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Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease of unknown etiology, characterized by overproduction of organ-nonspecific autoantibodies to various components of the cell nucleus and cytoplasm and the development of immune-inflammatory damage to internal organs. The debut of SLE is preceded by an asymptomatic period, characterized by impaired immunological tolerance to its own autoantigens, determined by the multifaceted interaction of external, genetic and epigenetic factors, hormonal disorders, microbiome pathology, stress effects, etc. Development of a certain spectrum of clinical symptoms characteristic of SLE along with the detection of a reflects the progression of the immunopathological process in SLE, however, there is no generally accepted term that defines the patient’s condition, which has individual serological and clinical signs characteristic of this disease. In rheumatology, the concept of «incomplete» SLE is currently most often used. The problems of early diagnosis of SLE, clinical and laboratory predictors of the transformation of “incomplete” SLE into “reliable” SLE, difficulties in diagnosing SLE during the COVID-19 pandemic are considered. Particular attention is paid to the comparative characteristics of the immunopathological mechanisms of SLE and COVID-19.

Objective: To define the role of IgA antibodies to cardiolipin (aCL) and IgA antibodies to beta-2 glycoprotein 1 (anti-β2-GP1) in the development of vascular complications in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Material and methods: A total of 187 patients with one of the following diagnoses: primary APS (PAPS), probable APS, SLE with APS, and SLE without APS. The comparison group consisted of 49 patients with other rheumatic diseases (RD), the control group included 100 relatively healthy individuals (without RD, oncological pathology, and infectious diseases). All patients underwent standard clinical, laboratory, and instrumental examinations before being included in the study and during follow-up. The aPL study included the determination of IgG/IgM aCL, IgG/IgM anti-β2-GP1 by enzyme-linked immunosorbent assay (ELISA), IgG/IgM/IgA aCL, IgG/IgM/IgA anti-β2-GP1 by chemiluminescence analysis (CLA), and lupus anticoagulant (LA). Results: IgA aCL were detected in 75 (40%) of the 187 patients with APS and SLE, in none of the comparison group, and in 2 (2%) of the control one. IgA anti-β2-GP1 were detected in 63 (34%) of the 187 patients with APS and SLE, in none of the patients in the comparison group, and in one (1%) of the control group. The prevalence of IgA aCL and IgA anti-β2-GP1 and their levels were statistically significantly higher in patients with APS (PAPS and SLE + APS) than the levels in patients with SLE and those of the comparison and control groups (p < 0.05). IgA aCL and IgA anti-β2-GP1 were significantly associated with thrombosis in APS (χ2 = 4.96; p = 0.02 and χ2 = 4.37; p = 0.04, respectively). The risk of thrombosis was 2.04 times higher in patients with positive IgA aCL than in patients without these antibodies, as well as in patients with positive IgA anti-β2-GP1; it was twice as high as in patients without antibodies. There was a high specificity of IgA aCL and IgA anti-β2-GP1 for both the diagnosis of APS and its clinical manifestations, despite a low sensitivity. Conclusions: The study revealed a relationship of thrombosis and APS with IgA aCL and IgA anti-β2-GP1. There was a high specificity of IgA aCL and IgA anti-β2-GP1 (95% and 93%, respectively) for the diagnosis of APS with a low sensitivity (54% and 44%, respectively). There were no patients with isolated positivity of IgA aCL and IgA anti-β2-GP1.

In this transglobal, randomized, double-blind, placebo-controlled, treat-to-target study, the maintenance of efficacy was compared between biologic–and biologic-free–disease-modifying antirheumatic drug (DMARD) combination regimens after low disease activity (LDA) was achieved with biologic DMARD induction therapy. Patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy received open-label etanercept 50 mg subcutaneously once weekly plus methotrexate with or without other conventional synthetic (cs) DMARDs for 24 weeks. Patients achieving LDA [disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR)

Background Recognizing systemic sclerosis (SSc) in patients without cutaneous involvement is a real challenge due to inapparent clinical picture. 1980 ACR classification criteria for SSc fail to verify the diagnosis in the majority of cases. Therefore, the diagnosis is usually established years and decades after SSc onset at the stage of full-blown visceral disease. Introduction of 2013 ACR/EULAR classification criteria into clinical practice allow early diagnosis of SSc even in cases without skin involvement thanks to the fact, that list of considered criteria includes telangiectasia, pulmonary arterial hypertension (PAH), abnormal nailfold capillaries and SSc-related autoantibodies. Objectives To identify specific features in the clinical course of SSc sine scleroderma (ssSSc) in patients with PAH. Methods 11 patients with verified SSc diagnosis according to 2013 criteria were included; participants did not have any SSc-specific signs of skin involvement, such as puffy fingers, fingers’ skin thickening/induration or skin atrophy. PAH was diagnosed in 11 patients during of right heart catheterization. Results Isolated Raynaud’s phenomenon (RP) was along-standing diagnosis (more than 5 years) in all patients, except for one whoman, in whom the disease manifested with signs of Sjogren’s syndrome (SjS) (parotitis). Benign, chronic, and gradually progressing during a long time disease was documented in all patients. In 7 patients out of 11 SSc diagnosis was initially suspected by cardiologists, and later confirmed by detection of antinuclear autoantibodies. The following signs were documented in SSc patients as initial manifesting non-Raynaud symptoms: esophageal dysmotility – in 3 patients, digital ulcers – in 2, telangiectasia – in 2 patients, and dyspnea (PAH symptom) – in 1 patient. None of the patients ever experienced skin thickening typical for SSc. RP was present in all 100%, but digital ischemic alterations – digital tip ulcers, pitting scars were found only in 3 patients. SSc diagnosis was verified based on abnormal nailfold capillaries (in 100% cases), and based on identification of SSc-specific antibodies (anticentromere antibodies – ACA) – in 7 patients. Anti-Ro-antibodies were found in 4 patients, anti-RNP-70 – in 3. SjS was established in 3 out of 4 anti-Ro-antibodies – positive patients and ruled out in one. Myositis was documented in past-medical history in one patient with anti-RNP-70-antibodies positivity. It should be noted, that 3 ACA-negative patients had, nevertheless, a “threshold” score value (9 scores) for SSc diagnosis, exhibiting many clinical features in favor of SSc diagnosis beyond any doubt. Esophageal dysmotility and associated symptoms were found in 10 out of 11 SSc patients. One patient had an SSc–rheumatoid arthritis overlap syndrome (erosive arthritis, joint deformities, positive ACA, rheumatoid factor, anti-CCP). Conclusion Introduction of 2013 ACR-EULAR classification criteria for SSc into clinical practice was highly relevant for identification of SSc cases without cutaneous involvement, providing therefore a timely diagnosis in this group of patients, and allowing to prognosticate the clinical course of PAH. 2013 ACR-EULAR classification criteria for SSc is an algorithm for SSc verification in patents with PAH, especially in the absence of typical for SSc cutaneous disease. The earlier PAH-SSc is diagnosed and PAH-specific therapy is initiated, the longer will be patient’ lifespan. Disclosure of Interests Natalia Yudkina: None declared, Alexander Volkov : None declared, Ekaterina Nikolaeva: None declared, Ildar Kurmukov: None declared, Evgeny Nasonov Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc.

Background: Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is used to control of chronic pain in osteoarthritis (OA), rheumatoid arthritis (RA) and to prevent the progression of ankylosing spondyloarthritis (AS). Amtolmetin guacil (AMG), which has a low risk of gastrointestinal complications, may have advantages for long-term use. Objectives: To evaluate the effect and safety of long-term use of aMG. Methods: AMG 600-1800 mg/day was prescribed to 442 patients with OA (60.6 + 10.2 years, women 88.7%), 126 with RA (55.0 + 14.0 years, women 84.2%) and 73 with the aS (47.0 + 12.0 years, women 30.0%). The primary end point was the dynamics of pain on a numerical rating scale (NRS), additional for OA - WOMAC pain and HAQ, for RA - DAS28-CRP, for aS - BASDAI, BASFI and aSDAS-CRP. The result of treatment was evaluated on 3 consecutive visits after 3 months (9 months of treatment). Results: After 9 months 65.2% of OA patients, 75.3% of RA patients, and 82.2% of aS patients continued to take aMG. In end of study, the median of pain decreased with OA from 5.6 [4.1–6.9] to 3.4 [1.7–5.1], with RA from 5.8 [4.0–7.5] to 3.4 [2.0-4.8], with aS from 5.8 [4.2-7.5] to 3.1 [1.5-5.0] NRS (p 3.5) decreased from 76.9% to 25.8%, p AMG tolerability was good. 15-25% patients had mild dyspepsia. Discontinuation of therapy due to side effects was only in 6 patients (0.93%). The development or worsening of arterial hypertension, as well as other cardiovascular complications, was not observed. Conclusion: AMG is an effective, well-tolerated NSAID, which is appropriate for long-term treatment of OA, RA and aS. Disclosure of interests: None declared

Background The latest data show that axial involvement in psoriatic arthritis (PsA) patients (pts) is associated with significantly worse disease status and widespread impairment of patient-reported outcomes (PRO’s) (1). Objectives To analyze clinical characteristics and PRO’s in PsA pts with and without radiographic sacroiliitis (rSI) in the Russian Psoriatic arthritis Registry (RU-PsART).I Methods 385 pts (M/F–172/213) with PsA according to CASPAR criteria were included in the RU-PsART. Data was collected from 25 rheumatology clinics from various regions of the Russian Federation. Median age 45 (Min 20-Max 80) years (yrs), disease duration 3.4 yrs (4 months-32 yrs). Pts underwent standard clinical examination of PsA activity. All pts were studied for patient global disease activity (PGA) and patients’ pain measured by Visual analogue Scale (VAS), and Health assessment Questionnaire (HAQ). Physician’s global assessment of disease activity (PG) was measured by VAS. The examination included X-ray of sacroiliac joints (pelvic radiographs). rSI was defined as bilateral grade ≥2 or unilateral grade ≥3. Pts were split into two groups (gr.): those with rSI [rSI(+)] and those without rSI [rSI(-)]. Medians and quartiles [Me (Q25; Q75)], [Min; Max], U-test and ORs with 95% CI were performed. All CI >1, p Results: gr. rSI(+) included 214 (55.6%) cases (M/F–106/108), gr. rSI(-) included 171 (44.4%) cases (M/F–66/105). Median age in gr. rSI(+) was 45 [Min 20-Max 80] yrs, in gr. rSI(-) it was 46 [Min 21- Max 82] yrs. Significant differences were revealed between gr. rSI(+) and gr. rSI(-). In Leeds Enthesitis index (LEI): in gr. rSI(+) LEI was 0 [0-2], in gr. rSI(-) it was 0 [0-1] (p=0.02). In frequency of dactylitis: in gr. rSI(+) 71 pts had dactylitis, 143 did not have; in gr. rSI(-) 32 pts had dactylitis, 139 did not have. OR 2.2 [1.3-3.5]. in PGA: in gr. rSI(+) it was 56.5 [42.3-70.0], in gr. rSI(-) it was 50.0 [30.0-60.0] (р= 0.00). In patients’ pain: in gr. rSI(+) it was 50.0 [40.0-70.0], in gr. rSI(-) it was 50.0 [20.5-58.8] (р=0.00). In PG: in gr. rSI(+) it was 54.0 [40.0-69.5], in gr. rSI(-) it was 40.0 [25.5-50.0] (р=0.00). In HAQ scores: in gr. rSI(+) it was 1.0 [0.6-1.5], in gr. rSI(-) it was 0 [0-2.2] (р=0.02). Conclusion Axial involvement is identified in more than half (55.6%) of the PsA pts. The presence of axial involvement in PsA pts is associated with significantly worse disease status as measured by frequency of enthesitis and dactylitis, worse PRO’s and with the reduction of patient’s functional capacity. Consequently, the diagnostics of axial involvement is critical in clinical practice. References [1] P. J. Mease, et al. J Rheumatol2018;45:1389-96 Disclosure of interests ELENA GUBAR: None declared, Elena Loginova Speakers bureau: Novartis, Celgene Corporation, Biocad, Janssen, abbVie inc, anastasia Koltakova: None declared, Yulia Korsakova Speakers bureau: Celgene Corporation, Janssen, Tatiana Korotaeva Consultant for: Pfizer, MSD, Novartis, abbVie, Celgene, Biocad, Janssen, UCB, Lilly and Novartis-Sandoz, Speakers bureau: Pfizer, MSD, Novartis, abbVie, Celgene, Biocad, Janssen, UCB, Lilly and Novartis-Sandoz, Evgeny Nasonov Speakers bureau: Pfizer, inc., MSD, Novartis, abbVie inc., Celgen Corporation, Biocad, Janssen, UCB, inc., Maria Sedunova: None declared, Igor Pristavsky: None declared, Irina Umnova: None declared, Irina Bondareva: None declared, Snezana Kudishina: None declared

Background: Pulmonary arterial hypertension (PAH) is a progressive fatal disease with a known gender dimorphism. However, data on gender differences at patients with pulmonary arterial hypertension, associated with connective tissue diseases (PAH-CTD), currently not enough. Objectives: Therefore, this study aimed to investigate the role of gender in clinical future, hemodynamic data and survival PAH-CTD. Methods: We examined the long-term prognosis of 97 consecutive PAH-CTD patients, mean age 49 years (7 males and 90 females) diagnosed in our Institute from January 2009 to December 2018. The primary outcome was death. We used nonparametric analysis, Cox regression and the Kaplan-Meier method to assess variables obtained at baseline. All patients received PAH-specific therapy according to the current recommendations. Results: We found that male patients had differences in diagnosis duration, level of creatinine, uric acid, RAP. We did not reveal differences in age, a functional class, a risk scale, and the majority clinical, tool and hemodynamic indicators. However, there were significant differences in survival. So, in male group survival was 21 [12; 51] months, in comparison in female group 74 [48; 119] months, p Conclusion: These results indicate that female PAH-CTD patients have better long-term prognosis than male, despite lack of many distinctions. It needs to be considered at outcome assessment. Disclosure of Interests: Alexander Volkov : None declared, Natalia Yudkina: None declared, Ekaterina Nikolaeva: None declared, Evgeny Nasonov Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc.

Background: In previous studies tofacitinib (TF) had demonstrated efficacy of two dosages (10 and 20 mg/day) in patients with rheumatoid arthritis (RA). However, the expected results of switching of TF’ dosages are unknown. Objectives: The aim of the study was to evaluate the results of switching of TF’s dosages in RA patients. Methods: Were analyzed the data from Russian national register of patients with RA treated with TF (tofacitinib). 415 patients were involved in the register (aug 2018). In statistical analysis were included data from 41 patients with RA (EULAR 2010), who switched dosage of TF at visit 3 and had complete clinical and laboratory data from 5 consecutive visits with an interval of 3 months between the visits. Demographical (age, sex) data, disease activity data DAS28 (Disease activity score), C-reactive protein level were collected, table 1. Changes in disease activity were calculated to patients with switching of the tofa’s dosage (the visit before and after the switching). Results: 1.28 (68%) of patients were treated with NSAIDs, 24 (50%) with 5-10 mg of prednisolone, 34 (82.9) – with methotrexate (10-25 mg/week), biologics – 5 (4.2%). From 41 persons with RA 32 patients, who never achieved low disease activity (DAS28 After escalation of TF dosage DAS28 decreased from 5.42±1.22 to 4.22±1.22 (p De-escalation of the dosage from 20 to 10 mg/day was not associated with significant changes of DAS28 (1.99 ± 1.25 increased to 2.1 ±0.96 respectively, p=0.82). Conclusion: Escalation of dosage of TF in RA lead to improvement of the disease activity in non-complete responders, who achieved DAS 28 3.2-5.1, but not in patients with absence of any response (DAS28 before escalation 5.3-6.9). De-escalation of TF’ dosage in patients with DAS28 References: [1] Fleischmann R, et al. Lancet. 2017 Jul 29;390(10093):457-468. doi: 10.1016/S0140-6736(17)31618-5. Acknowledgement: Pfizer is sponsor of register Technical support ASTON group Disclosure of Interests: Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: paiment from Pfizer, Novartis, Abbvie, Biocad, Selgene, MSD, Sanofy does not exceed 10 000 euros, V Mazurov Grant/research support from: JSC BIOCAD, Elizaveta Vasilenko: None declared, Evgeniy Zhilyaev: None declared, Vyacheslav Poncratov: None declared, Valentina Sorotskaya: None declared, Galina Lukina: None declared, Oxana Fomina: None declared, Aida Babaeva: None declared, N Lapkina: None declared, Anna Misiyuk: None declared, A Pavlova: None declared, Evgeny Nasonov: None declared

Background: The PsAID-12 is an instrument for assessment the impact of PsA on patients’ lives by examine both physical and psychological components of health. DAPSA is a valid and discriminative tool for evaluation of the PsA activity. There is limited data about the PsAID-12 correlations with PsA activity by DAPSA in clinical care [1]. The Russian Psoriatic arthritis Registry (RU-PsART) collected data from 25 rheumatology clinics in the Russian Federation regions. Objectives: to investigate the predictive value of the PsAID-12 for evaluate PsA activity by DAPSA in real-world settings. Methods: 138 (male/female–79/59) patients (pts), median age 40 (Min-Max/23-71), with PsA, according to CASPAR criteria, were included in the RU-PsART after signing consent participation forms. Every 6 months (259 visits total) all pts underwent evaluation of PsA activity: the Tender Joint count (TJC68), Swollen Joint Count (SJC66), Leeds Enthesitis index (LEI), physician’s global disease activity (PhGA) VAS, CRP (mg/l), ESR (mm/h), by PROs - patient pain global assessment VAS, Patient global disease activity (PGA) VAS and the PsAID-12. PsA activity was calculated by DAPSA. All pts were divided into 2 groups based on disease activity state by DAPSA: the first one with results ≤14 that interpreted as Remission and Low Disease activity (REM and LDA) and second one with results >14 that interpreted as Moderate and High Disease activity (MoDA and HDA). Pearson correlation coefficient and ROC-curve analysis were performed. All p Results: The Significant positive correlations between the PsAID-12 and all parameters of PsA activity, PROs were found (table 1). The Significant positive correlations for DAPSA (r=0,71) were found. The high prognostic value of the PsAID-12 for PsA activity by DAPSA showed by ROC-curve analysis (AUC=0,89, CI 95% (0,85-0,93)). The threshold for MoDA and HDA (DAPSA >14) by PsAID was 1. Conclusion: The PsAID-12 has a significant prognostic value for PsA activity by DAPSA. The questionnaire doesn’t include any physician’s or laboratory’s data, so it could be useful as a simple instrument for pts’ self-control and prognosis disease activity in daily clinical practice. References [1] Di Carlo M, Becciolini a, Lato V. et al. The 12-item Psoriatic arthritis Impact of Disease Questionnaire: Construct Validity, Reliability, and interpretability in a Clinical Setting. J Rheumatol. 2017;44(3):279-285. doi: 10.3899/jrheum.160924 Disclosure of interests: Anastasia Koltakova: None declared, Elena Loginova Speakers bureau: Novartis, Celgene Corporation, Biocad, Janssen, abbVie inc, ELENA GUBAR: None declared, Yulia Korsakova Speakers bureau: Celgene Corporation, Janssen, Tatiana Korotaeva Speakers bureau: Novartis, Celgene Corporation, abbVie inc, Biocad, Janssen, Pfizer, UCB, Lilly, Maria Sedunova: None declared, Igor Pristavsky: None declared, Irina Umnova: None declared, Irina Bondareva: None declared, Snezana Kudishina: None declared, Evgeny Nasonov: None declared

Background: Tofacitinib (TF) is an oral Janus Kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives: To evaluate the one-year effectiveness of tofacitinib as first-line therapy in RA conventional synthetic (cs) DMARDs non-responders. Methods: Data from 415 patients from Russian national register of patients with RA treated with TF were analyzed. 119 RA patients, who had complete clinical and laboratory data from 4 consecutive visits after baseline with an interval of 3 months between the visits and who used the TF as first-line therapy after failure of cs DMARDs, were included. Treatment with any biologics ever was an exclusion criteria. Demographical (age, sex) and RA activity data (DAS28, SDAI, number of tender and swollen joints (NTJ, NSJ), erythrocytes sedimentation rate (ESR), C-reactive protein (CRP), and HAQ, EQ5D were collected, table 1. Statistical analysis performed in SPSS2017. p-value Results: At baseline 12 (10%) were treated with NSAIDs, 15 (12.6) with 5-10 mg/dayof prednisolone, 82 (68.9) – with methotrexate (10-25 mg/week), 8 (6.7%) – with sulfasalazine (2.0-3.0 g/day). Changes in the disease activity in patients with RA, treated with tofacitinib after csDMARD are presented in Table 2 At visit 3 DAS28 Conclusion: Treatment with TF may provide good response rates in RA patients, refractory previous cs DMARDs. Acknowledgement: Study sponsored by Pfizer Disclosure of Interests: Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: paiment from Pfizer, Novartis, Abbvie, Biocad, Selgene, MSD, Sanofy does not exceed 10 000 euros, V Mazurov Grant/research support from: JSC BIOCAD, Evgeniy Zhilyaev: None declared, Iuliia Grabovetskaya: None declared, Irina Marusenko: None declared, Elizaveta Vasilenko: None declared, Diana Abdulganieva: None declared, Ilia Smitienko: None declared, Anna Misiyuk: None declared, Galina Lukina: None declared, Larisa Knyazeva: None declared, Elena Kalinina: None declared, Ruzana Samigullina: None declared, Irina Bondareva: None declared, Natalya Yudina: None declared, N Lapkina: None declared, Evgeny Nasonov: None declared

Background Persistence with bDMARDs has only been studied recently in the last few years. But this information is very relevant for choice of bDMARDs treatment in real-life practice. RU-PsART collected data from 25 rheumatology clinics in the Russian Federation. Objectives: to investigate drug survival and persistence rates, reasons for discontinuation of first-line bDMARDs in PsA pts in clinical practice. Methods 170 (M/F–87/83) PsA pts according to CASPAR criteria, median (Me) age 43 (Min 19 – Max 74) years (yrs.) who were treated with first-line bDMARDs were included in the present analysis. All information concerning the data for starting/withdrawing bDMARDs and reasons for discontinuation were taken at the time of being included to the RU-PsART registry. Pts took the following bDMARDs: adalimumab (ADA) (57pts), infliximab (INF) (40pts), Ustekinumab (UST) (36pts), Etanercept (ETN) (23pts), Golimumab (GOL) (14pts). Drug survival rate was evaluated with Kaplan-Meier cumulative analysis, Me [Min-Max],%, Breslow, Tarone-Ware, Log Rank tests were performed. All p≤0.05, were considered to indicate statistical significance. Results 71 out of 170 pts (41.8%) were treated with mono-bDMARDs and 99 out of 170 pts (58.2%) were treated with a combination with different sDMARDs. Among them aDA/INF/UST/ETN/GOL were used in combination with MTX in 66.7%/72.5%/33.3%/65.2%/35.7% of pts accordingly average (Me) duration of bDMARDs therapy was 13.5[0-74]/39[2-179]/15[0-55]/26[2-49]/19[4-33] months for aDA/INF/UST/ETN/GOL accordingly. 31 out of 170 pts (18.2%) stopped bDMARDs. InF/ADA/ETN/UST/GOL were stopped in 30%/22%/17%/5%/0% of cases accordingly. Among them 4 pts (2.35%) stopped due to inefficacy, 13 pts (7.6%) - due to loss of efficacy, 8 pts (4.7%) - due to adverse events, 6 pts (3.5%) - due to other reasons. No significant differences in drug survival rates were seen between all bDMARDs within two years of therapy. During long-term observations GOL had better persistence among iTNF agents. UST has shown significantly higher cumulative survival and persistence rates compared to aDA (p Conclusion In our real practice PsA pts cohort bDMARDs with different mechanisms of action were well tolerated and effective. During long-term observational periods UST has shown better cumulative survival rates compared to aDA. Disclosure of interests Tatiana Korotaeva Speakers bureau: Novartis, Celgene Corporation, abbVie inc, Biocad, Janssen, Pfizer, UCB, Lilly, Elena Loginova Speakers bureau: Novartis, Celgene Corporation, Biocad, Janssen, abbVie inc, anastasia Koltakova: None declared, ELENA GUBAR: None declared, Yulia Korsakova Speakers bureau: Celgene Corporation, Janssen, Maria Sedunova: None declared, Igor Pristavsky: None declared, Irina Umnova: None declared, Irina Bondareva: None declared, Snezana Kudishina: None declared, Evgeny Nasonov Speakers bureau: Pfizer, inc., MSD, Novartis, abbVie inc., Celgen Corporation, Biocad, Janssen, UCB, inc.

Background Despite the similar pathogenesis and clinical picture, pulmonary arterial hypertension in systemic sclerosis (PAH-SSc) in comparison with idiopathic pulmonary arterial hypertension (IPAH) is characterized by a more severe course, an unsatisfactory response to PAH-specific therapy, a poor survival and a disappointing prognosis. In this connection, before doctors of different specialties, first of all before rheumatologists, cardiologists and pulmonologists, there is a need to highlight the characteristics of the flow of PAH depending on the presence of SSc. Objectives To describe specific symptoms of PAH associated with SSc. Methods The study included 51 patients with PAH-SSc and 50 patients with IPAH formed the control group. To verify the diagnosis of PAH all patients underwent studies according to the program corresponding to the russian recommendations for the diagnosis and treatment of pulmonary hypertension with mandatory right heart catheterization. The diagnosis of SSc was established in accordance with the classification criteria ACR-EULAR 2013. Univariate logistic regression was used to calculate a probability (odds ratio (OR)) of SSc-associated symptoms. Results We identified 29 symptoms that were associated with PAH-SSc. The most significant of them, increasing the risk of detection of SSc in patients with PAH, were age over 45 years (OR 9.7, 95% CI 3.9-24.3, p 387 μmol/L (OR 3.8, 95% CI 1.5-9.6, p = 0.003), diffusion lung capacity (DLCO) 2 mg/l (OR 12.9, 95% CI 3.96-41.8, p 15.5 mm Hg. (OR 8.9, 95% CI 3.4-23.1, p 4.5 mm Hg. (OR 4.6, 95% CI 1.9-11.2, p = 0.0003). Symptoms that reduce the risk of detecting SSc in patients with PAH include mean pulmonary artery pressure >55 mmHg. (OR 0.4, 95% CI 0.2-0.9, p = 0.03), pulmonary vascular resistance >12 units Wood (OR 0.4, 95% CI 0.2-0.9, p = 0.02), hemoglobin level >146 g/l (OR 0.3, 95% CI 0.2-0.8, p = 0.007), presense of syncope (OR 0.3, 95% CI 0.1-0.9, p = 0.02). Conclusion The selection of features of the course of PAH that increase the likelihood of detection of SSc will contribute to the timely diagnosis of SSc, will allow to predict the course of PAH, to approach more carefully the selection and monitoring of the effectiveness of PAH-specific therapy. That will contribute to improving the survival and functional status of patients with PAH-SSc. Disclosure of Interests Natalia Yudkina: None declared, Alexander Volkov: None declared, Ekaterina Nikolaeva: None declared, Ildar Kurmukov: None declared, Evgeny Nasonov Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc.

Background Anxiety and depressive disorders (ADD) affect rheumatoid arthritis (RA) disease activity and remission rate. Psychopharmacotherapy (PPT) of ADD attempts to improve the remission rate. Objectives To determine factors associated with RA remission rate. Methods 128 RA-patients (pts) were enrolled, 86% were women with a mean age of 47,4±11,3 (M±SD) yrs. All pts met the full ACR criteria for RA. Remission was defined as DAS28 Results At 5-yrs endpoint in 83 RA-pts remission rate was 22,9% (8,3%, 34,5%, 19,0% and 33,3% in groups 1, 2, 3 and 4, respectively). Significantly higher proportion of patients achieved remission in cDMARDs + PPT group vs cDMARDs group (34,5% vs 8,3%, RR 1,8 (95%CI 0,35 – 9,2), p=0,024). By univariate logistic regression, male sex, younger age, shorter RA duration, RF and ACPA negativity, lower baseline DAS28 and HAQ, absence of extraarticular RA manifestations and depression at the beginning of the study, and remission of anxiety and depressive symptoms at the end of the study were significantly associated with RA remission (table 1). These variables were subjected to multivariate stepwise logistic regression. Only lower baseline DAS28 (OR 0,636 (95%CI 0,515 – 0,785), p Conclusion Lower baseline DAS28 and remission of anxiety and depressive symptoms at 5-yrs endpoint are associated with higher rheumatoid arthritis remission rate at five years follow-up. Disclosure of Interests None declared

Background Diabetes mellitus (DM) is known to be associated with proatherogenic lipid profile and cardiovascular complications. Insulin resistance (IR) is the major pathophysiological mechanism contributing to type II DM development. Established in general population correlation between IR and dyslipidemia sometimes even without DM, should nevertheless be confirmed in patients (pts) with rheumatoid arthritis (RA). Objectives To analyze IR rates and identify IR predictive lipid profile in RA patients without DM or hyperglycemia. Methods Totally 47 RA pts (41 women, 6 men, 56 [39; 62] years old) without established DM and with normal fasting glucose levels ( Results Median HOMA-IR levels were 1,7 [1,1;3,2]. HOMA-IR index correlates with age (r=0,3, p=0,04), body mass index (r=0,6, p Conclusion More than 30% of RA pts without DM and with normal serum fasting glucose concentration had IR. The IR was associated with increased TG levels and elevated TG/HDL-C ratio in RA pts. This proatherogenic lipid profile could be responsible for earlier development of cardiovascular complications. Disclosure of Interests None declared

Background The aim of psoriatic arthritis (PsA) therapy is to achieve minimal disease activity (MDA) or clinical remission. Methotrexate (MTX) is the first-line treatment; however, the extent of the disease-modifying effect of MTX on PsA is a matter of debate. It has been shown that the MTX treatment achieves MDA in 6 months in Objectives To show the efficacy of MTX in PsA pts in clinical practice and to compare the effectiveness of oral and subcutaneous (SC) MTX treatments. Methods 256 pts out of RU-PsART received synthetic disease-modifying antirheumatic drugs (sDMARDs), of whom 182 (71.1%) pts (M/F–68/114) received MTX, and were included in the study according to CASPAR criteria. Their median age 42 [Min 19-Max 73] years (yrs). Pts underwent standard clinical examination of PsA activity at the baseline and the follow-up visits. All pts were biological-naive. They all were treated with MTX monotherapy: 80 received SC and 102 oral MTX. The main purpose was to determine the cumulative frequency of achieving MDA after the MTX therapy onset. MDA is defined as: the presence of at least 5 out of the following 7 domains: tender joint count ≤1, swollen joint count (SJC) ≤1, Psoriasis Area Severity Index (PASI) ≤1 or body surface area ≤3%, tender entheseal points ≤1, Health Assessment Questionnaire score ≤0.5, patient global disease activity measured by Visual Analogue Scale (VAS) score ≤20, and patient pain VAS ≤15. Medians and quartiles [Me (Q25; Q75)], [Min; Max], ORs with 95% CI, Breslow, Long Rank, Tarone-Ware tests were performed. Cumulative frequency was computed using the Kaplan-Meier method. All CI >1, p Results Only 16.5% of all 182 pts treated with MTX, both orally and SC, achieved MDA. In the SC MTX group 25 pts (31%) achieved MDA, while 55 (69%) did not achieve it. In the oral MTX group 5 pts (5%) achieved MDA, while 97 (95%) did not achieve it. SC MTX treated pts significantly more often achieved MDA compared with those orally treated OR 8.8 [3.2 – 24.3]. Cumulative frequency of achieving MDA in 27 months from the treatment onset was 48% for SC administration, and 7% for the oral one (p Conclusion In clinical practice, the sDMARD given to the majority of pts is MTX, but its use achieves the recommended treatment target of MDA only in 16.5% of pts. The SC MTX treatment significantly, up to 30%, improves the achievement of MDA. The use of SC MTX could be a therapy optimized option in clinical practice. References [1] B.J. Sheane, et al. J Rheumatol. 2016;43(9):1718-23. [2] G.A. Vena et el. Ther Clin Risk Manag. 2018;14:105-16. Disclosure of Interests ELENA GUBAR: None declared, Elena Loginova Speakers bureau: Novartis, Celgene Corporation, Biocad, Janssen, AbbVie Inc, Anastasia Koltakova: None declared, Yulia Korsakova Speakers bureau: Celgene Corporation, Janssen, Tatiana Korotaeva Consultant for: Pfizer, MSD, Novartis, AbbVie, Celgene, Biocad, Janssen, UCB, Lilly and Novartis-Sandoz, Speakers bureau: Pfizer, MSD, Novartis, AbbVie, Celgene, Biocad, Janssen, UCB, Lilly and Novartis-Sandoz, Evgeny Nasonov Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc., Alexander Lila Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc., Maria Sedunova: None declared, Igor Pristavsky: None declared, Irina Umnova: None declared, Irina Bondareva: None declared, Snezana Kudishina: None declared

Background MDA is a treatment target of PsA. There is limited data about the frequency and the time of MDA achievement by the use of bDMARD therapy in early and long-term PsA in clinical practice. RU-PsART collected data from 25 rheumatology clinics in the Russian Federation. Objectives: to investigate the cumulative frequency and timing of MDA attainment in early and long-term PsA after starting bDMARDs in clinical practice. Methods 140 (M/F–77/63) bDMARD-naive PsA pts according to CASPAR criteria were included in the RU-PsART, after signing consent participation forms; median (Me) age 42 [Min 19-Max 73] years (yrs). All patients were divided into two groups based on PsA duration at the time of bDMARDs initiation: early PsA≤2 yrs (67pts) and long-term PsA>2 yrs (73pts). All pts underwent standard clinical examinations of PsA and psoriasis activity and were treated with the following bDMARDs: Infliximab (26pts), Etanercept (20pts), Adalimumab (37pts), Ustekinumab (33pts), Golimumab (19pts), Sekukinumab (4pts), Certolizumab pegol (1pts). MDA was defined as ≥ 5 of the following criteria: tender joint count ≤1, swollen joint count ≤1, PASI≤1 or BSA≤3, patient pain global assessment VAS≤15, patient’s global disease activity VAS≤20, HAQ≤0,5, enthesitis count ≤1. The cumulative frequency and the time of MDA attainment were calculated in both groups. Kaplan-Meier cumulative analysis, Me (CI95%), Min-Max,%, Breslow, Tarone-Ware, Log Rank tests were performed. All CI>1, p Results MDA has been achieved after bDMARDs initiation in 33 out of 67 (49%) pts with early PsA and in 23 out of 73 (32%) pts with long-term PsA. The Me time of MDA achievement was significantly shorter in early PsA in comparison to long-term PsA pts: 21 (CI 95%:13.1-28.9) months and 58 (CI95%:0-118.1) months of bDMARD therapy accordingly (p Conclusion Comparative analysis has shown that cumulative frequency of MDA achievement after bDMARDs initiation was significantly higher (49% vs 32%) and faster (21 vs 58 months) in early PsA than in long-term PsA. That confirms the benefit of bDMARD therapy initiation at the early stage of PsA. Disclosure of Interests Elena Loginova Speakers bureau: Novartis, Celgene Corporation, Biocad, Janssen, AbbVie Inc, Tatiana Korotaeva Speakers bureau: Novartis, Celgene Corporation, AbbVie Inc, Biocad, Janssen, Pfizer, UCB, Lilly, Anastasia Koltakova: None declared, ELENA GUBAR: None declared, Yulia Korsakova Speakers bureau: Celgene Corporation, Janssen, Maria Sedunova: None declared, Igor Pristavsky: None declared, Irina Umnova: None declared, Irina Bondareva: None declared, Snezana Kudishina: None declared, Evgeny Nasonov Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc.

Background BCD-020 (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 acute phase reactants, autoantibodies, immunoglobulins, cytokine profile and CD19+B lymphocytes in patients (pts) with RA during RTX and RTX biosimilar therapy Methods The study included 54 RA patients (pts), divided into two groups. The first group included 34 pts with RA (31 women, mean age 49(42-64), mean disease duration 66(36-132) months, mean DAS 28 6.2 (5.5-6.8)) who received two infusions of RTX - 35% at a dose of 500 mg, 65% of the dose of 1000 mg every two weeks in combination with DMARDs and glucocorticoids; 33 pts achieved a good/moderate EULAR response at week 24. The second group - 20 pts with RA (18 woman, mean age 61.5(54-66.5) years, mean disease duration 39.5(20-84) months, mean DAS 28 5.6(4.9-6.8)) who received two intravenous BCD-020 infusions (600mg No 2) in combination with DMARDs and glucocorticoids; 17 pts achieved a good/moderate EULAR response at week 24. Laboratory biomarkers were assessed at baseline and weeks 12 and 24 after the first infusion of RTX. ESR (mm/hr) (Westergren method); serum concentrations of CRP (mg/L), IgM RF (IU/ml) (laser nephelometry); anti-CCP2 (U/ml), IgA RF (U/ml), anti-MCV (U/ml) (ELISA kits); cytokine profile (xMAP technology) were assessed Results RTX and BCD-020 induced decreases in ESR, levels of CRP, IgMRF, IgARF, anti-MCV at week 12 and 24, p Conclusion RTM biosimilar (BCD-020) has a similar effect on inflammatory and immunological biomarkers to the original RTM. BCD-020 therapy induced a rapid and significant improvement in ESR, levels of CRP, IgM/IgARF, anti-MCV, proinflammatory, anti-inflammatory cytokines, growth factors, chemokines levels and CD19+B cells depletion in RA pts Disclosure of Interests Anastasia Avdeeva: None declared, Maria Cherkasova: None declared, Alexander Artyuhov: None declared, Eh. Dashinimaev: None declared, D. Kusevich: None declared, Alexander Lila Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc., Evgeny Nasonov: None declared

Background Prevalence of hyperuricemia worldwide has been steadily increasing over the past decades and becomes higher with age. The number of studies on the prevalence of hyperuricemia and its role in development of diseases in some social groups is low, yet there is data on its high frequency in professional athletes. Objectives: to assess impact of certain factors upon the risk of development of hyperuricemia in professional athletes in some sports. Methods the study was performed as retrospective. Out of 753 athletes in six sports, 267 athletes who met the study criteria were selected. The inclusion criteria: professional athletes aged 18-40, serum uric acid level Out of 753 athletes, 228 (30.3%) showed high uric acid level in their screening test, 258 (34.3%) athletes refused to undergo a medical examination. 267 people were included in the study, 130 men (48.7%) and 137 women (51.3%), with the mean age of 24.4±5.2 years and the average observation period of 3.0±0.3 years. Parameters under investigation: anthropometric measurements, laboratory tests (serum levels of lactate, creatinine, crude protein, triglycerides, thyroid-stimulating hormone (TSH), AST, ALT, myoglobin, testosterone, uric acid (UA)), glomerular filtration rate (GFR) (using the MDRD formula) with subsequent statistical analysis. Hyperuricemia was defined as SUA level >360 μmol/L. Hypercholesterinemia - as serum cholesterol level >5.0 μmol/L, hypertriglyceridemia - as serum TG level >1.7 mmol/L. High serum creatinine level as >100 μmol/L. Statistical analysis was conducted using the applied programs package of descriptive statistics STATISTICA 12.0 (StatSoft.Inc., USA). Results Hyperuricemia developed in 60 athletes (22.5%), including 51 (39.2%) men and 9 (6.6%) women. The frequency of risk factor detection was the following: hypercholesterinemia was detected in 91 (34%) professional athletes, hypertriglyceridemia - in 10 (3.7%), reduction in GFR 25 kg/m2 - in 65 (24.3%), BMI >30 kg/m2 - in 3 (1.1%), arterial hypertension in 0 (0%) professional athletes. The univariate analysis showed that out of all the factors under investigation, the following factors were significantly associated with the development of hyperuricemia: male sex (OR 9.181, 95% CI (4.285;19.674 p 25 kg/m2 (OR – 2.470, 95% CI (1.243;4.909) p=0.01), increased level of CPK (OR – 2.247, 95% CI (1.230;4.105) p=0.008). Age >25 years was associated with lower risk of development of hyperuricemia. According to the multifactor analysis, development of hyperuricemia is associated with male sex (OR – 13.4, 95% CI (3.6;49.6) p=0.00012) and BMI >25 kg/m2 (OR – 2.4, 95% CI (1.02;5.69) p=0.04). Conclusion: hyperuricemia developed in professional athletes in 22.5% cases in 3.0 years. This study confirms high risk of development of hyperuricemia in professional athletes (22.5% cases in the 3-year observation period) along with low frequency of many traditional risk factors (obesity, hypercholesterinemia, hypertriglyceridemia, chronic kidney disease), which can be linked to the peculiarities of diet. This fact calls for a detailed investigation of the dietary intake of athletes with the purpose of its optimization. Disclosure of Interests Maria Chikina: None declared, Maxim Eliseev : None declared, Olga Sheliabina Speakers bureau: Berlin Chemie Menarini, Svetlana Glukhova: None declared, Irina Kruglova: None declared, Evgeny Nasonov Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc., Alexander Lila Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc.

Background Adipose tissue is a highly active endocrine organ that produces a large number of various pro-inflammatory cytokines and adipocytokines (adiponectin, leptin, etc.) involved in the pathogenesis of rheumatoid arthritis (RA). The relationship of adipokines with activity markers and inflammation in RA and the effect of antirheumatic therapy on adipocytokine levels in patients with early RA is discussed. Objectives To assess the dynamics of adipocytokine levels (adiponectin, leptin) in patients with early RA (initial and after 24 weeks) using various treatment regimens: methotrexate monotherapy (MT) and combination therapy (MT + adalimumab (ADA). Methods The study included 47 patients with early RA (criteria ACR/EULAR, 2010.), 57 [46.5; 62.0] years, disease duration 6.0 [5.5;15.5] months, seropositive for IgM RF and anti-CCP, with highly active RA (DAS28 5,5 [5,1; 5,9]; SDAI 32,4 [22,4; 41,7], CDAI 29,0 [19,7; 39,5]). At study entry, all patients received methotrexate (MTX) (10 [10-15] mg/week), after 12 weeks, with inefficiency of MT, adalimumab (ADA) was administered 40 mg 1 time in 2 weeks. Serum concentration of adipokines (adiponectin, leptin) was measured with ELISA. Results By the 24th week of therapy, 23 (49%) patients with early RA received a combination therapy (adalimumab and methotrexate), 24 (51%) patients with RA received methotrexate monotherapy. In patients with RA, after 24 weeks, a significant decrease in adiponectin levels by 44 and 49% and an increase in the concentration of leptin by 39 and 43% were observed both against the background of MT monotherapy and with the use of combination therapy (p * -p Conclusion After 24 weeks of therapy, the adipocytokine levels in the two groups changed: the adiponectin concentration decreased, and the leptin level increased. MT monotherapy and combination therapy (MT + ADA) acted on changes in adipocytokine levels unidirectionally, although the changes were more pronounced in patients on combination therapy. Disclosure of Interests: None declared

Background The latest data show that axial involvement in psoriatic arthritis (PsA) patients (pts) is associated with significantly more severe disease status (1). Objectives To analyze, in clinical practice, disease activity and characteristics of PsA pts with and without radiographic sacroiliitis (rSI). Methods 385 pts (M/F–172/213) with PsA according to CASPAR criteria were included in the RU-PsART. Data was collected from 25 rheumatology clinics from various regions of the Russian Federation. Median age 45 (Min 20-Max 80) years (yrs), disease duration 3.4 yrs (4 months-32 yrs). Pts underwent standard clinical examination of PsA activity. Disease activity was measured by DAPSA, DAS28, BASDAI. The examination involved HLA B27 antigen status and X-ray of sacroiliac joints (pelvic radiographs). rSI was defined as bilateral grade ≥2 or unilateral grade ≥3. Skin lesion severity was evaluated in terms of body surface area (BSA) affected, and Psoriasis area Severity index (PASI). When BSA was ≥3%, PASI was calculated. Pts were split into two groups (gr.): those with rSI [rSI(+)] and those without rSI [rSI(-)]. Gr. rSI(+) included 214 (55.6%) cases (M/F–106/108), gr. rSI(-) 171 (44.4%) cases (M/F– 66/105). Median age in gr. rSI(+) was 45 [Min 20-Max 80] yrs, in gr. rSI(-) it was 46 [Min 20-Max 82] yrs. Medians and quartiles [Me (Q25; Q75)], [Min; Max], U-test and ORs with 95% CI were performed. All CI >1, p Results Significant differences were revealed between gr. rSI(+) and gr. rSI(-). In HLA-В27 antigen status: in gr. rSI(+) it was positive in 62 pts, negative in 64 pts, while in gr. rSI(-) it was positive in 26 pts, negative in 52 pts. OR 1.9 [1.1-3.5]. In tender joint count (TJC): in gr. rSI(+) TJC was 9 [14-18], in gr. rSI(-) it was 6 [3-12] (р=0.02). in disease activity measured by DAPSA: in gr. rSI(+) DAPSA was 28.40 [15.65-43.65], in gr. rSI(-) it was 20.0 [12.45-30.0] (р=0.00). In DAS28: in gr. rSI(+) DAS28 was 4.3 [3.3-5.6], in gr. rSI(-) it was 4.1 [3.0-4.9] (р=0.02).]. In disease activity measured by BASDAI: in gr. rSI(+) BASDAI was 1.6 [0-5.1], in gr. rSI(-) it was 0 [0-4.5] (р=0.00). In frequency of erosive radiographic arthritis of feet: in gr. rSI(+) 58 pts had erosive arthritis of feet, 156 did not have, while in gr. rSI(-) 29 pts had erosive arthritis of feet, and 142 did not have. OR 1.8 [1.1-3.0]. In more extensive skin lesion area: in gr. rSI(+) BSA 3% had 94 pts; while in gr. rSI(-) BSA 3% had 57 pts. OR 0.6 [0.4-0.97]. In CRP: in gr. rSI(+) CRP was 0.9 [0.4-2.2] mg/dl, in gr. rSI(-) it was 0.8 [0.3-1.3] mg/dl (p=0.03). Conclusion Axial involvement in PsA patients is associated with HLA-B27 positivity. Patients with axial involvement have significantly worse disease status as measured by disease activity and a higher CRP level; they are more likely to have more severe (erosive) peripheral arthritis and more extensive skin lesion area. Early detection of axial involvement is critical for choice of treatment approach and good prognosis. Reference [1] P. J. Mease, et al. J Rheumatol2018;45:1389-96 Disclosure of interests ELENA GUBAR: None declared, Elena Loginova Speakers bureau: Novartis, Celgene Corporation, Biocad, Janssen, abbVie inc, anastasia Koltakova: None declared, Yulia Korsakova Speakers bureau: Celgene Corporation, Janssen, Tatiana Korotaeva Consultant for: Pfizer, MSD, Novartis, abbVie, Celgene, Biocad, Janssen, UCB, Lilly and Novartis-Sandoz, Speakers bureau: Pfizer, MSD, Novartis, abbVie, Celgene, Biocad, Janssen, UCB, Lilly and Novartis-Sandoz, Evgeny Nasonov Speakers bureau: Pfizer, inc., MSD, Novartis, abbVie inc., Celgen Corporation, Biocad, Janssen, UCB, inc., Maria Sedunova: None declared, Igor Pristavsky: None declared, Irina Umnova: None declared, Irina Bondareva: None declared, Snezana Kudishina: None declared

Background: The basis of treatment of SLE are glucocorticoids (GCs), which since their introduction into clinical practice, have led to increased survival and reduced early mortality of SLE patients. However, the need to use high doses of GCs, as well as long-term use of medium doses to maintain disease remission, leads to the development of serious adverse reactions. This leads to an increase in the risk of irreversible organ damage. In this regard, it is important to search for ways to prevent the use of high doses of GCs, minimizing the dose of GCs. Objectives: To assess special aspects and dynamics of oral glucocorticoid (GC) therapy in SLE patients treated with anti-B-cell and anti-BlyS therapy. Methods: The study included 64 SLE pts (5М/58F), divided into 3 groups: Group I - 47 patients (SLEDAI2K 16[11;20] scores), receiving rituximab (RTX) i/v infusions by drop at 500 - 2000 mg dose-range. Group II included 10 patients (SLEDAI2K 10[8;11] scores) treated with Belimumab (BLM) at 10 mg/kg once a month. The remaining 7 patients from Group III (SLEDAI2K 10[9;16] scores) were administered a combination of RTX and BLM. They started treatment with RTX 500 (2 patients) or 1000 mg (5 patients) infusions, and 3 months later BLM at standard scheme of 10 mg/kg once a month was initiated for 8 months. SLICC damage index (DI) was documented at baseline - before initiation of RTX and BLM - in 26 out of 64 patients (40%) with SLICC DI score > 1 (1 - 5 scores); 20 patients out of them were administered RTX. Results: 47 patients on RTX therapy received different oral GCs doses: high GCs doses (Me 40[30;50]mg/day) were documented in 11 (24%) patients, moderate doses (Me 13[10;20]mg/day) – in 29 (61%) patients, and low doses (Me 5[5;7,5]mg/day) - in 7 (15%) patients. Patients on BLM and combination therapy were administered GCs at doses ≤ 20 mg (Me 15[5;20]mg/day and Me 8,75[5;15] mg/day, respectively) During first 3 month of treatment GCs doses in all 3 Groups remained unmodified. By Mo 6 25% reduction in oral GCs doses was documented in: patients on RTX - 20[15;20]mg/day, 10[8,75;10]mg/day, 5[5;5] mg/day (respectively, in the groups with initially high, moderate and low GCs doses); BLM 10[7,5;10] mg/day, combination therapy 8,75[5;15] mg/day. By Mo 12 Me GCs dose in all 3 Groups did not exceed 10 mg/day. In view of SLE exacerbations in patients from Group I (RTX) additional RTX infusions at Mo 6, 9 and 12 were administered in 8 (20%) patients. Figure 1 presents the dynamics of oral GCs doses in patients from Group I (RTX), who were divided in 3 subgroups based on baseline (high, moderate or low) GCs dose, and also dynamics of GCs dose in patients from Groups II (BLM) and III (RTX+BLM). Increase in SLICC score by Mo 12 of follow up was documented in patients on RTX therapy with baseline pre-existing organ damage (5 patients). There was no increase in SLICC scores in BLM and RTX+BLM treatment groups. Conclusion: Combination therapy results in achieving rapid control of SLE activity thanks to RTX effects, and the combination with BLM allows significantly prolongs this result, minimizing the risk of exacerbation. And a very specific gain from combination RTX+BLM therapy is a chance to manage patients on moderate-to-low oral GCs doses, therefore, reducing the risk of irreversible organ damage. Increasing organ damage score in RTX Group is most likely associated with intake of higher GCs doses. Disclosure of Interests: Anna Mesnyankina: None declared, Sergey Solovyev: None declared, Elena Aseeva: None declared, Evgeny Nasonov Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc.

Background: Genetic factors are known to substantially influence the production of cytokines. Objectives: This prospective study was aimed to explore whether the polymorphisms of immune response genes were associated with cytokines/chemokine production in patients with early rheumatoid arthritis (eRA) and whether a biological therapy affected this association. Methods: 44 eRA patients (36 females; median age 55.0 [46; 60,0]; median disease duration 7,0 [4,0; 11,0] months; DAS28 5.9 [4,8; 6,4]) were included. 89% were positive for IgM rheumatoid, 92% - anti-CCP positive. “Gene candidate” approach was used to search for the following gene polymorphisms (SNPs): PTPN22 (+1858 C/T, rs2476601), CTLA4 (+49A/G, rs231775), TNFAIP3 (rs675520, rs6920220, rs10499194), IL6 (-174G/C, rs1800795), IL6R (+358A/C, rs8192284), TNFA (-308A/G, rs1800629), MCP1/CCL2 (+2581A/G, rs1024611), IL10 (-592A/C, rs1800872, -1082 A/G, rs1800896). Serum levels of 27 cytokine/chemokines were measured using the xMAP multiplexing technology at baseline, at 12 and 24 weeks after initiation of therapy. All patients were treated with methotrexate and/or biological therapy in accordance with the treat-to-target strategy (REMARCA study). Results: Among all studied SNPs only polymorphism rs6920220 of gene TNFAIP3 was associated with a certain cytokine/chemokine production across all time-points: baseline, 12 and 24 weeks. At baseline, the carriers of GG genotype (27 pts) showed significantly higher serum levels of the following mediators, compared to the patients with GA/AA genotypes (17 pts): IL8 (42.8± 23.0 pg/ml vs 25.5±8.4 pg/ml, p Conclusion: The results suggest that polymorphism rs6920220 of gene TNFAIP3 is linked to a particular cytokine/chemokine pattern. Biological therapy used according to the treat-to-target strategy for 24 weeks does not lead to the reduced production of IL-8, IP-10, MIP-1b, and PDGF-BB in the carriers of GG genotype. Disclosure of Interests: None declared

The aim of the study was to examine lipid profiles, arterial stiffness (AS), carotid intima-media thickness (cIMT), in 55 women with RA without overt cardiovascular disease (СVD) treated with rituximab (RTX).The following parameters were recorded before and 24 weeks after RTX therapy (2 infusions of 500 or 1,000 mg RTX intravenously, fortnightly): plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, DAS 28-ESR, serum C-reactive protein (CRP), RF IgM, AS (SI - stiffness index, RI – reflection index) by digital volume pulse contour analysis (Micro Medical, UK), and common cIMT by high-resolution B-mode carotid ultrasound. Based on the European League Against Rheumatism (EULAR) criteria, patients were divided into two groups: 1) moderate/good response to RTX therapy after 24 weeks (41 patients, 75%), 2) no response to RTX therapy (14 patients, 25%). Effective RTX therapy resulted in 9% increase in TC, 23% increase in HDL-C and 14% decrease in atherogenic index, 57% decrease in SI and 24% decrease in RI. We observed a 9% decrease of cIMTmax at 24 weeks. The improvement of cardiovascular parameters was accompanied by statistically significant decreases of CRP, ESR, RF IgM and DAS 28 in group 1 (P < 0.05). There were not significant changes in lipid profile, AS parameters, and cIMT in group 2. Two infusions of RTX in case of moderate/good EULAR effect of therapy exerted favorable effects on lipid profile, AS and cIMT in women with RA without overt CVD., Graphical Abstract

Background:Olokizumab (OKZ) is a new humanized monoclonal antibody targeting IL-61, 2. Here we present the results of the first phase III study of OKZ in patients with Rheumatoid Arthritis (RA).Objectives:The primary objective was to evaluate the safety and efficacy of OKZ administered subcutaneously (SC) every 2 weeks (q2w) and 64mg SC every 4 weeks (q4w) vs placebo in the treatment moderate-to-severe RA.Methods:In this randomized, double-blind, placebo-controlled, multicenter study in patients with moderately to severely active RA despite methotrexate (MTX) (ClinicalTrials.gov IdentifierNCT02760368, CREDO-1) patients received SC injections of OKZ 64 mg q2w, OKZ 64 mg q4w and PBO q2w for 24 weeks. Starting at Week (Wk) 14, non-responders were rescued. After Wk 24, subjects were eligible for an open-label study extension.The primary endpoint was American College of Rheumatology 20% (ACR20) response at Wk 12.Secondary endpoints included: percentage of subjects with low disease activity, improvement of physical ability. Safety outcomes, including treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs) and laboratory abnormalities (via central lab) were assessed.Results:428 patients were randomized to OKZ 64mg q2w (n=143), OKZ 64mg q4w (n=142), and PBO (n=143). Baseline characteristics were comparable between treatment arms: mean (SD) age was 51.3 (12.0) years, 82.7% of patients were female, disease duration 8.14 (7.6) and all patients were on MTX. Mean (SD) baseline DAS28-CRP was 6.0 (0.76) and HAQ-DI was 1.72 (0.49).130 (90.9%) patients in q2w, 134 (94.4%) in q4w and 132 (92.3%) in PBO arms completed the study.Both regimens of OKZ were significantly better than PBO in all primary and secondary endpoints (Table 1).Table 1.Key efficacy results (intent-to-treat population) NRI1OKZ q2wOKZ q4wPBONumber of Subjects143142143ACR20 Response, n (%) Wk 12 (primary endpoint)91(63.6)***100(70.4)***37(25.9)DAS2848(33.6)***55(38.7)***5(3.5)HAQ-DI Wk 12 LSM (SE)-0.54(0.041)-0.56(0.042)-0.20(0.042)Treatment Comparison vs PBO LSM Difference (SE)-0.34***(0.059)-0.36***(0.059)97.5% CI for LSM Difference-0.47, -0.21-0.49, -0.23ACR50 Response, n (%) Wk 2461(42.7)***69(48.6)***11(7.7)CDAI ≤2.8 Response, n (%) Wk 2412(8.4)**11(7.7)**01– NRI, Non-Responder Imputation; LSM, Least Squares Mean; **p-value difference from PBO The key efficacy outcomes were maintained throughout the 24-week.Overall incidence of TEAEs was 58.0% in OKZ q2w arm; 57.0% in OKZ q4w arm and 43.7% in PBO, TEAEs leading to study treatment discontinuation were reported in 4.9%, 3.5% and 0.7% patients, respectively.At least one TESAE (subcutaneous abscess, pulmonary tuberculosis, staphylococcal sepsis, toxic shock syndrome, cervix carcinoma, obstructive pancreatitis, diabetic vascular disorder) was reported in 8 (5.6%) of OKZ groups, numerically higher than 4(2.8%) in PBO. There was one death due to septic shock in the OKZ q2w arm.Conclusion:Treatment with OKZ over a 24-week period was associated with significant improvements in the signs, symptoms and physical function of RA, with a safety profile consistent with Phase II data for OKZ and with the data for the agents with similar mechanism of action.There were no discernible differences between the two regimens of OKZ in efficacy or safety outcomes.References:[1]Genovese MC et al. Ann Rheum Dis. 2014 Sep; 73:1607; 2. Takeuchi T, et al. Mod Rheumatol. 2016; 26:1Acknowledgments:Investigators and patients of CREDO-1 study.Disclosure of Interests:Evgeny Nasonov Speakers bureau: Lilly, AbbVie, Pfizer, Biocad, R-Pharm, Rumen Stoilov Grant/research support from: R-Pharm, Tamara Tyabut: None declared, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

Netakimab (NTK) is a humanised monoclonal antibody targeting interleukin-17A, previously investigated in a phase 1 trial in healthy volunteers. Here, we report the results of a phase 2 trial, conducted to assess safety and pharmacokinetics (PK), to establish a therapeutic dose of NTK in a target population of patients with active ankylosing spondylitis (AS).89 patients with active AS, despite non-steroidal anti-inflammatory (NSAID) drug treatment, were randomised to receive 40, 80 or 120 mg of subcutaneous NTK or placebo at weeks 0, 1, 2 and q2wk thereafter until week 12. The primary endpoint was to achieve a proportion of patients with ≥20% improvement in Assessment of Spondyloarthritis.Rates of ASAS20 response at week 16 for NTK with 95%CI for difference in ASAS20 rates NTK vs. placebo were 72.73% [1.69%;58.05%], 81.82% [12.36%;65.56%], 90.91% [23.71%;72.39%] at doses of 40, 80 and 120 mg. The response rate in the placebo arm was 42.86%. The pre-specified margin of clinically non-meaningful difference was 10%. Superiority to placebo was confirmed for doses 80 and 120 mg. The most frequent adverse events (AEs) were lymphocytosis, neutropenia, and asymptomatic bacteriuria. No dose-dependent toxicity or serious adverse events (SAEs) were observed. The most effective dose with the fastest response onset and favourable safety profile was 120 mg.The data obtained demonstrate the efficacy and favourable safety profile of NTK in active AS. Clinical development of NTK will be continued in a phase 3 trial aimed to evaluate the efficacy of 1-year treatment with NTK 120 mg in patients with AS.

Objective.To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA).Methods.The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported.Results.Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96–8.58), infection 38.60 (36.24–41.12), serious infection 1.68 (1.35–2.07), malignancies 1.09 (0.84–1.42), and autoimmune disorders 1.33 (1.05–1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study.Conclusion.These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

OBJECTIVE: The osteoporosis drug strontium ranelate dissociates bone remodelling processes. It also inhibits subchondral bone resorption and stimulates cartilage matrix formation in vitro. Exploratory studies in the osteoporosis trials report that strontium ranelate reduces biomarkers of cartilage degradation, and attenuates the progression and clinical symptoms of spinal osteoarthritis, suggesting symptom- and structure-modifying activity in osteoarthritis. We describe the rationale and design of a randomised trial evaluating the efficacy and safety of strontium ranelate in knee osteoarthritis. RESEARCH DESIGN, METHODS, AND RESULTS: This double-blind, placebo-controlled trial (98 centres, 18 countries) includes ambulatory Caucasian men and women aged ≥50 years with primary knee osteoarthritis of the medial tibiofemoral compartment (Kellgren and Lawrence grade 2 or 3), joint space width (JSW) 2.5 to 5 mm, and knee pain on most days in the previous month (intensity ≥40 mm on a visual analogue scale). Patients are randomly allocated to three groups (strontium ranelate 1 or 2 g/day, or placebo). Follow-up is expected to last 3 years. The primary endpoint is radiographic change in JSW from baseline in each group versus placebo. The main clinical secondary endpoint is WOMAC score at the knee. Safety is assessed at every visit. It is estimated that 1600 patients are required to establish statistical significance with power >90% (0.2 mm ± 10% between-group difference in change in JSW over 3 years). Recruitment started in April 2006. The results are expected in spring 2012. CLINICAL TRIAL REGISTRATION: The trial is registered on www.controlled-trials.com (number ISRCTN41323372). CONCLUSIONS: This randomised, double blind, placebo-controlled study will establish the potential of strontium ranelate in improving structure and symptoms in patients with knee osteoarthritis.

The approved dose of rituximab (RTX) in rheumatoid arthritis is 1000 mg × 2, but some data have suggested similar clinical efficacy with 500 mg × 2. The purpose of this study was to compare the effectiveness of the regular and low doses given as first treatment course.Twelve European registries participating in the CERERRA collaboration (The European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis) submitted anonymized datasets with demographic, efficacy and treatment data for patients who had started RTX. Treatment effectiveness was assessed by DAS28 reductions and EULAR responses after 6 months.Data on RTX dose were available for 2,873 patients, of whom 2,625 (91.4 %) and 248 (8.6 %) received 1000 mg × 2 and 500 mg × 2, respectively. Patients treated with 500 mg × 2 were significantly older, had longer disease duration, higher number of prior DMARDs, but lower number of prior biologics and lower baseline DAS28 than those treated with 1000 mg × 2. Fewer patients in the low-dose group received concomitant DMARDs but more frequently received concomitant corticosteroids. Both doses led to significant clinical improvements at 6 months. DAS28 reductions at 6 months were comparable in the 2 dose regimens [mean DeltaDAS28 ± SD -2.0 ± 1.3 (high dose) vs. -1.7 ± 1.4 (low dose), p = 0.23 adjusted for baseline differences]. Similar percentages of patients achieved EULAR good response in the two dose groups, 18.4 % vs. 17.3 %, respectively (p = 0.36).In this large observational cohort initial treatment with RTX at 500 mg × 2 and 1000 mg × 2 led to comparable clinical outcomes at 6 months.

Objective(s): Strontium ranelate (SrRan) has potential beneficial effects on cartilage degradation in osteoarthritis (OA), stimulating human cartilage matrix formation in vitro and decreasing urinary CTX-II. SrRan has also been shown to reduce radiographic spinal OA progression and back pain in osteoporotic women with prevalent spinal OA. We compared the efficacy and safety of SrRan with placebo in the treatment of knee OA in a double-blind, placebo-controlled, randomised, international 3-year study (registration number: ISRCTN41323372).Material & Methods: 1683 patients with symptomatic primary knee osteoarthritis and with a Kellgren-Lawrencescore II or III were included and randomly allocated to SrRan 1 or 2 g/day, or placebo. The primary endpoint was radiographic joint space narrowing measured as the mean change from baseline to End in Joint Space Width (JSW) of the knee medial tibiofemoral compartment using a semiautomated centralised reading method. JSW was measured at selection, 12, 24, and 36 months on radiographs acquired using a postero-anterior, weight-bearing, fixed-flexion acquisition technique (described elsewhere1). Symptoms were primarily assessed by algofunctional WOMAC score and subscores and safety by adverse events and biological parameters.Results: The intention-to-treat population included 1371 (82%) patients (mean follow-up 29.810.5 months). Mean age was 62.8±7.2 years and 69% were female. Mean BMI was 30±5 kg/m2, mean JSWwas 3.50±0.83 mm, and 61% of randomised patients were Kellgren and Lawrence stage II. Treatment with SrRan was associated with less progression of cartilage degradation, decrease in JSW was -0.230.56 mm with 1 g/day; -0.270.63 mm with 2 g/day and -0.370.59 mm with placebo; treatment-placebo estimated differences (SE) were 0.14 (0.04), p

To describe disease characteristics and treatment regimens for adult patients with systemic lupus erythematosus (SLE) with autoantibody positive disease in three countries (the Russian Federation, Ukraine and Republic of Kazakhstan).The Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events (ESSENCE) study was a 1-year, retrospective, multicentre, observational study. Data included patients' characteristics, disease activity and severity, and healthcare resource use in 2010.Twelve centres enrolled 436 eligible patients: 232 in Russia, 110 in Kazakhstan and 94 in Ukraine. Mean age ranged from 36 to 42 years and median SLE duration from 3 to 6.8 years. According to study definitions, 69.2% of patients in Russia, 72.7% in Kazakhstan and 55.4% in Ukraine had severe disease at diagnosis. SLE activity (Nasonova classification, 1972) decreased from diagnosis to the last visit in 2010 in all countries. At the last visit, mean (SD) Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index score was 13.8 (10.5) in Russia, 19.4 (16.9) in Kazakhstan and 7.2 (6.8) in Ukraine, and Systemic Lupus International Collaborative Clinics/American College of Rheumatology damage index was 2.0 (2.2), 3.3 (3.2) and 2.2 (2.0), respectively. Treatment regimens included predominantly glucocorticoids (96.7-99.1%), immunosuppressants or cytotoxic drugs, for example, azathioprine and cyclophosphamide (20.7-53.2%), and antimalarial drugs (18.3-40.8%).The study provides reliable insight into the SLE clinical profiles in the referenced countries. Patients were 4-10 years younger in the study and had 3-7 years shorter SLE duration than in Western European countries and both SLE activity and severity were higher with higher rate of hospitalisations, but decreased during treatment. Local and international scales demonstrated correlation in SLE activity and organ damage evaluation. There were differences in clinical characteristics and healthcare features across the countries.

ObjectivesOSKIRA-4 evaluated the efficacy of fostamatinib monotherapy versus placebo on the signs and symptoms of rheumatoid arthritis over 6 weeks by Disease Activity Score C reactive protein (DAS-28(CRP)) and assessed non-inferiority to adalimumab monotherapy at Week 24 by DAS-28(CRP).MethodsOverall, 279 patients not currently taking disease-modifying antirheumatic drugs were randomised to: (A) fostamatinib 100 mg twice daily for 24 weeks plus placebo injection every 2 weeks (PBOI); (B) fostamatinib 100 mg twice daily for 4 weeks, then 150 mg once daily up to Week 24, plus PBOI; (C) fostamatinib 100 mg twice daily for 4 weeks, then 100 mg once daily up to Week 24, plus PBOI; (D) adalimumab 40 mg every 2 weeks for 24 weeks, plus oral placebo twice daily; or (E) oral placebo twice daily for 6 weeks, plus PBOI, then a switch to arm A or B.ResultsFostamatinib demonstrated a significant improvement in DAS-28(CRP) score from baseline versus placebo at Week 6 for arms A and B, but not C. Fostamatinib was significantly less effective than adalimumab at Week 24 based on DAS-28(CRP). Adverse events observed with fostamatinib treatment were consistent with those reported in previous studies, including hypertension and diarrhoea.ConclusionsFostamatinib demonstrated efficacy as monotherapy, showing superior DAS-28(CRP) score changes between baseline and 6 weeks when compared with placebo in treatment arms A and B. However, all fostamatinib regimens demonstrated inferior responses compared with adalimumab at Week 24.Trial registration numberClinicaltrials.gov: NCT01264770.

Introduction: Systemic sclerosis (SSc) is characterised by disturbed vessel morphology and an overproduction of vascular endothelial growth factor (VEGF). The VEGF gene located on chromosome 6p21.3 has several polymorphisms. Objective: To test the hypothesis that disturbed angiogenesis may be related to the genetic background of the VEGF gene. Materials and methods: EUSTAR centres included European Caucasian patients with SSc and matched controls with osteoarthritis. The VEGF gene was genotyped by polymerase chain reaction, followed by restriction enzyme analysis. The 634 C/T and 936 C/G mutations and an 18-base pair insertion/deletion at −2549 of the VEGF promoter region were tested. Results: 416 patients with SSc and 249 controls were included in the study population. Of the patients with SSc, 42% had a diffuse cutaneous subtype, 16% had increased pulmonary arterial pressure and 61% had decreased carbon monoxide diffusion capacity. The genotype frequencies in the patients with SSc and in controls were in Hardy–Weinberg equilibrium. The allele and genotype frequencies of the polymorphisms did not differ between patients with SSc and controls. No association was found between these polymorphisms and disease phenotypes. Conclusion: This study shows that there is no association between the three selected functional VEGF polymorphisms and SSc.

Biologics have mainly been assessed in patients with severe rheumatoid arthritis (RA) globally. Less attention has been paid to moderately active disease, especially in Central and Eastern Europe (CEE). Access to biologics and the disease features of RA patients may differ in CEE, relative to other regions. We assessed the clinical and patient-reported outcomes (PROs) of treatment from CEE patients in the multinational PRESERVE study ( NCT00565409 ). Patients with moderate RA 28-joint disease activity score ((DAS28) erythrocyte sedimentation rate (ESR) >3.2 and ≤5.1) despite methotrexate (MTX) treatment received open-label etanercept (ETN) 50 mg QW + MTX for 36 weeks. Low disease activity (DAS28 low disease activity (LDA) ≤3.2) and remission (DAS28 ESR

Background: Mitogen-activated protein (MAP) kinases are key regulators of cytokine production, and are therefore potential targets for treatment of rheumatoid arthritis (RA). Objective: This two-part phase II study investigated the efficacy and safety of a once-daily 50 mg GLPG0259 (an inhibitor of MAP kinase-activated protein kinase 5) dose vs placebo ( part A). An interim analysis after part A would determine whether the dose-finding part ( part B) would be performed. Methods: In part A, eligible methotrexate (MTX)- refractory patients with RA were randomised to receive either a once-daily 50 mg dose of GLPG0259 or placebo, in addition to a stable dose of MTX, for 12 weeks. The primary efficacy end point was the percentage of patients achieving an American College of Rheumatology 20% improvement (ACR20) response after 12 weeks. Results: The interim analysis showed no difference between the percentage of subjects achieving the primary efficacy variable of ACR20 or the secondary efficacy variables (ACR50, ACR70 and Disease Activity Score 28) at week 12 in the GLPG0259-treated (n=19) and placebo-treated (n=11) groups. Owing to lack of efficacy, the study was terminated, and part B was not initiated. Conclusions: This innovative study design quickly provided conclusive results on the lack of efficacy of GLPG0259 in patients with RA.

Background Low back pain (LBP) is the leading cause of Years Lived with Disability worldwide (1). The number of people suffering from LBP grew more than 50% from 1990 to 2013, to 651 million (1). Glucosamine-chondroitin sulfate (GCS) combination is widely used in the treatment of OA; however there are few prospective scientific investigations of its therapeutic merits in severe LBP. Objectives To study the efficacy of GCS in the decreasing disability in patients with severe disability due to chronic low back pain in a large open pilot prospective observational study. Methods We studied patients 40–65 years of age who had severe disability (Oswestry Score >40) due to LBP. The Oswestry scale contains ten sections on pain intensity, lifting, ability to care for oneself, walking, sitting, standing, sexual function, social life, sleep quality, and ability to travel. Each question is scored on a scale of 0–5 with the scores for all questions summed, then multiplied by two to obtain the index (range 0 to 100). Scores above 40 indicate severe disability. Major exclusion criteria were the presence of fibromyalgia, degenerative spondylolisthesis, and alcohol and/or drug abuse. All patients were treated with ARTRA (combination of glucosamine hydrochloride 500 mg and chondroitin sulfate 500 mg in tablet form; Unipharm Inc.) at a dose of 1 tab bid for the first month and then 1 tab daily for the next two months. Oswestry index was measured at enrollment into the study and then after 1 month, 2 months and 3 months of starting therapy. Results The study population included a total of 4,588 patients with Oswestry index of 40 or more (mean age 52.9±7.4 years, 66% women, mean BMI 27.7±5.4, median of duration of LBP 6 months, LQ-4.0; UQ-20.0). Intent-to-Treat (ITT) analysis with worst observation carried forward (WOCF) showed an improvement in disability Oswestry Scale mean (95%CI) from 58.4 (57.9 -58.7) to 13.9 (13.5–14.3) (p An adverse event (AE) was reported by 311 (6.8%) patients (mostly GI in origin, such as nausea, abdominal pain and dry mouth) but only 134 (2.9%) patients deemed the AE to be severe enough to discontinue therapy. Conclusions Although open and uncontrolled, this pilot, community-based efficacy and safety study shows dramatic reductions in pain and disability in patients with severe disability as measured with Oswestry index. With its benign safety profile, GCS therapy deserves serious evaluation in the management of severe LBP in a prospective randomized double-blinded clinical trial. References Vos T et al. Lancet. 2015; 386(9995): 743–800. Acknowledgement Supported by a research grant from Unipharm Inc. Disclosure of Interest G. Singh Grant/research support from: Unipharm, L. Alekseeva Grant/research support from: Unipharm, V. Alekseev Grant/research support from: Unipharm, D. Goriachev Grant/research support from: Unipharm, A. Barinov Grant/research support from: Unipharm, E. Nasonov Grant/research support from: Unipharm, A. Mithal: None declared, S. Pyanykh Employee of: Unipharm

Background BCD-020 is the first Russian rituximab (RTX) biosimilar which was approved for medical use in lymphoma patients in Russia and some CIS countries. Previous preclinical and clinical studies showed that BCD-020 is highly similar to innovator RTX. Since there are several differences in mechanism of action of RTX in NHL and RA it is recommended to conduct separate clinical studies in oncology and autoimmune indications to prove similar efficacy and safety of biosimilar and original medicine. Objectives The primary objective was to evaluate the efficacy and safety of BCD-020 used in combination with MTX in patients with RA with inadequate response or intolerance to other DMARDs including 1 or more TNF inhibitor. The secondary objectives included direct comparison of safety, efficacy, pharmacokinetics, pharmacodynamics and immunogenicity of RTX biosimilar and innovator RTX. Methods This international multicenter randomized double-blind phase 3 clinical study was conducted in patients with active RA despite DMARD therapy, which included 1 or more TNF inhibitor. After completion of screening all eligible patients were stratified by age ( Results A total of 160 patients were enrolled; 159 patients had data eligible for efficacy analysis. ACR20 at Week 24 was reported in 84.14% patients in BCD-020 arm and 87.01% in reference arm. The 95% CI for the difference in proportion of ACR20 between groups was [-13.95; 8.74%], where the limits of 95% CI lie within the pre-specified equivalence margin. Both drugs caused deep and sustained depletion of B-cells from peripheral blood without any toxicity to other cell populations. Favorable safety profiles were demonstrated in both groups without any significant differences: AEs have been reported in 59.34% patients from BCD-020 arm and 54.12% patients from reference arm. Treatment discontinuation caused by AE/SAE was reported only for 3 (3.30%) patients in BCD-020 arm and 4 (3.53%) patients in the reference arm (p=1.00). SAEs occurred only in the reference group (2.35%). Binding antibodies were revealed in 3 patients from BCD-020 arm and in 7 patients from reference arm (p=0.209). There were 2 events of neutralizing antibodies against RTX, both in the reference arm (p=0.232). Conclusions Equivalent efficacy of BCD-020 compared to innovator RTX in patients with active RA has been confirmed. Further clinical evaluation of BCD-020 is planned to confirm long-term efficacy and safety. References interim study report. Disclosure of Interest A. Eremeeva Employee of: CJSC BIOCAD, E. Chernyaeva Employee of: CJSC BIOCAD, R. Ivanov Employee of: CJSC BIOCAD, E. Nasonov: None declared, L. Knyazeva: None declared

ObjectivesTo compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide.Methods10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab.Results1195 patients were treated with rituximab plus methotrexate, 177 with rituximab plus leflunomide and 505 with rituximab alone. Significantly more patients achieved a European League Against Rheumatism good response at 6 months when treated with rituximab plus leflunomide (29.1%) compared with rituximab plus methotrexate (21.1%) and rituximab alone (19.3%; p=0.02 and p=0.01, respectively). Similar results were observed at 12 months. Adverse events occurred in 10.2%, 13.2% and 13.9% of patients on rituximab plus leflunomide, rituximab plus methotrexate and rituximab alone, respectively.ConclusionsLeflunomide is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. Slightly better results were obtained by the combination of rituximab and leflunomide than rituximab and methotrexate, raising the possibility of a synergistic effect of leflunomide and rituximab.

Forty-six patients (33 women, 13 men, mean age 40 years) with Sneddon''s syndrome characterized by an ischemic cerebrovascular disease combined with widespread livedo were studied. The clinical pictur

Item does not contain fulltext OBJECTIVE: To assess the 6-month effectiveness of the first rituximab (RTX) course in rheumatoid arthritis (RA) and to identify possible predictors of response. METHOD: 10 European registries submitted anonymised datasets (baseline, 3- and 6-month follow-up) from patients with RA who had started RTX, and datasets were pooled and analysed. Heterogeneity between countries was analysed by analysis of variance. Predictors of response were identified by logistic regression. RESULTS: 2019 patients were included (mean age/disease duration 53.8/12.1 years, 80.3% female, 85.6% rheumatoid factor (RF) positive and 76.8% (456/594 patients) anti-cyclic citrullinated peptide antibodies (anti-CCP) positive). For these patients an average of 2.7 disease-modifying antirheumatic drugs (DMARDs) (range 0-10) had failed, and RTX was given as the first biological agent in 36.6% of patients. There was significant heterogeneity between countries for several baseline characteristics, including the number of previous biological agents. Disease Activity Score based on 28 joint counts (DAS28) decreased from 5.8+/-1.4 at baseline to 4.2+/-1.4 at 6 months (p

Summary Background The aim of this study was to assess and compare patients’ access to biologic anti-RA drugs in selected Central and Eastern European (CEE) countries and to analyze the determinants of differences between countries. Material/Methods This is a multi-country survey study, based on a combination of desk research and direct contact with national RA stakeholders. Data was collected using a pre-defined questionnaire. Affordability was measured using an affordability index, calculated comparing the index of health care expenditures to the price index, using Poland as an index of 1. Results The percentage of patients on biologic treatment in 2009 was highest in Hungary (5% RA patients on biologic treatment), followed by Slovenia (4.5%), Slovakia (3.5%), Czech Republic (2.92%), Romania (2.2%), Estonia (1.8%), and Croatia, Serbia, Poland (below 1.5%). Infliximab, etanercept, adalimumab and rituximab were included in the reimbursement system in all countries, but abatacept and tocilizumab were included only in Slovakia. In Slovenia, public payer covered 75% of the price, and 25% is covered by supplementary health insurance; in Bulgaria public payer covered 50% of etanercept and adalimumab costs, and 75% of rituximab cost. In other countries, biologic drugs are reimbursed at 100%. Affordability index for biologic drugs was the lowest in Slovenia (0.4). In each country national guidelines define which patients are eligible for biologic treatment. Disease Activity Score (DAS28) of over 5.1 and failure of 2 or more disease-modifying anti-RA drugs, including methotrexate, are commonly used criteria. Conclusions The most important factors limiting access to biologic anti-RA treatment in the CEE region are macroeconomic conditions and restrictive treatment guidelines.

Background The data on how to optimally retreat patients with RA with rituximab (RTX) have been limited so far. Objectives The aim of this analysis was to compare two common retreatment strategies: A fixed retreatment approach and retreatment when a flare occurs. Methods Pooled data from the Collaborating European Registries for Rituximab in RA (CERERRA) project were used. We identified RA patients who had received at least 2 retreatments (3 courses) with RTX and who had available information about the strategy for retreatment (according to the physician9s opinion). The two retreatment strategies were compared by applying an adjusted mixed model analysis with DAS28 improvement as the dependent variable. Results A total of 800 patients were retreated at least twice: 616 patients retreated because of a flare (442 at 1st and 174 at 2nd retreatment) and 184 receiving fixed retreatment (128 at 1st and 56 at 2nd retreatment). Baseline characteristics (incl. age, sex, seropositivity, disease duration, number of prior DMARDs and biologics) at first course of RTX did not differ significantly between the two groups. However, patients retreated on flare had, as expected, a significantly higher DAS28-ESR at the time of 1st retreatment (5.1±1.3 vs. 4.1±1.4, p The baseline (=start of each cycle) deltaDAS28 (compared to the DAS28 at the time of RTX start) for the two groups is shown in figure 1. Patients receiving fixed retreatment had a significantly higher (in absolute number) deltaDAS28 (p Conclusions A fixed RTX retreatment strategy in RA seems to be more effective than the retreatment “on-flare” strategy. Disclosure of Interest K. Chatzidionysiou: None declared, E. Lie: None declared, E. Nasonov: None declared, G. Lukina: None declared, M. Hetland: None declared, U. Tarp: None declared, K. Pavelka: None declared, C. Gabay: None declared, D. Nordstrom: None declared, H. Canhao: None declared, M. Tomsic: None declared, P. van Riel: None declared, J. Gomez-Reino: None declared, I. Ancuta: None declared, T. Kvien Grant/research support: research funding to the Diakonhjemmet Hospital from AbbVie, BMS, MSD/Schering-Plough, Pfizer/Wyeth, Roche and UCB, Consultant for: AbbVie, BMS, Celltrion, Eli Lilly, Hospira, MSD/Schering-Plough, Orion Pharma, Pfizer/Wyeth, Roche, UCB, R. van Vollenhoven: None declared DOI 10.1136/annrheumdis-2014-eular.2571

ObjectiveTo identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc).MethodsA list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores.ResultsPhysicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as follows: skin domain (puffy fingers/puffy swollen digits turning into sclerodactily); vascular domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). Finally, the whole assembly of EUSTAR centres ratified with a majority vote the results in a final face-to-face meeting.ConclusionThe three Delphi rounds allowed us to identify the items considered by experts as necessary for the very early diagnosis of SSc. The validation of these items to establish diagnostic criteria is currently ongoing in a prospective observational cohort.

Effect of synthetic analogues of atrial natriuretic factor (ANF) on proliferative response and natural cytotoxic lymphocytes of human subjects was investigated in vitro. ANF-III and ANF-IV increased blast transformation lymphocytes induced by a Con-A suboptimal dose. The increase of cells activity was comparable with the effect of interleukin-2, added at a dose of 50-100 unit/ml.