Relevance. Pneumococci are among the most common causative agents of severe bacterial infections in humans. The prevalence of invasive pneumococcal infections among people with autoimmune inflammatory rheumatic diseases is 3–4 times higher than in the general population. Aim. To evaluate the effectiveness of vaccination with 13-valent pneumococcal conjugate vaccine (PCV 13) in patients with rheumatoid arthritis (RA). Materials and Methods. The data of scientific publications PubMed, Web of Science, elibrary, the National Inpatient Database of the USA, the Moscow Unified Register of Arthritis, the V. A. Nasonova Research Institute of Rheumatology were used in the review. V. A. Nasonova Research Institute of Rheumatology. Conclusion. In the presented review in adult patients with rheumatoid arthritis (RA) receiving various antirheumatic drugs, the immunogenicity (humoral response, opsonophagocytic activity), safety of vaccines of 13-valent conjugated pneumococcal vaccine (PCV13) was assessed. Based on the data presented, a conclusion was made about the safe management of PCV13 and the formation of antibodies to pneumococcus in RA patients with targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), biologic (bDMARDs) and Glucocorticoids (GCs < 15 mg daily). Methotrexate (MTX) in RA patients reduced the pneumococcal response and the functional activity of antibodies.

BACKGROUND:In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE:Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS:Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS:Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION:While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

Objective. - To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). Methods. - We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. Results. - A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was approximate to 2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48-0.87] for abatacept, and 1.04 [0.76-1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83-1.47] for abatacept, and 1.30 [0.96-1.78] for tocilizumab. Conclusion. - After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guide-lines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved. (c) 2023 L'Auteur(s). Publie ' par Elsevier Masson SAS au nom de Socie ' te ' franc, aise de rhumatologie. Cet article est publie ' en Open Access sous licence CC BY (http://creativecommons.org/licenses/by/4.0/).

The development of innovative technologies using mono- and multiplex methods of immune analysis contributed to an increase in the sensitivity and specificity of laboratory tests and a significant expansion of the range of laboratory biomarkers of systemic lupus erythematosus (SLE). The article presents modern aspects of laboratory diagnosis of SLE. Screening and confirmatory methods for the study of antinuclear antibodies (ANA), the main immunological marker of SLE, are considered in detail. New classification criteria for SLE are discussed (EULAR/ACR, 2019), which for the first time single out “seropositivity” for the antinuclear factor as a mandatory “incoming” criterion that allows diagnosing the disease as SLE. The characteristics of clinical and laboratory subtypes of SLE associated with the detection of various autoantibodies in serum (antibodies to dsDNA, histones, nucleosomes, Sm, Ro/SSA and La/SSB, U1 ribonucleoprotein,ribosomal protein P, antiphospholipid antibodies, antibodies to C1q) are given. The diagnostic value of defects in the components of the complement system in SLE is indicated. The relationship between ANA and cytokine profiles in SLE patients using multiplex immunoassay of these biomarkers based on xMAP microarray technology is described. It has been shown that the formation of ANA and high activity of SLE are associated with overexpression of the IP-10 and MCP-1 chemokines induced by IFN. The clinical and pathogenetic significance of subpopulations of B-lymphocytes and CD4+ CD25high+ FoxP3+ regulatory T-cells (Treg) of peripheral blood in SLE was noted. SLE is characterized by an increase in the number of double negative memory B cells (CD19+ CD27-IgD-) and plasma cells, a decrease in the levels of naive and transitional B cells in the blood. A positive correlation was found between the number of double negative B cells and the activity of SLE and ESR. The effect of therapy with genetically engineered biological agents (rituximab and belimumab) on B-cell subpopulations in patients with SLE was analyzed. The decrease in the number of Tregs is most pronounced in patients with an acute variant of the course of the disease, high activity of the pathological process, hyperproduction of IgG and expansion of autoreactive B-cells. The study of modern molecularcellular biomarkers allows diagnosing, assessing activity, the nature of the course, clinical and laboratory subtypes of SLE, and predicting the effectiveness of therapy for this disease at a qualitatively new level.

Background:Industry, regulators, and the rheumatology community have recognized the need for observational studies to monitor the safety of new antirheumatic agents. Registries provide a unique opportunity to understand the safety of newer therapies, but pharmacovigilance studies require large number of patients to evaluate rare drug-related adverse-events (AEs). Because JAK-inhibitors (JAKi) have only recently been approved for the treatment of rheumatoid arthritis, it makes sense to combine data from several registries in order to obtain a sufficiently large sample size to promote earlier detection of adverse events.Objectives:The purpose of this analysis was to evaluate how AEs are assessed in the various registries in preparation for a collaborative pharmacovigilance analysis, and present preliminary results.Methods:The “JAK-pot” collaboration includes 19 RA registries. The principal investigators of the participating registries were sent a structured questionnaire on AE assessment and 18 (94%) provided complete responses on the AE assessment procedures of their registries. We present simple descriptive statistics of the AE assessment procedures employed by the participating registries.Results:The 19 registries represent 7186 patients initiating a JAKi (Table 1), who are on average 57 years old, with a mean disease duration 11 years, seropositive (83%), female (82%) and with moderate disease activity at treatment initiation.Table 1.Country, registryN° of patients on JAKi includedAustria, BIOREG87Belgium, TARDIS2113Canada, RHUMADATA363Czech Republic, ATTRA197Denmark, DANBIO506Finland, ROB-FIN229Germany, RABBIT620Italy, GISEA244Israel, I-RECORD96Netherlands, METEOR4Norway, NOR-DMARD97Portugal, REUMA.PT44Romania, RRBR252Russia, ARBITER428Slovenia, biorx.si141Spain, BIOBADASER139Switzerland, SCQM738Turkey, TURKBIO404UK, BSRBR484After ineffectiveness, AEs was the second most common reason for JAKi discontinuation (25.5%), with large differences between registries (Figure 1).Of the participating registries, 2 registries do not collect AEs, while 16 (89%) assess incident AEs, by means of a pre-specified extraction form (3 registries), by free text (5 registries), by a combination of both (6 registries) and/or the use of linkage to external electronic records (3registries). AEs are coded using a predefined coding system by 11 registries (MeDRA (8), other (3)), but nearly all are recording the severity of the AE (15, 94%), AE related-death (15, 94%), or AE-related hospitalisation (15, 94%). AEs of special interest, such as serious infections (15, 94%), thromboembolic events (15, 94%), or shingles (9, 56%), are recorded by most registries. Incident AEs are linked by the treating physician to specific therapies in 11 registries (69%), while the other 5 registries extrapolate potential causal associations based on therapy start and stop dates. A pre-specified adjudication process for AEs is made only by 5 registries (31%).Conclusion:Substantial heterogeneity exists among registries regarding AE assessment within the JAK-pot collaboration. These differences must be taken into account when analysing the safety of JAKi across different countries in collaborative studies. For comparative analyses, stratified analyses by country are required to account for differential AE assessment and varying degrees of potential under-reporting.Disclosure of Interests:Kim Lauper: None declared, Denis Mongin: None declared, Sytske Anne Bergstra: None declared, Denis Choquette: None declared, Catalin Codreanu: None declared, Diederik De Cock: None declared, Lene Dreyer: None declared, Ori Elkayam: None declared, Kimme Hyrich: None declared, Florenzo Iannone: None declared, Nevsun Inanc: None declared, Eirik kristianslund: None declared, Tore K. Kvien: None declared, Burkhard Leeb: None declared, Galina Lukina: None declared, Dan Nordström: None declared, Karel Pavelka: None declared, Manuel Pombo-Suarez: None declared, Ziga Rotar: None declared, Maria Jose Santos: None declared, Anja Strangfeld: None declared, Delphine Courvoisier: None declared, Axel Finckh Speakers bureau: Eli-Lilly, Pfizer, Consultant of: Eli-Lilly, Pfizer, Grant/research support from: BMS, Pfizer.

Objectives The expanded therapeutic arsenal in rheumatoid arthritis (RA) raises new clinical questions. The objective of this study is to compare the effectiveness of cycling Janus kinase inhibitors (JAKi) with switching to biologic disease-modifying antirheumatic drug (bDMARD) in patients with RA after failure to the first JAKi. Methods This is a nested cohort study within data pooled from an international collaboration of 17 national registries (JAK-pot collaboration). Data from patients with RA with JAKi treatment failure and who were subsequently treated with either a second JAKi or with a bDMARD were prospectively collected. Differences in drug retention rates after second treatment initiation were assessed by log-rank test and Cox regression analysis adjusting for potential confounders. Change in Clinical Disease Activity Index (CDAI) over time was estimated using a linear regression model, adjusting for confounders. Results 365 cycling and 1635 switching patients were studied. Cyclers were older and received a higher number of previous bDMARDs. Both strategies showed similar observed retention rates after 2 years of follow-up. However, adjusted analysis revealed that cycling was associated with higher retention (p=0.04). Among cyclers, when the first JAKi was discontinued due to an adverse event (AE), it was more likely that the second JAKi would also be stopped due to an AE. Improvement in CDAI over time was similar in both strategies. Conclusions After failing the first JAKi, cycling JAKi and switching to a bDMARD appear to have similar effectiveness. Caution is advised if an AE was the reason to stop the first JAKi.

Background Results of the “ORAL Surveillance” trial showed higher risk of major adverse cardiovascular (CV) events (MACE) for Janus kinase inhibitors (JAKi) than for TNF-inhibitors (TNFi). Currently, there is limited evidence of the real-world cardiovascular safety of JAKi. Objectives To assess the incidence of MACE in rheumatoid arthritis (RA) patients treated with JAKi, compared to other biologic agents in a large multi-country real-world population. Methods Patients from 14 RA registers from across Europe, Turkey and Québec (Canada), starting JAKi, TNF-inhibitors or bDMARDs with other modes of action (OMA), were included. MACE comprised strokes, myocardial infarctions and transient ischemic attacks and were attributed to a treatment up to 3 months after treatment cessation (except for rituximab for which it was 1 year), loss of follow-up, death or end of study. Incidence rates (IR) of MACE per 1000 patient-years (PY) with 95% confidence intervals (CI) were computed. Poisson regression, with propensity score weighting (including country, disease-, and patient-characteristics, and comorbidities, see Figure 1), was used to obtain adjusted incidence rate ratios (IRR), with 95% CI. A sub-analysis was performed on patients aged ≥ 50 years and ≥ 1 CV risk factor, mimicking the “ORAL Surveillance” trial inclusion criteria (RCT-duplicate cohort). Results Over the 50'325 treatment initiations considered (Table 1) in 34'932 patients with a mean follow-up of 2.8 years, 182 incident MACE were reported. Crude incidence was higher for OMA (2.63/1000 PY) than for JAKi (1.76/1000 PY) and TNFi (1.86/1000 PY). The adjusted Poisson regression demonstrated no significant difference in the incidence of MACE between JAKi vs TNFi (IRR = 0.87 (95% CI 0.56; 1.35)), and OMA vs TNFi (IRR = 1.05 (95% CI 0.74; 1.49)) (Figure 1). The RCT-duplicate cohort accounted for 38.4% of treatment courses and had a higher incidence of MACE in each treatment group (OMA: 3.75/1000 PY, JAKi: 2.65/1000 PY, TNFi: 3.48/1000 PY). Similarly to the overall population, no significant difference in the incidence of MACE was observed between JAKi vs TNFi (IRR = 0.78 (95% CI 0.44; 1.38)), and OMA vs TNFi (IRR = 0.84 (95% CI 0.53; 1.32)). Conclusion In this real-world study, including 14 RA registers and all currently available JAKi in the respective countries, we did not find a significantly higher risk of MACE in RA patients treated with JAKi compared to TNFi. Inclusion of other registers to increase the statistical power and the evaluation of other adverse events such as thromboembolic events, cancers and serious infections are planned. References [1]Ann Rheum Dis 2022. doi: 10.1136/annrheumdis-2021-221915. Acknowledgements: NIL. Disclosure of Interests Romain Aymon: None declared, Denis Mongin: None declared, Sytske Anne Bergstra Grant/research support from: Pfizer, Denis Choquette Speakers bureau: Abbvie, Amgen, Pizer, Sandoz and Tevapharm, Consultant of: Abbvie, Amgen, Celltrion, Eli Lilly, Fresenius-Kabi, INESSS, Jamppharma, Pfizer, Sandoz and Tevapharm, Grant/research support from: Rhumadata is supported through grants from Abbvie, Amgen, Fresenius-Kabi, Eli Lilly, Pfizer, Sandoz and Tevapharm, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, René Lindholm Cordtz: None declared, De Cock Diederik: None declared, Lene Dreyer Grant/research support from: Research grant from BMS outside the present work, Ori Elkayam Consultant of: Pfizer, Lilly, Abbvie, Novartis, Jansen, BI, Doreen Huschek: None declared, Kimme Hyrich Speakers bureau: Abbvie, Grant/research support from: Pfizer and BMS, Florenzo Iannone Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, SOBI, Roche and UCB, Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, SOBI, Roche and UCB, Nevsun Inanc Speakers bureau: Abbvie, Amgen, Pfizer, Novartis, Roche, Lilly, MSD, Boehringer Ingelheim and Abdi İbrahim, Consultant of: Abbvie, Amgen, Pfizer, Novartis, Roche, Lilly, MSD, Boehringer Ingelheim and Abdi İbrahim, Lianne Kearsley-Fleet: None declared, Tore K. Kvien Speakers bureau: AbbVie, Amgen, Celltrion, Gilead, Grünenthal, Novartis, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, Celltrion, Gilead, Grünenthal, Novartis, Pfizer, Sandoz, UCB, Burkhard Leeb Speakers bureau: Eli-Lilly, Pfizer, Astropharma, Biogen, Celgene, Consultant of: Eli-Lilly, Pfizer, AbbVie, Biogen, Celgene, Galina Lukina Speakers bureau: AbbVie, Pfizer, Novartis, Dan Nordström Consultant of: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Fatos Onen Speakers bureau: Abbvie, Amgen, Pfizer, Novartis, Roche, Lilly, and MSD, Consultant of: Abbvie, Amgen, Pfizer, Novartis, Roche, Lilly, and MSD, Karel Pavelka Speakers bureau: Novartis, AbbVie, Eli Lilly, Pfizer, UCB, MSD, Biogen, Celltrion, Manuel Pombo-Suarez Speakers bureau: Janssen, Merck Sharp & Dohme, Novartis and Sanofi Genzyme, Consultant of: Janssen, Merck Sharp & Dohme, Novartis and Sanofi Genzyme, Sella Aarrestad Provan: None declared, Ana Maria Rodrigues Speakers bureau: Amgen, Phizer, Astrazeneca, Novartis, Roche and Nordic pharma, Consultant of: Amgen, Phizer, Astrazeneca, Novartis, Roche and Nordic pharma, Grant/research support from: Reuma.pt is supported througth grants from Abbvie, Bristol Myers Squibb, Lilly, MSD, Novartis, Pfizer, Boehringer Ingelheim, Astrazeneca and Amgen, Ziga Rotar Speakers bureau: Abbive, Amgen, Biogen, Eli Lilly, Medis, Mediasi, Novartis, Sandoz, Pfizer, MSD, Sanofi, Roche, SOBI., Consultant of: Abbive, Amgen, Biogen, Eli Lilly, Medis, Mediasi, Novartis, Sandoz, Pfizer, MSD, Sanofi, Roche, SOBI., Anja Strangfeld Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, Pfizer, Roche, Sanofi, UCB, Grant/research support from: Non-personal, joint grant from a consortium of 14 pharmaceutical companies for the biologics register RABBIT to my institute., Patrick Verschueren Speakers bureau: Abbvie, Eli Lilly, Galapagos, Consultant of: Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma and Sidekick Health, Jakub Zavada Speakers bureau: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis and UCB, Consultant of: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis and UCB, Delphine Courvoisier: None declared, Axel Finckh Consultant of: Pfizer, BMS, MSD, Eli-Lilly, AbbVie, Galapagos, Mylan, UCB, Viatris, Grant/research support from: Pfizer INC, AbbVie, Galapagos, Eli Lilly, Kim Lauper Speakers bureau: Pfizer, Viatris and Celltrion, Consultant of: Pfizer.Table 1Baseline characteristicsJAKi (TOFA, BARI, UPA, FILGO)n = 12'715OMA (RITU, TOCI, ABA, SARI)n = 16'048TNFi (ETN, ADA, GOL, CTZ, IFX)n = 22'102Treatment duration (median [IQR])1.4 [0.5, 2.7]1.3 [0.4, 2.7]1.5 [0.6, 2.9]Age (mean (SD))58.0 (12.4)59.5 (12.7)56.5 (13.7)Female (%)81.479.278.4Disease duration (median [IQR])11.4 [5.7, 19.0]12.4 [6.3, 20.7]9.2 [4.1, 17.0]Seropositivity (%)80.581.075.1Previous b/ts DMARD (%)023.319.544.1122.324.826.5217.921.715.5≥ 336.633.913.9Concomitant csDMARD (%)MTX22.422.423.9MTX + other9.39.914.0other15.318.017.7none53.052.044.5Concomitant GC (%)44.739.832.4CRP (mg/L) (mean (SD))12.4 (23.2)13.9 (29.0)12.5 (23.3)CDAI (mean (SD))25.4 (13.9)22.8 (13.9)24.7 (13.9)DAS 28 (mean (SD))4.7 (1.6)4.2 (1.7)4.5 (1.7)HAQ (mean (SD))1.2 (0.7)1.2 (0.8)1.1 (0.7)BMI (mean (SD))27.2 (5.9)27.3 (5.9)27.4 (6.3)Patients with at least one CV risk factor* (%)54.956.654.1csDMARDs = conventional synthetic DMARDs, MTX = methotrexate, GC = glucocorticoids, CRP = C-reactive protein, CDAI = Clinical Disease Activity Index, DAS 28 = Disease Activity Score 28, HAQ = Health Assessment Questionnaire, BMI = Body Mass Index. *Hypertension, hyperlipidaemia, diabetes, smoking, past history of strokes or myocardial infarctions

Background The question of the comparative efficacy of tumor necrosis factor-alpha (TNF-α) inhibitors is topical today, because the research data that were distributed in random sequence mainly reflect the efficacy of the only specific drug, and the available data obtained in the ankylosing spondylitis (AS) treatment use of a network meta-analysis are limited. Objectives To make a comparative evaluation of the efficacy of various TNF-α inhibitors for patients with AS in real clinical practice. Methods The study involved patients with a reliable diagnosis of AS (according to the 1984 New York criteria) who received TNF-α inhibitor during the 12-month course of therapy, from 2018 to 2022. The efficacy of the drugs was evaluated by the ASDAS (CRP) (Ankylosing Spondylitis Disease Activity Score) and BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) – disease activity indices obtained 6 and 12 months after the start of therapy. Comparison of indicators between drugs was carried out using a non-parametric Kruskal-Wallis test, designed to test the equality of the medians of several samples. Results The study involved 257 patients with AS who were treated with various TNF-α inhibitors, among which Adalimumab was taken by 77 patients (29.96%), Golimumab - 20 (7.78%), Infliximab - 15 (5.84%), Certolizumab pegol - 27 (10.51%) and Etanercept - 118 (45.91%). The mean age of the involved patients was 46.1 ± 11.4 years old, the mean age at the onset of the disease was 28.7 ± 11.7 years old. The majority of patients were males - 167 (64.98%), 143 (55.64%) had Higher education, 163 (63.42%) were married, 103 (40.08%) have been working and - 150 patients (58.37%) had never smoked before the study. Mean ASAS (CRP) and BASDAI, disease activity indices, values ​​for each drug before therapy, 6 and 12 months after the start of therapy are presented in Table 1. «Head-to-head» comparison of medical preparations revealed no significant differences between TNF-α inhibitors in terms of the studied parameters (p > 0.05). Table 1. Months since start of therapy BASDAI ASDAS (CRP) Adalimumab 0 5,84 3,38 6 3,52 1,91 12 4,11 2,24 Golimumab 0 5,91 3,29 6 5,17 2,91 12 4,61 2,68 Infliximab 0 3,56 2,25 6 2,59 1,08 12 2,20 1,39 Certolizumab pegol 0 6,57 3,80 6 3,38 2,17 12 3,50 2,81 Etanercept 0 6,13 3,79 6 3,75 2,20 12 3,80 2,28 ASDAS - Ankylosing Spondylitis Disease Activity Score; BASDAI - Bath Ankylosing Spondylitis Disease Activity Index; CRP - C-reactive protein Conclusion The studied TNF-α inhibitors demonstrate similar clinical efficacy in real clinical practice. A direct comparison of drugs didn’t reveal significant differences between TNF-α inhibitors. Disclosure of Interests None declared

Background Retention on therapy is the most important integrative indicator of the success of the drug, reflecting both the effectiveness and tolerability and general acceptability of treatment. This indicator can be evaluated with high accuracy in observational trials. Objectives to identify predictors of TNF inhibitors withdrawal risk in patients with PSA. Methods Patients with (PSA) from Moscow Unified Arthritis Registry (MUAR) treated with TNF inhibitors were analyzed. All treatment episodes interrupted due to non-medical reasons were excluded from the study. Breaks in biologic therapy up to 4 months were allowed (for infliximab a break in therapy up to 6 month was considered possible) The search for predictors of treatment withdrawal risk was carried out in two steps. At the first step possible predictors of the risk of TNF inhibitors therapy discontinuation were selected in univariate сorrelations. At the second step significant predictors of retention on TNF inhibitors therapy were selected by forward stepwise variable selection within multivariate Cox regression. The relationship between the line of anti-TNF treatment and the risk of therapy discontinuation was analyzed separately. Results We analyzed 371 treatment episodes in 239 patients with PSA enrolled in MUAR, 97 male (40.6%), 50.2±12.1 years old. The age of disease onset was 36.8 ± 12.7 years. The patients received adalimumab (ADA) (101 treatment episodes), golimumab (GOL) (n=32), infliximab (INF) (n=55), certolizumab pegol (CER) (n=31), etanercept (ETA) (n=152). There were 187 (50.4%) completed treatment episodes. The relationship between risk of TNF inhibitors discontinuation and the drug line was analyzed. We found that the withdrawal risk on the second TNF inhibitor didn’t significantly differ from the withdrawal risk on the first line anti-TNF drug (p=0,201). The third and subsequent lines of TNF inhibitors where associated with the significantly higher risk of withdrawal. Direct step-by-step selection of variables made possible to identify the following significant predictors of retention on therapy – social status, the presence of HLA B-27, fever during the disease, pain in sacral zone at the onset of the disease, coccidinia during the disease, patient reports on the association of the onset of the disease with a genital infection (uretritis, adnexitis, prostatitis, endometritis) (Table 1) Table 1. Independent predictors of anti-TNF treatment discontinuation Predictors Direction of association with the dicontinuitation risk p Social status Working patients had a lower risk 0.038 The presence of HLA-B27 HLA-B27 positive patients had lower risk 0.005 Temperature elevation during the disease Patients WHO reported an increase in body temperature during the disease had an increased risk < 0.001 Sacral pain at the onset of the disease Patients who reported sacral pain at the onset of the disease had an increased risk 0.037 Coccygeal pain during the disease Patients who reported pain in the coccyx during the disease had an increased risk 0.026 Presence of genital infections Patients who reported a link between the onset of the disease and a history of urethritis or endometritis had a high risk 0.011 After adjusting for the line of therapy and the identified predictors of the risk of drug withdrawal it was found that retention on all analyzed TNF inhibitors in patients with PSA didn’t differ significantly (Figure 1) Conclusion The identified significant mutually independent predictors of the risk of discontinuation of treatment may be useful when choosing biological therapy in patients with PSA. Discontinuation therapy risk of various TNF inhibitors does not differ significant. The risk of withdrawal therapy with the second TNF inhibitor is not significantly differ from the first one. Thus, in case of failure of the first attempt of treatment with an TNF inhibitor, a second attempt can be made The probability of success of subsequent attempts seems to be very low Figure 1. Adjusted analysis of treatment survival on TNF inhibitors Disclosure of Interests None declared

Background The main goal of rheumatoid arthritis (RA) patients therapy is to achieve low activity or remission of the disease (T2T strategy). However, it is sometimes necessary to interrupt effective treatment due to the development of adverse events. Objectives To reveal predictors of target drug withdrawal due to adverse RA. Methods The study includes patients with RA used bDMARDs, total 1217 treatment events. Search for predictors was carried out in two steps. At the first step were selected variables which demonstrated significant correlation with time to treatment discontinuation in Kaplan-Meier analysis. At the second step selected factors were included in the Cox regression model. The final set of independent significant predictors was obtained by backward stepwise variable selection. Results Of 661 patients 85,8% were women, the mean age of onset disease 58,7 ± 12,9 years, the mean disease duration 14,6 years. The longest mean time till withdrawal due to adverse events had Abatacept, Toficitinib, Tocilizumab, the shortest time had Infliximab. There were 146 cases of therapy discontinuation due to adverse events. The side effects that caused the cancellation of treatment were: infections of respiratory system, skin, urinary system, allergic and infusion reactions, drug-induced hepatitis, changes in the hematopoietic system, death and other. Рresence of rheumatoid nodules (p < 0.001), higher doses of glucocorticoids (p<0.001), lower doses of methotrexate (p = 0.009) were independent significant predictors of increased risk of bDMARDs withdrawal due to adverse events. Used target drug also showed independent significant correlation with this risk. Relative risk (compared to Etanercept) was for Infliximab - 6.57 (CI: 3.69-11.73), Certolizumab pegol - 2.61 (CI: 1.23-5.56), Abatacept - 1.23 (CI: 0.65-2.30), Adalimumab - 1.37 (CI: 0.75-2.50), Rituximab - 0.56 (CI: 0.26-1.20), Tofacitinib - 0.46 (CI: 0.15-1.40), Tocilizumab - 0.77 (CI: 0.37-1.60). Conclusion Growth glucocorticoid doses for every 1 mg increases the risk of discontinuation of therapy by 8.7%. Reducing the methotrexate doses for every 1 mg increases the risk of discontinuation of bDMARDs and tsDMARDS by 3%. There are significant differences between target drugs for the risk of cancellation due to adverse events. High risk of infliximab discontinuation was associated more with infusion reactions and infection, discontinuation of certolizumab pegol was associated with infection. References [1]The identified predictors for the treatment withdrawal due to side effects may be discussed to identify measures necessary to prevent adverse events in patients with RA who are using bDMARDs and tsDMARDs. These measures are: the use of full doses of methotrexate, avoid long-term use of glucocorticoids, or prescription of the targeted drug with lower risk of adverse events. Disclosure of Interests None declared

BackgroundAnkylosing spondylitis (AS) is an immune-mediated inflammatory disease of the musculoskeletal system, that is often accompanied with a subclinical intestinal inflammation. Inflammatory bowel diseases (IBD), including, Crohn’s disease (CD) and ulcerative colitis (UC), are the most frequent extra-articular manifestation in patients (pts) with AS. Several autoantibodies and antimicrobial antibodies are used as additional non-invasive serological markers for the diagnosis of CD and UC [1]. The evaluation of IBD-associated antibodies in AS pts provided conflicting results [2, 3].ObjectivesThe aim of the study was to determine the serum levels of IBD-specific antibodies in AS.MethodsWe studied 51 pts with AS fulfilled modified New York criteria (1984); (40M/11F); median and interquartile range (25th—75th percentile) of age 44.0; 34.0-49.0 years; disease duration 12.0; 5.0-20.0 years; BASDAI - 5.3; 4.5-6.4; ASDAS ESR - 3.6; 3.0-4.4; ASDAS CRP - 3.7; 2.8-4.5; 40% HLA-27 positive. In 22% of pts with AS, IBD (CD and UC) were diagnosed. The control group included 44 healthy donors (HC). Atypical perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) were detected using indirect immunofluorescence. The serum levels of IgA/IgG antibodies to Saccharomyces cerevisiae (ASCA), IgA/IgG antibodies to glycoprotein 2 (GP2), IgG antibodies to cathepsin G, lactoferrin, elastase and bactericidal permeability-increasing protein (BPI) were detected by ELISA.ResultsAS pts without signs of IBD and AS with IBD (AS/IBD) pts had significantly higher serum levels of IgA ASCA, IgA anti-GP2, anti-elastase antibodies than HC (4.5; 2.6-6.4 U/ml and 4.9; 3.7-7.3 U/ml vs 1.9; 0.6-2.6 U/ml, p=0.0008, p=0.001; 1.2; 0.8-5.5 U/ml and 1.2; 0.9-11.8 U/ml vs 0.7; 0.6-1.3 U/ml, p=0.007, p=0.02; 8.2; 5.9-9.9 U/ml and 9.1; 8.5-10.5 U/ml vs 5.6; 4.7-8.3 U/ml, p=0.01, p=0.003). The median concentration of anti-cathepsin G antibodies was greater for AS/IBD pts than AS pts (0.8; 0.5-1.0 U/ml vs 0.4; 0.3-0.6 U/ml, p=0.02). In AS and AS/IBD, the occurrence of anti-elastase antibodies (23.0%, 33.0%) was higher than for HC (0%, p=0.05, p=0.01). The positivity rate of IgA anti-GP2 in AS/IBD exceeded that in HC (27.0% vs 0%, p=0.025). AS/IBD pts demonstrated a higher prevalence of pANCA (36.0%), and anti-BPI antibodies (36.0%), when compared to AS alone (4.8%, p=0.005, and 8.0%, p=0.02) and HC (0%, p=0.0001, and 0%, p=0.008).ConclusionOur findings indicate that elevated serum levels of IgA ASCA, IgA anti-GP2, anti-elastase antibodies in AS did not differ from those in AS/IBD and may serve as potential biomarkers for predicting intestinal inflammation at an early stage. For AS/IBD, the most useful diagnostic markers were atypical pANCA, IgA ASCA, IgA anti-GP2, anti-elastase and anti-BPI antibodies.References[1]Prideaux L, De Cruz P, Ng SC, Kamm MA. Serological antibodies in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis. 2012; 18(7):1340-55.[2]Benfaremo D, Luchetti M, Gabrielli A. Biomarkers in inflammatory bowel disease-associated spondyloarthritis: state of the art and unmet needs. J Immunol Res. 2019 May 30; 2019:8630871.[3]De Vries M, Van Der Horst-Bruinsma I, Van Hoogstraten I., et al. pANCA, ASCA, and OmpC antibodies in patients with ankylosing spondylitis without inflammatory bowel disease. J Rheumatol. 2010; 37(11):2340–4.Disclosure of InterestsNone declared

Currently, a large number of highly effective biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are used for the treatment of rheumatoid arthritis (RA). However, in addition to effectiveness, it is necessary to evaluate the risk of adverse events (AEs) when using them.Objective: to determine the predictors of bDMARDs and tsDMARDs discontinuation due to AEs in patients with RA.Patients and methods. The study included 661 patients with RA who took bDMARDs and tsDMARDs. The search for predictors of targeted therapy discontinuation due to AEs was carried out in two stages. At the first stage, using the Kaplan-Meier method, we selected indicators that showed the greatest significant single-factor relationship with the duration of retention on therapy. At the second stage, significant independent indicators were obtained by iterative selection of variables within the multivariate proportional risk model according to Cox.Results and discussion. The presence of rheumatoid nodules (p<0.001), high doses of glucocorticoids (GC; p<0.001), low doses of methotrexate (MT; p=0.009) are significant independent factors for increasing the risk of drugs discontinuation due to the development of AEs. The type of bDMARDs/tsDMARD used also significantly correlated with the risk of discontinuation of therapy due to AEs. A relatively high risk of treatment discontinuation was observed with infliximab (IFN) and certolizumab pegol (CZP). Cancellation of IFN was associated with the occurrence of infusion reactions and infectious complications, and CZP was associated with infectious complications.Conclusion. An increase in the dose of MT and decrease in the use of GCs can help prevent the development of AEs leading to the abolition of biologics and tsDMARDs. Significant differences were found between bDMARDs in terms of the risk of their cancellation due to AEs.

BackgroundWith the advent of medications with different mechanisms of action in the treatment of rheumatoid arthritis (RA), clinicians face the challenge of personalizing the approach to the treatment of RA patients. One of the steps in this direction is to identify predictors of the effectiveness of the therapy. This work is devoted to the identification of predictors of the therapy effectiveness with the blocker of T cells co-stimulation - abatacept (ABA).ObjectivesSearch for clinical and immunological predictors of the effectiveness of ABA therapy.Methods91 patients were included in the study, most of them women, with high disease activity of RA (DAS28=5.1±1.0, SDAI=28±13.4, CDAI=25±12) and failure of previous biologics (51, 6%) and DMARDs (100%). Moreover, in 20% (n=18) of patients the inefficiency more than 2 biologics were recorded. The average duration of the disease was 3.0 (1.4–12) years, most patients were positive for RF 72.5%, ACCP 77%, AMCV 86%. In 44 patients the levels of RF, ACCP, AMCV and MMP-3 were assessed after 24 weeks of ABA therapy. In 36 patients enzyme-linked immunoassay was used to measure serum concentrations of biomarkers IL-1β, IL-6, IL-17AF, TNF-α, VEGF-A, IP-10, YKL-40 at baseline and after 24 weeks of ABA therapy. The effectiveness of therapy was assessed according to the EULAR criteria. ABA IV infusions were performed according to the standard schedule. Methods of parametric and non-parametric statistics were used in statistical analysis.ResultsABA treatment led to a significant decrease of disease activity assessed by DAS28, SDAI, CDAI starting from 3 months of therapy (p<0.05). More than half of the patients were in remission and had low disease activity according to the DAS28 (65.7%, n=35) after 48 weeks of treatment. After 48 weeks, the highest percentage of patients with RA remission was registered by the DAS28 (37.4%, n=20), the lowest — SDAI (21.6%, n=11). After 24 weeks of therapy, ABA led to a significant decrease in the serum levels of IL-6 from 2.4 [1.1 - 6,4] to 1.29 [0.9-2.2] pg/ml, (p=0.0006), IP-10 from 21 [12,9-49,8] to 14 [7.5-28] pg/ml, (p=0.007) and matrix metalloproteinase 3 (MMP3) from 30.1 [13-82] pg/ml to 10 [7.4-55] pg/ml, (p = 0.0003). A decrease in the serum level of IL-6 significantly correlated with a decrease in the DAS28 and SDAI (r=0.5 and r=0.479, p<0.05), IP-10 with DAS28 (r=0.326, p<0.05). Initially, the serum level of TNF-α was significantly lower in patients who achieved low disease activity by the SDAI (72.6%, n=37) after 48 weeks of therapy, compared with the rest. On the contrary, a significantly higher level of IP-10 before treatment was recorded in patients with a good response according to the EULAR criteria (39%, n=29) after 48 weeks of ABA treatment (Figure 1). The ROC-analysis revealed that an initially high concentration of TNF-α may indicate with 71% sensitivity and 77% specificity about the possible ineffectiveness of ABA therapy after 48 weeks of treatment, the area under the curve was 0.7, 95% CI (0.5– 0.9). In patients initially positive for AMCV, low RA activity by SDAI was significantly more often registered after 24 (p=0.04) and 48 weeks. (p=0.01). 89% (n=34) of AMCV-positive patients achieved low disease activity after 48 weeks therapy by the SDAI and CDAI. It is noteworthy that a cohort of patients with insufficient effect after 48 weeks consisted entirely of AMCV-negative patients.ConclusionABA therapy led to a significant decrease in disease activity according to the main indices (DAS28, SDAI, CDAI). During ABA treatment, there was a decrease of important immunoinflammatory markers - IL-6, IP-10, MMP-3. AMCV positivity is significantly associated with higher efficacy of ABA therapy. Also, a high basal concentration of TNF-α could use as a predictor of possible failure of ABA therapy, and a high initial level of IP-10, on the contrary, indicates the possible efficacy of ABA therapy.ReferencesNoneDisclosure of InterestsNone declared

BackgroundThe incidence of infections, mainly pneumonias, is significantly increased in patients with rheumatoid arthritis (RA). The risk increases more in persons treated with targeted anti-inflammatory drugs (tDMARDs), biological or targeted synthetic.Pneumococcal vaccination is recommended for most patients with rheumatic diseases. However, only the immunological effectiveness of such vaccination has been sufficiently confirmed. There is sparse evidence of its clinical efficacy in patients with rheumatic diseases.Objectivesto evaluate the effect of 23-valent pneumococcal polysaccharide vaccine (PPV23) and 13-valent pneumococcal conjugate vaccine (PCV13) on the risk of infections in RA patients receiving tDMARDs.MethodsThe data from the Moscow Unified Arthritis Registry (MUAR) for the period 2018-2020 were analyzed. We included patients with RA, over 18 years old, received tDMARDs (all available biologics or tofacitinib).The analysis included episodes of observation from the moment of vaccination with pneumococcal vaccine until the development of the analyzed event (any infection, respiratory infection or serious infection) or until the end of follow up. For unvaccinated patients, episodes began since October 20, 2018 (the average date of vaccination of persons who received immunization).The risks were compared using Cox regression. An adjustment was made for confounders identified in an earlier study: age and smoking.ResultsThe analysis included 832 patients: 40 were vaccinated with PCV13, 35 – with PPV23. There were 144 men (17.3%). The mean age was 55.4 ± 12.1 years. The duration of observation was 319 ± 198 days.A total of 237 infectious events were registered, of which 201 were respiratory and 21 serious (Table 1). There was a significantly lower risk of any infection (relative risk (RR) – 0.39 CI: 0.18 - 0.84, p = 0.015) and the risk of respiratory infection (RR - 0.32; CI: 0.13 -0.79; p = 0.014) in the group of patients vaccinated with PCV13 compared with unvaccinated. The differences remained statistically significant after adjusting for the age and smoking, Figure 1.Table 1.Registered infectious eventsEvent groupsLocalisationNumberOf them seriousRespiratory infectionsEar, paranasal sinuses, tonsils162Upper respiratory tract1660Pneumonia1814Lung abscess11Other infectionsEye and appendages30Skin and subcutaneous tissue71Bones and joint22Urogenital tract60Digestive system, including the oral cavity21Herpes infections*160* - events are included in the group, regardless of localization, these events were not included in other sectionsFigure 1.Survival without infectious events (A) and without respiratory infections (B) adjusted for age and smokingThe interaction of the effects of vaccination with the factor of the used tDMARD, as well as with the factor of the use of methotrexate in their effect on the risk of any and respiratory infections was evaluated. There was no significant interaction between these variables.There were no significant differences in the risk of serious infections due to a small number of events of this kind. No serious infections were registered among patients vaccinated with PCV13.ConclusionVaccination with 13-valent conjugated pneumococcal vaccine in patients with rheumatoid arthritis receiving tDMARDs can significantly reduce the risk of infectious complications, mainly due to acute respiratory infections. We found no significant effect of targeted drug and treatment with methotrexate on the effectiveness of vaccination.Disclosure of InterestsEvgeniy Zhilyaev Speakers bureau: UCB Pharma, Biocad, Galina Lukina Speakers bureau: Pfizer, MSD, Biocad, Ekaterina Koltsova: None declared, Dzhamilya Murtazalieva: None declared, Evgeniya Shmidt: None declared, Karine Lytkina Speakers bureau: UCB Pharma, Anna Shmitko: None declared, Dmitry Blagovidov: None declared, Mikhail Kostinov: None declared

Background JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. Methods In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. Results We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. Conclusion The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.

Background Systemic juvenile idiopathic arthritis (sJIA) debuts in childhood and persists throughout the patient’s lifetime. Currently there is not enough information about the course and therapeutic approaches in patients who have reached the age of 18 and moved from pediatric service to adult healthcare system. Objectives Evaluate long - term outcomes in patients with sJIA over 18 years of age. Methods Thirty - two patients with sJIA have been analyzed after their transition to adult rheumatological chain. The following parameters have been estimated: clinical manifestations, disease duration, radiological changes, medication intake, disease activity, number of arthroplasties, pregnancy, level of education. Disease activity has been assessed using a standardized DAS28 index (remission - less than 2.6, low activity - from 2.6 to 3.2, moderate activity - from 3.2 inclusive to 5.1, high activity - more than 5.1) and counting systemic manifestations. Results Among patients included in the study, there were 11 men (34.38%) and 21 women (65.62%); the average age at the time of inclusion was 23.68 (±5.93). In 13 (40.63%) patients the onset of the disease occurred before the age of 5, in 7 (21.87%) - from 6 to 10 years and in 12 (37.50%) - after 11 years. In 9 (28.13%) patients the duration of the disease was less than 10 years, in 23 (71.87%) patients – more than 11 years. The onset of the disease was accompanied by the following symptoms: fever - 28 (87.50%) patients, arthritis - 21 (65.63%), rash - 17 (53.13), arthralgia - 6 (18.75%), pericarditis - 4 (12.50%), sore throat - 4 (12.50%), lymphadenopathy - 3 (9.38%), hepatomegaly - 2 (6.25%). Among patients with arthritis 11 (52.38%) had oligoarthritis, 10 (47.62%) had polyarthritis. 2 patients (6.25%) were diagnosed with uveitis. According to the X-ray examination (Steinbrocker’s classification of radiographic changes): 5 (15.63%) patients had the I stage, 13 (40.62%) - the II stage, 4 (12.50%) - the III stage, 6 (18. 75%) - the IV stage and 4 (12.50%) had no radiological changes. Three (9.38%) were diagnosed with aseptic necrosis and these patients underwent arthroplasty. Four (12,50%) patients had pregnancy. Education: 17 (53.13%) people study at higher educational institutions. Two (6.25%) have a higher educational level. Disease activity: 24 (75%) patients are currently in low activity or disease remission, 8 (25%) are in moderate activity. Twenty (62.50%) patients receive therapy with disease - modifying antirheumatic drugs (DMARDs), 14 of them take methotrexate at an average dose of 12.68 (±3.98) mg. 6 (18.75%) patients take glucocorticoids at a dose of 1 to 8 mg per day. Non - steroidal anti - inflammatory drugs (NSAIDs) are received by 2 (6.25%) patients. Biological disease - modifying antirheumatic drugs (bDMARDs) are used by 27 (84.38%) patients, 18 (66.67%) of whom are on therapy with tocilizumab. Among the patients with low activity and disease remission: 15 out of 24 (62.50%) are treated with tocilizumab, 3 (12.50%) – with canakinumab, 3 (12.50%) – with etanercept, and 1 (4.17%) – with adalimumab; 2 (8.33%) patients don’t take bDMARDs. Conclusion The use of bDMARDs helps successfully control the disease in patients with sJIA, maintain long - term remission and improve long - term outcomes in adult patients with sJIA. Disclosure of Interests None declared

Background Rheumatoid arthritis (RA) is accompanied by a significant increase in the risk of infection and serious infections, among which pneumonia occupies a leading place. (1) The use of targeted anti-inflammatory drugs is accompanied by an additional increase in the risk of infectious complications. In this regard, vaccination is crucial in the management of such patients. Objectives To evaluate the safety and efficacy of the 13-valent pneumococcal vaccine in patients with RA undergoing various types of antirheumatic therapy. Methods The study included 60 patients with a reliable diagnosis of RA, according to the criteria of ACR/EULAR, among them 8 men and 52 women, average age 63 years (from 29 to 69 years) with disease activity at the time of inclusion of Das-28 – 4.9 (2.2-7.7), bionaive patients with insufficient response to DMARDs who will be prescribed tofacitinib (TOFA) for the first time or receiving TOFA for at least 3 months (30 patients in each group). Both groups of patients were further subdivided into two groups, 15 vaccinated and unvaccinated patients in each. The exclusion criteria were: age over 70 years; patients with infectious diseases in the acute stage; having a history of intolerance to diphtheria toxoid, patients who had previously been vaccinated with pneumococcal vaccines. For the prevention of pneumococcal infection, a pneumococcal 13-valent polysaccharide conjugated adsorbed vaccine was used. Visits to assess the condition were made in the period of 0-3-12 months. The activity of the disease was assessed by the DAS 28, CDAI, SDAI indices. Results Among vaccinated patients with PCV 13 the most common adverse events were: pain at the injection site (16%), fever up to 37.6C (13%), redness at the injection site (6%), infiltration at the injection site (2%), myalgia (2%). These adverse events resolved spontaneously within 3 days. In a comparative assessment of infectious events during 12 months before vaccination and the next 12 months after it, there were no significant differences between vaccinated and unvaccinated patients. In patients who had a history of pneumococcal etiology infections after vaccination, the incidence decreased by 33%. Conclusion Vaccination against pneumococcal infection is a safe and effective method of preventing pneumococcal infection in patients with rheumatoid arthritis. References [1]Koivuniemi R., Leirisalo-Repo M., Suomalainen R., etc. Infectious causes of death in patients with rheumatoid arthritis: an autopsy study. Scand J Rheumatol 2006; 35)4): 273-6 Disclosure of Interests Galina Lukina Speakers bureau: Ebbvie, Biocad, Pfizer, Roche, Dzhamilya Murtazalieva: None declared, Ekaterina Koltsova: None declared, Mikhail Kostinov: None declared, Anna Shmitko: None declared, Dmitry Blagovidov: None declared, Evgeniy Zhilyaev Speakers bureau: Ebbvie, Biocad, Pfizer, Roche