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The aim – to evaluate the clinical effectiveness, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of seniprutug (BCD-180) in patients with radiographic active axial spondyloarthritis (r-axSpA, or ankylosing spondylitis).Subjects and methods. 260 patients with active r-axSpA and inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs) were randomized into three groups: seniprutug (BCD-180) at doses of 5 mg/kg or 7 mg/kg, or placebo. BCD-180 was administered on weeks 0–12–36. Patients in the placebo group were switched to BCD-180 at a dose of 5 mg/kg at week 24 and continued therapy at week 36. The primary endpoint was the proportion of patients achieving 40% improvement by Assessment in Spondyloarthritis International Society scale (ASAS40) at week 24. Secondary endpoints were proportion achieving ASAS20/40, improvement of 5 out of 6 criteria of ASAS (ASAS5/6), ASAS partial remission, clinically important improvement in ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score with C-reactive protein) (ASDAS-CII) and major improvement in ASDAS-CRP (ASDAS-MI). The dynamics of the disease activity status according to ASDAS-CRP, the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) indices, as well as the dynamics of laboratory markers (C-reactive protein anderythrocyte sedimentation rate (ESR)) were analyzed. Safety was assessed by the frequency and profile of adverse events (AEs) and adverse reactions (ARs).Results. The proportion of patients achieving ASAS40 at week 24 with seniprutug (BCD-180) at the dose of 7 mg/kg and 5 mg/kg was 51.4% and 40.8%, respectively, compared with 24% in the placebo group (p=0.0012 and p=0.0417, respectively). Analysis of secondary endpoints showed that in patients with r-axSpA, BCD-180 at both study doses was significantly superior to placebo at week 24 in the following measures: decrease in the proportion of subjects with very high disease activity (ASDAS-CRP>3.5) achieving ASDAS-CII, ASAS20, ASAS5/6. A statistically significant decrease in the ASDAS-CRP, BASDAI, BASFI indices, as well as the concentration of CRP and ESR were demonstrated. Tolerability of seniprutug therapy was assessed as acceptable. Infusion reactions were the most common observed adverse events, the vast majority of which were mild to moderate in severity according to CTCAE 5.0 (Common Terminology Criteria for Adverse Events) and developed predominantly during the first administration. The proportion of patients with binding antibodies was 5.1%. However, no neutralizing antibodies were detected.Conclusion. Seniprutug (BCD-180) demonstrated superiority over placebo in clinical efficacy with a favorable safety profile and low immunogenicity as a treatment of r-axSpA.

The article presents the results of the three-year use of netakimab (NTK) in patients with ankylosing spondylitis (AS) as part of the phase III BCD-085-5/ASTERA study.Objective: to evaluate the long-term efficacy and safety of NTK over a three-year period in patients with active AS.Material and methods. BCD-085-5/ASTERA – double-blind, multicenter, randomized phase III clinical trial that enrolled patients with active AS (BASDAI ≥4) and a back pain intensity ≥4 on a numeric rating scale with inefficacy or intolerance of non-steroidal anti-inflammatory drugs or biologic drugs. A total of 228 patients were randomized in a 1:1 ratio and assigned to either the NTK group or the placebo/NTK group. Starting at week 16, patients who did not achieve ASAS20 (20% improvement according to ASAS criteria) received NTK 120 mg once every 2 weeks in an open-label regimen. Patients who achieved ASAS20 response at week 52 in the NTK group and week 68 in the placebo/NTK group continued to receive NTK (120 mg every 2 weeks) until week 156 in the NTK group and until week 172 in the placebo/NTK group.Results and discussion. Over the course of three years of NTK use, most patients experienced a sustained decline in AS activity (according to ASDAS-CRP, BASDAI) with sustained response (ASAS20/40, ASAS5/6) to therapy. Most adverse events reported were mild to moderate. 36.7% of patients had adverse events, which were mainly laboratory abnormalities, blood and lymphatic system abnormalities and infectious complications.Conclusion. The clinical effect of NTK was maintained in most patients with AS over a three-year period, with no significant loss of response. NTK was well tolerated and the safety profile remained favorable.

Background. Netakimab has shown high efficacy in controlled clinical trials in the treatment of patients with ankylosing spondylitis (AS). This article presents results of an observational study of netakimab using in routine clinical practice.Methods. Patients were recruited for the study from August 2020 to December 2021 at 23 centers in the Russian Federation. The study included patients who were prescribed netakimab therapy before enrollment, so clinical and medical history data for the first visit were entered retrospectively, and following visits at weeks 12, 24 and 52 of therapy were collected within the study. Drug survival rate has been calculated according to Kaplan – Meier analysis.Results. The study included 137 patients (93 men and 14 women) with AS. The average age of patients was 42.3 (±11.9) years, 34.3% of patients had previously received therapy with genetically engineered biologic drugs, mainly tumor necrosis factor inhibitors. At the end of the analyzed period (52 weeks of therapy), 90.4% [95% CI: 85.4–95.7] of patients continued treatment with netakimab. The BASDAI and ASDAS-CRP showed statistically significant decreases in scores from baseline at all time points. Netakimab was well tolerated by patients; adverse effects (AEs), related to therapy according to the investigator’s opinion, were reported in 7 (5.1%) patients. 2 patients stopped taking netakimab due to AEs: terminal ileitis and chronic colitis.Conclusions. In real-world clinical practice, netakimab demonstrated high retention rates, a favorable safety profile, and sustained efficacy throughout the first year of therapy.

The article contains the data obtained during the 156-week follow-up of patients with ankylosing spondylitis (AS) in the ASTERA phase III study.Objective: to evaluate the effect impact of netakimab (NTK) on quality of life (QoL), back pain and work capacity in patients with active AS.Material and methods. The study enrolled 228 patients with active AS who were randomized 1:1 to receive NTK 120 mg or placebo. At week 52, patients in Group 1 (NTK) who achieved ASAS20 continued therapy (NTK at a dose of 120 mg once every 2 weeks) until week 156. Patients in Group 2 (placebo/NTK) received the study drug at a dose of 120 mg subcutaneously every 2 weeks from week 20 until week 68, after which the efficacy of therapy was determined (by achieving an ASAS20 response). Patients who achieved ASAS20 received treatment (NTK at a dose of 120 mg once every 2 weeks) until week 172.Results and discussion. Under NTK therapy, a significant improvement in QoL was observed in the assessment of the physical and psychological components of the SF-36 questionnaire, which was maintained during the three years of therapy: increase in indicator by 12.68±9.92; 13.27±10.14; 12.92±10.03; 14.10±10.35; 14.76±9.77 and 6.10±11.59; 5.50±11.82; 6.32±11.01; 5.87±11.45; 5.25±11.98 points at week 52, 76, 104, 128 and 156, respectively. During the extended therapy period, a reduction in the proportion of working hours missed for health reasons, an improvement in work capacity and work efficiency and an increase in daily activity were observed. Back pain (BASDAI question 2) and nocturnal back pain decreased steadily during the entire follow-up period compared to the screening values.Conclusion. NTK is an effective therapy for active AS that improves QoL scores, significantly reduces pain intensity and improves work productivity.

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. Here we present 1-year efficacy and safety data of the SOLAR study.Objective – 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 have completed the study between November 2019 and October 2021.154 adults, aged ≥18 years with confirmed diagnosis of RA were randomly assigned (2:1) to receive either levilimab (162 mg, SC, QW) + MTX (n=102) or placebo + MTX (n=52).After W24 of the study all subjects continued to receive open label levilimab. Subjects who have achieved DAS28-CRP≤2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP>2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was done in a population of all randomized subjects. 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 on dose of LVL (n=152).Results. Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach 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 (

Levilimab is anti-interleukin-6 receptor (IL6R) monoclonal antibody. The article presents data obtained during 24 weeks of the SOLAR phase III study.Objective: to confirm efficacy and safety of levilimab in combination with methotrexate (MTX) in patients with methotrexate resistant active rheumatoid arthritis (RA).Patients and methods. 154 adult patients, aged ≥18 years with the diagnosis of RA (ACR/EULAR 2010) and confirmed disease activity at screening despite treatment with MTX for at least 12 weeks (in a stable dose 15-25 mg/week). Patients were randomized 2:1 in levilimab (162 mg once a week, subcutaneously) + MTX (n=102) or placebo + MTX (n=52) group.The hypothesis of superiority of levilimab over placebo was tested for two co-primary efficacy endpoints: proportion of subjects who achieved ACR20 at week 12 and proportion of subjects who achieved low disease activity (LDA) of RA (DAS28-CRP

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.

Netakimab (NTK) is a humanized monoclonal antibody targeting interleukin-17A.Objective. The main objective of BCD-085-5/ASTERA study was to prove superiority of NTK over placebo and assess its’ safety in patients with active AS.Subjects and methods. BCD-085-5/ASTERA was a double-blind, multicenter, randomized, placebo-controlled, phase III study, which included 228 adult patients with active AS, persisting despite active treatment with NSAIDs. AS was considered active at BASDAI score ≥ 4.0. Patients were blindly randomized (1:1) to receive subcutaneous injections of NTK (120 mg) or placebo at weeks 0, 1, 2 and then every other week up to week 14. Starting from week 16 all patients from NTK group and patients from placebo group not achieving ASAS20 were switched to open label 120 mg NTK s/c once every two weeks. The total duration of treatment with NTK was 3 years.Results. Higher proportion of patients had ASAS40 response at week 16 (primary endpoint) in NTK arm compared to placebo (40,4 vs 2,6%, р

The paper presents the results of a double-blind (BCD-085-3/AILAS) phase II clinical trial of the original interleukin 17A (IL17A) inhibitor BCD-085 prescribed at different doses to patients with active ankylosing spondylitis (AS) and those of an extended (BCD-085-3ext/AILAS-II) trial characterizing the efficacy and safety of this drug when used for a year.The objective of the AILAS study is to determine the therapeutically effective and safe dose of BCD-085 in the treatment of active AS. The efficacy, safety, and immunogenicity of BCD-085 during its annual use were additionally evaluated in the extended trial.Subjects and methods. The investigation enrolled 89 patients diagnosed as having active (BASDAI scores >4.0; mean spinal pain scores >4.0) AS that met the 1984 New York classification criteria. After the end of the screening period, the patients were randomized at a ratio of 1:1:1:1 in one of four groups that received 40; 80 or 120 mg of BCD-085 subcutaneously or placebo on day 1 of weeks 0, 1, 2 and then once every two weeks up to week 12. The primary end point was the number of patients who achieved an ASAS20 response at week 16. The investigation evaluated the safety of the drug, by calculating the total incidence of adverse events (AEs) and serious AEs (SAEs) and the number of cases of premature therapy termination because of AEs.Results and discussion. An ASAS20 response at week 16 was achieved in 72.7% of patients receiving 40 mg of BCD-085, in 81.8% of those receiving 80 mg, in 90.9% of those receiving 120 mg, and in 42.9% of cases in the placebo group (p=0.004). The superiority of BCD-085 over placebo was proven for 80- and 120-mg doses. The fastest and most pronounced effect was observed in patients treated with 120 mg of BCD-085. In the extended study, an ASAS20 response at week 52 was recorded in 86.4% of patients. One or more AEs during the first 16 weeks of therapy were reported in 11 (50.0%) patients of the 40-mg group; in 6 (27.3%) of the 80 mg group; in 4 (18.2%) of the 120 mg group and in 7 (31.8%) of the placebo group (p=0.183). The frequency and spectrum of AEs did not significantly differ in patients who received placebo and BCD-085 in different doses. No SAE was recorded.Conclusion. Phase II study yielded data demonstrating the high efficacy and good tolerance of BCD-085 in the treatment of active AS. The best effect and optimal tolerance were demonstrated for a dose of 120 mg.

The paper gives data on the clinical efficiency and safety profile of long-term use of the infliximab (INF) biosimilar BCD-055 versus the reference drug Remicade® (REM) in a population of patients with active ankylosing spondylitis (AS).Subjects and methods. An international multicenter randomized double-blind Phase III clinical trial was conducted in 199 patients who were randomized into two groups in a 2:1 ratio and who received BCD-055 or REM at a dose of 5 mg/kg at 0, 2, and 6 weeks, then every 8 weeks. Efficiency assessment was made at 14, 30 and 54 weeks in patients who received at least one dose of INF [intent-to-treat (ITT)], as well as at 54 weeks in those who completed the study according to the Protocol (PP) (per protocol). The efficiency endpoints were the proportion of patients who had achieved ASAS20/ASAS40 responses; changes in BASDAI, BASMI, BASFI, MASES, and SF-36 scores. Immunogenicity was assessed by the proportion of patients in each group with identified binding and neutralizing antibodies (BAbs and NAbs) against INF. The safety analysis included the overall rate of adverse events (AEs), including those that met the respective criteria for serous AEs (SAEs), and grade 3–4 toxicity, as well as the number of cases of early termination of the study because of AEs and SAEs.Results and discussion. The ITT population included 199 patients and the PP one consisted of 161 people. The groups were not statistically different in the rate of and reasons for patient withdrawal from the study. A comparable number of patients achieved ASAS20/ASAS40 responses at 14, 30, 54 weeks (р ≥ 0.05). At 54 week, the proportion of patients who received BCD-055 and REM therapy and achieved an ASAS20 response was 67.42 and 52.24% in the ITT population (p = 0.053) and 80.91 and 68.63% in the PP population (p = 0.128). The BCD-055 and drug comparison groups achieved an ASAS40 response in 53.03 and 38.81% in the ITT population (p = 0.081) and in 63.64 and 50.98% in the PP one (p = 0.177). The proportion of persons with identified BAbs and NAbs was comparable: 21.26 and 3.15% in the BCD-055 group (p = 0.920) and 20.63 and 6.35% in the group REM (p = 0.443), respectively. It was found that the presence of NAbs did not affect the therapeutic response. Both groups did not differ in the detection rate and profile of AEs and SAEs or in the rate of patient withdrawal due to AEs. Most identified AEs were mild to moderate.Conclusion. The efficacy of the INF biosimilar BCD-055 used long in patients with AS did not significantly differ from that of the original drug REM; the safety profile of both drugs was comparable.

This article presents results from two clinical trials of infliximab biosimilar, BCD-055, including comparative data on the pharmacokinetics (PK), efficacy and safety of BCD-055 and innovator infliximab (IFX) in patients with ankylosing spondylitis (AS).Objective: The purpose of phase I clinical study ASART-1 was to evaluate the pharmacokinetic and safety profile of BCD-055 and to prove its equivalence with Remicade®, phase III study ASART-2 was conducted to evaluate the efficacy and tolerability of BCD-055 in comparison with Remicade® in patients with active AS.Patients and methods: Both studies were conducted as international multi-center randomized double-blind studies in direct comparison with innovator IFX. Inclusion and exclusion criteria, main examination methods, and drug regimens were the same in both trials. A total of 199 patients were enrolled in the studies. After the screening, the patients were stratified by CRP and BASDAI score, randomized (1:1 ratio in ASART-1; 2:1 ratio in ASART-2) into 2 arms and received BCD-055 or innovator IFX at a dose 5 mg/kg IV at 0, 2, 6 and then every 8 weeks (up to week 54). The primary endpoint for PK profile evaluation was the area under the concentration-time curve (AUC(0-tau)), maximum serum concentration of infliximab at steady state Cmax,ss. Efficacy was assessed by achieving ASAS20 at week 30, the endpoints for safety profile were the incidence of adverse events and serious adverse events during the maintenance-dosing phase and withdrawals from the study due to the safety reasons.Results: A total of 81 patients (ASART-1 study) were included in PK analysis, 199 patients were in efficacy and safety analysis. AUC(0-tau) value were 25,420,996.25±11,635,015.74 (ng/ml) Cmax,ss for BCD-055 and 26,114,705.71±12,102,376.9 (ng/ml)⋅h for INF innovator (p>0.05). Cmax,ss for BCD-055/Remicade® was 122,752 [99,401–151,553] ng/ml and 119,844 [98,120–132,772] ng/ml, respectively (p>0.05). ASAS20 was achieved at week 30 by 81.30% of the patients in the BCD-055 group, and 67.74% in the INF innovator group (p=0.061). The analysis of secondary endpoints (BASDAI, BASMI, BASFI, MASES, quality of life, chest excursion, and number of pathologically changed joints) showed no difference between the biosimilar and innovator groups. BCD-055 and innovator IFX showed highly similar safety profiles in both studies without cases of unexpected toxicity. The rates of AEs were equivalent for both drugs and were 48.48% and 58.21% of patients in the BCD-055 and Remicade®, respectively.Conclusion: BCD-055 is found to be equivalent in terms of PK, and showed the similarity in efficacy and safety profile compared with innovator IFX in patients with active AS.