scholarly journals POS0455 EFFECT OF ANTI-Ro/SSA ANTIBODIES FOR TREATMENT RESPONSE TO METHOTREXATE IN RHEUMATOID ARTHRITIS: A RETROSPECTIVE MULTICENTER OBSERVATIONAL STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 458.1-458
Author(s):  
R. Yokochi ◽  
H. Tamai ◽  
T. Kido ◽  
Y. Yagyu ◽  
D. Waki ◽  
...  

Background:Several previous observational studies have suggested that patients with anti-Ro/SSA antibody-positive rheumatoid arthritis (RA) may respond poorly to treatment, including tumor necrosis factor inhibitors1. However, its influence on methotrexate (MTX) treatment, which is the anchor drug of treat-to-target strategy in RA treatment, remains unclear.Objectives:We compared the clinical response to MTX in both anti-Ro/SSA antibody-positive and -negative patients with MTX-naiive RA and investigated the reasons for the difference in response.Methods:We recruited 210 consecutive patients with RA who were newly started on MTX in this retrospective cohort study. The effect of the presence of anti-Ro/SSA antibodies on achieving low disease activity (LDA) of DAS28-CRP at six months after initiating MTX was investigated by using logistic regression analysis. CDAI, SDAI, concomitant using DMARDs and painkillers, patient’s and evaluator’s VAS, tender joint counts, and swollen joint counts at six months were also compared between the anti-Ro/SSA-positive patients and -negative patients. Missing data were imputed by using multiple imputations before multivariate analysis.Results:32 anti-Ro/SSA antibody-positive patients and 178 anti-Ro/SSA antibody-negative patients were included. The rate of achieving DAS28-LDA at six months was significantly lower in the anti-Ro/SSA antibody-positive patients than those in the anti-Ro/SSA antibody-negative patients (56.2% versus 75.8%, P=0.03). in the logistic regression analysis, the presence of anti-Ro/SSA antibodies was an independent negative predictor for achieving DAS-28-LDA at six months (OR:0.431, 95%CI: 0.190-0.978, P=0.044) (Table1). Anti-Ro/SSA antibody-positive patients had significantly higher patient’s VAS at six months (median [IQR]: 22 [15-41] vs 19 [5-30], P=0.038), and prescribed NSAIDs (37.5% vs 18.0%, P=0.018). CDAI and SDAI after six months were not significantly different between the group.Conclusion:The presence of anti-Ro/SSA antibodies might be one of the predictive factors for the insufficient response to treat to target strategy in RA treatment. Residual pain was suspected as one of the mechanisms contributing to the lesser clinical response of MTX in anti-Ro antibody-positive RA.References:[1]Ran Matsudaira wt al. J Rheumatol 2011;38(11):2346-54Table 1.Logistic regression analysis for the rate of achieving DAS28 low disease activity at six months.Risk factor Odds ratio95%CIP valueAge at onset0.9930.968-1.0180.586Sex (woman)0.6430.300-1.3840.258RF-positive1.9620.853-4.5110.112ACPA-positive0.5520.225-1.3510.192Anti-Ro/SSA antibody-positive0.4310.190-0.9780.044Disclosure of Interests:None declared

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1406.1-1407
Author(s):  
S. H. Nam ◽  
J. S. Lee ◽  
S. J. Choi ◽  
W. J. Seo ◽  
J. S. Oh ◽  
...  

Background:Several recent studies have reported that MTX could be discontinued in patients with low disease activity who are taking biologic DMARDs or tofacitinib. However, there are limited studies on whether MTX could be discontinued in patients with low disease activity who have taken MTX for a long term.Objectives:We investigated the disease flare rate in patients with rheumatoid arthritis (RA) who achieved low disease activity following long-term methotrexate (MTX) treatment and the factors related to flare.Methods:This retrospective longitudinal cohort study included patients with RA and low disease activity who were exposed to MTX for >10 years. Disease flare was defined as an increase in DAS28 of >1.2 within 6 months of discontinuation of MTX. Logistic regression analysis was performed to identify the factors associated with flare.Results:In total, 97 patients with RA were included in the study. The mean baseline DAS28 was 1.96 ± 0.56. The median cumulative MTX dose was 11.7g; the median duration of exposure to MTX was 19 years. Following MTX discontinuation, flare occurred in 43 (44.3%) patients; the mean time to flare was 98 ± 37.7 days. According to univariable logistic regression analysis, C-reactive protein, erythrocyte sedimentation rate (ESR) at discontinuation, the average ESR in the 6 months before discontinuation of MTX, a weekly dose of MTX before discontinuation, and use of other conventional synthetic DMARDs were associated with a higher risk of disease flare. In multivariable analysis, a weekly dose of MTX before discontinuation (OR, 1.014; 95% CI, 1.014–1.342; p = 0.031) was significantly associated with flare risk.Conclusion:Among patients with RA who achieved low disease activity with long-term treatment with MTX, more than half of the patients remained flare free after MTX discontinuation. A higher MTX dose before discontinuation was associated with a high flare risk.Disclosure of Interests:None declared


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0255854
Author(s):  
Fabiola Gonzalez-Ponce ◽  
Jorge I. Gamez-Nava ◽  
Emilio E. Perez-Guerrero ◽  
Ana M. Saldaña-Cruz ◽  
Maria L. Vazquez-Villegas ◽  
...  

Background Chemerin has a potential role in perpetuating inflammation in autoimmune diseases. Nevertheless, to date, there is no conclusive information on whether high chemerin levels increase the severity of rheumatoid arthritis (RA). Therefore, this study evaluated whether serum chemerin is a biomarker of disease activity in RA patients. Methods Study design: cross-sectional. The assessment included clinical and laboratory characteristics, body mass index (BMI) and fat mass. The severity of the disease activity was identified according to the DAS28-CRP index as follows: A) RA with a DAS28-CRP≤2.9 (remission/mild activity) and B) RA with a DAS28-CRP>2.9 (moderate/severe activity). Serum chemerin concentrations were measured by ELISA, and ≥103 ng/mL was considered a high level. Logistic regression analysis was applied to determine whether high chemerin levels were associated with disease activity in RA after adjusting for confounders. Multiple regression analysis was performed to identify variables associated with chemerin levels. Results Of 210 RA patients, 89 (42%) subjects had moderate/severe disease activity and had higher serum chemerin levels than patients with low disease activity or remission (86 ± 34 vs 73± 27; p = 0.003). Serum chemerin correlated with the number of swollen joints (r = 0.15; p = 0.03), DAS28-CRP (r = 0.22; p = 0.002), and C-reactive protein levels (r = 0.14; p = 0.04), but no correlation was observed with BMI and fat mass. In the adjusted logistic regression analysis, high chemerin levels (≥103 ng/mL) were associated with an increased risk of moderate/severe disease activity (OR: 2.76, 95% CI 1.35–5.62; p = 0.005). In the multiple regression analysis, after adjusting for potential confounders, serum chemerin levels were associated with higher DAS28-CRP (p = 0.002). Conclusions Higher chemerin levels increased the risk of moderate and severe disease activity in RA. These results support the role of chemerin as a marker of inflammation in RA. Follow-up studies will identify if maintaining low chemerin levels can be used as a therapeutic target.


2021 ◽  
Author(s):  
Hideo Sakane ◽  
Koichi Okamura ◽  
Yoichi Iizuka ◽  
Akira Honda ◽  
Eiji Takasawa ◽  
...  

Abstract Background: To investigate the prevalence and risk factors for vertebral fractures in patients with rheumatoid arthritis (RA) during an era of tight management.Methods: We retrospectively reviewed 426 RA patients who had visited our outpatient RA clinic between July 2017 and June 2020. Among them, we included 107 patients (19 males and 88 females) who had undergone lateral X-ray of the thoracolumbar spine and dual-energy X-ray absorption spectroscopy for the assessment of osteoporosis. We assessed the disease activity score for 28 joints (DAS28), the history of medication for RA and osteoporosis, the number and location of vertebral fractures, and the bone mineral density (BMD). Two board-certified specialists determined osteoporotic vertebral fractures on a lateral X-ray of the thoracolumbar spine.Results: The mean age, average disease duration, and average DAS28 of the analyzed patients were 67.9 years, 14.9 years, and 2.8, respectively. Vertebral fractures were found in 33 patients (30.8%). In this population, 84.8% of patients with vertebral fractures and 59.5% of those without vertebral fractures were treated for osteoporosis with active vitamin D3, bisphosphonate, and/or denosumab. RA patients with vertebral fractures had significantly higher DAS28 values, a higher rate of patients with a history of glucocorticoid use, and lower BMD in comparison to those than without vertebral fractures (p = 0.009, p = 0.004, and p = 0.01, respectively). Logistic regression analysis showed DAS28 (p = 0.038) and BMD (p = 0.004) were independent factors associated with the presence of vertebral fractures. The ordered logistic regression analysis also showed DAS28 (p = 0.043) and BMD (p = 0.024) were independent factors that explained the number of vertebral fractures.Conclusions: Vertebral fractures were frequently observed in RA patients, even when patients were treated the recommended anti-osteoporotic agents. A high disease activity score and low BMD were associated with the presence and number of vertebral fractures in patients with RA.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1487.2-1487
Author(s):  
E. Gotelli ◽  
A. Sulli ◽  
G. Ferrari ◽  
G. Pacini ◽  
C. Schenone ◽  
...  

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune multisystemic disease, that can begin with a wide range of clinical manifestations, and requires immunosuppressive therapies (1). A treat-to-target strategy leads to a high rate of clinical remission among patients (2). Several “remission” definitions have been provided in the last years and Lupus Low Disease Activity State (LLDAS) seems one of the best tools to evaluate it in clinical practice (3).Objectives:To evaluate the prevalence of SLE signs and symptoms at onset and the drugs used to induce and maintain the clinical remission, evaluated by LLDAS, in a real-life cohort of SLE patients.Methods:Thirty female SLE patients (mean age 52±15 years; mean age at disease onset 34±16 years, mean disease duration 18±13 years) in clinical remission have been enrolled (EULAR/ACR 2019 criteria) (4). Remission was defined by LLDAS (SLEDAI-2K < 4 and no activity in major organ systems, no hemolytic anemia; no new features of activity compared with previous assessment, physician global assessment (PGA) ≤ 1, prednisone dose ≤7.5 mg/day, well tolerated and stable therapy with maintenance doses of immunosuppressive drugs). Clinical and serological manifestations, SLEDAI-2K and pharmacological treatments were recorded at baseline and during follow-up.Results:Mucocutaneous involvement (57%), arthritis (30%), serositis (30%), nephritis (27%), leukopenia (23%), thrombocytopenia (20%), hemolytic anemia (13%), antiphospholipid syndrome manifestations (16%), neuro-psychiatric lupus symptoms (6%) were present in various combinations at disease onset. Baseline mean SLEDAI-2K was 10.5±2.5. Patients were treated with different dosages of glucocorticoids (100%), hydroxychloroquine (HCQ, 73%), cyclofosfamide (20%), mycophenolate mofetile (MMF, 13%), azathioprine (AZA, 13%), methotrexate (MTX, 13%), cyclosporine A (CSA, 6%), rituximab (3%), abatacept (ABA, 3%). Glucocorticoids were prescribed together with a single DMARD in 50% of cases and with two DMARDs in the remaining 50% of patients. Patients reached LLDAS remission after a mean time of 14±12 years, with a mean remission duration of 4.2±3.2 years (mean SLEDAI-2K at last visit 1±1; Mean PGA 0.4±0.1). Maintenance therapies during remission were prednisone ≤ 5 mg/day and/or HCQ ≤ 400 mg/day and/or CSA ≤ 200 mg/day and/or MTX ≤ 10 mg/weekly and/or MMF ≤ 2 g/day and/or AZA ≤ 100 mg/day. In particular, only prednisone 7%, only HCQ 3%, prednisone + HCQ 53%, prednisone + single DMARD (different from HCQ) 7%, prednisone + HCQ + DMARDs 30%.Conclusion:After reaching the clinical remission by a treat to target strategy, the administration of low dose of prednisone and HCQ in the majority of SLE patients (63%) seems useful to prevent new SLE flares. The retrospective design and the absence of a control group of patients with active disease limit this study.References:[1]Lisnevskaia L et al. 2014.Lancet384(9957):1878-1888.[2]Van Vollenhoven RF et al. 2014.Ann Rheum Dis73(6): 958-967.[3]Franklyn K et al. 2016.Ann Rheum Dis. 75(9): 1615-21.[4]Aringer M et al. 2019.Arthritis Rheumatol.71(9): 1400-1412.Disclosure of Interests:Emanuele Gotelli: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Giorgia Ferrari: None declared, Greta Pacini: None declared, Carlotta Schenone: None declared, Massimo Patanè: None declared, Pietro Francesco Bica: None declared, Carmen Pizzorni: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Sabrina Paolino: None declared


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Nopparat Ruchakorn ◽  
Pintip Ngamjanyaporn ◽  
Thanitta Suangtamai ◽  
Thanuchporn Kafaksom ◽  
Charin Polpanumas ◽  
...  

Abstract Background Identification of universal biomarkers to predict systemic lupus erythematosus (SLE) flares is challenging due to the heterogeneity of the disease. Several biomarkers have been reported. However, the data of validated biomarkers to use as a predictor for lupus flares show variation. This study aimed to identify the biomarkers that are sensitive and specific to predict lupus flares. Methods One hundred and twenty-four SLE patients enrolled in this study and were prospectively followed up. The evaluation of disease activity achieved by the SLE disease activity index (SLEDAI-2K) and clinical SLEDAI (modified SLEDAI). Patients with active SLE were categorized into renal or non-renal flares. Serum cytokines were measured by multiplex bead-based flow cytometry. The correlation and logistic regression analysis were performed. Results Levels of IFN-α, MCP-1, IL-6, IL-8, and IL-18 significantly increased in active SLE and correlated with clinical SLEDAI. Complement C3 showed a weakly negative relationship with IFN-α and IL-18. IL-18 showed the highest positive likelihood ratios for active SLE. Multiple logistic regression analysis showed that IL-6, IL-8, and IL-18 significantly increased odds ratio (OR) for active SLE at baseline while complement C3 and IL-18 increased OR for active SLE at 12 weeks. IL-18 and IL-6 yielded higher sensitivity and specificity than anti-dsDNA and C3 to predict active renal and active non-renal, respectively. Conclusion The heterogeneity of SLE pathogenesis leads to different signaling mechanisms and mediates through several cytokines. The monitoring of cytokines increases the sensitivity and specificity to determine SLE disease activity. IL-18 predicts the risk of active renal SLE while IL-6 and IL-8 predict the risk of active non-renal. The sensitivity and specificity of these cytokines are higher than the anti-dsDNA or C3. We propose to use the serum level of IL-18, IL-6, and IL-8 to monitor SLE disease activity in clinical practice.


2020 ◽  
Vol 51 (5) ◽  
pp. 529-539
Author(s):  
Tingting Zeng ◽  
Liming Tan ◽  
Yang Wu ◽  
Jianlin Yu

Abstract Background Early identification and disease monitoring are challenges facing rheumatologists in the management of rheumatoid arthritis (RA). Methods We utilized enzyme-linked immunosorbent assay (ELISA) to determine 14-3-3η and anticyclic citrullinated peptide antibody (anti-CCP) levels, with rheumatoid factor (RF) level detected by rate nephelometry. The diagnostic value of each index was determined via receiver operating characteristic (ROC) curve, and the association between 14-3-3η and osteoporosis was assessed using multiple logistic regression analysis. Results Serum levels of 14-3-3η were 3.26 ng per mL in patients with RA. These levels were helpful in identifying patients with the disease, with the area under the curve (AUC) being 0.879 and 0.853, respectively, from all healthy control individuals and patients with RA. Combining 14-3-3η with RF or anti-CCP increased the diagnostic rate. Logistic regression analysis identified 14-3-3η as an independent risk factor for RA-related osteoporosis (odds ratio [OR], 1.503; 95% confidence interval [CI], 1.116–2.025; P &lt;.01). Conclusions Serum 14-3-3η detection by itself or combined with other serum indices was helpful in differentiating patients with RA. Also, it was a promising biomarker for disease monitoring in RA.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12112-e12112
Author(s):  
Enrique Alanya Rodríguez ◽  
Catalina Falo Zamora ◽  
Miguel J. Gil Gil ◽  
Petit Anna ◽  
Raul Ortega ◽  
...  

e12112 Background: Pathological complete response (pCR) after neoadjuvant chemotherapy for BC has been related with survival, and the sequence of anthracyclines followed by taxanes (AT) has been the strategy to achieve this response. Some studies suggest that the reverse sequence (TA) might improve cancer outcomes. The aim of our study was to compare clinical response, toxicity and efficacy in terms of pCR rate (ypT0/pTis, ypN0) between both sequences Methods: A retrospective cohort study was designed. TA cohort received Docetaxel (100 mg/m2) x 4, followed by AC (60/600 mg/m2) x 4. AT cohort received the reverse sequence at the same doses. To be included, it was necessary to have received at least one cycle in the planned sequence. Logistic regression analysis was performed to obtain a model adjusted by age, menopausal status, tumor size, nodal status, grade, estrogen receptor (ER), progesterone receptor, and Ki67 Results: From June 2008 to December 2015, 135 consecutive patients with stage II – III HER2 negative BC were treated: TA (n = 48) and AT (n = 87). No significant differences in patient characteristics between groups were found, except for histological grade 3 (63.2% to AT vs. 35.4% to TA), and ER negative (41.4% to AT vs. 22.9% to TA). The pCR rate for TA was 16.7% (8 of 40) vs. 14.9% (13 of 74) for AT. Multivariate logistic regression analysis found OR = 3.65 to achieve pCR for TA (95%CI 1.03 – 12.94; p = .045). We also performed the same analysis for two clinical parameters of response: Neoadjuvant response index (NRI) with cut-off > 0.5 (OR 3.96, 95%CI 1.42-11.08; p = .009) and Clinical response (CR) > 50% (OR 3.65, 95%CI 1.03 – 12.94; p = .045). These parameters were correlated in our series with DFS (p = .011 to NRI and p = .00023 to CR) and OS (p = .034 to NRI and p = .0014 to CR) using the Kaplan-Meier method. No significant differences between rates of either, hospitalizations, neutropenia or dose intensity were found Conclusions: Sequence of T followed by A was slightly significantly more effective to achieve pCR as well as better clinical outcomes in our series of HER2 negative BC than classical sequence of A followed by T, and support the design of large prospective studies to confirm these results


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