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.

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.

OBJECTIVES Netakimab is a humanised camelid-derived monoclonal antibody targeting interleukin-17A. Here, we report the results of post-hoc analysis of the ASTERA phase 3 study (NCT03447704, February 27, 2018) in patients with active radiographic axial spondyloarthritis (r-axSpA) grouped by baseline C-reactive protein (CRP), baseline sacroiliac joint (SIJ) inflammation through magnetic resonance imaging (MRI) or presence of peripheral arthritis (PA). METHODS In this double-blinded, multicentre, randomised, placebo-controlled, phase 3 ASTERA study, 228 adult patients with active r-axSpA received 120 mg of subcutaneous netakimab or placebo at weeks 0, 1, 2, and thereafter every other week. For the subanalysis, 16-week data of 114 netakimab-treated patients with the available baseline CRP and SIJ MRI were grouped by normal (<5 mg/L) or abnormal (≥5 mg/L) CRP, by the grade of sacroiliitis (SI) based on the SPARCC MRI score <2 (MRI-SI-) or ≥2 (MRI-SI+), or by the presence of PA. ASAS-recommended activity, spinal mobility, and function endpoints for r-axSpA were analysed. RESULTS At week 16, an improvement in all the outcomes was similar for MRI-SI- and MRI-SI+ patients, except for a change in ASspi-MRI-a which was significantly greater in MRI-SI+. Netakimab was effective regardless of baseline CRP and PA. For patients with CRP ≥5 mg/L, a more pronounced decline in r-axSpA activity was observed with a trend towards the most prominent improvement in ASDAS-CRP and BASDAI for patients with CRP >20 mg/L. CONCLUSIONS Subcutaneous netakimab is effective in patients with r-axSpA irrespective of baseline CRP and inflammation on SIJ MRI. The benefit in patients with high CRP (>20 mg/L) was more pronounced.

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 <3.2) at week 24. Safety was assessed through monitoring of adverse events (AEs).Results and discussion. Seventy (68.6%) subjects who received levilimab and 20 (38.5%) who received placebo achieved ACR20 response at week 12. Fifty three (52%) subjects who received levilimab and 3 (5,8%) subjects who received placebo achieved LDA at week 24. The most common adverse events (reported in ≥5% of subjects) in levilimab and placebo arms, respectively were (by decreasing frequency): blood c holesterol increase (24% vs 12%), alanine aminotransferase elevation (11% vs 8%), lymphocyte count decrease (9% vs 8%), blood total bilirubin increase (11% vs 0%), blood triglycerides increase (10% vs 2%), aspartate aminotransferase elevation (7% vs 4%), positive interferon-gamma release assay (IGRA) with M.tuberculosis antigen blood test (5% vs 6%), absolute neutrophil count 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. Levilimab showed favorable safety profile and low immunogenicity. No new important safety risks were detected.

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 <0,0001, 95% CI [27,4%; 48,1%]). Spinal pain subsided and laboratory inflammation markers decreased within one week after the first NTK injection. NTK safety profile was comparable to that of placebo. The most common for NTK adverse events were neutropenia (7,0%) and ALT increase (6,1%).Conclusion. Subcutaneous NTK at 120 mg dose demonstrated superior efficacy vs placebo, with fast onset of response and favorable safety profile when used in patients with ankylosing spondylitis.

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 <0,0001, 95% CI [27,4%; 48,1%]). Spinal pain subsided and laboratory inflammation markers decreased within one week after the first NTK injection. NTK safety profile was comparable to that of placebo. The most common for NTK adverse events were neutropenia (7,0%) and ALT increase (6,1%). Conclusion . Subcutaneous NTK at 120 mg dose demonstrated superior efficacy vs placebo, with fast onset of response and favorable safety profile when used in patients with ankylosing spondylitis.

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.

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.

The article considers the results of an international multicenter randomized clinical trial of the efficacy and safety of the brand-name drug rituximab (MabThera), a monoclonal antibody against CD20 antigen of B cells, and its biosimi-lar drug (Acellbia®) (the BIORA study) in patients with rheumatoid arthritis (RA) refractory to therapy with tumor necrosis factor-а inhibitors.Objective: to provide evidence for the therapeutic equivalence of Acellbia® and MabThera® and also to assess their interchangeability.Subjects and methods. The trial enrolled adult patients with active seropositive RA, who were randomized into two groups (1:1): 1) the patients who received Acellbia® 1000 mg intravenously on days 1 and 15; 2) those who had MabThera® in a similar way. When RA activity persisted at 24 weeks, there was re-randomization (1:1) with a partial overlap: Group 1 patients were randomized into group AA (the drug of the second therapy cycle was Acellbia®) or Group AM (that was MabThera®), the similar methodology was followed in Group 2 (Groups MM and MA). Throughout the study, the patients received methotrexate at a stable dose of 7.5—25 mg/week and folic acid at a dose of 5 mg/week. The follow-up lasted 48 weeks.Results and discussion. 24 weeks after treatment initiation, the ACR20 response was observed in 84.1% of the patients in the Acellbia® group (95% CI, 74.75—90.50) and in 87% in the MabThera® group (95% CI, 77.71—92.79%; p = 0.773), which suggests that the drugs are therapeutically equivalent. In the second phase of the study, the efficiency of therapy remained high; there were no differences in Groups AA/MM, AA/AM and MM/MA. In both phases, the safety profile of the drugs was comparable; the immunogenicity of treatment remained low. The findings suggest that the brand-name MabThera® and its biosimilar drug Acellbia® are equivalent. Switching from the biosimilar drug to the brand-name one and vice versa has no negative impact on treatment outcomes.