The search for new therapeutic options for the treatment of systemic sclerosis (SSc) is an urgent issue in rheumatology. The article presents the results of the double-blind, randomized, placebo-controlled phase III clinical trial BCD-132-5/LIBERIUS on the efficacy and safety of divozilimab (BCD-132) in the treatment of SSc.Objective: to investigate the efficacy and safety of divozilimab in patients with SSc compared to placebo.Material and methods. After enrolment in the study, patients received divozilimab or placebo for 48 weeks, after which they were switched to an open-label divozilimab therapy until week 96.Results and discussion. Divozilimab was superior to placebo regarding the primary endpoint change in mRSS at week 48 compared to baseline, and the therapy had a positive effect on respiratory function parameters. Divozilimab treatment was well tolerated.Conclusion. Thus, divosilimab may represent a new therapeutic option for patients with SSc.

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.

Osteoarthritis (OA) is a chronic heterogenic progressive disease involving the deterioration of the cartilage tissue within joints, bone remodeling and the development of osteophytes that cause such clinical manifestations as pain, stiffness, edema and reduced joint function. The review elucidates modern views on the pathogenesis of OA and the up-to-date approaches to its diagnostics and treatment. Today, the emphasis is made on relieving pain and improving the quality of life of patients with OA. Symptomatic slow-acting drugs for osteoarthritis (SYSADOA) are used in OA clinical practice. The drugs of this class have beneficial effects on OA symptoms and their long-term use exerts disease-modifying action. SYSADOA are recommended for use as the first-line therapy and the treatment of choice in OA. Chondroitin sulfate (CS) is considered as a SYSADOA drug whose effectiveness has been proven in multiple clinical trials. CS is included in the EULAR recommendations for the treatment of patients with OA. The use of chondroitin has been shown to reduce pain and improve mobility of the affected joints. The authors present a clinical report of CS beneficial effects in a patient with OA. KEYWORDS: osteoarthritis, pathogenesis, treatment, quality of life, SYSADOA, chondroitin sulfate. FOR CITATION: Zhugrova E.S., Belyaeva I.B., Samigullina R.R. Insights in osteoarthritis from the perspectives of evidence-based medicine and authors' own experience. Russian Medical Inquiry. 2023;7(3):167–173 (in Russ.). DOI: 10.32364/2587-6821-2023-7-3-167-173.

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.

Aim. To evaluate the effect of COVID-19 on the clinical course of immunoinflammatory rheumatic diseases (IRD). Material and methods . The clinical course of IRD was analyzed in 324 patients who underwent new coronavirus infection (NCI) from March 2020 to February 2021 and were treated at Clinical Rheumatology Hospital No. 25 (Saint-Petersburg, Russia) for exacerbation of the underlying disease. Results. The risk factors of severe COVID-19 course in IRD were: age older than 60 years, presence of comorbid conditions (IHD, CHD, COLD), use of glucocorticoids in dose more than 12.5 mg per day and erythrocyte sedimentation rate values ≥ 40 mm/h before development of NCI. The use of immunosuppressive therapy and biological therapy had no effect on the worsening of the course of the viral infection in patients with IRD. The development of post-covid syndrome (asthenia, dyspnea, weight loss, memory loss) was noted in ¼ of the patients. Post-covid articular syndrome was characterized by the formation of arthritis associated with viral infection in 3.6% of patients, transformation of undifferentiated arthritis (UDA) into specific nosological forms in 49.0% (more often into early rheumatoid arthritis, RA), and exacerbation of joint syndrome in 83.4% of patients with advanced stage RA. In patients with diffuse connective tissue disease (DCTD), a significant increase in immunological activity due to antinuclear antibodies (maximum 1: 163840) was noted. We present clinical cases of arthritis associated with viral infection and fatal outcome in a patient with systemic sclerosis and interstitial lung damage after COVID-19. Conclusions. In the cohort of patients with IRD observed at Clinical Rheumatology Hospital No. 25 (Saint-Petersburg, Russia) COVID-19 had a moderate to severe course in half of patients, initiated the development of pneumonic complications in 68.6% of patients, arthritis associated with viral infection in 3.6%, transformation of UDA into IRD in 49.0% of cases and exacerbation of the main disease in the great majority of patients. Patients with DCTD with interstitial lung damage have a high risk of adverse outcome of NCI, especially in cases of unstable course of the disease, pronounced immunosuppression and require special monitoring. The authors present their own clinical experience with the use of Alflutop in a comorbid patient with osteoarthritis and increased pain after undergoing CCI, which indicates its effectiveness and cardiovascular safety. An important practical advantage of Alflutop should be considered the absence of its effect on the parameters of hemocoagulation and the reduction in the need for NSAIDs, which reduces the risk of thrombotic complications characteristic of long-term COVID. A short course of Alflutop (ten intramuscular injections of 2.0 ml every other day) contributes to ease of use and increased adherence to therapy in patients with osteoarthritis.

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.

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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).

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.

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.

Aim. To compare efficiency of combined Infliximab (Inx) and Methotrexate (M) therapy versus monotherapy with Methotrexate in patients with rheumatoid arthritis (RA). Material and methods. The study comprised 50 patients (45 female, 5 male) with an average age of 52,5±2,0 years. Average duration of RA was 10,4±1,1 years. The examination included clinical and acute phase rates. The efficiency of the treatment was estimated using ACR 20 %, 50 %, 70 %, improvements, DAS283V and HAQ tests. All patients were divided into two groups: patients in group I were treated with combined Inx and M therapy; patients in group II were treated with MT. Results. By the 22nd week patients in group I achieved significant decrease in DAS283V from 7 to 4,2, while patients in group II had DAS283V 5,6. The improvement in ACR criteria of 20 %, 50 %, 70 % was achieved in 26 %, 50 %, 24 % of patients after 22 weeks, accordingly. The improvement in ACR data in group II was achieveded in 47 %, 13 %, 10 % of patients, accordingly, and 30 % of no response. More significant decrease in HAQ index was in group I. Conclusion. Combined therapy with Inx and M results in decreasing RA activity and improving clinical status, joint function and quality of life. Key words: rheumatoid arthritis, methotrexate, tumour necrosis factor-a, infliximab, glucocortioids, quality of life, HAQ, DAS28, ACR.