Background: Previously, 24-week results of phase III double-blind, placebo-controlled randomized clinical study (SOLAR) of levilimab in subjects with active rheumatoid arthritis (RA) proved a superiority of levilimab over placebo ¹ . Here we present 1-year efficacy and safety data of the open-label period of the SOLAR study.

Objectives: To evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA.

Methods: The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects had completed the study between November 2019 and October 2021.

154 adults, aged ≥ 18 years with confirmed diagnosis of RA ¹ were randomly assigned (2:1) to receive either levilimab, 162 mg, SC (LVL QW) + MTX (n=102) or placebo (PBO) + MTX (n=52).

After W24 of the study all subjects continued to receive open label levilimab +MTX. Subjects who had achieved DAS28-CRP ≤ 2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab + MTX at W28: LVL QW/Q2W arm (n=27) and PBO/LVL Q2W arm (n=1). Those with DAS28-CRP > 2.6 at W28 continued with levilimab QW regimen + MTX: LVL QW/QW arm (n=75) and PBO/LVL QW arm (n=51).

The efficacy analysis was done in a population of all randomized subjects (n=154). Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases.

Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least one dose of LVL (n=152). Two subjects randomized to receive placebo were discontinued within first 24 weeks of the study, thus did not received any dose of levilimab and were excluded from safety analysis.

Results: Obviously, better response to the treatment was observed in LVL QW/Q2W arm as it was composed of those who had reached DAS28-CRP ≤ 2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (< 2.6) and 7/27 (25.9%) achieved ACR/EULAR2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP < 2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%).

LVL QW/QW arm was diminished by subjects who had achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, the ACR70, and remissions rate in this arm were close to zero at W24. However, continuation of LVL QW in those who had not achieved DAS28-CRP ≤ 2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52.

The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%). blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with M.tb antigen positive (7.2%) and injection site reactions (5.9%). No deaths were occurred.

Conclusion: Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to maintenance (Q2W) regimen of levilimab in those who achieved remission of RA at week 24.

Trial registration: Clinicaltrials.gov identifier NCT04397562

REFERENCES:

[1]Mazurov V, Korolev M, Kundzer A, et al POS0624 EFFICACY AND SAFETY OF LEVILIMAB IN COMBINATION WITH METHOTREXATE IN SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS: PHASE III, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED TRIAL Annals of the Rheumatic Diseases 2021;80:550-551.

Acknowledgements: We thank all contributors to the SOLAR clinical trial

Disclosure of Interests: V Mazurov: None declared, Maxim Korolev: None declared, Andrei Pristrom: 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, Ekaterina Puntus: None declared, Tatiana Raskina: None declared, Ludmila Shilova: None declared, Tatyana Kropotina: None declared, Olga Nesmeyanova: None declared, Tatiana Popova: None declared, Irina Vinogradova: None declared, Iulia Linkova Employee of: JSC BIOCAD, Aleksandra Plotnikova Employee of: JSC BIOCAD, Polina Pukhtinskaia Employee of: JSC BIOCAD, Arina Zinkina-Orikhan Employee of: JSC BIOCAD, Anna Eremeeva Employee of: JSC BIOCAD, Anton Lutckii Employee of: JSC BIOCAD