SAT0206 Tocilizumab Serum Levels and Antidrug Antibodies and Its Relationship with Disease Activity in Rheumatic Diseases

Objective: Since obesity has been associated with a higher inflammatory burden and worse response to therapy in patients with chronic inflammatory rheumatic diseases (CIRD), we aimed to confirm the potential association between body mass index (BMI) and disease activity in a large series of patients with CIRDs included in the Spanish CARdiovascular in rheuMAtology (CARMA) registry. Methods: Baseline data analysis of patients included from the CARMA project, a 10-year prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) attending outpatient rheumatology clinics from 67 Spanish hospitals. Obesity was defined when BMI (kg/m2) was >30 according to the WHO criteria. Scores used to evaluate disease activity were Disease Activity Score of 28 joints (DAS28) in RA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS, and modified DAS for PsA. Results: Data from 2234 patients (775 RA, 738 AS, and 721 PsA) were assessed. The mean ± SD BMI at the baseline visit were: 26.9 ± 4.8 in RA, 27.4 ± 4.4 in AS, and 28.2 ± 4.7 in PsA. A positive association between BMI and disease activity in patients with RA (β = 0.029; 95%CI (0.01–0.05); p = 0.007) and PsA (β = 0.036; 95%CI (0.015–0.058); p = 0.001) but not in those with AS (β = 0.001; 95%CI (−0.03–0.03); p = 0.926) was found. Disease activity was associated with female sex and rheumatoid factor in RA and with Psoriasis Area Severity Index and enthesitis in PsA. Conclusions: BMI is associated with disease activity in RA and PsA, but not in AS. Given that obesity is a potentially modifiable factor, adequate control of body weight can improve the outcome of patients with CIRD and, therefore, weight control should be included in the management strategy of these patients.

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POS0407 PROTEOMICS ANALYSIS COMPARING THE MODE OF ACTION OF UPADACITINIB BETWEEN NON-BIOLOGIC-DMARD-IR AND BIOLOGIC-DMARD-IR PsA PATIENTS IDENTIFIES DISTINCT PATHOGENIC PATHWAYS IN THE SELECT-PsA 1 AND SELECT-PsA 2 PHASE 3 STUDIES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1652 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 433.1-433

Author(s):

T. Sornasse ◽

J. Anderson ◽

K. Kato ◽

A. Lertratanakul ◽

I. McInnes ◽

...

Keyword(s):

Disease Activity ◽

Clinical Response ◽

Rheumatic Diseases ◽

Inadequate Response ◽

Protein Biomarkers ◽

Research Support ◽

Positive Correlation ◽

Disease Biology ◽

Biologic Dmard ◽

Favorable Clinical Response

Background:Treatment of non-biologic-DMARD-IR1 (DMARD-IR) and biologic-DMARD-IR2 (bio-IR) PsA patients with upadacitinib (UPA) at 15 mg QD, an oral JAK1 selective inhibitor, resulted in significant improvement in signs and symptoms compared to placebo.Objectives:Using a pre-defined set of inflammation-related plasma protein biomarkers (pBM), to explore immunological pathway modulation by UPA 15 mg QD in PsA patients with active disease despite treatment with non-biologic or biologic DMARDs in the context of clinical response vs. non-response to treatment.Methods:Patients from the SELECT-PsA 1 (DMARD-IR) and the SELECT-PsA 2 (bio-IR) studies were randomly selected (PBO, n=100; UPA 15 mg QD, n=100 for each study). The levels of 92 inflammation related protein biomarkers (pBM) were analyzed using a multiplexed Proximity Extension Assay platform in plasma samples collected at baseline, week 2, and 12; change from baseline in protein levels was expressed as Log2 Fold Change; a Repeated Measure Mixed Linear Model was used to identify pBM modulated by UPA compared to Baseline, and those differentially modulated between responders (R) and non-responders (NR) according to ACR50, PASDAS Minimal Disease Activity, and PASI75 at week 12. Correlation of disease activity measures with relative levels of pBM were derived using Pearson’s correlation; PASI score was transformed as Log10 (x+1) prior to the analysis. Functional pathway prediction was performed in silico with a commercial distributed software.Results:At baseline, the relative levels of 37 pBM correlated with at least one baseline disease activity measure, with a marked positive correlation of IL6 with musculoskeletal end points (PASDAS and DAS28CRP), and a strong positive correlation of IL20, IL17A, IL17C, and TGFA with baseline PASI.At the single pBM-level, treatment with UPA 15 mg QD resulted in a down modulation of pBM associated with T cells, myeloid cells, and IFN-, IL6-, and TNF-related pathways in both DMARD-IR and bio-IR PsA patients. Overall effects of UPA on single pBMs were broadly similar between DMARD-IR and bio-IR patients. However, analysis of pBMs differentially modulated by UPA in R vs NR indicated that favorable clinical response (achievement of ACR50, PASDAS MDA, and PASI75) in DMARD-IR patients was associated with the down modulation of pBMs predicted to be linked to IFN, IL10, IL17, IL22, and IL27 pathways; while favorable clinical response in bio-IR patients was associated with the down modulation of multiple pBM predicted to be linked to the IL17, IL23, and IL1 pathways.Conclusion:UPA effects in both DMARD-IR and bio-IR PsA patients likely stem from the direct and indirect inhibition of multiple biological pathways belonging to the adaptive and innate immune systems. Responder/Non-Responder analysis suggests a possible shift from a TH1 biased biology in DMARD-IR PsA patients to a more TH17 biased biology in bio-IR PsA patients. This apparent change in the disease biology of PsA patients after inadequate response to prior therapy could be attributed to the actual alteration of the disease biology, treatment outcome-based patient selection, or both. Considering the clinical efficacy of UPA in both DMARD-IR and bio-IR PsA patients, this observation highlights the importance of targeting multiple pathways with drugs such as UPA for the treatment of a broad range of PsA patients.References:[1]McInnes, I. et al. Annals of the Rheumatic Diseases 79, 16-17 (2020).[2]Mease, P.J. et al.Annals of the Rheumatic Diseases, annrheumdis-2020-218870 (2020).Acknowledgements:AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.Disclosure of Interests:Thierry Sornasse Shareholder of: AbbVie, Employee of: AbbVie, Jaclyn Anderson Shareholder of: AbbVie, Employee of: AbbVie, Koji Kato Shareholder of: AbbVie, Employee of: AbbVie, Apinya Lertratanakul Shareholder of: AbbVie, Employee of: AbbVie, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB Pharma, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB Pharma, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB Pharma, Grant/research support from: AbbVie, Amgen, UCB

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Serum Neopterin Levels and the Clinical Presentation of COVID-19

Pteridines ◽

10.1515/pteridines-2020-0013 ◽

2020 ◽

Vol 31 (1) ◽

pp. 185-192

Author(s):

Deniz Öğütmen Koç ◽

Hande Sipahi ◽

Cemile Dilşah Sürmeli ◽

Mustafa Çalık ◽

Nilgün Bireroğlu ◽

...

Keyword(s):

Disease Activity ◽

Clinical Presentation ◽

Serum Levels ◽

Neutrophil Lymphocyte Ratio ◽

Serum Neopterin ◽

Protein Levels ◽

Reactive Protein ◽

Group 2 ◽

Immune Activation Marker ◽

Group 1

AbstractIn Coronavirus disease 2019 (COVID-19), it is important to evaluate disease activity and investigate possible biomarkers. Therefore, in this study, we investigated the relationship between disease activity and serum levels of possible immune activation marker neopterin in patients with COVID-19. The study enrolled 45 patients (23 females, 51.1%) treated for COVID-19. The patients were divided into two groups according to their clinical presentation: those who recovered quickly (Group 1) and those who worsened progressively (Group 2). The neopterin and C-reactive protein levels were high in all patients on admission. In Group 1, neopterin concentrations and serum neopterin/creatinine ratios were significantly higher on admission compared to Day 14 of the disease, whereas in Group 2, levels were significantly higher at Day 14 of the disease than on admission. Neopterin levels at admission were significantly higher in Group 1. The serum neopterin concentrations at admission were markedly higher in patients with a derived neutrophil–lymphocyte ratio (dNLR) > 2.8 compared to those with a dNLR ≤ 2.8 (p < 0.05). Serum neopterin levels can be used as a prognostic biomarker in predicting disease activity in COVID-19.

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AB0051 SERUM AMYLOID A AND PENTRAXIN 3: INNATE IMMUNE RESPONSE AND DISEASE ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1933 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1328.1-1328

Author(s):

R. Assandri ◽

G. Martellosio ◽

A. Montanelli

Keyword(s):

Disease Activity ◽

Lupus Erythematosus ◽

Serum Amyloid A ◽

Serum Levels ◽

Innate Immune ◽

Pentraxin 3 ◽

Systemic Lupus ◽

Amyloid A ◽

Group 2 ◽

Group 1

Background:Systemic Lupus Erythematosus (SLE) is an autoimmune disease that involves several molecular patterns with a wide spectrum of clinical manifestations and symptoms. Inflammation and related pathway play a role in SLE pathogenesis. The pentraxin superfamily including long and short pentraxin, C Reactive Protein CRP, Serum amyloid A (SAA), Pentraxin 3 (PTX3) are key components of innate immune system and induce a variety of inflammation associated pathway. However Literature provides several evidences that CRP serum levels not correlated with clinical and immunological manifestations. This situation affected clinical practice and the patient follow up. PTX3 have been identified as a component of inflammatory status in several autoimmune conditions. SAA is an acute phase protein secreted in large quantity during inflammation.Objectives:We want to evaluated SAA, PTX3 and CRP concentrations, their correlation between SLE Disease Activity Index (SLEDAI), that including complement fractions C3, C4.Methods:We enrolled fifty patients that fulfilled the SLE American College of Rheumatology criteria and fifty healthy subjects. The SLE disease activity was classified with the SLEDAI (0 to 12). Patients were divided into two groups according to SLEDAI score: inactive group (Group 1, 25 patients, 50%: SLEDAI < 4) and active group (Group 2, 25 patients, 50%: SLEDAI 5 to 12). PTX3 concentration was measured by a sandwich ELISA kit (Hycult) with 2.8 ng/mL cut-off point. SAA concentration was detected by nephelometry performed on a BN ProSpec System (Siemens, Germany), with assay kit based on polyclonal antibodies (Siemens Healthcare Diagnostics Products, Germany, 6.5 mg/L cut-off point). High sensitive CRP concentrations were determined using the ci8200 platform (Abbott Laboratories Chicago, Illinois).Results:Plasma PTX3 and serum SAA levels was significantly higher in SLE patients than in the healthy subjects (PTX311.5 ± 7.3 ng/mL vs 2.3 ± 1.1; p < 0.001; SAA: 87 ±77 mg/L vs 2.6±2.5; p < 0.001). These differences were not evident in CRP levels (8.5 ± 7.8 mg/L vs 6.2± 2.5). Considering two groups, there were statistical differences in PTX3 level (Group 2: 14.9 ± 12 ng/mL vs Group 1: 2.16 ±0.5 ng/mL, p<0,05) and SAA concentration (Group 2: 114 ± 89 ng/mL vs Group 1: 3.6 ±1.7 ng/mL, p<0,05) but not in CRP concentration (Group 2: 11.5 ± 8.4 mg/L vs Group 1: 9.5 ±3.5). There was a significantly negative correlation between C3, C4 fractions, PTX3 and SSA levels (respectively r = −0.74, p=<0.05, and r = −0.79, p<0.05). No statistical correlation were appeared between C3, C4 fractions and CRP serum levels (r= −0,12., p= 0.82, and r= −0.18, p= 0,21). We noted a positive significant correlation between SLEDAI, PTX3 and SAA concentration (r = 0.79, p < 0.05, 0.83, p < 0.05, respectively) an increase in PTX3 and SAA levels followed the lupus flare and symptoms. No significant correlation appeared between SLEDAI and CRP (r= 0.15, p=0.89)Conclusion:PTX3 and SAA concentration was significantly higher in SLE patients than the healthy control subjects and their levels reflected disease activity. We showed a direct correlation between PTX3 and SAA. In SLE patients PTX3 and SAA concentrations were correlated with SLEDAI. We suggest an integrate viewpoint in witch SAA and PTX3 may play a role as a biomarker of disease activity, with synergic work during SLE events. Evidences suggested that PTX3 and SAA could trigger the same molecular pathway, by TLR4, via NF-kB.References:[1]Assandri R, Monari M Montanelli A. Pentraxin 3 in Systemic Lupus Erithematosus: Questions to be Resolved, Translational Biomedicine (2015)Disclosure of Interests:None declared

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POS0630 COMPARISON OF THE EFFICACY AND SAFETY OF ORIGINAL AND BIOSIMILAR ADALIMUMAB MOLECULES IN CHILDHOOD RHEUMATIC DISEASES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2979 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 553.1-553

Author(s):

K. Ulu ◽

F. Demir ◽

T. Coşkuner ◽

Ş. Çağlayan ◽

B. Sözeri

Keyword(s):

Adverse Events ◽

Disease Activity ◽

Rheumatic Diseases ◽

Behcet’S Disease ◽

Behçet's Disease ◽

Inactive Disease ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Significant Difference ◽

Abp 501

Background:The TNF-α inhibitor adalimumab is a biological disease modifying anti-rheumatic drug (bDMARD) that has been used in different rheumatic diseases with a resistant course. ABP-501 is a biosimilar product (BP) of adalimumab, recently approved by the FDA and EMA. To our knowledge, there is no study assess the efficacy and safety of these two molecules on pediatric patients.Objectives:We aimed to compare the efficacy and safety of the original and biosimilar adalimumab (ABP-501) molecules in childhood rheumatic diseases.Methods:This non-interventional, retrospective, single-centre analysis carried out in Umraniye Training and Resrach Hospital, Pediatric Rheumatology Clinic, Istanbul, Turkey. The study group consisted of patients who were followed due to chronic rheumatic disease between January 1, 2016 and June 1, 2020, and received reference or biosimilar adalimumab therapy for at least three months. Demographic and clinical data of patients were collected at baseline, 3rd, 6th, and 12th months of treatment. Disease activity assessment was made with JADAS-27 in JIA patients, with SUN criteria in uveitis patients, and with Behçet’s Disease Activity Index in BD patients. Efficacy and safety of treatments were compared between reference and biosimilar adalimumab groups.Results:A total of 89 patients (65 with original and 24 with biosimilar molecule) treated with adalimumab, were included in the study. There were 45 female and 44 male in the study, and the median age at the initiation of the adalimumab was 166 months (min-max: 36-231). Of the 89 patients evaluated, the primary diagnoses of 62 were juvenile idiopathic arthritis, 13 were idiopathic uveitis, eight were Behçet’s disease, three were Blau syndrome, two were chronic recurrent multifocal osteomyelitis and one was Vogt-Koyanagi-Harada syndrome. 63 of the patients were biologic-naïve, and 13 were switched from etanercept, 11 from infliximab, and two from other bDMARDs. The median exposure time of adalimumab was 16 months (min-max:3-70) in RP and 14.5 months (min-max: 3-23) in BP. All patients had active disease before treatment. In the group treated with RP, inactive disease was achieved in 60%, 76.6% and 87.2% of the patients at the 3rd, 6th and 12th months, respectively. Also, inactive disease was achieved in 62.5%, 78.2% and 78.2% of the patients at the 3rd, 6th and 12th months in the group treated with BP, respectively. There was no statistically significant difference in efficacy between the groups at the 3rd, 6th and 12th months (p=0.83, 0.07 and 0.32). Serious adverse events were seen in one patient in each groups (lymphoma in RP group, tuberculous meningitis in BP group). Non-serious adverse events were observed in eight patients (12.3%) in the RP group and in two patients (8.3%) in the BP group, without statistically significant difference between groups (p=0.86).Conclusion:No significant difference was observed between the biosimilar adalimumab ABP-501 and RP adalimumab in terms of efficacy and safety.References:[1]Renton, William D et al. Pediatr Rheumatol Online J. 2019;17(1):67.[2]Lovell DJ, Ruperto N, Goodman S, et al. N Engl J Med. 2008;359(8):810-820.[3]Kingsbury, Daniel J et al. Clin Rheumatol 2014;33(10):1433-41.Disclosure of Interests:None declared

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FRI0651-HPR A RANDOMIZED PROSPECTIVE OPEN-LABEL CONTROLLED TRIAL COMPARING THE PERFORMANCE OF A CONNECTED MONITORING INTERFACE IN PATIENTS WITH RHEUMATOID ARTHRITIS VERSUS PHYSICAL ROUTINE MONITORING

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1822 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 929.1-930

Author(s):

Y. M. Pers ◽

V. Valsecchi ◽

T. Mura ◽

S. Aouinti ◽

N. Filippi ◽

...

Keyword(s):

Quality Of Life ◽

Rheumatoid Arthritis ◽

Disease Activity ◽

Rheumatic Diseases ◽

Tight Control ◽

Link Type ◽

Functional Scores ◽

Monitoring Group ◽

Disease Modifying

Background:Telemedicine has found wider application in chronic diseases for encouraging tight home-monitoring in order to improve patients’ outcome (Smolen et al. 2017).In previous studies, a high feasibility and high patient-satisfaction rate was found as well as the evidence for a superior or equal effectiveness of telemedicine compared to the standard face-to-face approach, however the results were weakened by some methodological biases and wide heterogeneity of interventions, thus preventing to draw definitive conclusions (Piga et al. 2017; Najm, Gossec, et al. 2019).Objectives:In rheumatoid arthritis (RA), telemedicine may allow a tight control of disease activity while reducing hospital visits. We developed a smartphone application connected with a physician’s interface to monitor RA patients. We aimed to assess the performance of this e-Health solution in comparison with routine practice in the management of patients with RA.Methods:A 6-month pragmatic, randomized, controlled, prospective, clinical trial was conducted in RA patients with high to moderate disease activity starting a new Disease Modifying Anti-Rheumatic Drug (DMARD) therapy. Two groups were established: “connected monitoring” and “conventional monitoring”. The primary outcome was the number of physical visits between baseline and 6 months. Secondary outcomes included adherence, satisfaction, changes in clinical, functional, and health status scores (SF-12).Results:Of the 94 randomized patients, 89 completed study: 44 in the “conventional monitoring” arm and 45 in the “connected monitoring” arm. The total number of physical visits between baseline and 6 month was significantly lower in the “connected monitoring” group (0.42 ± 0.58 versus 1.93 ± 0.55; p<0.05). No differences between groups were observed in the clinical and functional scores. A better quality of life for SF-12 subscores (Role-Physical, Social-Functioning and Role-Emotional) were found in the “connected monitoring” group.Conclusion:According to our results, a connected monitoring reduces the number of physical visits while maintaining a tight control of disease activity and improving quality of life in patients with RA starting a new treatment.References:[1] Najm, Aurelie, Laure Gossec, Catherine Weill, David Benoist, Francis Berenbaum, and Elena Nikiphorou. 2019. “Mobile Health Apps for Self-Management of Rheumatic and Musculoskeletal Diseases: Systematic Literature Review.”JMIR MHealth and UHealth7 (11): e14730.https://doi.org/10.2196/14730.[2] Piga, Matteo, Ignazio Cangemi, Alessandro Mathieu, and Alberto Cauli. 2017. “Telemedicine for Patients with Rheumatic Diseases: Systematic Review and Proposal for Research Agenda.”Seminars in Arthritis and Rheumatism47 (1): 121–28.https://doi.org/10.1016/j.semarthrit.2017.03.014.[3] Smolen, Josef S, Robert Landewe, Johannes Bijlsma, Gerd Burmester, Katerina Chatzidionysiou, Maxime Dougados, Jackie Nam, et al. 2017. “EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: 2016 Update.”Annals of the Rheumatic Diseases76 (6): 960–77.https://doi.org/10.1136/annrheumdis-2016-210715.Disclosure of Interests:None declared

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Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort

Mediators of Inflammation ◽

10.1155/2015/328078 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Conti Fabrizio ◽

Ceccarelli Fulvia ◽

Perricone Carlo ◽

Massaro Laura ◽

Marocchi Elisa ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Clinical Laboratory ◽

Renal Involvement ◽

Serum Levels ◽

Activity Measurement ◽

Systemic Lupus ◽

Before And After ◽

Dsdna Antibodies

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status.Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM).Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.;P=0.001). Serositis resulted significantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.;P<0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA − (21.8%,P=0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P=0.7).Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.

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AB0686 Association between drug serum levels and disease activity in espondiloarthritis patients treated with golimumab

10.1136/annrheumdis-2017-eular.5881 ◽

2017 ◽

Author(s):

C Redondo ◽

A Martínez ◽

C Plasencia ◽

A Jochems ◽

D Pascual-Salcedo ◽

...

Keyword(s):

Disease Activity ◽

Serum Levels

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