Antibodies executing catalytic activity are referred to as antibody enzymes or short "abzymes" and may have diagnostic relevance. Abzymes with deoxyribonuclease (DNase) activity have been demonstrated in patients with autoimmune and infectious diseases. Despite several reports on the occurrence of DNase abzymes in systemic autoimmune rheumatic diseases, conclusive data about DNase activity of antibodies in patients with spondyloarthritides (SpAs) are lacking. In recent cross-sectional studies evaluating levels of IgG DNase activity in patients with psoriatic arthritis (PsA), reactive arthritis (ReA), and ankylosing spondylitis (AS), DNase activity of IgG has been assessed by the rivanol clot method and confirmed by agarose gel electrophoresis. Remarkably, levels of IgG DNase activity were significantly higher in sera of SpA patients than those in control subjects. In patients with PsA, ReA, and AS, a positive correlation of DNase IgG activity with synovitis, disease activity, and stage of spondylitis was observed, respectively. Given the involvement of autoimmune reactions in cytolysis and connective tissue degradation in PsA, ReA, and to a lesser extent in AS, abzymes might have an impact on the pathophysiology of SpAs. Detection of IgG DNase activity in patients suffering from SpA represents an exciting new research field and may assist in the differential diagnosis of SpA.

Background:The presence of sacroiliitis in patients (pts) with ankylosing spondylitis (AS) on imaging can be established both by sacroiliac joint (SIJ) X-ray or MRI. Active sacroiliitis on MRI as defined by ASAS is predictor of good treatment response to biological disease modifying anti-rheumatic drugs [1, 2]. Netakimab (NTK) is a humanized anti-interleukin-17A antibody approved for the treatment of AS, psoriatic arthritis, moderate-to-severe plaque psoriasis in Russia and Belarus. The difference in treatment response to NTK in AS pts with and without active sacroiliitis on MRI (MRI+/MRI−) is unclear.Objectives:To report the changes in AS activity in pts with and without sacroiliitis on MRI at week 16 of NTK treatment.Methods:ASTERA (NCT03447704) is an ongoing phase 3 placebo (PBO)-controlled clinical study, aimed at evaluating NTK efficacy in AS. All pts fulfilled modified New York criteria. Evaluation of acute inflammation on SIJ MRI was performed at the baseline but was not an inclusion criterion. This analysis includes pts received subcutaneous NTK 120 mg every 2 wks with available baseline SIJ MRI. The presence of sacroiliitis on MRI was defined as SPARCC>2. Efficacy endpoints included ASAS20/40, ASAS partial remission (PR), changes from baseline in BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score).Results:67 MRI+ and 46 MRI− pts were included into analysis. Baseline characteristics were balanced across both arms. 42.4% of MRI+ pts and 38.3% of MRI− pts achieved ASAS40 at week 16 (p≥0.05), ASAS20 was observed in 65.2%/55.3% pts in the same arms respectively (p≥0.05). ASAS PR was reported for 15.2% MRI+ and 17.0% MRI− pts (p≥0.05). Improvements in BASDAI and ASDAS-CRP were similar across both arms. At wk 16, mean change from baseline in BASDAI was −2.7 vs −3.0 for MRI+ and MRI− pts respectively, mean change in ASDAS-CRP was −1.7 vs −1.4 in the same arms (p≥0.05 for all), (figure 1).Figure 1.Clinical improvements in AS disease activity. Mean change from baseline is shown for (A) ASDAS-CRP, and (B) BASDAIConclusion:NTK leads to decline of disease activity in AS pts irrespectively of sacroiliitis on MRI.References:[1]Rudwaleit M, et al. MRI in predicting a major clinical response to anti-tumour necrosis factor treatment in ankylosing spondylitis. Ann Rheum Dis. 2008;67(9):1276-81.[2]Sieper J, et al. A randomized, double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2015;67(10):2702-12.Acknowledgements:This study was sponsored by JSC BIOCAD.Disclosure of Interests:Inna Gaydukova Speakers bureau: Abbvie, Biocad, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, V Mazurov: None declared, Shandor Erdes: None declared, Tatiana Dubinina: None declared, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Anna Eremeeva Employee of: Biocad

BackgroundEfficacy and safety of netakimab (NTK), a humanized anti-IL17A antibody, was established in phase 2 clinical trials in patients (pts) with radiographic axial spondyloarthritis (r-axSpA)1 and psoriasis2.ObjectivesThe abstract presents 16-week data from ongoing ASTERA study (NCT03447704) in pts with active r-axSpA.MethodsASTERA is a phase 3 international double-blind placebo (PBO)-controlled study. 228 adult pts with r-axSpA, active (BASDAI ≥ 4) despite the standard NSAIDs, were randomly assigned (1:1) to receive 120 mg NTK or PBO SC at Week (Wk) 0,1,2 and then q2w through Wk 16. After Wk 16 all pts will start to receive NTK up to Wk 52. Primary endpoint was ASAS40 rate at Wk 16.ResultsThe mean age at baseline was 39.14±9.9 years, the mean symptoms duration was 4.3±4.5 years. 76.8% of pts were naïve to biological treatment. At Wk 16 ASAS40 rate was higher in NTK arm compared to PBO: 40.35% versus (vs.) 2.63% pts (95% CI for the difference in ASAS40 rate was [27.37%; 48.07%] (p<0.0001, Figure 1). Efficacy of NTK was also proved by comparison of secondary endpoints (Figure 2); improvement in BASDAI, MASES, BASFI became significant from Wk 4 and remained during the study (no data presented). Most reported adverse events (AE) and treatment-related AEs (TRAE) were mild/moderate (Table 1). The most frequent AEs were anemia, neutropenia, ALT increase. One serious AE (SAE), not related to the treatment (bone fracture), was reported in NTK arm.ConclusionNTK at a dose 120 mg is well-tolerated drug with favorable safety profile that leads to decline in r-axSpA activity, function improvement and axial mobility in 16 Wks.References[1] Mazurov V, et al. Ann Rheum Dis 2018;77:A64. 2Samtsov A, et al. Vestn Dermatol Venerol 2017;0(5):52-63.Table 1Safety data % of patients with NTK (n = 114) PBO (n = 114) p-value AE/SAE 33.3% (38) 25.4% (29)0.245TRAE17.5% (20)14.0% (16)0.586SAE0.9% (1)01.0Grade 3-4 AEs2.6% (3)3.5% (4)1.0Grade 3-4 TRAEs1.8% (2)1.8% (2)1.0Local reactions1.8% (2)0.9% (1)1.0Figure 1Figure 2Disclosure of InterestsInna 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, Shandor Erdes Grant/research support from: JSC BIOCAD, Speakers bureau: JSC BIOCAD, Tatiana Dubinina: None declared, Olga Nesmeyanova Grant/research support from: JSC BIOCAD, Elena Ilivanova Grant/research support from: JSC BIOCAD, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Aleksander Kastanayan Grant/research support from: JSC BIOCAD, Tatyana Povarova Grant/research support from: JSC BIOCAD, Elena Zhugrova Grant/research support from: JSC BIOCAD, Tatyana Plaksina Grant/research support from: JSC BIOCAD, Pavel Shesternya Grant/research support from: JSC BIOCAD, Tatyana Kropotina Grant/research support from: JSC BIOCAD, Olga Antipova Grant/research support from: JSC BIOCAD, Elena Smolyarchuk Grant/research support from: JSC BIOCAD, Oksana Tciupa Grant/research suppo...

Background:Previously, the results of phase II AURORA clinical study of levilimab in subjects with active rheumatoid arthritis (RA) have been reported1. Here we report topline 24-weeks results of preliminary primary efficacy and safety analysis of phase 3 double-blind, placebo-controlled randomized clinical study (SOLAR).Objectives:To confirm that levilimab in combination with methotrexate is superior to placebo in combination with methotrexate in achieving ACR20 at week 12 and low disease activity (LDA) at week 24 in subjects with methotrexate (MTX) resistant active RA.Methods:The study is ongoing at 21 clinical sites in Russia and Belarus. All randomized subjects have completed 24 weeks of study between November 2019 and January 2021.154 adults, aged ≥18 years with the diagnosis of RA (ACR 2010) for at least 24 weeks, and confirmed disease activity at screening despite treatment with MTX for the last 12 weeks (in a stable dose 15-25 mg/week, for at least 4 weeks) were randomly assigned (2:1) to receive either levilimab (162 mg, SC, QW) + MTX (n=102) or placebo + MTX (n=52). The randomization and treatment allocation were carried out by a central computer-based system. Subjects, caregivers, and those assessing the outcomes were blinded to group assignment.The hypothesis of superiority of levilimab over placebo was tested for two co-primary efficacy outcomes: proportion of subjects who achieved ACR20 at week 12 and proportion of subjects who achieved LDA of RA (DAS28-CRP <3.2) at Week 24 of the study.For ethical reasons, subjects who haven’t achieved minimal clinical response at week 12 (≥20% reduction in the number of tender/swollen joints; 66/68) received rescue therapy at the discretion of the Investigator, and all subsequent efficacy assessments for those were considered missing.For the primary efficacy analysis, subjects with missing data due to study discontinuation or rescue therapy prescription were considered non-responders (non-responder imputation, NRI). Otherwise, the analysis was performed on observed cases.Safety was assessed through monitoring of adverse events (AEs).Results:The primary analysis was based on 149 randomized subjects (n=99 and n = 50) for ACR20 and 154 randomized subjects (n= 102 and n = 52) for LDA.70/99 (71%) of subjects who received levilimab and 20/50 (40%) who received placebo achieved ACR20 response at week 12. The difference in proportion was 30% with a lower bound of 97.5% CI 12.8%; p=0.0003 (Pearson’s chi-squared test).53/102 (52%) of subjects received levilimab and 3/52 (6%) received placebo achieved LDA at week 24. The difference in proportion was 46% with a lower bound of 97.5% CI 31.2 %; p<0.0001 (Pearson’s chi-squared test).The safety population included all subjects, who received investigational product (n=154).The most common adverse events (reported in ≥5% of subjects) in levilimab and placebo arms, respectively were: blood cholesterol increase (19% vs. 10%), ALT increase (11% vs. 8%), lymphocyte count decrease (9% vs. 8%), blood bilirubin increase (11% vs. 0%), blood triglycerides increase (9% vs. 2%), AST increase (7% vs. 4%), IGRA with M.tuberculosis antigen positive (5% vs. 6%), ANC decrease (8% vs. 0%). No deaths were occurred.Conclusion:The study confirmed superior efficacy of levilimab + MTX over placebo + MTX in subjects with MTX resistant active RA. No new safety signals were detected.Trial registration: Clinicaltrials.gov identifier NCT04397562References:[1]Mazurov V, Zotkin E, Ilivanova E, et al. FRI0114 EFFICACY OF LEVILIMAB, NOVEL MONOCLONAL ANTI-IL-6 RECEPTOR ANTIBODY, IN COMBINATION WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: 1-YEAR RESULTS OF PHASE 2 AURORA STUDY. Annals of the Rheumatic Diseases 2020;79:637-638.Acknowledgements:We thank all contributors to the SOLAR clinical trialDisclosure of Interests:V Mazurov: None declared, Maxim Korolev: None declared, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Aleksander Kastanayan: None declared, Tatyana Povarova: None declared, Tatyana Plaksina: None declared, Olga Antipova: None declared, Diana Kretchikova: None declared, Svetlana Smakotina: None declared, Oksana Tciupa: None declared, Tatiana Raskina: None declared, Tatyana Kropotina: None declared, Olga Nesmeyanova: None declared, Tatiana Popova: None declared, Ekaterina Dokukina Employee of: JSC BIOCAD, Aleksandra Plotnikova Employee of: JSC BIOCAD, Anton Lutskii Employee of: JSC BIOCAD, Arina Zinkina-Orihan Employee of: JSC BIOCAD

Background:Psoriatic arthritis (PsA) is associated with multiple manifestations, resulting in reduced health-related quality of life (HR-QoL) of patients (pts). Netakimab (NTK) is a humanized anti-IL17A antibody approved for the treatment of moderate-to-severe plaque psoriasis.Objectives:To assess the impact of NTK on patient-reported outcomes (PROs) in active PsA pts, based on data of 24-week (wk) data from the ongoing PATERA study (NCT03598751).Methods:PATERA is an international double-blind, placebo-controlled clinical study. 194 eligible adult pts with PsA (CASPAR, 2006), with inadequate response to csDMARD or one TNFi, were randomized (1:1) to receive NTK 120 mg or placebo (PBO) at Wk 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. Pts from PBO arm failed to achieve ACR20 (20% improvement of the American College of Rheumatology criteria) by Wk 16 were switched to NTK. PROs included changes from baseline (BL) in Work Productivity and Activity Impairment General Health (WPAI GH), 36-item Short Form Health Survey (SF-36), European Quality of Life Questionnaire (EQ-5D-5L), Dermatology Quality of Life Index (DLQI), Health assessment questionnaire disability index (HAQ-DI).Results:BL demographics and PsA characteristics were similar between treatment arms (Table 1). The proportion of pts with an improvement of ≥1 level in EQ-5D domains at Wk 24 (among pts who reported problems at BL) was higher in NTK arm compared to PBO (Figure 1). The assessment of physical disability showed positive dynamics in NTK arm: at Wk 24 mean change in HAQ-DI from BL was -0.6 for NTK vs -0.1 for PBO (p<0.0001). DLQI was assessed in pts with ≥3% body surface area involvement at BL (N=76 in NTK arm, N=72 in PBO arm). A greater reduction in DLQI was observed in NTK-treated pts (-11.4) compared to PBO-treated pts (-1.8) (p<0.0001). After 24 wks WPAI response for NTK was better than for PBO in all aspects, except work time missed due to PsA (Table 2). Positive dynamics were reported for both SF-36 components, however, the difference between NTK and PBO was not statistically significant. At Wk 24 mean change from baseline in SF-36 PCS in NTK arm was 10.4 vs 7.7 in PBO (p=0.29), mean change in SF-36 MCS was 6.4 vs 9.0 in the same arms, respectively (p=0.56).Table 1.BL demographics and PsA characteristicsArmNTK (N=97)PBO (N=97)Age (years)*44.0 (11.7)43.1 (11.9)Male, n (%)52 (53.6)50 (51.6)PsA duration, mo*63.1 (73.1)68.2 (77.5)HAQ-DI*1.15 (0.6)1.21 (0.6)DLQI*14.8 (6.5)13.9 (7.3)SF36 PCS*32.39 (9.5)31.10 (8.9)SF36 MCS*45.29 (10.7)46.04 (11.5)* mean (standard deviation), N=number of pts, mo=months, PsA=psoriatic arthritis, HAQ-DI=Health assessment questionnaire disability index, DLQI=Dermatology Quality of Life Index, SF36=36-item Short Form Health Survey, MCS=Mental Component Summary, PCS=Physical Component SummaryTable 2.WPAI change from BL at wk 24 (mean±standard deviation)ParameterNTKPBOAbsenteeism (%)-8.7±29.1N=60-9.1±31.8N=47Presenteeism (%)-22.1 ±22.1N=57-1.0±26.5N=42Overall work impairment (%)-18.6±21.8N=570.6±26.7N=42Activity impairment (%)-25.5±25.2N=96-5.4±29.1N=97N=number of pts in the analysis categoryFigure 1.Improvement in EQ-5D categoriesConclusion:NTK demonstrated rapid improvement in QoL, work productivity and physical function in pts with PsA.Acknowledgments:This study was sponsored by JSC BIOCAD.Disclosure of Interests:Tatiana Korotaeva Consultant of: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, Speakers bureau: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: Pfizer, Novartis, AbbVie, JSC BIOCAD, Сelgene, MSD, Sanofi, V Mazurov: None declared, Aleksey Samtsov Grant/research support from: JSC BIOCAD, Novartis, Eli Lilly, Johnson&Johnson, Celgene, Glenmark, Galderma, Sanofi, Vladislav Khayrutdinov Grant/research support from: Akrikhin, Alkoy, Belupo, JSC BIOCAD, Bosnaliejk, Verteks, Glenmark, Elfa, Leo Pharma, MSD, Novartis, Pfizer, Sun Pharma, Sanofi, Celgene, Pharmtec, AbbVie, Eli Lilly, Jadran, Janssen, Andrey Bakulev Grant/research support from: AbbVie, Eli Lilly, Pfizer, UCB, MSD, Novartis, Galderma, Celgene, Leo Pharma and Johnson&Johnson, JSC BIOCAD, Consultant of: Novartis, Celgene and Johnson&Johnson, Speakers bureau: AbbVie, Eli Lilly, Galderma, UCB, Novartis, Celgene and Johnson&Johnson, Muza Kokhan Grant/research support from: AbbVie, Eli Lilly, Pfizer, UCB, MSD, Novartis, Galderma, Celgene, Leo Pharma and Johnson&Johnson, JSC BIOCAD, Consultant of: Novartis, Celgene and Johnson&Johnson, Speakers bureau: AbbVie, Eli Lilly, Galderma, UCB, Novartis, Celgene and Johnson&Johnson, Alena Kundzer: None declared, Nikolaj Soroka Grant/research support from: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Anna Eremeeva Employee of: JSC BIOCAD