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.

Цель. Изучить взаимосвязь полиморфных вариантов rs1800470 гена трансформирующего ростового фактора β1 (TGF-β1) с тяжестью атеросклероза коронарных артерий (КА). Материал и методы. В исследование включено 256 больных ИМ (216 мужчин и 40 женщин) европеоидной расы в возрасте ≤65 лет (52,1±8,4). Геномную ДНК выделяли из венозной крови фенол-хлороформным методом. Полиморфизм rs1800470 гена TGF-β1 тестировали с помощью полимеразной цепной реакции (ПЦР) в режиме реального времени (зонды TaqMan, AB 7900HT). Оценка степени тяжести поражения коронарного русла производилась по протоколу стандартной полипроекционной коронароангиографии с расчетом индекса Gensini. Результаты. Впервые в сибирской популяции у мужчин доказана взаимосвязь аллеля А rs1800470 гена TGF-β1 с тяжестью коронарного атеросклероза. Носители аллеля А rs1800470 гена TGF-β1 имели отношение шансов (ОШ) многососудистого поражения КА (ОШ =2,84 (95% ДИ 1,37-5,87), p=0,004) и коронарного атеросклероза проксимального типа (ОШ =2,66 (95% ДИ 1,29-5,47), p=0,007). В целом индекс Gensini был значительно выше у носителей рискового аллеля А rs1800470 гена TGF-β1: генотип АА-57,33±41,89; генотип AG-52,86±40,74; генотип GG-43±28,83 (р>0,05), однако статистически значимыми различия были в верхней квартили (р=0,028). Риск тяжелого поражения КА (индекс Gensini >80 баллов) у носителей аллеля А rs1800470 гена TGF-β1 составило ОШ =3,64 (95% ДИ 1,06-12,49). У женщин статистически значимой взаимосвязи генотипа rs1800470 гена TGF-β1 с тяжестью поражения КА выявлено не было. Заключение. Аллель А rs1800470 гена TGF-β1 ассоциирован с тяжестью коронарного атеросклероза у мужчин.

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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 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.