Pub Date : 2023-11-01DOI: 10.1142/s2661341723740292
B. Salim, Anum Khan, Haris Gul, Saba Samreen, Shahida Perveen
Background Systemic lupus erythematosus (SLE) has varying clinical and serological features in juvenile and adult-onset disease groups, depending on the ethnicity. Objectives: To compare the disease characteristics of patients with adult-onset (ASLE) and juvenile-onset systemic lupus erythematosus (JSLE). Methods It is a cross-sectional study, carried out at Rheumatology department Fauji Foundation Hospital. 184 SLE patients were included. They were divided into adult (n=152) and juvenile (n=32) group. The clinical and serological features at the time of disease onset were compared between the two groups. Statistical analysis was done using chi square and t-test. Results The mean age was 36.22 ± 11.48 in adults and 19.94 ± 7.17 in the juvenile group (t = 7.71, p<0.001). The duration of disease was 46.05 ± 45.74 months(adult) and 62.43 ± 84.00 months (juvenile). There was no significant difference in disease activity, SLE disease activity index (SLEDAI) was 13 in adult lupus patients and 14.5 in the juvenile, t-value=1.1 and p-value=0.39. Sicca symptoms were significant in the ASLE (p=0.004). Neuropsychiatric manifestations (p=0.03), thrombocytopenia (p=0.048) and low complement levels (0.02) were significantly higher in JSLE. Serological profiles did not differ significantly in the two groups. Conclusion The features of SLE differ in adult and juvenile patients. Neurological involvement and thrombocytopenia were more prevalent in JSLE, whereas sicca symptoms were more frequently found in ASLE.
{"title":"Abstract 13 — Comparison of Clinical and Serological Features in Juvenile and Adult-Onset Systemic Lupus Erythematosus","authors":"B. Salim, Anum Khan, Haris Gul, Saba Samreen, Shahida Perveen","doi":"10.1142/s2661341723740292","DOIUrl":"https://doi.org/10.1142/s2661341723740292","url":null,"abstract":"Background Systemic lupus erythematosus (SLE) has varying clinical and serological features in juvenile and adult-onset disease groups, depending on the ethnicity. Objectives: To compare the disease characteristics of patients with adult-onset (ASLE) and juvenile-onset systemic lupus erythematosus (JSLE). Methods It is a cross-sectional study, carried out at Rheumatology department Fauji Foundation Hospital. 184 SLE patients were included. They were divided into adult (n=152) and juvenile (n=32) group. The clinical and serological features at the time of disease onset were compared between the two groups. Statistical analysis was done using chi square and t-test. Results The mean age was 36.22 ± 11.48 in adults and 19.94 ± 7.17 in the juvenile group (t = 7.71, p<0.001). The duration of disease was 46.05 ± 45.74 months(adult) and 62.43 ± 84.00 months (juvenile). There was no significant difference in disease activity, SLE disease activity index (SLEDAI) was 13 in adult lupus patients and 14.5 in the juvenile, t-value=1.1 and p-value=0.39. Sicca symptoms were significant in the ASLE (p=0.004). Neuropsychiatric manifestations (p=0.03), thrombocytopenia (p=0.048) and low complement levels (0.02) were significantly higher in JSLE. Serological profiles did not differ significantly in the two groups. Conclusion The features of SLE differ in adult and juvenile patients. Neurological involvement and thrombocytopenia were more prevalent in JSLE, whereas sicca symptoms were more frequently found in ASLE.","PeriodicalId":15538,"journal":{"name":"Journal of Clinical Rheumatology and Immunology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139298205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1142/s2661341723740358
Isaac T Cheng, Ho So, C. C. Y. Yip, YING-YING Leung, Kichul Shin, Muhammad Ahmed Saeed, P. Chiowchanwisawakit, M. Hammoudeh, Muhammad Haroon, S. Nallasivan, S. Angkodjojo, James Ho Yin Chung, Mitsumasa Kishimoto, James Wei, L. Tam
Background: Studies have reported that female patients with spondyloarthritis have different disease courses and treatment responses compared to male patients. Whether patients’ sex is associated with a different outcome after receiving one-year of tight control, treat-to-target (T2T) strategy remains uncertain. Thus, this study aimed to evaluate the differences in the clinical response between male and female patients from the APLAR SpA Registry. Methods: Patients who fulfilled the CASPAR 2006 classification criteria for PsA and 2009 ASAS classification for axSpA were recruited. They received 1 year of protocolized treatment aiming at 1) MDA or DAPSA-LDA for PsA patients, and 2) ASDAS-LDA for axSpA patients. Patients were assessed every 3-monthly and treatment was escalated if target was not reached. Results: Ninety-one male (age: 45.6±16.1, 43 PsA, 48 axSpA) and 52 female (age: 49.2±13.4, 36 PsA, 16 axSpA) patients were included. There was no significant difference between the 2 sexes at baseline, except a higher ESR and more severe enthesitis in female patients. During the study period, the use of csDMARDs and NSAIDs decreased slightly, whilst the use of bDMARDs significantly increased across both sexes (Fig. 1a). Considering the whole cohort, there were significant improvement in disease activity in PsA after 1-year and disease activity in axSpA remained low. Despite similar bDMARDs use at 1-year, female PsA patients had a lower MDA achievement rate (36% in female vs 51% in male). Female patients also remained to have a higher physician global assessment score (2.61±1.76 in female vs 1.98±1.57 in male, p=0.03), greater functional impairment (HAQ: 0.54±0.57 in female vs 0.32±0.46 in male, p=0.01) and more severe enthesitis (SPARCC: 0.83±1.67 in female vs 0.16±1.09 in male, p=0.005) at 1-year. There was also a trend of higher perceived disease burden and peripheral involvement in female (Fig. 1b). Conclusion: There may be differential treat-to-target responses between male and female SpA patients. The causes of such differential characteristics should be further explored to potentially implement a sex-specific treat-to-target strategy for spondyloarthritis.
{"title":"Abstract 19 — Treat-to-Target in Spondyloarthritis (SpA): Are There Sex-Related Differential Responses?","authors":"Isaac T Cheng, Ho So, C. C. Y. Yip, YING-YING Leung, Kichul Shin, Muhammad Ahmed Saeed, P. Chiowchanwisawakit, M. Hammoudeh, Muhammad Haroon, S. Nallasivan, S. Angkodjojo, James Ho Yin Chung, Mitsumasa Kishimoto, James Wei, L. Tam","doi":"10.1142/s2661341723740358","DOIUrl":"https://doi.org/10.1142/s2661341723740358","url":null,"abstract":"Background: Studies have reported that female patients with spondyloarthritis have different disease courses and treatment responses compared to male patients. Whether patients’ sex is associated with a different outcome after receiving one-year of tight control, treat-to-target (T2T) strategy remains uncertain. Thus, this study aimed to evaluate the differences in the clinical response between male and female patients from the APLAR SpA Registry. Methods: Patients who fulfilled the CASPAR 2006 classification criteria for PsA and 2009 ASAS classification for axSpA were recruited. They received 1 year of protocolized treatment aiming at 1) MDA or DAPSA-LDA for PsA patients, and 2) ASDAS-LDA for axSpA patients. Patients were assessed every 3-monthly and treatment was escalated if target was not reached. Results: Ninety-one male (age: 45.6±16.1, 43 PsA, 48 axSpA) and 52 female (age: 49.2±13.4, 36 PsA, 16 axSpA) patients were included. There was no significant difference between the 2 sexes at baseline, except a higher ESR and more severe enthesitis in female patients. During the study period, the use of csDMARDs and NSAIDs decreased slightly, whilst the use of bDMARDs significantly increased across both sexes (Fig. 1a). Considering the whole cohort, there were significant improvement in disease activity in PsA after 1-year and disease activity in axSpA remained low. Despite similar bDMARDs use at 1-year, female PsA patients had a lower MDA achievement rate (36% in female vs 51% in male). Female patients also remained to have a higher physician global assessment score (2.61±1.76 in female vs 1.98±1.57 in male, p=0.03), greater functional impairment (HAQ: 0.54±0.57 in female vs 0.32±0.46 in male, p=0.01) and more severe enthesitis (SPARCC: 0.83±1.67 in female vs 0.16±1.09 in male, p=0.005) at 1-year. There was also a trend of higher perceived disease burden and peripheral involvement in female (Fig. 1b). Conclusion: There may be differential treat-to-target responses between male and female SpA patients. The causes of such differential characteristics should be further explored to potentially implement a sex-specific treat-to-target strategy for spondyloarthritis.","PeriodicalId":15538,"journal":{"name":"Journal of Clinical Rheumatology and Immunology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139305850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1142/s2661341723740425
F. AlKindi, Ahmad Chaaban, M. Al Hakim, Abraham George, Nihal AlBashir, Mohamed Saad, M. Budruddin, Imran Khan, Shamma AlNokhatha, Toqa Fahmawee, Hiba Khogali, S. Al-Salam, Y. Boobes
Introduction Familial Mediterranean fever (FMF) is an inherited genetic disorder characterized by recurrent episodes of fever, serositis, arthritis, and skin rash. Uncontrolled disease can lead to amyloid A disposition, nephrotic syndrome and progressive renal failure. Recurrence of AA amyloidosis post kidney transplantation has been reported. Long-term colchicine therapy will reduce the FMF attacks and risk of AA amyloidosis. Although there is high prevalence of FMF in MENA region, the data of end stage renal disease (ESRD) in FMF is limited. We report our center experience. Method A retrospective chart review study was conducted at Tawam Hospital over 12 years (January 2010 to January 2023). We included adult ESRD on hemodialysis with FMF disease and studied their management outcomes. Descriptive analysis was used. Results 1900 ESRD patients were on hemodialysis during study period, and only two patients were diagnosed with FMF and renal amyloidosis. Case 1: A 60-year-old male patient from Syria who is known to have FMF and polycystic kidney disease leading to ESRD. He underwent successful LRD kidney transplantation in 2009. He was on mycophenolic acid: 540 mg, BID, prednisolone: 5 mg, tacrolimus: 1 mg am, 0.5 mg and colchicine 0.5 mg BID. He developed progressive renal allograft dysfunction with evidence of nephrotic syndrome. The renal biopsy revealed recurrence of AA amyloidosis due to FMF in kidney allograft in 2018. He had decline in renal function over years was initiated on hemodialysis on 2022. He developed two attacks of FMF peritonitis while on hemodialysis that responded well to steroid/colchicine therapy. Case 2: 48 years old male, from Egypt, known to have irritable bowel syndrome. He presented to our hospital with bilateral lower limb edema, and progressive shortness of breath for one month. Investigations revealed heavy proteinuria (8.98 g/g Creat) and acute kidney injury. Serology and autoimmune workup were negative. Kidney biopsy showed renal amyloidosis, and chronic tubulointerstitial nephritis with severe interstitial fibrosis (60%). History taken again and was positive for FMF in his uncle. Genetic study and clinical confirmed the diagnosis of FMF. He was started on colchicine, but developed ESRD within 8 months and initiated on hemodialysis. He had attacks of FMF. Conclusion Renal amyloidosis in FMF patient leads to progressive renal failure despite colchicine therapy. In our dialysis cohort over 12 years, only two FMF patients were identified. Colchicine therapy is required in ESRD-FMF in order to managed FMF attacks and prevent other organ AA amyloidosis.
{"title":"Abstract 26 — Clinical Characteristics of Familial Mediterranean: Fever in Hemodialysis Patients","authors":"F. AlKindi, Ahmad Chaaban, M. Al Hakim, Abraham George, Nihal AlBashir, Mohamed Saad, M. Budruddin, Imran Khan, Shamma AlNokhatha, Toqa Fahmawee, Hiba Khogali, S. Al-Salam, Y. Boobes","doi":"10.1142/s2661341723740425","DOIUrl":"https://doi.org/10.1142/s2661341723740425","url":null,"abstract":"Introduction Familial Mediterranean fever (FMF) is an inherited genetic disorder characterized by recurrent episodes of fever, serositis, arthritis, and skin rash. Uncontrolled disease can lead to amyloid A disposition, nephrotic syndrome and progressive renal failure. Recurrence of AA amyloidosis post kidney transplantation has been reported. Long-term colchicine therapy will reduce the FMF attacks and risk of AA amyloidosis. Although there is high prevalence of FMF in MENA region, the data of end stage renal disease (ESRD) in FMF is limited. We report our center experience. Method A retrospective chart review study was conducted at Tawam Hospital over 12 years (January 2010 to January 2023). We included adult ESRD on hemodialysis with FMF disease and studied their management outcomes. Descriptive analysis was used. Results 1900 ESRD patients were on hemodialysis during study period, and only two patients were diagnosed with FMF and renal amyloidosis. Case 1: A 60-year-old male patient from Syria who is known to have FMF and polycystic kidney disease leading to ESRD. He underwent successful LRD kidney transplantation in 2009. He was on mycophenolic acid: 540 mg, BID, prednisolone: 5 mg, tacrolimus: 1 mg am, 0.5 mg and colchicine 0.5 mg BID. He developed progressive renal allograft dysfunction with evidence of nephrotic syndrome. The renal biopsy revealed recurrence of AA amyloidosis due to FMF in kidney allograft in 2018. He had decline in renal function over years was initiated on hemodialysis on 2022. He developed two attacks of FMF peritonitis while on hemodialysis that responded well to steroid/colchicine therapy. Case 2: 48 years old male, from Egypt, known to have irritable bowel syndrome. He presented to our hospital with bilateral lower limb edema, and progressive shortness of breath for one month. Investigations revealed heavy proteinuria (8.98 g/g Creat) and acute kidney injury. Serology and autoimmune workup were negative. Kidney biopsy showed renal amyloidosis, and chronic tubulointerstitial nephritis with severe interstitial fibrosis (60%). History taken again and was positive for FMF in his uncle. Genetic study and clinical confirmed the diagnosis of FMF. He was started on colchicine, but developed ESRD within 8 months and initiated on hemodialysis. He had attacks of FMF. Conclusion Renal amyloidosis in FMF patient leads to progressive renal failure despite colchicine therapy. In our dialysis cohort over 12 years, only two FMF patients were identified. Colchicine therapy is required in ESRD-FMF in order to managed FMF attacks and prevent other organ AA amyloidosis.","PeriodicalId":15538,"journal":{"name":"Journal of Clinical Rheumatology and Immunology","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139293898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1142/s2661341723740218
W. Xie, Zhuoli Zhang
Background In patients with rheumatoid arthritis (RA), glucocorticoids (GC) should be firstly discontinued before considering tapering conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) or other biological agents. We aim to determine risk factors for flare after GC withdrawal in RA patients undergoing csDMARDs. Method RA patients who discontinued GC with continuation of csDMARD were selected from a longitudinal real-world cohort. Established RA was defined as disease duration over 12 months. Dissatisfied RA control was defined as the proportion of simplified disease activity index (SDAI)-based remission time to total time from GC initiation to discontinuation less than 50%. Logistic regression was used to analyze the independent risk factors for flare after GC discontinuation and results were expressed as odds ratio (OR). Results There were 115 eligible RA patients discounted GC with continuation of csDMARDs (methotrexate: 80%; hydroxychloroquine: 61%; csDMARDs combination: 79%). Of these, 24 patients experienced flare after GC discontinuation. Compared with relapse-free patients, flare patients were more likely to have established RA (75% vs. 49%, p=0.025), higher median cumulative prednisolone dosages (3.3g vs. 2.2g, p=0.004), and higher proportion of dissatisfied RA control during GC usage (66% vs. 33%, p=0.038). In multivariate analysis, significantly increased flare risk was predicted by established RA (OR 2.93 [1.02-8.43]), cumulative prednisolone dose > 2.5g (OR 3.69 [1.34-10.19]) and dissatisfied RA control (OR 3.00 [1.09-8.30]). Flare risk was increased with increases in number of risk factors, with highest OR of 11.56 in patients with three risk factors (p for trend=0.002). Conclusions Flare following GC withdrawal is not common in RA patients with undergoing csDMARDs therapy. Established RA, higher cumulative GC dose and dissatisfied RA control before GC discontinuation are important factors associated with flare after GC withdrawal.
背景 对于类风湿性关节炎（RA）患者，在考虑减量使用常规合成改善病情抗风湿药物（csDMARD）或其他生物制剂之前，应首先停用糖皮质激素（GC）。我们旨在确定接受 csDMARDs 治疗的 RA 患者停用 GC 后病情复发的风险因素。方法 从一个纵向真实世界队列中选取停用 GC 并继续使用 csDMARD 的 RA 患者。病程超过 12 个月即为已确立的 RA。对 RA 控制不满意的定义是，基于简化疾病活动指数（SDAI）的缓解时间占从开始使用 GC 到停药的总时间的比例低于 50%。采用逻辑回归分析停用 GC 后复发的独立风险因素，结果以几率比（OR）表示。结果 有115名符合条件的RA患者在继续使用csDMARDs（甲氨蝶呤：80%；羟氯喹：61%；csDMARDs联合用药：79%）的情况下对GC进行了折扣。其中，24 名患者在停用 GC 后复发。与未复发的患者相比，复发患者更有可能已建立RA（75%对49%，P=0.025），中位泼尼松龙累积剂量更高（3.3克对2.2克，P=0.004），使用GC期间对RA控制不满意的比例更高（66%对33%，P=0.038）。在多变量分析中，已确诊的 RA（OR 2.93 [1.02-8.43]）、泼尼松龙累积剂量大于 2.5 克（OR 3.69 [1.34-10.19]）和 RA 控制不满意（OR 3.00 [1.09-8.30]）均可显著增加复发风险。随着风险因素数量的增加，复发风险也随之增加，具有三个风险因素的患者的 OR 值最高，为 11.56（趋势 p=0.002）。结论 在接受 csDMARDs 治疗的 RA 患者中，停用 GC 后发生发炎的情况并不常见。已确诊的RA、较高的GC累积剂量以及停用GC前对RA控制不满意是与停用GC后复发相关的重要因素。
{"title":"Abstract 5 — Prediction of Flare Following Glucocorticoids Withdrawal in Rheumatoid Arthritis Patients with Continuation of csDMARDs: A Real-Life Study","authors":"W. Xie, Zhuoli Zhang","doi":"10.1142/s2661341723740218","DOIUrl":"https://doi.org/10.1142/s2661341723740218","url":null,"abstract":"Background In patients with rheumatoid arthritis (RA), glucocorticoids (GC) should be firstly discontinued before considering tapering conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) or other biological agents. We aim to determine risk factors for flare after GC withdrawal in RA patients undergoing csDMARDs. Method RA patients who discontinued GC with continuation of csDMARD were selected from a longitudinal real-world cohort. Established RA was defined as disease duration over 12 months. Dissatisfied RA control was defined as the proportion of simplified disease activity index (SDAI)-based remission time to total time from GC initiation to discontinuation less than 50%. Logistic regression was used to analyze the independent risk factors for flare after GC discontinuation and results were expressed as odds ratio (OR). Results There were 115 eligible RA patients discounted GC with continuation of csDMARDs (methotrexate: 80%; hydroxychloroquine: 61%; csDMARDs combination: 79%). Of these, 24 patients experienced flare after GC discontinuation. Compared with relapse-free patients, flare patients were more likely to have established RA (75% vs. 49%, p=0.025), higher median cumulative prednisolone dosages (3.3g vs. 2.2g, p=0.004), and higher proportion of dissatisfied RA control during GC usage (66% vs. 33%, p=0.038). In multivariate analysis, significantly increased flare risk was predicted by established RA (OR 2.93 [1.02-8.43]), cumulative prednisolone dose > 2.5g (OR 3.69 [1.34-10.19]) and dissatisfied RA control (OR 3.00 [1.09-8.30]). Flare risk was increased with increases in number of risk factors, with highest OR of 11.56 in patients with three risk factors (p for trend=0.002). Conclusions Flare following GC withdrawal is not common in RA patients with undergoing csDMARDs therapy. Established RA, higher cumulative GC dose and dissatisfied RA control before GC discontinuation are important factors associated with flare after GC withdrawal.","PeriodicalId":15538,"journal":{"name":"Journal of Clinical Rheumatology and Immunology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139294423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1142/s2661341723740401
M. Rasool, Ann Miriam Jose
Background Rheumatoid arthritis (RA) is an autoimmune disorder characterized by destructive polyarthritis and extra-articular manifestations. Myricetin, a flavonoid, possesses several pharmacological benefits, including anti-arthritic effects. However, the specific role and molecular basis of myricetin in IL-21 mediated T follicular helper (Tfh) cell differentiation and activation of fibroblast-like synoviocytes (FLS) in RA remain unknown. In the present study, we decoded the therapeutic intervention of myricetin as an anti-arthritic small-molecule drug for impeding Tfh cell differentiation and for abrogating the RA-FLS-transformed aggressive phenotype. Methods In vivo experiments were conducted using an adjuvant-induced arthritis animal model to evaluate the effects of myricetin on Tfh cell differentiation, IL-21 production, choline kinase (ChoK) activation, and the JAK/STAT signaling pathway. Results In this study, myricetin was found to significantly inhibit the interaction between IL-21 and IL-21R, and at the molecular level, it suppressed JAK/STAT signaling and the downstream transcription factor Bcl-6, which decreased Tfh cell differentiation. Additionally, myricetin suppressed the IL-21-induced hyperproliferation of AIA-FLSs by downregulating the ChoK signaling cascade (Ras, Ral-GDS, and PI3K). Myricetin treatment reduced ChoK enzymatic activity and the proliferative, migratory, and invasive properties of AIA-FLS. Conclusion Taken together, our results demonstrated that myricetin is a promising therapeutic compound that abates IL-21-induced Tfh cell differentiation and the invasive behavior of AIA-FLS.
{"title":"Abstract 24 — Myricetin Impedes Tfh Cell Differentiation and Ameliorates the Tumorigenic Phenotype of Adjuvant-Induced Arthritis FLS in Rheumatoid Arthritis","authors":"M. Rasool, Ann Miriam Jose","doi":"10.1142/s2661341723740401","DOIUrl":"https://doi.org/10.1142/s2661341723740401","url":null,"abstract":"Background Rheumatoid arthritis (RA) is an autoimmune disorder characterized by destructive polyarthritis and extra-articular manifestations. Myricetin, a flavonoid, possesses several pharmacological benefits, including anti-arthritic effects. However, the specific role and molecular basis of myricetin in IL-21 mediated T follicular helper (Tfh) cell differentiation and activation of fibroblast-like synoviocytes (FLS) in RA remain unknown. In the present study, we decoded the therapeutic intervention of myricetin as an anti-arthritic small-molecule drug for impeding Tfh cell differentiation and for abrogating the RA-FLS-transformed aggressive phenotype. Methods In vivo experiments were conducted using an adjuvant-induced arthritis animal model to evaluate the effects of myricetin on Tfh cell differentiation, IL-21 production, choline kinase (ChoK) activation, and the JAK/STAT signaling pathway. Results In this study, myricetin was found to significantly inhibit the interaction between IL-21 and IL-21R, and at the molecular level, it suppressed JAK/STAT signaling and the downstream transcription factor Bcl-6, which decreased Tfh cell differentiation. Additionally, myricetin suppressed the IL-21-induced hyperproliferation of AIA-FLSs by downregulating the ChoK signaling cascade (Ras, Ral-GDS, and PI3K). Myricetin treatment reduced ChoK enzymatic activity and the proliferative, migratory, and invasive properties of AIA-FLS. Conclusion Taken together, our results demonstrated that myricetin is a promising therapeutic compound that abates IL-21-induced Tfh cell differentiation and the invasive behavior of AIA-FLS.","PeriodicalId":15538,"journal":{"name":"Journal of Clinical Rheumatology and Immunology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139297609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1142/s2661341723740413
F. AlKindi, Nihal AlBashir, Ahmad Chaaban, Abraham George, Mohamed Saad, M. Hakim, M. Budruddin, Imran Khan, Y. Boobes
Background Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by acute symmetrical synovitis, and pitting edema involving, the dorsal part of hands and feet. It affects more men aged more than 50 years. The inflammatory markers are usually elevated, with negative rheumatoid factor. The underlying etiology is not clear but has been associated with drugs exposure, infections, malignancy in 30% of cases, and coexist with other autoimmune diseases. The clinical course is benign with significant improvement to low-dose prednisolone therapy for 2 to 3 months. It has been rarely reported in dialysis patients. Methods and case description A 54 years old male, known to have long standing uncontrolled diabetes mellitus, hypertension, chronic kidney disease and diabetic retinopathy. Recently, he was treated for left foot cellulitis and advanced renal failure (813 micromol/L) initiated on hemodialysis. He presented one week later with progressive painful bilateral upper limb and lower limb pitting edema, with limited range of movement in hands and reduce urine output. He was resumed on hemodialysis for management of volume overload. Despite removal of almost 12 liters of fluids during consecutive dialysis sessions and improvement of lower limb edema, his bilateral hand edema was persistence with pain and limited movement. Further investigations were done to evaluate for rheumatological condition. Results Hand X ray was normal and ultrasound of the hand revealed features of synovitis, diffuse subcutaneous oedema and possible cellulitis. He was started on IV antibiotics without major improvement and blood culture was negative. CT chest showed left pleural effusion. The ESR was elevated 120, while serology for HBV. HCV, HIV, and parvovirus were negative. In addition, the autoimmune workup were negative (CCP, RF, ANA, ANCA, C3, C4, ACEI). He was diagnosed with remitting seronegative symmetric synovitis with pitting edema (RS3PE). He was treated with IV hydrocortisone once 100 mg, followed by oral prednisolone 10 mg for 5 days with dramatic improvement in bilateral hand edema and movement. He had hyperglycemia steroid related managed with adjustment of insulin therapy. At follow up in 1 week, patient regain full function of both hands, and he was on regular hemodialysis trice per week. Conclusion RS3PE is rare in hemodialysis patients, with favorable response to steroid therapy. We used shorter duration of 5 days steroid therapy with complete recovery and no recurrence at 1 year follow up. Screening for underlying autoimmune, infection or malignancy in RS3PE is essential.
{"title":"Abstract 25 — Remitting Seronegative Symmetric Synovitis with Pitting Edema (RS3PE) in Dialysis Patient","authors":"F. AlKindi, Nihal AlBashir, Ahmad Chaaban, Abraham George, Mohamed Saad, M. Hakim, M. Budruddin, Imran Khan, Y. Boobes","doi":"10.1142/s2661341723740413","DOIUrl":"https://doi.org/10.1142/s2661341723740413","url":null,"abstract":"Background Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by acute symmetrical synovitis, and pitting edema involving, the dorsal part of hands and feet. It affects more men aged more than 50 years. The inflammatory markers are usually elevated, with negative rheumatoid factor. The underlying etiology is not clear but has been associated with drugs exposure, infections, malignancy in 30% of cases, and coexist with other autoimmune diseases. The clinical course is benign with significant improvement to low-dose prednisolone therapy for 2 to 3 months. It has been rarely reported in dialysis patients. Methods and case description A 54 years old male, known to have long standing uncontrolled diabetes mellitus, hypertension, chronic kidney disease and diabetic retinopathy. Recently, he was treated for left foot cellulitis and advanced renal failure (813 micromol/L) initiated on hemodialysis. He presented one week later with progressive painful bilateral upper limb and lower limb pitting edema, with limited range of movement in hands and reduce urine output. He was resumed on hemodialysis for management of volume overload. Despite removal of almost 12 liters of fluids during consecutive dialysis sessions and improvement of lower limb edema, his bilateral hand edema was persistence with pain and limited movement. Further investigations were done to evaluate for rheumatological condition. Results Hand X ray was normal and ultrasound of the hand revealed features of synovitis, diffuse subcutaneous oedema and possible cellulitis. He was started on IV antibiotics without major improvement and blood culture was negative. CT chest showed left pleural effusion. The ESR was elevated 120, while serology for HBV. HCV, HIV, and parvovirus were negative. In addition, the autoimmune workup were negative (CCP, RF, ANA, ANCA, C3, C4, ACEI). He was diagnosed with remitting seronegative symmetric synovitis with pitting edema (RS3PE). He was treated with IV hydrocortisone once 100 mg, followed by oral prednisolone 10 mg for 5 days with dramatic improvement in bilateral hand edema and movement. He had hyperglycemia steroid related managed with adjustment of insulin therapy. At follow up in 1 week, patient regain full function of both hands, and he was on regular hemodialysis trice per week. Conclusion RS3PE is rare in hemodialysis patients, with favorable response to steroid therapy. We used shorter duration of 5 days steroid therapy with complete recovery and no recurrence at 1 year follow up. Screening for underlying autoimmune, infection or malignancy in RS3PE is essential.","PeriodicalId":15538,"journal":{"name":"Journal of Clinical Rheumatology and Immunology","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139298052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1142/s2661341723740371
Chi Ngai Lo, Victoria Yu En Teo, Nur Farah Ain Binte Abdul Manaff, Tessa Chu Yu Seow, Bernard Pui Lam Leung
Background Non-specific neck and shoulder pain is a prevalent condition among working adults. The surge in remote work and online activities following the COVID-19 pandemic has raised concerns about the potential increase in such pain due to prolonged usage of electronic devices. However, recent literature has introduced the possibility that desk-bound computer work may not necessarily correlate with neck and shoulder pain. This study aims to explore the relationship between the severity of neck and shoulder pain and the duration of electric device usage, alongside other lifestyle factors. Methods An online survey was distributed through email and advertisements to individuals aged 21 and above in Singapore. The survey collected data on participant demographics, the extent of neck and shoulder pain experienced, the duration of computer and smartphone usage, as well as lifestyle factors like sleep duration and exercise frequency. The Institutional Review Board approval number of this study is 2023014. Results A total of 268 valid responses were collected, comprising 182 participants experiencing neck and shoulder pain (I group) and 86 participants without such pain (C group). Both groups exhibited similar demographics. Notably, a significant difference was identified in the exercise frequency per week (I = 2.17 days; C = 2.95 days, p < 0.01), while the difference in sitting duration approached statistical significance (I = 7.13 hrs; C = 6.38 hrs, p = 0.085). No statistically significant differences were observed in the duration of smartphone usage (I = 5.19 hrs; C: 4.62 hrs, p = 0.18), computer use (I = 6.24 hrs; C = 5.94 hrs, p = 0.51), and average daily exercise time (I = 1.87 hrs; C = 1.85 hrs, p = 0.99). Within the group experiencing neck and shoulder pain, a significant correlation emerged between pain levels and age (r = 0.19, p = 0.01). Conversely, no significant correlations were detected between pain levels and computer or smartphone usage duration, prolonged sitting, sleep duration, exercise frequency or duration. Conclusion In this ongoing study, preliminary findings indicate that the existence of neck and shoulder pain does not exhibit a significant association with the duration of sitting work, smartphone or computer use. Interestingly, the exercise frequency might have a potential relationship with neck and shoulder pain. Notably, our data demonstrates a weak yet statistically significant correlation between the severity of neck and shoulder pain and the age of participants but not other lifestyle factors.
{"title":"Abstract 21 — A Cross-Sectional Study on the Prevalence of Non-Specific Neck Pain and Its Association with Lifestyle Factors","authors":"Chi Ngai Lo, Victoria Yu En Teo, Nur Farah Ain Binte Abdul Manaff, Tessa Chu Yu Seow, Bernard Pui Lam Leung","doi":"10.1142/s2661341723740371","DOIUrl":"https://doi.org/10.1142/s2661341723740371","url":null,"abstract":"Background Non-specific neck and shoulder pain is a prevalent condition among working adults. The surge in remote work and online activities following the COVID-19 pandemic has raised concerns about the potential increase in such pain due to prolonged usage of electronic devices. However, recent literature has introduced the possibility that desk-bound computer work may not necessarily correlate with neck and shoulder pain. This study aims to explore the relationship between the severity of neck and shoulder pain and the duration of electric device usage, alongside other lifestyle factors. Methods An online survey was distributed through email and advertisements to individuals aged 21 and above in Singapore. The survey collected data on participant demographics, the extent of neck and shoulder pain experienced, the duration of computer and smartphone usage, as well as lifestyle factors like sleep duration and exercise frequency. The Institutional Review Board approval number of this study is 2023014. Results A total of 268 valid responses were collected, comprising 182 participants experiencing neck and shoulder pain (I group) and 86 participants without such pain (C group). Both groups exhibited similar demographics. Notably, a significant difference was identified in the exercise frequency per week (I = 2.17 days; C = 2.95 days, p < 0.01), while the difference in sitting duration approached statistical significance (I = 7.13 hrs; C = 6.38 hrs, p = 0.085). No statistically significant differences were observed in the duration of smartphone usage (I = 5.19 hrs; C: 4.62 hrs, p = 0.18), computer use (I = 6.24 hrs; C = 5.94 hrs, p = 0.51), and average daily exercise time (I = 1.87 hrs; C = 1.85 hrs, p = 0.99). Within the group experiencing neck and shoulder pain, a significant correlation emerged between pain levels and age (r = 0.19, p = 0.01). Conversely, no significant correlations were detected between pain levels and computer or smartphone usage duration, prolonged sitting, sleep duration, exercise frequency or duration. Conclusion In this ongoing study, preliminary findings indicate that the existence of neck and shoulder pain does not exhibit a significant association with the duration of sitting work, smartphone or computer use. Interestingly, the exercise frequency might have a potential relationship with neck and shoulder pain. Notably, our data demonstrates a weak yet statistically significant correlation between the severity of neck and shoulder pain and the age of participants but not other lifestyle factors.","PeriodicalId":15538,"journal":{"name":"Journal of Clinical Rheumatology and Immunology","volume":"399 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139304208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1142/s2661341723740279
Myun Soo Kim, Sunyoung Park, Chang Kyu Gu
Background KINE-101, a novel synthetic nonapeptide, is being developed for the treatment of rheumatoid arthritis with a distinctive mode of action. A study using a collagen-induced arthritis (CIA) mouse model showed that KINE-101 suppressed cartilage damage through inhibiting osteoclastogenesis. KINE-101 showed its therapeutic effects in suppressing auto-immune responses by activating Regulatory T cells (Tregs), a specialized subpopulation of T cells, in in-vivo studies using mouse models of RA. Following the in-vivo studies, the phase 1 clinical study for KINE-101 was conducted to assess the safety and tolerability in healthy subjects in the US. Methods Total 40 healthy subjects were enrolled to assign in 5 cohorts. Each cohort included 8 subjects composed of 6 active and 2 placebo treatment. The subjects of first 4 cohorts were administrated with 10, 30, 100, 300 mg of KINE-101 by intravenous (IV) infusion as single ascending doses (SAD), and the Cohort 5 subjects were subcutaneously (SC) injected with 96.8 mg of KINE-101. Results Except for 2 subjects in placebo group, all subjects completed the study. All the randomized subjects were included in the safety evaluation. No deaths, SAEs (Serious Adverse Events), or AEs (Adverse Events) leading to discontinuation were reported during the study periods. While total 9 TEAEs (Treatment-Emergent Adverse Events) were reported, all were assessed as mild. It included 3 headaches, 1 catheter site edema, 1 contusion and 1 nasal congestion in the treatment group, and 1 catheter site pain, 1 oral contusion and 1 COVID-19 infection in the placebo group. Oral contusion and COVID-19 occurred in the same subject, and all the other events were singular TEAEs reported in individual subjects. No injection site reactions were reported and no clinically significant changes in any laboratory values were noted. In terms of pharmacokinetic (PK) profile, KINE-101 was observed in the blood samples during and up to 5 minutes after infusion. Conclusion In the phase I clinical study, Treg activator KINE-101 demonstrated a favorable safety and tolerability profile. The most common AEs were headaches reported in 3 subjects, but all were mild and transient events. As typically seen in peptide drugs, KINE-101 has a short half-life. However, given that KINE-101 uses Treg as a proxy to exerts anti-inflammatory effects, its pharmacodynamic (PD) activity is likely to last longer. The next stage for KINE-101 will proceed to oral formulation and the Phase 2 clinical study in RA patients.
{"title":"Abstract 11 — Development of a Novel Treg Activator KINE-101 for a New Treatment Option for Rheumatoid Arthritis","authors":"Myun Soo Kim, Sunyoung Park, Chang Kyu Gu","doi":"10.1142/s2661341723740279","DOIUrl":"https://doi.org/10.1142/s2661341723740279","url":null,"abstract":"Background KINE-101, a novel synthetic nonapeptide, is being developed for the treatment of rheumatoid arthritis with a distinctive mode of action. A study using a collagen-induced arthritis (CIA) mouse model showed that KINE-101 suppressed cartilage damage through inhibiting osteoclastogenesis. KINE-101 showed its therapeutic effects in suppressing auto-immune responses by activating Regulatory T cells (Tregs), a specialized subpopulation of T cells, in in-vivo studies using mouse models of RA. Following the in-vivo studies, the phase 1 clinical study for KINE-101 was conducted to assess the safety and tolerability in healthy subjects in the US. Methods Total 40 healthy subjects were enrolled to assign in 5 cohorts. Each cohort included 8 subjects composed of 6 active and 2 placebo treatment. The subjects of first 4 cohorts were administrated with 10, 30, 100, 300 mg of KINE-101 by intravenous (IV) infusion as single ascending doses (SAD), and the Cohort 5 subjects were subcutaneously (SC) injected with 96.8 mg of KINE-101. Results Except for 2 subjects in placebo group, all subjects completed the study. All the randomized subjects were included in the safety evaluation. No deaths, SAEs (Serious Adverse Events), or AEs (Adverse Events) leading to discontinuation were reported during the study periods. While total 9 TEAEs (Treatment-Emergent Adverse Events) were reported, all were assessed as mild. It included 3 headaches, 1 catheter site edema, 1 contusion and 1 nasal congestion in the treatment group, and 1 catheter site pain, 1 oral contusion and 1 COVID-19 infection in the placebo group. Oral contusion and COVID-19 occurred in the same subject, and all the other events were singular TEAEs reported in individual subjects. No injection site reactions were reported and no clinically significant changes in any laboratory values were noted. In terms of pharmacokinetic (PK) profile, KINE-101 was observed in the blood samples during and up to 5 minutes after infusion. Conclusion In the phase I clinical study, Treg activator KINE-101 demonstrated a favorable safety and tolerability profile. The most common AEs were headaches reported in 3 subjects, but all were mild and transient events. As typically seen in peptide drugs, KINE-101 has a short half-life. However, given that KINE-101 uses Treg as a proxy to exerts anti-inflammatory effects, its pharmacodynamic (PD) activity is likely to last longer. The next stage for KINE-101 will proceed to oral formulation and the Phase 2 clinical study in RA patients.","PeriodicalId":15538,"journal":{"name":"Journal of Clinical Rheumatology and Immunology","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139305449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1142/s2661341723740140
Keigo Ikeda
While magnetic resonance imaging (MRI) is the most established imaging modality to assess autoimmune myositis (AIM), there is a need for less expensive and more accessible tools. To analyze whether there is sufficient data from published literature to demonstrate that ultrasound presents good metric properties (truth, discrimination and feasibility) in AIM, the OMERACT ultrasound group for myositis performed a systematic literature review. The inclusion criteria required original research involving adult humans, reported in English, assessing ultrasound and elastography in patients with an AIM. Conference abstracts and computer-assisted diagnostics that focused on technique and not ultrasound domains were excluded. Approximately 2670 articles were identified. 41 full-text articles were included in the final analysis. There were 551 AIM patients studied. Eighteen studies (43.9%) had a control group, of which 15 (63.3%) were healthy controls. The age of participants (including controls) varied from 18 to 86 years, and most were females (59%). Diagnosis of AIM was largely biopsy-proven, although some were derived through clinical presentation, positive clinical imaging (ultrasound or otherwise) and/or electromyography and steroid responsiveness. The features examined with ultrasound in the 41 included articles consisted of: muscle echogenicity, bulk, atrophy, architecture, power Doppler, perfusion characteristics, shear wave modulus, shear wave velocity, elasticity index and fasciculations. 12 studies (29.2%) used quantitative methods to assess these characteristics, whilst others used semi-quantitative, dichotomous/binary and descriptive scoring systems. Criterion validity was met in 14 studies (12/14, 85.7%) and construct validity in 22 studies (22/25, 88.0%). Most published articles reported Level 3b to Level 5 evidence with varying degrees of bias. There was only one longitudinal study examining discrimination. Reliability and feasibility were under-reported. This was the first systematic review studying the utility of ultrasound in AIM, which suggested some evidence for criterion and construct validity. Further validation processes are underway.
{"title":"Symposium 5","authors":"Keigo Ikeda","doi":"10.1142/s2661341723740140","DOIUrl":"https://doi.org/10.1142/s2661341723740140","url":null,"abstract":"While magnetic resonance imaging (MRI) is the most established imaging modality to assess autoimmune myositis (AIM), there is a need for less expensive and more accessible tools. To analyze whether there is sufficient data from published literature to demonstrate that ultrasound presents good metric properties (truth, discrimination and feasibility) in AIM, the OMERACT ultrasound group for myositis performed a systematic literature review. The inclusion criteria required original research involving adult humans, reported in English, assessing ultrasound and elastography in patients with an AIM. Conference abstracts and computer-assisted diagnostics that focused on technique and not ultrasound domains were excluded. Approximately 2670 articles were identified. 41 full-text articles were included in the final analysis. There were 551 AIM patients studied. Eighteen studies (43.9%) had a control group, of which 15 (63.3%) were healthy controls. The age of participants (including controls) varied from 18 to 86 years, and most were females (59%). Diagnosis of AIM was largely biopsy-proven, although some were derived through clinical presentation, positive clinical imaging (ultrasound or otherwise) and/or electromyography and steroid responsiveness. The features examined with ultrasound in the 41 included articles consisted of: muscle echogenicity, bulk, atrophy, architecture, power Doppler, perfusion characteristics, shear wave modulus, shear wave velocity, elasticity index and fasciculations. 12 studies (29.2%) used quantitative methods to assess these characteristics, whilst others used semi-quantitative, dichotomous/binary and descriptive scoring systems. Criterion validity was met in 14 studies (12/14, 85.7%) and construct validity in 22 studies (22/25, 88.0%). Most published articles reported Level 3b to Level 5 evidence with varying degrees of bias. There was only one longitudinal study examining discrimination. Reliability and feasibility were under-reported. This was the first systematic review studying the utility of ultrasound in AIM, which suggested some evidence for criterion and construct validity. Further validation processes are underway.","PeriodicalId":15538,"journal":{"name":"Journal of Clinical Rheumatology and Immunology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139296433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1142/s266134172374022x
W. Xie, Yue Hou, Zhuoli Zhang
Background Dysregulation of several inflammatory cytokines including tumor necrosis factor (TNF) in dementia patients has also been identified as a key factor in the pathogenesis of rheumatoid arthritis (RA). We aimed to investigate the association of disease-modifying anti-rheumatic drugs (DMARDs) therapy for RA with risk of incident dementia. Methods Electronic database searches of PubMed, EMBASE and Cochrane Library were performed. Observational studies that assessed the association of dementia with DMARDs in RA were included. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used as summary statistic. The certainty of evidence using the GRADE system. Results Fourteen studies involving 940,442 patients with RA were included. Pooled RR for developing dementia was 0.76 (95%CI 0.72-0.80) in patients taking biological DMARDs overall versus those taking conventional synthetic DMARDs, with 24% for TNF inhibitors (RR 0.76, 95%CI 0.71-0.82), 24% for non-TNF biologics (RR 0.76, 95%CI 0.70-0.83), separately. There was a significant subgroup effect among different types of TNF inhibitors (RR 0.58, 0.65, 0.80 for etanercept, adalimumab, infliximab, respectively; P-value between groups=0.002). However, compared with nonusers of DMARDs or investigative treatment, no significant effect on dementia incidence was observed in those receiving conventional synthetic DMARDs overall (RR 0.84, 95%CI 0.59-1.20), methotrexate (RR 0.78, 95%CI 0.54-1.12), hydroxychloroquine (RR 0.95, 95%CI 0.63-1.44), except for sulfasalazine (RR 1.27, 95%CI 1.06-1.50). Conclusions Biological DMARDs for RA are associated with decreased dementia risk, while protective effect is not observed in conventional synthetic DMARDs. Controlled clinical trials on TNF inhibitors is necessary to test their neuroprotective potentials.
{"title":"Abstract 6 — Are Disease-Modifying Antirheumatic Drugs: for Rheumatoid Arthritis Associated with a Lower Risk of Dementia? A Systematic Review with Meta-Analysis","authors":"W. Xie, Yue Hou, Zhuoli Zhang","doi":"10.1142/s266134172374022x","DOIUrl":"https://doi.org/10.1142/s266134172374022x","url":null,"abstract":"Background Dysregulation of several inflammatory cytokines including tumor necrosis factor (TNF) in dementia patients has also been identified as a key factor in the pathogenesis of rheumatoid arthritis (RA). We aimed to investigate the association of disease-modifying anti-rheumatic drugs (DMARDs) therapy for RA with risk of incident dementia. Methods Electronic database searches of PubMed, EMBASE and Cochrane Library were performed. Observational studies that assessed the association of dementia with DMARDs in RA were included. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used as summary statistic. The certainty of evidence using the GRADE system. Results Fourteen studies involving 940,442 patients with RA were included. Pooled RR for developing dementia was 0.76 (95%CI 0.72-0.80) in patients taking biological DMARDs overall versus those taking conventional synthetic DMARDs, with 24% for TNF inhibitors (RR 0.76, 95%CI 0.71-0.82), 24% for non-TNF biologics (RR 0.76, 95%CI 0.70-0.83), separately. There was a significant subgroup effect among different types of TNF inhibitors (RR 0.58, 0.65, 0.80 for etanercept, adalimumab, infliximab, respectively; P-value between groups=0.002). However, compared with nonusers of DMARDs or investigative treatment, no significant effect on dementia incidence was observed in those receiving conventional synthetic DMARDs overall (RR 0.84, 95%CI 0.59-1.20), methotrexate (RR 0.78, 95%CI 0.54-1.12), hydroxychloroquine (RR 0.95, 95%CI 0.63-1.44), except for sulfasalazine (RR 1.27, 95%CI 1.06-1.50). Conclusions Biological DMARDs for RA are associated with decreased dementia risk, while protective effect is not observed in conventional synthetic DMARDs. Controlled clinical trials on TNF inhibitors is necessary to test their neuroprotective potentials.","PeriodicalId":15538,"journal":{"name":"Journal of Clinical Rheumatology and Immunology","volume":"224 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139303315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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