scholarly journals Dynamics of the level of calprotectin in patients with rheumatoid arthritis during rituximab biosimilar (Acellbia “Biocad”) therapy

2021 ◽  
Vol 59 (4) ◽  
pp. 401-405
Author(s):  
A. S. Avdeeva ◽  
M. V. Cherkasova ◽  
E. L. Nasonov
Keyword(s):  
Rheumatoid Arthritis ◽  
Growth Factors ◽  
Disease Activity ◽  
Initial Level ◽  
Methotrexate Therapy ◽  
Laboratory Parameter ◽  
Acute Phase Reactants ◽  
Healthy Donors ◽  
Effect Of Therapy ◽  
The Relationship

Objective. To study the relationship between the level of calprotectin (CP) and RA activity, the level of acute phase reactants, proinflammatory cytokines, chemokines and growth factors, to assess its dynamics during rituximab (RTM) biosimilar therapy.Material and methods. 20 patients with RA were examined. All patients received 2 intravenous infusions of RTM (Acellbia®) at a dose of 600 mg with an interval of 2 weeks against the background of methotrexate therapy. The level of CP in blood serum was measured by ELISA.Results. Before starting DAS28 (5.6 [4.9–6.8]), SDAI (27.17 [23.08–39.9]) and CDAI (26.6 [22.25–37.0]) corresponded to the high disease activity. A decrease in disease activity was noted after 12 and 24 weeks of therapy: the DAS28 value was 4.28 [3.24–4.75] and 4.14 [3.11–4.66], respectively (p<0.05). Before the start of therapy, patients with RA had a higher CP level compared with healthy donors 9.68 (4.5–21.5) and 2.39 (1.52–4.45) μg/ml, respectively (p<0.05). Against the background of RTM therapy, there was a decrease in the CP level 12 weeks after the first infusion of the drug in the group as a whole by 26.5% from the initial level, among patients with moderate/no effect of therapy – by 32.7% from the initial level.Conclusion. The CP level significantly decreases during therapy and can be used to monitor the effectiveness of therapy. The predictive value of this laboratory parameter requires further study.

scholarly journals Expression of interferon-stimulated genes in patients with rheumatoid arthritis on anti-B-cell therapy (preliminary results)

2021 ◽  
Vol 15 (5) ◽  
pp. 12-17
Author(s):  
A. S. Avdeeva ◽  
E. V. Chetina ◽  
G. A. Markova ◽  
E. L. Nasonov
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Therapy ◽  
Disease Activity ◽  
B Cell ◽  
Total Dose ◽  
Interferon Stimulated Genes ◽  
Average Value ◽  
Healthy Donors ◽  
Effect Of Therapy ◽  
Moderate Effect

Objective: to evaluate the expression of interferon-stimulated genes (ISG) – interferon (IFN) signature – in patients with rheumatoid arthritis (RA) and its dynamics during anti-B-cell therapy.Patients and methods.We examined 20 patients with RA who received two infusions of the biosimilar rituximab (RTM) Acellbia® in a total dose of 1200 mg. Five genes were selected to evaluate IFN signature: IFI44L, MX1, IFIT1, RSAD2, EPSTI1. The expression of IFI44L and IFIT1 could not be determined for technical reasons, and further analysis included three genes – MX1, EPSTI1, RSAD2. IFN signature was calculated as the average value of the expression of three selected genes (IFN-score).Results and discussion. The initial expression level of MX1 was 11.48 (5.45–19.38), EPSTI1 – 12.83 (5.62–19.64), RSAD2 – 5.16 (2.73–10.4) and IFN-score –10.3 (5.18–17.12), in patients with RA it was statistically significantly higher than in healthy donors: 1.26 (0.73–1.6); 1.06 (0.81–1.48); 0.93 (0.72–1.19) and 1.09 (0.92–1.42), respectively (p<0.05). The IFN-score was high in 15 (75%) patients, low in 5 (15%). The use of RTM was accompanied by a statistically significant decrease in disease activity and the level of acute phase parameters (ESR, CRP) after 12 and 24 weeks of therapy (p<0.05). In the group as a whole, as well as in patients with a moderate effect of therapy or its absence, by the 24th week of treatment, an increase in the expression of RSAD2 (p<0.05) and a tendency to an increase in the IFN-score level (p=0.06) were observed.Conclusion. In patients with RA, an increased expression of ISH was found compared to healthy donors. An increase in the expression of RSAD2 and IFN-score is observed both in patients with a satisfactory effect of RTM and with no effect. The obtained results can be important for predicting the course of the disease and personalizing therapy.

scholarly journals POS0611 THE EFFECT OF RITUXIMAB BIOSIMILAR THERAPY ON THE EXPRESSION OF INTERFERON-STIMULATED GENES (“INTERFERON SIGNATURE”) IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 542.2-542
Author(s):  
A. Avdeeva ◽  
E. Tchetina ◽  
G. Markova ◽  
E. Nasonov
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Signature ◽  
Response To Therapy ◽  
Type I Interferons ◽  
Control Group ◽  
Type I ◽  
Acute Phase Reactants ◽  
Interferon Signature ◽  
Interferon Stimulated Genes ◽  
Healthy Donors

Background:Type I interferons (IFN-Is) are a group of molecules with pleiotropic effects on the immune system forming a crucial link between innate and adaptive immune responses. The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including rheumatoid arthritis. IFN activity is usually quantified using expression of interferon-stimulated genes (ISGs) referred to as an IFN signature. Acellbia (BIOCAD) is the first Russian rituximab (RTX) biosimilar which was approved for medical use in rheumatoid arthritis (RA) patients in Russia and some CIS countries.Objectives:To evaluate the changes in expression of ISGs in patients (pts) with RA during RTX biosimilar therapyMethods:20 RA pts (18 woman, Me;IQR age 61.5(54-66.5) years, disease duration 39.5(20-84) months, mean DAS 28 5.6(4.9-6.8)) received two intravenous RTX biosimilar infusions (600 mg №2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and 24 weeks after the first infusion of RTX. 5 genes (IFI44L, MX1, IFIT 1, RSAD2, EPSTI1) were selected for evaluation of the “interferon signature” (Type I IFN gene signature – IFNGS). IFI44L and IFIT1 expression was undetectable, therefore the remaining three genes (MSX1, EPSTI1, RSAD2) were included into further analysis. IFNGS was calculated as the average expression values of the three selected genes. The control group included 20 age and gender matching healthy donors.Results:The baseline expression levels of MX1-11.48 (5.45-19.38), EPSTI1-12.83 (5.62-19.64), RSAD2-5.16 (2.73-10.4), and IFNGS-10.3 (5.18-17.12) in RA patients were significantly higher compared to healthy donors– 1,26 (0,73-1,6); 1,06 (0,81-1,48); 0,93 (0,72-1,19); 1,09 (0,92-1,42), (p<0.05, respectively). IFNGS was detected in 15 (75%) patients, and was not found in 5 (15%) patients. RTX induced reduction in disease activity, and the level of acute phase reactants (ESR, CRP) after 12 and 24 weeks of therapy, p<0.05 (fig.1). Increased RSAD 2 expression (p<0.05) and a trend to increasing IFNGS levels (p=0.06) were documented in the whole group, and also in patients with moderate treatment effects by week 24. Among patients with a good EULAR response to therapy, changes in expression were not significant (p> 0.05) (fig.1)Figure 1.Conclusion:Expression of IFN-stimulated genes was increased in RA patients compared to healthy donors. Increased RSAD2 and IFNGS expression was documented in patients with moderate effect of RTX therapy, therefore, these findings have important clinical relevance as predictors of RA clinical course which necessitates personified approach to treatment.Disclosure of Interests:None declared

scholarly journals POS0009 THE RELATIONSHIP BETWEEN DIFFERENT IGG AND IGA ANTI-MODIFIED PROTEIN AUTOANTIBODIES IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 206.1-207
Author(s):  
C. Grönwall ◽  
L. Liljefors ◽  
H. Bang ◽  
A. Hensvold ◽  
M. Hansson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Comprehensive Evaluation ◽  
Patient Characteristics ◽  
Post Translational Modifications ◽  
Cell Clones ◽  
Thermo Fisher Scientific ◽  
History Of ◽  
The Relationship ◽  
Fisher Scientific

Background:Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), anti-acetylated (KAc), and anti-malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. By using RA patient single-cell derived monoclonal antibodies we have previously shown that individual ACPA clones recognize small distinct citrulline-containing epitopes giving them extensive multireactivity when these epitopes are found in many peptides and proteins. Moreover, certain CCP2+ multireactive ACPA clones bind also to cabamylated and acetylated autoantigens [1].Objectives:To provide a comprehensive evaluation of serum IgG and IgA autoreactivity to different post-translational modifications in RA.Methods:We analyzed 30 different IgG and IgA AMPA reactivities to modified antigens by ELISA and autoantigen arrays, in N=1985 newly diagnosed RA patients and population controls. The study utilized both previously established (i.e IgG and IgA CCP2; IgG ACPA fine-specificities; IgG anti-Carb fibrinogen and Carb FCS; IgG and IgA Cit/Carb/KAc/Orn(Ac)-vimentin), and novel assays (e.g. IgG anti-MAA and IgG anti-acetylated histones). Association with patient characteristics such as smoking and disease activity were explored. The newly developed assays were also evaluated in SLE disease controls and CCP2+ RA-risk individuals without arthritis.Results:Carb and KAc reactivities by different assays were primarily seen in patients also positive for citrulline-reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG acetylation reactivity was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone 2B reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles.Conclusion:We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Anti-Carb and anti-KAc could be considered reactivities within the “Cit-umbrella” similar to ACPA fine-specificities, while MAA is distinctly different.References:[1]Sahlström P, Hansson M, Steen J, Amara K, Titcombe PJ, Forsström B, Stålesen R, Israelsson L, Piccoli L, Lundberg K, Klareskog L, Mueller DL, Catrina AI, Skriner K, Malmström V, Grönwall C. Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Arthritis. Arthritis Rheumatol. 2020 Oct;72(10):1643-1657. PMID: 32501655Caroline Grönwall: None declared, Lisa Liljefors: None declared, Holger Bang Employee of: Employee at ORGENTEC Diagnostika GmbH, Aase Hensvold: None declared, Monika Hansson: None declared, Linda Mathsson-Alm Employee of: Employee at Thermo Fisher Scientific, Lena Israelsson: None declared, Anna Svärd: None declared, Cyril CLAVEL: None declared, Elisabet Svenungsson: None declared, Iva Gunnarsson: None declared, Guy Serre: None declared, Saedis Saevarsdottir: None declared, Alf Kastbom: None declared, Lars Alfredsson: None declared, Vivianne Malmström: None declared, Johan Rönnelid: None declared, Anca Catrina: None declared, Karin Lundberg: None declared, Lars Klareskog: None declared

scholarly journals AB0101 THE IMPACT OF TIME SPAN TO ACHIEVE BOOLEAN REMISSION FOR MAINTAINING DISEASE ACTIVITY AFTER ACQUISITION IN RHEUMATOID ARTHRITIS PATIENT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1079.1-1079
Author(s):  
I. Yoshii
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Duration ◽  
Remission Rate ◽  
Mean Value ◽  
Time Span ◽  
Mean Values ◽  
The Mean ◽  
The Relationship

Background:Boolean remission criteria is one most popular and stringent criteria in treating patient with rheumatoid arthritis (RA), because it may guarantees a stable clinical course after attaining remission.Objectives:Impact of time span from initiation to achieving Boolean remission on maintaining disease activity, daily activities, and quality of life after attaining Boolean remission was investigated from daily clinical practice data.Methods:685 patients with RA since August 2010 under the T2T strategy were treated. They were monitored for their TJC, SJC, PGA, EGA, CRP, and disease activity indices such as CDAI, SDAI, DAS28, and Boolean criteria at every visit. HAQ-DI score, pain score using visual analog scale (PS-VAS), and EQ-5D were also monitored, and the quality of life score (QOLS) calculated from EQ-5D was determined at every visit from the time of diagnosis (baseline).Of 685 patients, 465 patients had achieved Boolean remission >1 times, and were consecutively followed up for >3 years. These patients were enrolled in the study. Time span from the first visit to first Boolean remission was calculated. The relationship between the time span and each of background parameters, and the relationship between the time span and each of the mean values of the SDAI score, HAQ score, PS-VAS, SHS, and QOLS at the first Boolean remission and thereafter was evaluated statistically.Patients were subsequently divided into the G ≤ 6 and G > 6 groups based on the achievement of first Boolean remission within two groups: time span G ≤ 6 months and G > 6 months. The two groups were compared with regard to the SDAI score, HAQ score, PS-VAS, SHS, and QOLS at first visit and at the time of first Boolean remission, and the mean values of these parameters after remission were evaluated statistically. Moreover, changes of these parameters and the mean Boolean remission rate after the first remission, and SDAI remission rate at the first Boolean remission to thereafter were compared between the two groups statistically.Results:Out of 465 patients, females comprised 343 (73.7%), and the mean age was 67.8 years (range, from 21–95 years). The mean disease duration at first visit was 6.1 years (range, from 1 months–45 years). The mean follow up length was 88.1 months (range: 36–122 months; median: 85 months) and mean time span from the first visit to the first Boolean remission was 8.1 months. The mean SDAI score, HAQ score, PS-VAS, and the QOLS at first visit were 13.3, 0.467, 33.2, and 0.834, respectively. Among the study parameters, PS-VAS and QOLS were significantly correlated with the time span. For parameters at the first Boolean remission, HAQ-DI score, PS-VAS, and QOLS demonstrated significant correlation with the time span, whereas SDAI, HAQ-DI score, PS-VAS, SHS, and QOLS after the Boolean remission demonstrated significant correlation with the time span.The comparison between the G ≤ 6 and the G > 6 groups revealed that the disease duration, HAQ score, and PS-VAS at baseline in the G > 6 were significantly higher than that in the G ≤ 6 group, and QOLS in the G ≤ 6 group was significantly higher than that in the G > 6 group at baseline. Similarly, the HAQ score and PS-VAS at the first Boolean remission in the G > 6 group were significantly higher than that in the G ≤ 6 group, whereas QOLS in the G ≤ 6 group demonstrated no significant difference compared with that in the G > 6 group.The mean value of the SDAI score after the first Boolean remission in the G > 6 group was significantly higher than that in the G ≤ 6 group. Similarly, the SDAI score, HAQ score, and PS-VAS after the first Boolean remission in the G > 6 group were also significantly higher than those in the G ≤ 6 group, and the mean value of the QOLS in the G ≤ 6 group were significantly higher than that in the G > 6 group. The Boolean remission rate and SDAI remission rate after the first Boolean remission were significantly higher in the G ≤ 6 group than those in the G > 6 group.Conclusion:Attaining Boolean remission ≤ 6 months for RA has significant benefit for more stable disease control, that leads good maintenance of ADL.Disclosure of Interests:None declared

scholarly journals Artrite Reumatoide e a Poluição do Ar

UNICIÊNCIAS ◽  
2021 ◽  
Vol 24 (2) ◽  
pp. 195-200
Author(s):  
Dayane Dos Santos Souza Magalhães ◽  
Leticia Rosa Espírito Santo de Freitas ◽  
Maria Amélia Dos Santos Peres Santos Souza ◽  
Vander Fernandes ◽  
Walkiria Shimoya-Bittencourt ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Air Pollution ◽  
Disease Activity ◽  
Air Pollutants ◽  
Activity Index ◽  
Age Groups ◽  
Unknown Etiology ◽  
World Population ◽  
Artrite Reumatoide ◽  
The Relationship

A artrite reumatoide é uma doença inflamatória, crônica, autoimune, sistêmica e progressiva com etiologia ainda desconhecida, que causa danos progressivos ao sistema musculoesquelético. Esta doença atinge aproximadamente 0,5% a 1% da população mundial, predomina no sexo feminino e acomete todas as faixas etárias com maior prevalência entre 40-60 anos. A atividade da doença é avaliada pelo Índice de Atividade da Doença (DAS28) analisando 28 articulações. Estudos demonstram que a poluição atmosférica está associada aos agravos à saúde humana e à perda de qualidade de vida. Este estudo teve como objetivo relatar o papel da poluição atmosférica na artrite reumatoide, através de uma revisão narrativa de literatura, a partir das bases de dados PubMed e Scielo. Incluíram-se artigos nos idiomas inglês e português publicados em periódicos, nacionais e internacionais, acerca da temática da pesquisa. A relação entre o desenvolvimento da AR e diferentes poluentes atmosféricos foi analisada em diversos estudos, que demostraram associação entre diferentes poluentes atmosféricos e o desenvolvimento da doença, no entanto, nenhum estudo publicado até a data atual, avaliou a relação com a exacerbação da atividade da doença.   Palavras-chave: Artrite Reumatoide. Poluição do Ar. Doenças Autoimunes.   Abstract Rheumatoid arthritis is an inflammatory, chronic, autoimmune, systemic and progressive disease with a still unknown etiology that causes progressive damage to the musculoskeletal system. This disease affects approximately 0.5% to 1% of the world population, predominates in females and affects all age groups with a higher prevalence between 40-60 years. The disease activity is assessed by the Disease Activity Index (DAS28) analyzing 28 joints. Studies show that air pollution is associated with damage to human health and loss of quality of life. This study aimed to report the role of air pollution in rheumatoid arthritis, through a literature narrative review, using the PubMed and Scielo databases. Articles in English and Portuguese published in national and international journals about the research theme were included. The relationship between the RA development and different air pollutants has been analyzed in several studies, which showed an association between different air pollutants and the development of the disease, however, no study published to date has evaluated the relationship with the disease activity exacerbation.   Keywords: Rheumatoid Arthritis. Air Pollution. Autoimmune Diseases.    

THU0620-HPR MEASUREMENT OF LOW DISEASE ACTIVITY USING THE CLINICAL DISEASE ACTIVITY INDEX (CDAI) VERSUS THE DISEASE ACTIVITY SCORE 28 (DAS 28): IMPACT OF INFLAMMATION MARKERS ON THE COMPARATIVE EFFECTIVENESS OF BIOLOGICS FOR THE TREATMENT OF RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 553.1-553
Author(s):  
K. Janke ◽  
K. Biester ◽  
D. Krause ◽  
B. Richter ◽  
C. Schürmann ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Comparative Effectiveness ◽  
Inflammatory Markers ◽  
Activity Index ◽  
Disease Activity Index ◽  
Signs And Symptoms ◽  
Acute Phase Reactants ◽  
Das 28 ◽  
Effectiveness Studies

Background:Biologics for the treatment of rheumatoid arthritis (RA) have different modes of action to target auto-inflammatory processes causing the signs and symptoms of the disease. Different biologics may thus have different effects on inflammatory markers. For instance, previous studies have shown that the interleukin-6-inhibitor tocilizumab (TOC) decreases the level of acute phase reactants (APRs) [1]. Such direct effects on inflammatory markers may lead to an overestimation of clinical response if disease activity is measured via scores including inflammatory markers, such as the Disease Activity Score 28 (DAS 28). The detected changes in disease activity may not adequately reflect the clinical improvement of signs and symptoms.Objectives:In our study, we compared biologics with each other using two different disease activity scores: the DAS 28 including APRs and the clinical disease activity index (CDAI) excluding APRs. The aim of this study was to assess whether the use of the two different scores affects comparative effectiveness studies on biologics for the treatment of RA.Methods:We compared results on the comparative effectiveness of biologics using the corresponding thresholds for low disease activity (LDA) for the DAS 28 (< 3.2) and the CDAI (≤ 10). We performed two separate network meta-analyses (NMAs) after a thorough step-by-step evaluation of the similarity, homogeneity and consistency assumptions of the patient populations and the study data.Our study formed part of a systematic review (including NMAs) that was largely based on clinical study reports and re-analyses of LDA using individual patient data provided by sponsors for studies conducted up to 2017. Thus, the analyses include hitherto unknown data on LDA analysed by means of the CDAI, especially data from older studies. An extensive comparison of DAS 28 and CDAI in different patient populations was possible.Results:For all analysed patient populations, comparisons of TOC versus other biologics yielded remarkable results: advantages for TOC were found in NMAs using the DAS 28, which were not confirmed in NMAs using the CDAI. For methotrexate (MTX)-naïve patients, using the DAS 28, TOC showed a greater benefit than abatacept (ABA), certolizumab pegol (CZP), and etanercept (ETA), which was not confirmed by the CDAI. In contrast, TOC showed less benefit than adalimumab (ADA) and ETA. For patients after MTX failure and using the DAS 28, TOC showed a greater benefit than ABA, ADA, anakinra (ANA), ETA, golimumab (GOL), and infliximab (INF). With the exception of ANA, these advantages were not confirmed by the CDAI. Similar differences between DAS 28 and CDAI were shown in patients treated with biologics in monotherapy or after failure of biologics.Conclusion:In comparative effectiveness studies of biologics, the assessment of LDA using the DAS 28 instead of the CDAI leads to a consistent overestimation of the benefit of TOC in all patient populations, regardless of pre-treatment or combined therapy with MTX. The inclusion of APRs in disease activity scores may thus introduce bias. A score excluding inflammatory markers should therefore be used to ensure valid results.References:[1]Smolen JS, Aletaha D. Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants. Arthritis Rheum 2011; 63(1): 43-52.Disclosure of Interests:Kirsten Janke: None declared, Katharina Biester: None declared, Dietmar Krause Grant/research support from: Pfizer and AbbVie (Abbott), Bernd Richter: None declared, Christoph Schürmann: None declared, Katharina Hirsch: None declared, Beate Wieseler: None declared

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