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Netakimab (NTK) is a humanized anti-interleukin-17A monoclonal antibody. To date, the drug has been approved to treat ankylosing spondylitis (AS), psoriatic arthritis, and plaque psoriasis. The paper gives the data obtained during 52-week follow-up of AS patients in the phase III ASTERA study.Objective: to study the efficacy and safety of NTK when used long in patients with active AS.Patients and methods. The investigation enrolled 228 patients with active AS, in whom nonsteroidal anti-inflammatory drugs or biological agents were ineffective. The patients were randomized in a 1:1 ratio to receive NTK 120 mg or placebo. The drug was administered subcutaneously at weeks 0, 1, 2, and then once every 2 weeks. Patients who received placebo and achieved a 20% improvement according to the ASAS criteria (ASAS20) were excluded from the study at week 16. At this week, patients who took placebo and did not achieve an ASAS20 response were switched to subcutaneous NTK at 120 mg dose once every two weeks. The follow-up period was 52 weeks.Results and discussion. Patients with active AS who received NTK were more likely to respond to treatment than those who took placebo. The proportion of people who achieved 40% improvement (ASAS40) during treatment with NTK increased throughout the follow-up period and amounted to 80.7% at week 52. Positive changes were achieved in all used clinical and laboratory parameters of AS activity. There was also a decrease in inflammatory changes, as shown by magnetic resonance imaging (MRI). The adverse events (AEs) were mainly laboratory abnormalities and upper respiratory tract infections. Treatment-related AEs were recorded in no more than one third of patients and they were mild to moderate. Severe AEs were singular.Conclusion. Response to NTK therapy generates in the first weeks of drug use and increases throughout a year. The safety profile of NTK when used long is generally favorable.

BackgroundVitamin D is regarded as modulator of the immune response [1]. Treatment with 1,25(OH)2D can ameliorate autoimmune disorders in rodent models of experimental allergic encephalitis, nephritis, inflammatory bowel disease, and diabetes mellitus [2,3]. Vitamin D deficiency is common among patients with antiphospholipid syndrome (APS) and is associated with clinically defined thrombotic events [4].ObjectivesTo evaluate the effects on antiphospholipid antibodies level of an oral Cholecalcipherol supplementation for 3 months in APS patients.MethodsThe study included 16 patients (men - 4, women - 12) with APS (Sidney, 2006) mean age 34±6,4 years treated with warfarin – 5,0–7,5 mg/day and acetylsalicylic acid – 75 mg/day. 3 patients were diagnosed with vitamin D insufficiency, 13 – with deficiency [5]. Cholecalciferol - 1000 IU/day was added to the therapy for 3 months. Anticardiolipin (aCL) and anti-β2-glycoprotein I (aβ2GPI) IgG and IgM antibodies, serum 25(OH)D level were tested using commercially available ELISA kits before and after treatment with Cholecalciferol. Lupus anticoagulant was not investigated due to possibility of false positive results in warfarine-treated patients.ResultsBaseline level of aCL IgG was median 6,21 intarquartile range 2,72–65,77 GPL, aCL IgM – 85,30 (12,66–154,26) MPL, aβ2GPI IgG –16,40 (7,99–44,32) U/ml, aβ2GPI IgM – 15,89 (6,24–67,60) U/ml, serum 25(OH)D - 15,04 (13,00–19,00) ng/ml. After treatment with Cholecalciferol for 3 months the levels of antiphospholipid antibodies and vitamin D were the following: aCL IgG – 4,69 (2,91–12,42) GPL, aCL IgM – 7,38 (4,42–110,35) MPL, aβ2GPI IgG – 9,43 (5,42 - 13,04) U/ml, aβ2GPI IgM – 29,97 (8,13–71,30) U/ml, serum 25(OH)D - 27,16 (23,06–32,90) ng/ml. We found significant increase in serum 25(OH)D level (p=0,007) and decrease in aβ2GPI IgG level (p=0,038) after treatment with Cholecalciferol. The level of other antiphospholipid antibodies did not differ significantly (p>0,05) before and after Cholecalciferol treatment.ConclusionsOur preliminary results indicate that vitamin D supplementation might be associated with decreased serum aβ2GPI IgG level. This can indicate a possible correlation between vitamin D status and thrombotic risk in APS.ReferencesArnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis 2007;66:1137–1142.Penna G, Amuchastegui S, Laverny G, Adorini L. Vitamin D receptor agonists in the treatment of autoimmune diseases: selective targeting of myeloid but not plasmacytoid dendritic cells. J Bone Miner Res. 2007;22(Suppl 2):V69–V73.Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–281.N Agmon-Levin, M Blank, G Zandman-Goddard, et al. Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression. Ann Rheum Dis 2011;70:145–150.Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 2009;19:73–78.Disclosure of InterestNone declared

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