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

Experience with abatacept used in the treatment of patients with rheumatoid arthritis

The efficiency and safety of therapy with abatacept in combination with methotrexate were studied in patients with rheumatoid arthritis. The performed therapy was shown to reduce the activity of an immune inflammatory process and the magnitude of articular syndrome and to improve the patients' functional status

DYNAMICS OF CYTOKINE PROFILE IN PATIENTS WITH RHEUMATOID ARTHRITIS AS INFLUENCED BY INFLIXIMAB (REMIKEID) ADMINISTRATION

Abstract. Rheumatoid arthritis (RA) is a chronic autoimmune systemic disease with predominantly destructive lesions of peripheral joints, with prevalence of 0.6 to 1.6% in general population. An important pathogenetic role in this disease is now attributed to imbalance between pro- and antiinflammatory cytokines. Clinical introduction of biological preparations, such as Infliximab (monoclonal antibodies to TNFα) within last years have changed therapeutic approach to treatment of rheumatic diseases. The aim of our research was to evaluate dynamics of pro- and antiinflammatory cytokine profile in the patients with rheumatoid arthritis (RА) during combined therapy with Infliximab and Methotrexate (MT). The study included 30 patients (27 females, 3 males, mean age of 52.5±2.0 years) who received combined therapy with МТ and Infliximab (Inx). Inx was initially injected at a single dose of 3 mg/kg intravenously, followed by administration 2 and 6 weeks later, and then repeated every 8 weeks. Regular examination of the patients included clinical and laboratory studies (ESR, levels of IL-6, IL-8, TNFα, IL-4, IL-10, GSM-CSF, IFNγ). Levels of antibodies against Infliximab in the groups of RА patients were determined before treatment and 22 weeks later. Efficiency of the therapy was estimated according to DAS28 3V Index and to HAQ Questionnaire.Upon decreased activity of disease, as assessed by DAS28, and improvement of HAQ parameters, a marked decrease in proinflammatory cytokine levels (IL-6, IL-8, TNFα) was detected, that confirming a pathogenetic significance of cytokine in RА patients. In patients with marked clinical effect (group I), an initially normal contents of TNFα was found in blood serum, and this group showed better response to Infliximab therapy, than groups II and III (resp., moderate and absent response) with initially high contents of TNFα and other cytokines, that was proven by correlations with ACR criteria and HAQ functional index. These events were accompanied by more significant improvement of RА course and increased functional abilities of joints. In patients from group III (absence of clinical effects), the level of antibodies to Infliximab before therapy was high, and it was increased by 22 week of treatment. It was shown that, in cases of initially high levels of endogenous anti-TNFα antibodies, clinical response to Infliximab therapy is likely to be reduced. Thus, it is possible to suggest that determination of initial TNFα and IL-10 levels, as well as starting levels of antibodies to Infliximab, and their changes in the course of therapy can be used as immunological parameters, thus allowing to predict the responses to Infliximab therapy. (Med. Immunol., 2008, vol. 10, N 2-3, pp 251-260)

RISK FACTORS FOR OSTEOPOROSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS (PRELIMINARY RESULTS ACCORDING TO THE MATERIALS OF THE MULTICENTER PROGRAM «OSTEOPOROSIS IN RHEUMATOID ARTHRITIS: DIAGNOSIS, RISK FACTORS, FRACTURES, TREATMENT»)

Osteoporosis (OP) in rheumatoid arthritis (RA) is 2–3 times more common than in the population; however, the data on the risk factors (RFs) of OP in this disease are ambiguous.Objective: to study RFs for OP in RA within the framework of the multicenter program “Osteoporosis in rheumatoid arthritis: Diagnosis, risk factors, fractures, treatment”.Subjects and methods. The trial enrolled 261 women (mean age 56.7±11.4 years) with RA; of them 151 (59%) patients were found to have OP (Group 1) and 107 (41%) were not (Group 2). All the patients underwent unified clinical, laboratory, and instrumental examination.Results. Comparison of the patients with and without OP showed that the women with OP were older (59.5±10.8 and 52.9±11.2 years, respectively; p < 0.01) had longer RA duration (14.5±9.2 and 11±8.0 years; p < 0.01), higher Health Assessment Questionnaire (HAQ) functional disability index scores (1.7±0.8 and 1.4±0.9; p < 0.01), higher C-reactive protein (CRP) levels (13.5 [7; 31] and 11 [2,7; 26] mg/l; p < 0.01); a larger number of erosions (49 [11; 90] and 8 [1;36]; p < 0.01), and a more marked joint space narrowing (112 [90; 131] and 77 [51; 102]; p < 0.01). The women with OP received longer (72 [26.5; 120] and 48 [11; 79.5] months; p < 0.01) and more frequently glucocorticoids (GC) orally (65.6 and 38.3%; p < 0.01) and as pulse therapy (41.2 and 20.4%; p < 0.01), had a larger cumulative dose (14.4 [5.4; 24.2] and 7.2 [1.5; 14.4] g; p < 0.01) and a larger GC dose at their examination (6.0 [4.0; 8,0] and 5.0 [4.0; 6.0]mg/day, respectively; p = 0.05).Conclusion. The presence of OP in RA correlates with age, RA duration, articular dysfunction, CRP levels, X-ray change magnitude, hormone therapy duration, and a cumulative GC dose

Risk factors for fractures in patients with rheumatoid arthritis (preliminary results of the multicenter program «Osteoporosis in rheumatoid arthritis: Diagnosis, risk factors, fractures, treatment»)

In patients with rheumatoid arthritis (RA), bone fractures occur 1.5-2 times more frequently than in the population. They often lead to reduced quality of life, to disability and death in the patients. It should be noted that risk factors (RFs) for fractures have not been studied on a sufficient sample in Russia; there are no recommendations on the prevention of fractures in this category of patients. Objective: to compare groups of RA patients with and without a history of fractures to further identify possible RFs for fractures. Subjects and methods. The trial included 254 patients aged 18 to 85 years, diagnosed with RA, from the database of the multicenter program «Osteoporosis in rheumatoid arthritis: Diagnosis, risk factors, fractures, treatment», who had been followed up in 2010 to 2011. The patients were divided into two groups: 1) 101 (39.8%) patients with a history of low-trauma fractures and 2) 153 (60.2%) patients without a history of fractures. In Group 1, the patients were older than in Group 2 (mean age 59.8 and 56.1 years, respectively). Menopause was recorded in 88.1 and 77.8% of cases, respectively. The groups differed in the duration of RA an average of 15.5 and 11.5 years, respectively Results. The fractures in the history were associated with the use of glucocorticoids (GC), their higher cumulative dose and use duration. In Group 1 patients, the bone mineral density (BMD) was lower in all study skeleton portions and more frequently corresponded to osteoporosis. RA complications, such as amyloidosis and osteonecrosis, were more common in the patients with a history of fractures. Conclusion. In RA patients, the most likely RFs of fractures are age, the long-term intake of large-dose GC, low BMD, the severe course of RA, and the presence of its complications

New treatment possibilities for rheumatoid arthritis: the Russian experience in using certolizumab pegol

Certolizumab pegol (CZP) is a new drug from the group of tumor necrosis factor a inhibitors. The efficacy and safety CZP in the treatment of rheumatoid arthritis (RA) have been studied in the international 52-week RAPID-1 and 24-week RAPID-2 clinical trials that studied the use of CZP in combination with methotrexate (MTX) in patients with active RA unresponsive to MTX. The study populations of the RAPID 1 and RAPID 2 trials constituted the major portion of Russian patients (11.8 and 18.4%, respectively), including that in the prolonged open-labeled phases. The results of using CZP in Russian patients in the RAPID trials showed that they displayed a highly stable response to treatment and a rapidly developing clinical effect, that a therapy response could be predicted in the first 12 weeks, and that the incidence of local postinjection reactions was low

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

The Effects of Telmisartan and Its Combinations on Office Blood Pressure: Results of Prospective Observational Study TAINA

Aim. To evaluate the effectiveness and safety of telmisartan, used in monotherapy or in combination with hydrochlorothiazide or amlodipine, in real clinical practice in patients with diagnosed arterial hypertension who have not reached the target levels of blood pressure (BP).Material and methods. The study was a non-intervention, prospective, multicenter, comparative, observational, epidemiological program, which was carried out in Russian medical institutions. The total patient population in which the prescribed therapy was administered included 1933 people (758 men and 1175 women, mean age 57.0-59.3 years). Participants were followed-up for 12 weeks. The change in office BP was evaluated on the 4th and 12th week.Results. Significant (p<0.001 in all cases) change in office BP compared with the initial data were recorded in all study groups of therapy already at 4 weeks of treatment and became even more pronounced at 12 weeks. In the telmisartan monotherapy group, BP decreased from 155.7±10.7/92.2±7.6 mm Hg to 131.4±12.1/80.8±7.3 mm Hg at the end of the 4th week and to 125.3±7.6/78.2±6.1 mm Hg – at the end of the 12th week. Similarly, after treatment with the combination of telmisartan and hydrochlorothiazide, BP decreased from 162.7±12.6/94.3±7.9 mm Hg to 133.2±12.5/81.6±8.4 mmHg at the end of the 4th week and to 126.0±7.8/78.4±6.7 mm Hg – at the end of the 12th week. In telmisartan/amlodipine group, a decrease in BP also occurred, from 162.5±13.2/94.6±8.6 mm Hg to 132.8±14.5/81.3±7.5 mm Hg on the 4th week and to 125.4±8.7/78.4±5.6 mm Hg at the end of follow up (12 weeks). The proportion of patients who reached the target BP (<140/90 mm Hg) after treatment with telmisartan as monotherapy was 91.7%, after treatment with telmisartan+hydrochlorothiazide – 89.6%, after treatment with telmisartan+amlodipine – 92.8%. Throughout the program, prescribed therapy was well tolerated by patients. During the study, 47 adverse events (AEs) were recorded in 36 patients: 31 AEs with telmisartan monotherapy, 5 AEs with telmisartan/hydrochlorothiazide combination, and 11 AEs with telmisartan/amlodipine combination. Most of the AEs registered during the trial resolved by the end of the study, in four cases the date of AEs resolve is unknown, in two cases, at the time of completion of the study, AEs continued.Conclusion. In the TAINA study a high antihypertensive efficacy and a comparable favorable safety and tolerability profile of telmisartan, used as monotherapy and in combination with hydrochlorothiazide or amlodipine was determined