Сравнительная эффективность и безопасность биоаналога инфликсимаба (BCD-055) и оригинального инфликсимаба у пациентов с анкилозирующим спондилитом (результаты международных многоцентровых рандомизированных двойных слепых клинических исследований I и III фазы)

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.В статье приведены результаты международных, многоцентровых рандомизированных двойных слепых клинических исследований (КИ) I и III фазы биоаналога инфликсимаба (ИНФ) – BCD-055. Представлены сравнительные данные о фармакокинетике (ФК), эффективности и безопасности BCD-055 и оригинального препарата у пациентов с активным анкилозирующим спондилитом (АС).Цель исследования: КИ I фазы ASART-1 проводилось для доказательства фармакокинетической эквивалентности и равной безопасности препаратов BCD-055 и Ремикейд® (РЕМ), КИ III фазы ASART-2 – для установления не меньшей эффективности и равной безопасности препарата BCD-055 в сравнении с препаратом РЕМ у больных активным АС.Пациенты и методы. Критерии включения и невключения в обоих исследованиях, основные методики обследования, схема применения препаратов были аналогичными. Всего в анализ включенно 199 пациентов. В результате рандомизации (1:1 в ASART-1, 2:1 в ASART-2) пациенты были распределены на две группы и получали BCD-055 или оригинальный препарат в дозе 5 мг/кг на 0–2–6-й неделе, затем каждую 8-ю неделю. Первичной конечной точкой для оценки ФК были: площадь под кривой «концентрация – время» до достижения равновесного состояния (AUC(0-tau)), максимальная концентрация ИНФ в равновесном состоянии (Cmax,ss). Эффективность оценивалась по достижению критерия ASAS20 на 30-й неделе. Безопасность препаратов определяли по общей частоте случаев развития серьезных нежелательных явлений (СНЯ) и нежелательных явлений (НЯ), частоте случаев НЯ 3–4-й степени токсичности, случаев досрочного прекращения участия в исследовании по причине развития НЯ и СНЯ.Результаты. В анализ ФК (ASART-1) был включен 81 пациент, в анализ эффективности и безопасности (ASART-2) – 199. Значения AUC(0-tau) составляли 25 420 996,25±11 635 015,74 (нг/мл) ⋅ ч для BCD-055 и 26 114 705,71±121 02 376,9 (нг/мл) ⋅ ч для оригинального ИНФ (p>0,05). Cmax,ss после введения BCD-055/РЕМ равнялась 122 752 [99 401–151 553] и 119 844 [98 120–132 772] нг/мл соответственно (p>0,05). ASAS20 на 30-й неделе достигли 81,30 и 67,74% пациентов в группе BCD-055 и РЕМ соответственно (р=0,061). При анализе дополнительных конечных точек (индексы BASDAI, BASMI, BASFI, MASES, показатели качества жизни, экскурсия грудной клетки, счет патологически измененных суставов) достоверных различий в эффективности между группами биоаналога и оригинального препарата не выявлено. На протяжении исследования какие-либо НЯ зарегистрированы у 48,48 и 58,21% пациентов в группах BCD-055 и РЕМ соответственно. Инфузионная реакция развилась у 1 (0,76%) пациента в группе BCD-055 и у 1 (1,49%) в группе препарата сравнения (р=1,000). Выводы. Параметры ФК были эквивалентны для BCD-055 и оригинального ИНФ, препарат BCD-055 характеризовался не меньшей эффективностью и равной безопасностью по сравнению с оригинальным ИНФ при применении у пациентов с АС

Долгосрочное влияние нетакимаба на качество жизни, боль в спине и работоспособность пациентов с анкилозирующим спондилитом: результаты международного многоцентрового рандомизированного двойного слепого клинического исследования III фазы BCD-085-5/ASTERA

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.В статье приведены данные, полученные в ходе 156 нед наблюдения за пациентами с анкилозирующим спондилитом (АС) в исследовании III фазы ASTERA.Цель исследования – оценить влияние нетакимаба (НТК) на качество жизни (КЖ), боль в спине и работоспособность пациентов с активным АС.Материал и методы. В исследование включено 228 больных активным АС, которые были рандомизированы в соотношении 1:1 в группу НТК 120 мг или группу плацебо. На неделе 52 пациенты группы 1 (НТК), достигшие ASAS20, продолжили получать терапию (НТК в дозе 120 мг 1 раз в 2 нед) до недели 156. Пациенты группы 2 (плацебо/НТК), начиная с недели 20, использовали исследуемый препарат в дозе 120 мг подкожно 1 раз в 2 нед до недели 68, после которой у них была определена эффективность терапии (по достижению ответа ASAS20). Пациенты, достигшие ASAS20, получали лечение (НТК в дозе 120 мг 1 раз в 2 нед) до недели 172.Результаты и обсуждение. На фоне лечения НТК наблюдалось значимое улучшение КЖ при оценке физического и психологического компонентов опросника SF-36, которое сохранялось на протяжении 3 лет терапии: повышение показателя на 12,68±9,92; 13,27±10,14; 12,92±10,03; 14,10±10,35; 14,76±9,77 и 6,10±11,59; 5,50±11,82; 6,32±11,01; 5,87±11,45; 5,25±11,98 балла на неделях 52, 76, 104, 128, 156 соответственно. В течение продленного периода терапии было выявлено снижение доли рабочего времени, пропущенного по состоянию здоровья, улучшение работоспособности и эффективности труда, а также повышение повседневной активности. Боль в спине (вопрос 2 BASDAI) и ночная боль в спине стойко уменьшались на протяжении всего периода наблюдения по сравнению с их показателями на момент скрининга.Заключение. НТК является эффективным методом терапии активного АС. Под действием НТК улучшаются показатели КЖ, в том числе значимо снижается интенсивность боли и улучшается производительность труда

Результаты неинтервенционного наблюдательного многоцентрового исследования тактики ведения пациентов с аксиальным псориатическим артритом в условиях реальной клинической практики (NiSaXPA)

Psoriatic arthritis (PsA) is a chronic immunoinflammatory disease of the joints, spine and entheses from the group of spondyloarthritis, which is usually observed in patients with psoriasis. In recent years, the axial form of PsA (axPsA) has been actively researched. However, there is insufficient data on approaches to the diagnosis and treatment of patients with axPsA in real-life clinical practice. This article presents the results of an interim analysis of data from a non-interventional multicenter observational study on the treatment of patients with axPsA in real-life clinical practice (NiSaXPA) in Russian centers.Objective: to identify patients with axPsA, their characteristics and describe treatment tactics in real-life clinical practice.Material and methods. Patients with PsA who met the inclusion criteria were prospectively followed up during routine visits to a rheumatologist. Participants' axial radiographs were uploaded to a database in order for it to be confirmed the presence or absence of axPsA by two independent experts, a rheumatologist and a radiologist. Patients with a confirmed axPsA diagnosis participated in a further data collection phase (Visit 2, week 24).Results and discussion. Six hundred patients were enrolled into the study. At the time of analysis, 386 (64.3%) of them (209 men and 177 women) were screened for axPsA. The diagnosis of axPsA was confirmed in 241 (62.4%) cases; these patients formed the Per Protocol (PP) population. The mean age of patients with axPsA in the PP population was 46.30±12.6 years and the body mass index (BMI) was 27.4±5.2 kg/m2 . In 14.9% of patients, the duration of psoriasis was less than 1–5 years, in 21.5% – 5–10 years and in 63.6% – more than 10 years. The duration of PsA symptoms was less than 1–5 years in 31.2 % of patients, 5–10 years in 31.6 % and more than 10 years in 37.2 %. Low disease activity (BASDAI ˂ 4) was achieved in 33.3 % of patients with axPsA at visit 1 and in 64.3 % at visit 2; the BASDAI index declined on average from 4.67±1.95 to 3.31±1.89 points.In real-life clinical practice, patients were most frequently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) – 88.7% and 71.7% (visits 1 and 2, respectively), and synthetic disease-modifying antirheumatic drugs (sDMARDs) –79.1% and 70.7%, respectively; therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) was initiated in 40.2% and 60.6% of patients, respectively.Conclusion. The results of the interim analysis of this observational study showed that in 87.2% of patients who met the CASPAR criteria for PsA there was a suspicion of axial manifestations of PsA on the primary care level. However, only 62.4% of them had a confirmed diagnosis of axPsA on centralized expert assessment, which may indicate a possible overdiagnosis of axial lesions in real-life practice and emphasizes the importance of collaboration between a rheumatologist and a radiologist when analyzing the results of imaging studies. 33.3% of patients with axPsA had low disease activity according to BASDAI at baseline and 64.3% after 24 weeks, meaning that the disease was only adequately controlled in one third of cases despite therapy; the number of these patients doubled after a change in therapy. In real-world clinical practice, patients with axPsA are most commonly prescribed drugs from the NSAID and sDMARD groups; the frequency of use of biologic drugs varied between 40.2 and 60.6% by the end of the observation period.Псориатический артрит (ПсА) – хроническое иммуновоспалительное заболевание суставов, позвоночника и энтезисов из группы спондилоартритов, которое обычно наблюдается у больных псориазом. В последние годы активно изучается аксиальная форма ПсА (аксПсА). Вместе с тем данных о подходах к диагностике и ведению пациентов с аксПсА в реальной клинической практике недостаточно. В настоящей публикации представлены результаты промежуточного анализа данных неинтервенционного наблюдательного многоцентрового исследования тактики ведения пациентов с аксПсА в условиях реальной клинической практики (NiSaXPA) в российских центрах.Цель исследования – выявление пациентов с аксПсА, их характеристика и описание тактики ведения в условиях реальной клинической практики.Материал и методы. Во время плановых визитов к ревматологу проводилось проспективное наблюдение пациентов с ПсА, соответствовавших критериям включения. Аксиальные рентгенограммы участников были загружены в базу данных для подтверждения наличия или отсутствия аксПсА двумя независимыми экспертами – ревматологом и рентгенологом. Пациенты с подтвержденным диагнозом аксПсА участвовали в дальнейшей фазе сбора данных (визит 2, неделя 24).Результаты и обсуждение. В исследование включено 600 пациентов. На момент проведения анализа с целью выявления аксПсА обследовано 386 (64,3%) из них (209 мужчин и 177 женщин). Диагноз аксПсА подтвержден в 241 (62,4%) случае; эти больные составили популяцию по протоколу (PP, Per Protocol). У 145 (37,6%) пациентов аксПсА не выявлен. Возраст пациентов с аксПсА в популяции РР составил в среднем 46,30±12,6 года, индекс массы тела (ИМТ) – 27,4±5,2 кг/м2 . У 14,9% пациентов длительность псориаза была менее 1–5 лет, у 21,5% – 5–10 лет и у 63,6% – более 10 лет. Давность симптомов ПсА у 31,2% пациентов составляла менее 1–5 лет, у 31,6% – 5–10 лет и у 37,2% – более 10 лет. Низкой активности заболевания (BASDAI ˂ 4) к визиту 1 достигли 33,3% больных аксПсА, к визиту 2 – 64,3%; было отмечено снижение индекса BASDAI в среднем с 4,67±1,95 до 3,31±1,89 балла. В реальной клинической практике пациентам наиболее часто назначали нестероидные противовоспалительные препараты (НПВП) – 88,7% и 71,7% (визиты 1 и 2 соответственно) и синтетические базисные противовоспалительные препараты (сБПВП) – 79,1% и 70,7% соответственно; терапия генно-инженерными биологическими препаратами (ГИБП) была инициирована 40,2% и 60,6% больных соответственно.Заключение. Результаты промежуточной оценки данного наблюдательного исследования показали, что у 87,2% пациентов, отвечавших критериям CASPAR для ПсА, исходно при обследовании по месту жительства были заподозрены аксиальные проявления ПсА. Однако при центральной экспертной оценке диагноз аксПсА был верифицирован только у 62,4% из них, что может свидетельствовать о возможной гипердиагностике аксиального поражения в реальной практике и подчеркивает важность кооперации ревматолога и рентгенолога при анализе результатов визуализационных методов обследования. 33,3% пациентов с аксПсА имели низкую активность заболевания по BASDAI исходно и 64,3% – через 24 нед. Таким образом, несмотря на проводимую терапию, адекватно контролировать заболевание удавалось только в трети случаев, после смены терапии число таких пациентов увеличилось вдвое. В реальной клинической практике пациентам с аксПсА наиболее часто назначают препараты из группы НПВП и сБПВП, частота использования ГИБП варьировалась от 40,2 до 60,6% к концу наблюдения

Comparative efficacy and safety of infliximab biosimilar (BCD-055) and innovator infliximab in patients with ankylosing spondylitis (results of international, multiple-center, double-blind phase I and phase III clinical studies)

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

COMPARATIVE EVALUATION OF THE LONG-TERM EFFICACY AND SAFETY OF THE INFLIXIMAB BIOSIMILAR BCD-055 AND REFERENCE INFLIXIMAB IN PATIENTS WITH ANKYLOSING SPONDYLITIS: RESULTS OF THE INTERNATIONAL MULTICENTER RANDOMIZED DOUBLE-BLIND PHASE III CLINICAL STUDY ASART-2

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

ANALYSIS OF THE RESULTS OF TOFACITINIB THERAPY IN REAL CLINICAL PRACTICE ACCORDING TO THE ALL-RUSSIAN ARTHRITIS REGISTRY (OREL)

Objective: to analyze the results of tofacitinib (TOFA) therapy in real clinical practice according to the All-Russian Arthritis Registry (OREL). Subjects and methods. The OREL Registry included 347 patients (286 (82%) women and 61 (18%) men) with rheumatoid arthritis (RA) who initiated TOFA therapy. The male:female ratio was 1:4.7. The patients’ median age at onset of the disease was 42 years; its duration was 8 years. Most of the patients included in the registry had extended- (n=171 (52%)) or late- (n=148 (45%)) stage of RA. Results and discussion. Prior to initiation of TOFA therapy, RA activity according to DAS28 was high and moderate in 91 (64.5%) and 40 (28.4%) patients, respectively; the median DAS28 value was 5.5 [4.6; 6.2]; SDAI – 30.5 [21.4; 42.9], and CDAI – 28.2 [20.0; 37.1]. The use of TOFA was accompanied by significant decrease of disease activity. After 12 weeks, high RA activity was persistent in 32 (22.7%) patients; the number of patients with moderate activity increased to 77 (54.6%), that of those with low activity rose to 15 (10.6%); remission was observed in 17 (12.1%) patients. 216 (62.6%) and 76 (22%) patients received TOFA as first- and second-line therapy, respectively. TOFA was most frequently prescribed when tumor necrosis factor-á inhibitors (19.6%), rituximab (7.8%), tocilizumab (4.3%), and abatacept (5.2%) were insufficiently effective or poorly tolerated. Conclusion. The results of using TOFA in real clinical practice may suggest that the drug has high efficacy in patients with RA. TOFA can be used at a dose of 5 or 10 mg twice daily as both alone and in combination with disease-modifying anti-rheumatic drugs. TOFA showed similar efficacy in patients who had earlier taken biological agents and in those who had not

Efficacy and safety of a new original interleukin 17A inhibitor in the treatment of patients with active ankylosing spondylitis: results of a basic (BCD-085-3/AILAS) and extended (BCD-085-3ext/AILAS-II) phase II clinical trial

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 RESULTS OF A PHASE III COMPARATIVE CLINICAL TRIAL OF RITUXIMAB (ACELLBIA® AND MABTHERA®) IN RHEUMATOID ARTHRITIS (THE BIORA STUDY)

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

Efficacy and safety of netakimab, anti-IL-17A monoclonal antibody, in patients with ankylosing spondylitis. Results of phase III international, multicenter, randomized double-blind clinical trial BCD-085-5/ASTERA

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