase-II studies. Conclusions: Tofacitinib at dosages of 5 and 10 mg twice daily was found to be effectivein patients with active RA that inadequately responded to methotrexate ordisease-modifying antirheumatic drugs, and showed a manageable safety profile.

Associations between TRAF1-C5 Gene Polymorphisms and Rheumatoid Arthritis: A Meta-Analysis

Song, Gwan Gyu,Bae, Sang-Cheol,Kim, Jae-Hoon,Lee, Young Ho Informa Healthcare USA, Inc. 2014 Immunological investigations Vol.43 No.2

<P><I>Objective</I>: The aim of this study is to determine whether tumor necrosis factor receptor-associated factor 1-complement 5 (TRAF1-C5) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA) in different populations.</P><P><I>Methods</I>: We conducted a meta-analysis of associations between the TRAF1-C5 polymorphisms and RA susceptibility.</P><P><I>Results</I>: A total of 24 comparative studies were included in this meta-analysis, including 22,682 patients with RA and 23,493 controls. The meta-analysis showed an association between the second allele of rs10818488 and RA in Europeans, but not in Asians (OR 1.229, 95% CI 1.094-1.381, <I>p</I> = 0.001; OR 1.060, 95% CI 0.930-1.335, <I>p</I> = 0.092). The meta-analysis also indicated an association between the second allele of rs3761847 and RA in Europeans, but not in Asians (OR 1.156, 95% CI 1.006-1.327, <I>p</I> = 0.041; OR 1.049, 95% CI 0.952-1.156, <I>p</I> = 0.333). The meta-analysis revealed an association between the second allele of the rs2900180 and rs10760130 polymorphisms and RA risk in Europeans (OR 1.224, 95% CI 1.065-1.405, <I>p</I> = 0.004; OR 1.072, 95% CI 1.002-1.147, <I>p</I> = 0.042).</P><P><I>Conclusions</I>: This meta-analysis confirms that the TRAF1-C5 rs10818488, rs3761847, rs2900180 and rs10760130 polymorphisms are associated with RA susceptibility in Europeans.</P>

Comparison of Disease Activity Score 28 Using C-reactive Protein and Disease Activity Score 28 Using Erythrocyte Sedimentation Rate in Assessing Activity and Treatment Response in Rheumatoid Arthritis: A Meta-analysis

( Gwan Gyu Song ),( Young Ho Lee ) 대한류마티스학회 2016 대한류마티스학회지 Vol.23 No.4

Objective. We compared the Disease Activity Score 28 (DAS28) using C-reactive protein (DAS28-CRP) with DAS28 using erythrocyte sedimentation rate (DAS28-ESR) in assessing rheumatoid arthritis (RA) activity and determining European League Against Rheumatism (EULAR) response criteria. Methods. We searched the PubMed, EMBASE, and Cochrane databases and performed a meta-analysis to examine comparisons between DAS28-CRP and DAS28-ESR by RA activity and EULAR response criteria. Results. A total of ten studies were included in this meta-analysis. Significantly more patients were classified as having remission or low disease activity when using DAS28-CRP than when using DAS28-ESR (odds ratio [OR]=1.869, 95% confidence interval [CI]=1.180 to 2.959, p=0.008; OR=1.411, 95% CI=1.256 to 1.586, p=7.0×10^-8), whereas fewer patients were classified as having high disease activity when using DAS28-CRP than when using DAS28-ESR (OR=0.534, 95% CI=0.388 to 0.734, p=1.1×10^-4). More patients were classified as having good response with criteria were based on DAS28-CRP than with DAS28-ESR (OR=1.390, 95% CI=1.183 to 1.632, p=6.10×10^-5). Conclusion. Our meta-analysis demonstrates that DAS28-CRP underestimates disease activity and overestimates response by the EULAR response criteria compared to DAS28-ESR. (J Rheum Dis 2016;23:241-249)

경증 및 중등도 고혈압에서 Captopril 소량요법의 강압효과

송관규(Gwan Gyu Song),박창규(Chang Gyu Park),오동주(Dong Joo Oh),노영무(Young Moo Ro) 대한내과학회 1988 대한내과학회지 Vol.34 No.2

N/A The efficacy and safety of oral captopril, an angiotensin-converting enzyme inhibitor, were in 19 Korea patients (10 males, 9 females) with mild to moderate essential hypertension. The subjects with a sitting blood pressure of 140-189mmHg (systolic) and 95-114mmHg (diastolic) 2 weeks after the first blood pressure measurement while off all antihypertensive agents were enrolled in the study and were received captopril 25 mg bid for 6 weeks, b1ood pressure being measured every 2 weeks. Captopril significantly reduced systolic pressure from 161.6±14.6 to 146.6±15.5mmHg, diastolic pressure from 101.8±6.1 to 90.8±7.9mmHg, and mean pressure from 121.8±4.3 to 109.8±7.9mmHg (mean±SD, P<0.001 vs post-treatment 6th week blood pressure). Fall in systolic and diastolic pressure was 15.5±14.4mmHg and 11.1±9.5mmHg, respectively. In 66.6% diastolic blood pressure and in 37.5% systolic blood pressure were normalized. Side effects were noted in 2 cases (10.5%). One case showed transient elevation of transaminase level and the other headache, These findings suggest that low-dose captopril is an effective and safe first-line monotherapy for mild to moderate eseential hypertension.

전신성 홍반성 낭창 환자에서 유리형 Fas 단백질에 대한 연구

송관규 ( Gwan Gyu Song ),이영호 ( Young Ho Lee ) 대한류마티스학회 1996 대한류마티스학회지 Vol.3 No.1

전신성 홍반성 낭창의 발병기전에 대한 연구의 일환으로 전신성 홍반성 낭창 환자에서 유리형 Fas 단백질의 존재 여부를 확인함에 있다. 대상 및 방법: 30명의 전신성 홍반성 낭창 환자를 대상으로 하였으며 섬유조직염으로 진단받은 11명의 환자를 대조군으로 하였다. 환자의 대조군에서 모두 혈청을 채취하여 70℃의 냉장고에 보관한 후 sandwich ELISA 방법으로 동시에 측정하였다. 결과: 1. 전신성 홍반성 낭창 환자 30명중 6명(20%), 대조군은 11명중 1명(9.%)에서 양성으로 검사되어 전신성 홍반성 낭창 환자에서 양성율이 높은 경향을 보였다(p=0.41). 2. 환자의 연령은 sFas 양성인 군과 음성군간에 차이가 없었으나 sFas 양성군에서 이환기간이 짧고 질병의 활성도도 sFas 양성군에서 의미있게 높았으며 부신피질 호르몬의 투여량도 의미있게 낮았다. 3. 전신성 홍반성 낭창 환자를 다시 이환 기간 1개월 이하와 그 이상으로 나누어보면 1개월 이하의 이환 기간을 가진 12명중 6명(50%)에서 sFas가 검출되었고 1개월 이상의 이환 기간을 가진 18명의 환자에서는 1명도 sFas가 검출되지 않았다(p-0.0008, Table 2). 4. 전신성 홍반성 낭창 환자중 이환 기간이 1개월 이하인 환자 12명을 대상으로 sFas 양성과 음성의 2군으로 나누어 분서하면 2군간의 나이, 부신피질 호르몬의 투여용량, 질병의 활성도는 모두 차이가 없었으나 부신피질 호르몬의 투여용량은 sFas 양성군에서 적은 경향을 보였다(p=0.07). 결론: 이상의 결과로 이환 기간이 짧고 질병의 활동성이 높은 전신성 홍반성 낭창의 일부 환자에서는 혈중 유리형 Fas단백질이 증가되어 있고 유리형 Fas단백질에 의하여 apoptosis의 장애가 발생할 가능성이 있을 것으로 생각된다. Objective: To investigate soluble Fas(sFas) protein in the sera of patients with systemic lupus erythematosus (SLE). Methods: sFas protein was measured by sandwich ELISA method in the sera of 30 patients with SLE (mean age: 27.4±8.46, F:M=29:1) and 11 patients with fibromyalgia (mean age 35.8±11.5, F:M-11:0) as a control group. Results: sFas was elevated in 6 (20%) patients of SLE and 1 (9%) of patients with fibromyalgia (p=0.41). sFas level was correlated with a shorter duration, lower dosage of systemic steroid and higher disease activity in patients with elevated sFas levlel compared to patients with normal serum levels of sFas. All patients with elevated sFas had been diagnosed with SLE for less than 1 month. Fifty % (6 out of 12) patients with SLE for less than 1 month showed elevated sFas in serum. There was no difference of in the age between patients with elevated and normal levels of sFas. Conclusion: These data indicate that elevated sera levels of sFas was associated with the early active phase of disease in some patients with SLE and may play a role in defective apoptosis.

배양된 연골세포에서 각종 Cytokine과 성장인자가 β1-integrin 및 ICAM-1의 발현에 미치는 영향

송관규 ( Gwan Gyu Song ),노영무 ( Young Moo Ro ),유대현 ( Dae Hyu Yoo ),김성윤 ( Seong Yoon Kim ) 대한류마티스학회 1995 대한류마티스학회지 Vol.2 No.1

Objective: The cell-cell and cell-extracellular matrix interactions are critical to the embryogenesis, morphogenesis, maintenance of tissue integrity, and function of cells. This interactions are mediated by membrane glycoproteins called adhesion molecules. βl-integrins are heterodimeric transmembrane glycopro-teins which play critical roles in the ability of cells to elaborate and maintain extracellular matrix. ICAM-l is a sialylated glycoprotein and mediates various cell-cell interactions in immunity and inflammation. Articular cartilage consists of chondrocytes embedded in an extensive extracellular matirx. In normal tissue, the chondrocytes actively effect the stable equili-brium between the synthesis and degradation of matrix components, so that a constant concentration of these components is maintained. In osteoarthritis, the stable equilibrium is disrupted and the rate of loss of proteoglycan exceeds the rate of depositon of newly synthesized moleclues. This equilibrium is influenced by cytokines and growth factors such as IL-I, TNF-α, IGF-1 and TGF-β. Integrins and their ligands may mediate some of the interactions of chondrocytes and cellular matrix, and the cytokines and local growth factors may affect the expression of integrins on chondrocytes. ICAM-1 may mediate interactions with other cells in osteoarthritic joint, and also may be modulated by cytokines and growth factors. The effect of IL-I, TNF-α, IGF-1 and TGF-β in the expression of, β1-integrin (CD29) and ICAM-1(CD54) on chondrocytes was investigated. Methods: Cultured chondrocytes(3rd passages) from 2 osteoarthritc patient were used. Cells were incubated for 24hours with and without IL-1β 25U/ml, IL-l 50U/ml, TNF-α 1ng/ml, TNF-α 10ng/ml, IFN-γ 100U/ml, IGF-1 10ng/ml, IGF-1 50ng/ml, IGF-1 100ng/ml, TGF-β 10ng/ml, and TGF-β 30ng/ml. Chondrocytes were stained with monoclonal antibodies against, β1-integrin (CD29) and ICAM-1 (CD54), and positve cells were counted under the light microscpe. Results: 1) Cultured chondrocytes readily expressed, β1-integrin (82.9%). 2) β1-integrin was down-regulated by IL-1β(75.4%), TNF-α(61.2%), and TGF-β (77.0%), and was slightly up-regulated by IFN-γ(85.0%) and IGF-1 (88.9%). 3) ICAM-1 was presented in only 18.0% of cells. 4) Expression of ICAM-1 was readily up-regulated by IL-1β(84.0%) and TNF-α(80.3%), and mildly up-regulated by IFN-γ(33.0%), IGF-1(35.0%), and TGF-β(29.3%). Conclusions: The presence of, 81-integrin and ICAM-1 on chondrocytes and the modulation of their expression by cytokines and local growth factors suggest that they have important roles in the interaction of chondrocytes with cartilage matrix and with other cells of osteoarthritic joints. Their roles should be elucidated by further researches.

경피증 환자의 폐섬유화에 대한 cyclophosphamide 강압 요법과 소량의 부신피질 호르몬을 경구투여한 병합 요법의 효과에 관한 연구

송관규 ( Gwan Gyu Song ),이영호 ( Young Ho Lee ),심재정 ( Jae Jeong Shim ),강경호 ( Kyung Ho Kang ) 대한류마티스학회 1996 대한류마티스학회지 Vol.3 No.2

Objective: To investigate the efficacy of combined intravenous cyclophophamide pulse and low dose oral prednisolone treatment in patients with systemic sclerosis with interstitial lung disease. Method: Six patients with systemic sclerosis with interstitial lung disease were treated with intravenous infusion of cyclophosphamide (0.75g/m2 body surface area) and low dose oral prednisolone (10mg/day). Results: 1) Respiratory symptoms, cough and dyspnea, were improved in all patients in both frequency and severity. 2) The mean value of FVC, FEVl, and DLCO test showed tendency of increase during the follow up period (upto 24 months) compared to decrease in the past studies. 3) There was no serious side effect during the trreatment. Herpes zoster was developede in 1 patient during treament. Conclusions: Combined intravenous cyclophosphamide pulse and low dose oral prednisolone treatment is effective for the patients with systemic sclerosis with interstitial lung disease. A controlled prospective trial is warranted in patients with systemic sclerosis with interstitial lung disease.

조직 생검으로 확인된 측두동맥염 1 예

송관규(Gwan Gyu Song),정문기(Moon Gi Chung),권오상(Oh Sang Kwon),박창규(Chang Gyu Park),백세현(Sei Hyun Baik),서홍석(Hong Seog Seo),오동주(Dong Joo Oh),이창홍(Chang Hong Lee),원남희(Nam Hee Won) 대한내과학회 1995 대한내과학회지 Vol.48 No.5

N/A Temporal arteritis is an inflammatory disease of the elastic artery with unknown etiology. It usually affects patients over the age of 50, and is often associated with polymyalgia rheumatica. We have experienced a 66-year-old female patient with temporal arteritis who presented as a new onset headache and temporal artery abnormalities. Temporal artery biopsy was performed, which showed typical findings of temporal arteritis. To our knowledge, this is the first case of temporal arteritis in Korea. We hereby report a case of temporal arteritis with a brief review of literature.