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

The JAK inhibitor tofacitinib (TOFA) blocks the intracellular signaling pathway that activates the synthesis of cytokines and mediators involved in the development of pain and central sensitization (CS), which determines the rapid analgesic effect. However, it is not clear how pain reduction is associated with achieving low activity in rheumatoid arthritis (RA).The aim of the study was to assess the relationship between the early clinical response to tofacitinib and a decrease in rheumatoid arthritis activity after 3 and 6 months.Material and methods. The study group consisted of 88 RA patients (age – 53±11.5 years; 79.3% of women) who received basic anti-inflammatory drugs (59.5% – methotrexate, 19.8% – leflunomide) and who were prescribed TOFA in a dose 10 mg/day. Seropositivity for rheumatoid factor was 89.8%; the value of the DAS28 index is 5.2±1.2. The severity of pain was assessed using the Brief Pain Inventory questionnaire, the neuropathic component of pain (NCP) – using the PainDETECT questionnaire, signs of CS – using the Central Sensitization Inventory (CSI) questionnaire in the early stages after the administration of TOFA, RA activity – using the DAS28-CRP index after 3 and 6 months.Results. The mean severity of pain at baseline was 5.3±2.0 on the visual analogue scale (VAS); 51.1% of patients had signs of CS (CSI>40), 15.9% had NCP (PainDETECT>18). 7 days after the start of therapy, there was a significant decrease in pain – to 4.1±1.8 according to VAS (p<0.05) and CS – 40.4±13.5 to 36.5±12.5 according to CSI (p=0.01). After 28 days, the effect was even more significant: the level of pain according to the VAS was 2.8±1.6 (p=0.000), the NCP decreased from 11.8±5.6 to 6.8±3.1 (p=0.000), CS – up to 31.6±13.9 (p=0.000). The value of the DAS28-CRP index after 3 and 6 months was 3.7±1.3 and 3.6±1.2, respectively. The number of patients with pain relief ≥50% after 28 days was 59.9%, low RA activity after 3 months. (DAS28-CRP≤3.2) was acieved in 64.4% of patients. There was a clear correlation between the number of patients with a pain reduction of ≥50% at 28 days and the number of patients who achieved low RA activity at 3 and 6 months. (rS=0.548, p=0.000 and rS=0.790, p=0.000). 6 patients dropped out of the study due to inefficiency or social reasons. No serious adverse reactions were noted.Conclusions. The use of the JAK inhibitor TOFA allows achieving a quick analgesic effect and reducing the signs of CS. An early clinical response to TOFA (pain relief) predicts a decrease in RA activity after 3 and 6 months of therapy.

Objective: to studythe clinical, dynamic and prognostic aspects of acute transient psychoticdisorders. Methods: 67 inpatients with acutepsychotic state which was developed for the first time, free of schizophreniasymptoms (23.0 F; F 23.3; 23.8 F; F 23.9 ICD-10) were examined. Mean age ofthe patients: 31,7±11 years. Clinical and psychopathological, clinical follow-up,statistical methods were used. The followup period of observation lasted 6years from the moment of reduction of psychotic symptoms of the 1st psychotic episode.

Background:JAK inhibitors block intracellular signaling pathways responsible for the synthesis of cytokines and mediators involved in the development of chronic pain and central sensitization (CS). This determines a very rapid clinical response to JAK inhibitors. However, it is not clear how the significant pain reduction in the first weeks of therapy is associated with the achievement of low rheumatoid arthritis (RA) activity.Objectives:to assess the relationship between the early clinical response to tofacitinib and the decrease in RA activity after 3 and 6 months.Methods:Study group included 88 patients with RA, their age was 53±11,5, 79.3% of women, 89.8% of RF “+”, DAS28 5.2±1.2, receiving DMARDs (methotrexate 59.5% and leflunomide 19.8%), who were administered with tofacitinib 5 mg 2 times a day due to inefficacy or intolerance of biological DMARDs. There were assessed the pain severity using Brief pain inventory (BPI) questionnaire, the presence of neuropathic pain component (NPC) using PainDETECT questionnaire and signs of CS using Central Sensitisation Inventory (CSI) questionnaire at early time after tofacitinib administration, RA activity using DAS28 after 3 and 6 months.Results:The mean pain severity at baseline was 5.3±2.0 according to the visual analogue scale (VAS 0-10), 51.1% of patients had signs of central sensitization (CSI ≥ 40), 15.9% had NPC (PainDETECT ≥18). 7 days after tofacitinib intake there was statistically reliable reduction of pain severity – up to 4.1±1.8 (р<0.05) and CS – CSI from 40.4±13.5 to 36.5±12.5 (р=0.01). After 28 days, the effect was higher: the pain level (VAS) was 2.8±1.6 (p=0.000), PainDETECT decreased from 11.8±5.6 to 6.8±3.1 (p=0.000), CSI – to 31.6±13.9 (p=0.000). DAS28 after 3 and 6 months was 3.7±1.3 and 3.6±1.2. The number of patients with pain decrease of ≥50% after 28 days of therapy was 59.9%. Low RA activity after 3 months. (DAS28 ≤3.2) was achieved in 64.4% of patients. There was a clear correlation between the number of patients with significant pain reduction at 28 days and the number of patients with low RA activity after 3 and 6 months (rS=0.548, p=0.000; rS=0.790, p=0.000). Six patients withdrew from the study due to inefficacy or social reasons. There were no serious adverse reactions.Conclusion:The application of JAK inhibitor tofacitinib allows to reach a fast analgesic effect and reduce CS signs. An early clinical response to tofacitinib (pain relief) predicts a decrease in RA activity after 3 and 6 months of the therapy.Limitation: Open-label observatory study.Disclosure of Interests:None declared