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Currently, systemic glucocorticoids are taken by about 1–3% of the general population, up to 1.8% long-term. Moreover, about 50% of patients taking these drugs orally develop glucocorticoid-induced adrenal insufficiency (GIAI) after their withdrawal. Despite this scale of the problem and the length of time the issue has been studied, there are currently no standard algorithms for reducing the dose or discontinuing glucocorticoids. The evidence base on this issue has been performed on relatively few clinical studies, which are extremely heterogeneous with respect to the populations studied, designs, regimens of glucocorticoid use, and diagnostic approaches to adrenal insufficiency. Thus, the weight of evidence on this issue remains inadequate, resulting in each institution having its own approach to dose reduction and discontinuation of glucocorticoids, or no approach at all. This article summarizes current information about GIAI, allowing for improved approaches to dose reduction or discontinuation of glucocorticoids. Improving the management tactics of patients who have been receiving glucocorticoids for a long time will lead to a reduction in the risk of complications of GIAI, including life-threatening ones, as well as to a significant improvement in the quality of life of patients.

Background. Previously, 24-week results of phase III double-blind, placebo-controlled randomized clinical study (SOLAR) of levilimab in subjects with active rheumatoid arthritis (RA) proved a superiority of levilimab over placebo. Here we present 1-year efficacy and safety data of the SOLAR study.Objective – to evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA.Methods. The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021.154 adults, aged ≥18 years with confirmed diagnosis of RA were randomly assigned (2:1) to receive either levilimab (162 mg, SC, QW) + MTX (n=102) or placebo + MTX (n=52).After W24 of the study all subjects continued to receive open label levilimab. Subjects who have achieved DAS28-CRP≤2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP>2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was done in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases.Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n=152).Results. Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP≤2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (

Osteoarthritis (OA) is the most common joint disease due to the increasing life expectancy of the world's population. Every 2nd patient over the age of 50 suffers from knee or hip OA, and this is directly related to the increased burden on healthcare. Accumulated data on the comorbid profile of patients with OA dictate the need to identify disease phenotypes in order to provide personalized care. Individual clinical manifestations of OA also require a differential approach: the pain treatment requires consideration of the patient's psycho-emotional profile and the possibility of involving nociceptive pathways in the process. However, due to the ambiguity of existing clinical guidelines, most experts note a number of difficulties in prescribing treatment for patients with OA.The resolution presents an agreed opinion of experts on the algorithms for managing patients with OA, starting from the primary level, with the gradual involvement of related specialists. Some issues of a personalized approach are considered depending on the presence of comorbid pathology and the severity of individual symptoms of the disease. The prospects of the combined use of pharmacological and non-drug methods of treatment are noted; emphasis was placed on the importance of rehabilitation measures at the first level of medical care, provided to patients with OA, long before the development of structural changes.The proposed algorithms for managing patients can be considered as the basis for future recommendations for managing patients with this pathology.

The article presents an analysis of the therapeutic effect of the drug diacerein (D), which has been used in osteoarthritis (OA) for more than 20 years and is included in the clinical guidelines of the Association of Rheumatologists of Russia (2021) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO, 2019) for the treatment of OA. The main pathogenic effect of D in OA is to suppress the synthesis of interleukin 1, stimulate the production of articular cartilage proteoglycans, and slow down abnormal remodeling of the subchondral bone. The advantages of D in the treatment of patients with OA and comorbidities are presented – a prolonged anti-inflammatory and analgesic effect and good tolerability. These properties of D allow to control the symptoms of OA and improve the quality of life of patients. The structure-modifying effect of D is based on its ability to stimulate the synthesis of articular cartilage proteoglycans with long-term use and prevent abnormal remodeling of the subchondral bone, which leads to a decrease in the risk of OA progression and a delay in total joint arthroplasty. An important advantage of D is its positive metabolic effect in patients with type 2 diabetes mellitus and obesity, which is associated with the ability of D to reduce the level of glycated hemoglobin and body mass index. Data are presented on the absence of adverse cardiovascular effects when using D, which allows us to recommend its use in patients with OA who have comorbid cardiovascular diseases, as well as contraindications for non-steroidal anti-inflammatory drugs.

The article describes a clinical case of systemic lupus erythematosus (SLE) resistant to traditional treatment regimens and the first successful experience with the type I interferon inhibitor – anifrolumab, as part of an early access program in the Russian Federation. High efficacy and safety of the drug in the treatment of SLE with active lesions of the skin, mucous membranes and joints were noted.

The aim of the study was to evaluate the effectiveness of UPA in RA patients in real clinical practice after 3 and 6 months of therapy.Material and methods. The study included 63 RA patients with high activity of the disease. Activity was assessed according to the DAS28 (ESR), DAS28 (CR P), SDAI, CDAI; functional ability to HAQ; quality of life to the EQ-5D; disease activity according to the patient’s RAPID-3 index; the level of depression and anxiety to the HADS scale. The effectiveness of therapy was evaluated after 3 (n=45) and 6 (n=31) months of UPA therapy.Results. Remission or low activity of the disease by 3 months of therapy was achieved by most patients: remission of 69.8% of patients, low activity of the disease – 16.3% of patients. Moderate or high activity persisted in 13.9% of patients. By the 6th month of UPA therapy, the number of remissions reached 90% , low activity – 3.3%, moderate activity persisted in 6.7% of patients, high activity of the disease was not in any patient. 20% improvement in function was achieved in 71.8% of patients by the 3rd month of therapy and in 77.8% – by the 6th month of treatment; the difference in average HAQ values by the 3rd month of therapy was 0.38 points, by the 6th month – 0.58 points. After 3 months of follow-up, 31.1% of patients continued taking GC, by 6 months – 24.2%. The dose of GC was reduced from an average of 7.23 mg/d to 5.6 mg/d. The percentage of patients requiring NSAIDs decreased from 95.2% to 35.6% and 33.3%, respectively. DMARDs continued to be received by 75.6% of patients by 3 months and 69.7% by 6 months of follow-up.Conclusion. Achieving remission or low activity of the disease in patients with RA receiving UPA in real clinical practice is possible in most patients. A rapid decrease in inflammatory activity is accompanied by a significant improvement in the functional state and quality of life of patients. UPA therapy reduces the need for the use of NSAIDs and reduces the dose of GC in a third of patients.

One of the methods of treating severe forms of systemic scleroderma is hematopoietic stem-cell autotransplantation (auto-HSCT). The article describes two clinical cases of auto-HSCT followed by rituximab (RTM) therapy in patients with diffuse systemic scleroderma with progressive interstitial lung disease (ILD), high immunological activity, high skin score, and an unfavorable prognosis. The assessment of the course of these diseases was carried out in the course of dynamic observation of patients for 10–11 years. In all cases, auto-HSCT followed by RTM made it possible to achieve remission / low activity, as well as to stabilize the progressive of ILD.

The review presents an analysis of the therapeutic effect in osteoarthritis (OA) of the original complex injectable drug Alflutop (bioactive concentrate of small marine fish), which is one of the most widely used symptomatic slow acting drugs (SYSADOA) in Russia. It stimulates the proliferation of chondrocytes, activates the synthesis of the extracellular matrix by modulating transforming growth factor β (TGFβ), inhibits hyaluronidase, oxidative stress and the activity of extracellular expression of proinflammatory cytokine genes – interleukin (IL) 1β, IL6 and IL8 in vitro.The results of prospective clinical studies are presented, which demonstrate the ability of Alflutop to slow down the X-ray progression of OA of the knee joints (inhibit the narrowing of the joint space, the growth of osteophytes and increase the intra-articular concentration of hyaluronic acid), as well as restore the mobility of the hip joints when it is locally introduced into the zone of pathological changes in the articular lip of the acetabulum. Combined therapy with Alflutop leads to activation of reparative processes and significant clinical improvement in patients with post-traumatic OA, and also slows down the progression of chondrodegeneration according to magnetic resonance imaging. The new Alflutop administration regimen for knee OA (2 ml every other day, №10) can increase patient adherence to therapy.The results of clinical studies presented in the review prove the structural-modifying effect of Alflutop in OA of various localization and substantiate its widespread use in this disease in rheumatological, traumatological and orthopedic practice.

Upadacitinib (UPA), a JAK inhibitor, is a new therapeutic option that allows patients with insufficient response to therapy with basic anti-inflammatory drugs (DMARDs) or genetically engineered biological drugs (GEBDs) to achieve the goals of therapy for rheumatoid arthritis (RA). Despite the availability of convincing data from international randomized clinical trials, there is insufficient information about the efficacy and safety profile of UPA, the quality of life of patients receiving the drug in real clinical practice.Aim of the study – to assess the efficacy and tolerability of the UPA drug at a dose of 15 mg/day in patients with rheumatoid arthritis with moderate and high disease activity and to assess their quality of life in real clinical practice.Materials and methods. The study included 41 patients with RA with insufficient effect of previous therapy with DMARDs or GEBDs, persisting moderate or high disease activity, who were initiated with UPA therapy in 7 rheumatological centers of the Russian Federation. To assess the activity of the disease, standard indices were used: DAS28- ESR, DAS28-CRP, SDAI, CDAI. Functional ability was assessed according to the HAQ questionnaire, quality of life – according to the EQ-5D questionnaire, the activity of the disease according to the patient’s opinion – according to the RAPID-3 index. The HADS scale was used to identify the states of depression, anxiety and emotional disorder.Results. During the first week of taking the drug, there was a marked decrease in pain from 60 to 30 mm on a visual analogue scale, which lasted until the third month of therapy. There was a statistically significant decrease in morning stiffness, the number of painful and swollen joints, health assessments by the doctor and patient, erythrocyte sedimentation rate and C-reactive protein (p≤0.001). A decrease in disease activity was also noted according to the dynamics of the activity indices DAS28, SDAI, CDAI (p

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

In mid-2021, the SARS-CoV-2 (Severe Acute Respiratory coronavirus 2) infection, which caused the coronavirus disease (COVID-19) pandemic, affected more than 157 million people in all regions of the world and led to more than 3.2 million deaths. It is assumed that elderly age, uncontrolled inflammation, anti-inflammatory therapy, comorbid pathology, genetic and other factors can potentially lead to an increase in “sensitivity” to viral and bacterial infections, including SARS-CoV-2. The new version of the recommendations of the Association of Rheumatologists of Russia formulates the main provisions concerning the tactics of managing patients with Immune-mediated Rheumatic Diseases during the ongoing COVID-19 pandemic.

Levilimab (LVL) is a monoclonal antibody against the interleukin-6 receptor (IL6R). The article presents data obtained during 56 weeks of the AURORA phase II study.Objective: to evaluate the efficacy safety and immunogenicity of LVL in methotrexate (MTX) resistant patients with active rheumatoid arthritis (RA).Materials and methods. 105 patients with active RA were randomized in a 1:1:1 ratio into two LVL or placebo groups. LVL was administered subcutaneously at a dose of 162 mg every week (QW) or every other week (Q2W). All patients received MTX. After evaluating the primary endpoint of 20% improvement in ACR criteria (ACR20) at week 12, patients in the placebo group were switched to LVL Q2W. The study duration was 56 weeks. The frequency, profile, degree and severity of adverse events were determined in each group for safety assessment. The immunogenicity of LVL was determined by the proportion of patients with identified binding and neutralizing antidrug antibodies. Results. LVL in both regimens was superior to placebo. At week 12, the incidence of ACR20 achievement was 77.1% (LVL QW), 57.1% (LVL Q2W), and 17.1% (placebo) with 95% confidence intervals [37.53; 82.54] (p

Netakimab is a humanized anti-interleukin-17А monoclonal antibody approved for the treatment of psoriatic arthritis, ankylosing spondylitis, moderate to severe psoriasis. Herein, we report the accumulated efficacy data and safety findings of 54-week netakimab treatment during the PATERA study.The aim of the study was to assess the long-term efficacy and safety of netakimab in patients with active psoriatic arthritis.Materials and methods. 194 patients with active psoriatic arthritis despite the previous therapy with nonsteroidal anti-inflammatory drugs, conventional or biologic disease-modifying antirheumatic drugs were initially randomized to receive 120 mg netakimab or placebo (1:1) at weeks 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. At week 16 inadequate responders in placebo group were reassigned to netakimab in a blinded manner. From week 24 all patients receive open-label netakimab. The analyzed period includes 54 weeks.Results. Netakimab demonstrated sustained treatment response. 94.9% of patients in the netakimab group achieved ACR20 at week 54; 89.5% achieved PASI75 response. Axial disease, dactylitis, and enthesitis significantly improved with netakimab. A similar pattern was observed for placebo/netakimab treated patients. Netakimab was well tolerated. The majority of adverse events were mild and moderate. The most frequent treatment-related adverse events were lymphopenia, increased alanine aminotransferase, hypercholesterolemia. Adverse events of grade 3–4 were observed in 2%.Conclusion. Netakimab demonstrated sustained efficacy in key psoriatic arthritis domains at week 54 with a favorable longterm safety profile.

Introduction of biosimilars of biological disease-modifying antirheumatic drugs (bDMARs) into clinical practice has significantly expanded the availability of bDMARD therapy for a wide range of patients with chronic immuno-inflammatory diseases.In 2020, the first biosimilar etanercept Erelzi®, was registered in the Russian Federation. On May 22, 2021, an interdisciplinary Expert panel meeting was held on the use of Erelzi® for the treatment of rheumatic diseases and psoriasis. The leading Russian rheumatologists and dermatologists participated in this meeting. In the resolution of the Expert panel, it was stated that according data from randomized clinical trials and real clinical practice and due to low immunogenic potential of Erelzi, it can be used in initial therapy and in switching from other bDMARDs therapy in patients, who develop adverse reactions or face loss of their therapy effectiveness.

IgA anti-CD74 can be a promising marker for diagnosis, assessment of activity and prognosis for ankylosing spondylitis.The aim of the study was to determine the level of IgA anti-CD74 in patients with ankylosing spondylitis and to evaluate its relationships with ankylosing spondylitis activity and carriership of genetic alleles.Materials and methods. In 48 patients with a reliable diagnosis of ankylosing spondylitis, aged 18 to 69 years were measured the ASDAScrp, BASDAI, level of highly sensitive С-reactive protein, concentration of IgA anti-CD74. The polymorphisms of the genes interleukin (IL)-17A197 a/g, IL-17F7 histidine (His) / arginine (Arg), IL-17F11139 c/g, TNF-a-863, TNFα-308, TNFα-238, IL-1B-31, IL- 4-590, IL-6-174, IL-10-1082, IL-10-592, vascular endothelial growth factor (VEGF)-2578, VEGF-936, matrix metalloproteinase (MMP)2-1306, MMP3-5A6A, MMP9-1562, HLA-B27 were evaluated in their relationships with AS activity and IgA anti-CD74 levels.Results. The mean age of patients was 45.1±14.2 years, male - 72.9%, psoriasis - 10.4%, IBD - 2.1%, BASDAI -2.99±0.28, ASDAS - 2.29±0.16, CRP - 6.5±1.65 mg/L, IgA эпй-СВ74 - 18.6±1.73 U/mL (72.9% of the patients with >12 U/mL). The relationship between an increase in concentration of IgA anti-CD74 and ASDAScrp, BASDAI activity indices, between an increase in the level of CRP and the presence of the IL-17A genotype heterozygous for the AA allele (r=0.965) was determined. CRP did not demonstrate the relationship with the BASDAI.An association of IL-17F-11139 СС and the presence of psoriasis (r=0.870) was established. 93.8% of patients with ankylosing spondylitis were carriers of the homozygous histidine allele IL-17F7 (his/his) and the TNF238 allele (GG).Conclusions. The increase in anti-CD74 IgA level was found in 72.9% of patients with ankylosing spondylitis receiving inhibitors of TNF-a and NSAIDs and associated with clinical and laboratory indicators of ankylosing spondylitis activity and with carriage of the homozygous histidine allele IL-17F7 (his/his) detected in 93.8% of patients. Carriage of TNF-238 GG; TNF-863 CC; HLA-B27; TNF-308 GG; IL-4-590 CC; IL-6-174 CG;MMP9-1562 CC; MMP9-1562 CC; VEGF- 936 CC alleles was not associated with an increase in concentration of IgA anti-CD74. CRP demonstrated an association with IL-17A-197 AA (r=0.965) detected in 29.2% of patients with no correlation with the clinical ankylosing spondylitis activity in patients receiving treatment with iTNF-α and NSAIDs.

The article presents the actuality of the problem of hyperuricemia (HU) and gout in modern medicine, caused by the high prevalence and socio-economic consequences associated with the development in patients with these pathologies of earlier and more severe course of atherosclerosis, coronary heart disease, chronic kidney disease (CKD) and increased mortality. Illustrated pathogenetic mechanisms of HU influence on the cardiovascular system, which are characterized by the formation of endothelial dysfunction, increased adhesion and aggregation of thrombocytes, blood rheology disorders, increased levels of inflammatory markers, renal function disorders. It is highlighted that in arterial hypertension (AH) a possible mechanism for increasing the concentration of uric acid (UA) is a violation of renal excretion due to reduced tubal secretion. The data of the studies are presented, showing that in patients with type 2 diabetes mellitus and higher UA concentration is associated with increased risk of fatal and non-fatal stroke. Modern recommendations of HU correction, approved in the Russian Federation, are highlighted, where the expediency ofcomorbid condition therapy, correction of diet and lifestyle are noted. The consensus of the European Society of Cardiology and the Russian Society of Cardiology (RSC) on the management of patients with HU with high cardiovascular risk (CVR) and the RSC Clinical Practice Guidelines for AH are presented. Based on these documents, all patients with AH are recommended to evaluate the level of UA in serum and consider it high - more than 360 pmol/l, it is recommended to perform urate-lowering therapy for patients with high CVR, with the target level below 300 pmol/l. Modern possibilities of pathogenetic therapy of gout are presented. It is noted that the use of febuxostat demonstrates not only higher efficiency in reducing and maintaining the level of UA, but also better tolerance, in comparison with allopurinol. It is emphasized that elderly people do not need to correct the dose of febuxostat, it can be used by patients with CKD.

Objective: to study risk factors for invasive aspergillosis (IA), its etiology, clinical manifestations, and treatment efficiency in patients with rheumatic diseases (RD).Patients and methods. The first study of proven and probable IA (EORT/MSGERC, 2019) was conducted in 18 patients with RD, who accounted for 3% of all adult IA patients (n=699) included in the 1998–2020 registry of the Department of Clinical Mycology, Allergology, and Immunology, I.I. Mechnikov North-Western State Medical University (Group 1). This group comprised 56% women; the median age was 59 [21; 75] years. Group 2 (a comparison group) included 610 adult hematology patients with IA (median age, 45 [18; 79] years; 42% women). A prospective case-control study was conducted to identify risk factors for IA in patients with RD: 36 rheumatic patients without IA (median age, 58 (18–79) years; 61% women) (a control group).Results and discussion. Patients with RD were found to often develop IA in the presence of anti-neutrophilic cytoplasmic antibody-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) and systemic lupus erythematosus (50 and 16%, respectively). It was shown for the first time that the likelihood of IA in patients with RD increases with prolonged (median 14 days) lymphocytopenia during RD treatment (odds ratio 13.0; 95% confidence interval, 3.3–50.3). The main causative agents of IA were A. fumigatus (50%) and A. niger (29%). IA was more severe in Group 1 than in Group 2: in the resuscitation and intensive care units, there were 44 and 18%, respectively (p=0.01). Group 1 versus Group 2 more frequently had respiratory failure (61 and 37%, respectively; p=0.03), hemoptysis (28 and 7%; p=0.0001), chest pain (17 and 7%; p=0.04), and cardiac involvement (11 and 1%; p=0.0001), and less frequently had fever (67 and 85%; p=0.01). The common site of IA was the lung (83%); the characteristic feature detected by computed tomography (CT) is pulmonary cavitation (44%). Antifungal therapy was used in 89% of Group 1 patients; the overall 12-week survival was 69%.Conclusion. In patients with RD, it is difficult to differentiate between the progression of the underlying disease, adverse drug reactions, infectious complications, or a combination of these disorders due to the similarity of their clinical manifestations. When RD patients with infectious syndrome and respiratory failure develop prolonged lymphocytopenia during combination therapy, AI should be suspected and lung CT, bronchoscopy, and mycological examination of the material obtained by bronchoalveolar lavage be done.

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.

Psoriatic arthritis (PsA) is a chronic immune-mediated disease from a group of spondyloarthritis, which is characterized by damage to the musculoskeletal system with a wide range of different clinical manifestations and is usually associated with psoriasis. Activation of the interleukin (IL) 23/IL17 axis plays a key role in the pathogenesis of PsA and psoriasis. When non-steroidal and synthetic disease-modifying antirheumatic drugs are insufficiently effective, biological drugs are recommended. In recent years, there have been considerable advances in PsA treatment with tumor necrosis factor-α (IFN-α) inhibitors and IL-12/23 inhibitors. However, in some cases, this therapy fails to provide the desired effect and a search for new treatments for PsA seems to be an urgent task. The paper desctibes a clinical case demonstrating the efficacy of the IL17A inhibitor ixekizumab in a patient with high PsA activity and recurrent uveitis in both eyes. Ixekizumab therapy resulted in positive changes as the reduced severity of articular syndrome and psoriasis and normalization of acute phase parameters. Assessing the activity of PsA over time when using ixekizumab during a year showed an average decrease in ESR from 72 to 19 mm/h, in CRP from 162.1 to 0 mg/L, BSA from 51 to 0.25%, PASI from 43. 6 to 0, DAPSA from 78.2 to 2, ASDAS-SRB from 5.11 to 1.12, BASDAI from 4.85 to 1, BASFI from 5.3 to 0.7, BASMI from 5.0 to 2.6, MASES from 6 to 0, LEI from 2 to 0, SPARCC from 6 to 0, and NAPSI from 28 to 8. Thus, this clinical case is an example of successful treatment with the IL17 inhibitor ixekizumab for PsA with recurrent uveitis in the patient who has previously received three drugs from the TNFα group without any effect.

Netakimab (NTK) is a humanized anti-interleukin-17А (IL-17A) monoclonal antibody approved for the treatment of psoriatic arthritis, ankylosing spondylitis, moderate to severe psoriasis. Here, we present the results of the 24-weeks double blind period of the PATERA study.Objective. The objective of the study was to evaluate the efficacy and safety of NTK compared to placebo in patients with psoriatic arthritis (PsA).Patients and methods. 194 patients with active PsA with an inadequate response to previous therapy with nonsteroidal anti-inflammatory drugs, conventional or biologic disease-modifying antirheumatic drugs, were randomized in a 1:1 ratio to receive subcutaneous 120 mg NTK or placebo at weeks 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. At week 16 ACR20 (20% improvement in the American College of Rheumatology response criteria) non-responders in placebo group were reassigned to NTK in a blinded manner. The primary endpoint was the proportion of patients achieved ACR20 response at week 24.Results. 82,5% of patients in the NTK group and 9.3% of patients in the placebo group achieved ACR20 at week 24 with the 95% CI [0,63; 0,84] (p < 0,0001). Skin manifestations and axial disease significantly improved with NTK. The safety profile of NTK was comparable to placebo. The most frequent treatment-related AEs were expected and common for all other IL-17 inhibitors: increased alanine aminotransferase (ALT), infections, lymphopenia.Conclusion. NTK in the dose of 120 mg has superior efficacy over placebo in patients with active psoriatic arthritis. The safety profile is consistent with other IL-17 inhibitors.

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

The article presents the relevance of the problem of postmenopausal osteoporosis (OP) in modern medicine, due to the social and economic consequences of fractures. The pathogenetic mechanisms of its formation are highlighted, indicating that during postmenopausal women amid estrogen deficiency, there is a violation of bone remodeling processes with increased bone resorption and decreased bone formation. Modern recommendations of the pathogenetic therapy of OP are presented, in which it is noted that the drugs of the first choice are drugs of the bisphosphonate class (BF). The ability of BF to suppress the pathological resorption of bone tissue and stimulate bone formation determines their therapeutic effect in OP. One of the drugs of the BF class is alendronate. In the treatment with alendronate, the processes of resorption by osteoclasts are suppressed and the processes of bone metabolism are restored to the premenopausal level, microarchitectural disturbances and bone loss are prevented. It has been demonstrated that the processes of bone metabolism remain stable during prolonged treatment with alendronate for 10 years, while the accumulation of the drug in the bone does not lead to excessive suppression of bone metabolism, but rather remains at the premenopausal level. The data of international and Russian randomized placebo-controlled trials (RCTs) are presented, which indicate the high effectiveness of alendronate at a dose of 70 mg 1 time / week in the treatment of primary OP in postmenopausal women: it had a positive effect on bone mineral density (BMD), reduced pain and, as a result, reduced the restriction of physical activity of patients. Quite good tolerability of the drug was noted, side effects in the treatment group were comparable to those in the placebo group. An analysis of the action of alenadronate shows that it has an aftereffect within a 12-month period after the end of treatment in relation to the BMD of the spine.

The article discusses the participation of interleukin-6 (IL6) in the formation of pathogenetic mechanisms of immuno-inflammatory diseases (IID). IL6 is one of the central cytokine in progressive IID. The biological activity of IL6 is determined by its ability to activate target genes that regulate differentiation, apoptosis and proliferation of immunocompetent cells. The immune-inflammatory effects of IL6 include regulation of the acute phase reaction, differentiation of immune cells, switching from innate to adaptive type of immune response (activation of T-helper 17 (Th17) cells and T-follicular Th-cells, suppression of the formation of T-regulatory cells, synthesis antibodies by B cells), stimulation of hematopoiesis (maturation of myeloid progenitors and megakaryocytes, leading to neutrophilia and thrombocytosis), neoangiogenesis, osteoclast-mediated bone remodeling. Currently, the use of a humanized monoclonal antibody to the IL-6α receptor (tocilizumab) is one of the most promising directions in the treatment of rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, large arterial vasculitis – aortoarteritis, temporal arteritis. The use of tocilizumab is included in the draft recommendations for the treatment of IID in conditions of coronavirus disease 2019 (COVID-19) developed by the All-Russian public organization “Association of Rheumatologists of Russia”. The presented data from international and domestic studies, as well as our own clinical experience, suggest that Tocilizumab (Actemra) is a highly effective and safe genetic engineering biological drug (GEBD) in the treatment of IID, and its use leads to a decrease in clinical and immunological activity and helps to improve life prognosis both when appointing as a first-line GEBD therapy and in case of ineffectiveness of other biological drugs and basic anti-inflammatory drugs in this category of patients.

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.

Janus kinase (JK) inhibitors block the intracellular signaling pathways that are responsible for the synthesis of proinflammatory cytokines and mediators, which in turn cause the activation of pain receptors and central sensitization (CS). It is suggested that JK inhibitors can rapidly eliminate pain and reduce the severity of CS.Objective: to evaluate the effect of the JK inhibitor tofacitinib (TOFA) on the intensity of pain and the signs of CS in patients with active rheumatoid arthritis (RA) at 7 and 28 days after therapy initiation.Patients and methods. A study group consisted of 39 patients (79.5% female) (mean age 50.9±11.1 years) with RA (DAS28 5.8±0.6). Of these, 89.7% were seropositive for rheumatoid factor; 82.0% took methotrexate and 18.0% received leflunomide. All the patients were prescribed TOFA 5 mg twice daily due to the inefficacy or intolerance of biological agents. The investigators estimated pain intensity using a Brief Pain Inventory (BPI), rated the presence of a neuropathic pain component (NPC) with the PainDETECT questionnaire, and assessed the signs of CS with the Central Sensitization Inventory (CSI) during the first 4 weeks after TOFA administration.Results and discussion. The patients initially experienced moderate or severe pain (the mean scores of 5.33±2.51 on the numerical rating scale (NRS) included in BPI); 53.8% had signs of CS (CSI scores of ≥40); 17.9% had signs of a NPC (PainDETECT scores of >18). Already on day 7 after the start of TOFA administration, there was a statistically significant decrease in the mean NRS pain intensity scores to 4.06±2.2 (p=0.01) and by 29.4±17.9%, as shown by the patient's assessment of the analgesic effect of therapy (BPI), as well as the severity of CS, namely a decrease in the mean NRS pain score to 35.9±11.2 (p=0.01). On 28 days, the effect became better: there was a reduction in the level of NRS pain to 2.32±1.57 (p

Osteoarthritis (OA) belongs to diseases with high comorbidity and most frequently concurrent with obesity, diabetes mellitus (DM), hypertension, and other cardiovascular diseases (coronary heart disease, atherosclerosis), gastrointestinal tract diseases, and chronic diseases of the lung and kidney. Irrational treatment of OA in the presence of comorbidity and without considering characteristics of drug interactions leads to a pronounced increase in the number of adverse reactions (ARs) and to aggravation of the course of all concomitant diseases. From this point of view, therapy seems to be relevant when the latter involves drugs that have both symptom- and structure-modifying properties and have a high safety profile.Objective: to compare the safety of alternating and standard treatment regimens with Alflutop® in patients with knee OA.Patients and methods. 130 patients were enrolled in the trial who had Kellgren-Lawrence Grade II–III primary tibiofemoral knee OA with pain intensity on walking ≥40 mm on a visual analogue scale and who needed to take nonsteroidal anti-inflammatory drugs (≥30 days in the previous 3 months). The patients were randomized into two groups: Group 1 was prescribed Alflutop® 1.0 ml intramuscularly (IM) daily for 20 days (a standard regimen); Group 2 was given 2 ml IM every other day (a total of 10 injections) (an alternating regimen). The duration of follow-up was 14 weeks. The safety of Alflutop® was evaluated by the incidence of ARs and serious ARs (SARs) varying in severity according to medical records, laboratory tests, physical examination, assessment of a patient' vital signs, and electrocardiography (ECG). The patients were examined at the beginning, at the end, and 1 month after therapy.Results and discussion. No SARs were recorded during the study period and follow-up. There were 10 ARs in the group of patients receiving Alflutop® in the standard regimen and 19 ARs in the other group (the alternating regimen). All ARs corresponded to mild and moderate severity, were unassociated with the test drug, and resolved by the end of the follow-up. 12-lead ECG identified only clinically insignificant abnormalities in the patients of both groups. Patients without DM displayed no clinically significant increase in glucose levels. Those with DM had no increased glycemia tendency. Biochemical studies in both groups revealed only clinically insignificant abnormalities, the frequency of which was insignificant.Conclusion. This study has confirmed the comparable high safety of Alflutop® in both standard and alternative therapy regimens. It has also shown that the drug has a good safety profile and can be recommended for wide clinical application in any use regimen: 1 ml daily (a total of 20 injections) or 2 ml every other day (a total of 10 injections).

Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by the overproduction of organ-specific autoantibodies to various components of the cell nucleus and by the development of immune-mediated inflammatory damage to internal organs. SLE is the prototype of a systemic human autoimmune disease; it is an extremely heterogeneous disease in terms of both clinical manifestations and a genetic predisposition and pathogenetic mechanisms, which often complicates the early diagnosis of the diseases and makes it impossible to personify therapy. Despite the fact that in the 21st century, the 15-year survival rate for SLE has increased up to 85%, the inadequate control of disease activity and the need for almost constant intake of glucocorticoids and immunosuppressive drugs result in the accrual of irreversible damages to internal organs and, as a consequence, in decreases in quality of life, disability, social maladaptation, and premature death. The paper considers the new 2019 EULAR/ACR diagnostic criteria for SLE, the contemporary 2019 EULAR recommendations for the management of SLE, and new pharmacotherapy options for this condition, which are based on the deciphering of the mechanisms of SLE immunopathogenesis.

Success in practical rheumatology of the latest decade achieved mainly due to monoclonal antibodies (MABs) appearance in routine medical practice. At the same time, the experience of practical application of MABs is limited both by observation period and exposure and their clinical and pharmacological properties do not allow to fully characterizing their safety profile with the data from clinical studies. The use of MABs is associated with the risk of delayed adverse drug reactions (ADRs) — types B (immunoallergic reactions), C (new diseases) and D (delayed teratogenic and oncogenic effects). Determination of risk factors in real medical evidence is especially important. The risk factors of ADRs including serious ADRs were studied based on an analysis of the spontaneous reports database of the Federal Service for Supervision in Healthcare and the data from rheumatologic register of patients receiving MABs — the E.E. Eikhvald Clinic in North-Western State Medical University named after I.I. Mechnikov. It was shown that the factors coming from the patient (gender, age group) do not affect the severity of the risk of occurrence of ADR, including serious ADRs, while the risk factor for monoclonal antibodies can be considered the choice of tocilizumab, which increases the risk of serious ADRs.

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 JAK inhibitor tofacitinib (TOFA) blocks the intracellular signaling pathway that activates the synthesis of cytokines and mediators involved in the development of pain and central sensitization (CS), which determines the rapid analgesic effect. However, it is not clear how pain reduction is associated with achieving low activity in rheumatoid arthritis (RA).The aim of the study was to assess the relationship between the early clinical response to tofacitinib and a decrease in rheumatoid arthritis activity after 3 and 6 months.Material and methods. The study group consisted of 88 RA patients (age – 53±11.5 years; 79.3% of women) who received basic anti-inflammatory drugs (59.5% – methotrexate, 19.8% – leflunomide) and who were prescribed TOFA in a dose 10 mg/day. Seropositivity for rheumatoid factor was 89.8%; the value of the DAS28 index is 5.2±1.2. The severity of pain was assessed using the Brief Pain Inventory questionnaire, the neuropathic component of pain (NCP) – using the PainDETECT questionnaire, signs of CS – using the Central Sensitization Inventory (CSI) questionnaire in the early stages after the administration of TOFA, RA activity – using the DAS28-CRP index after 3 and 6 months.Results. The mean severity of pain at baseline was 5.3±2.0 on the visual analogue scale (VAS); 51.1% of patients had signs of CS (CSI>40), 15.9% had NCP (PainDETECT>18). 7 days after the start of therapy, there was a significant decrease in pain – to 4.1±1.8 according to VAS (p

Metal constructions can cause fever even after a few years post implantation. This paper describes a case of 27 year old female with a fever associated with titanium construction implanted for kyphoscoliosis. 3 years post-operatively she developed afever (up to 39°С) and associated back pain. Examination revealed a hepatomegaly and lymphadenopathy (cervical and inguinal groups). Other investigations showed: neutrophilic leukocytosis (16×109\L), thrombocytosis (620×109\L), elevation of the C-reactive protein (76 ng/ml), ESR (62 mm/h) and ferritin (1615 ng/ml). There were no features of infection, connective tissue disease or hemoblastosis. A short course of therapy with methylprednisolone led to transient improvement. The metal device was surgically removed which caused an immediate elimination of fever and subsequent resolution of leukocytosis, thrombocytosis, lymphadenopathy and hepatomegaly.

Significant successes in the use of biological agents (BA) have been achieved in the treatment of rheumatoid arthritis (RA); nonetheless, about 36% of patients cannot respond to therapy or achieve the expected effect. A new area in the treatment of RA is the use of Janus kinase (JAK) inhibitors, targeted synthetic disease-modifying anti-rheumatic drugs (chemical molecules with a molecular weight

Using of more convenient drug regimens is one of the ways to increase patient adherence to treatment for osteoarthritis (OA).Objective: to evaluate the efficacy of Alflutop® in an alternating dosing regimen versus its standard administration to patients with knee OA. Patients and methods. The investigation included 130 randomized patients who had Kellgren—Lawrence Grade II—IIIprimary tibiofemoral knee OA with pain intensity on walking at least 40 mm on a visual analogue scale and needed to take nonsteroidal anti-inflammatory drugs (at least 30 days in the previous 3 months). The patients were divided into two groups: 1) those who received Alflutop® 2 ml intramuscularly (IM) every other day (a total of 10 injections); 2) those who used the drug 1.0 ml IM daily for 20 days. The duration of the investigation was 14 weeks. Results and discussion. Just on days 20/21 of treatment, the patients of both groups were recorded to have statistically significant reductions in knee pain on walking (p

There are few studies of the efficiency of therapy with disease-modifying antirheumatic drugs (DMARDs) and biological agents (BAs) in patients with early rheumatoid arthritis (eRA) as part of a treat-to-target strategy.Objective: to investigate the effects of DMARDs and BAs used in combination with methotrexate (MTX) on clinical course, quality of life (QoL), and the evolution of articular erosions and synovitis in patients with RA.Patients and methods. The investigation enrolled 151 patients with eRA. At the first stage, the patients received DMARDs. At the second stage, 101 patients with persistent moderate and high disease activity were prescribed MTX at a dose of 25 mg/week or 20 mg/week in combination with infliximab (INF), or 20 mg/week in combination with rituximab (RTX). At the third stage, 20patients with persistent high disease activity were switched to tocilizumab (TCZ) therapy.Results and discussion. At 12 months of DMARD therapy, a clinical remission was more often achieved in the MTX group. The use of INF or RTX significantly improved QoL in the patients. That of TCZ as a second- and third-line drug led to a significant decrease in DAS28-CRP. Conclusion. There were no statistically significant differences between the INF and RTMgroups with respect to the time course of changes in CRP, ESR, circulating immune complexes, and the indicators of X-ray progression, which confirms the possibility of switching from a first-line BA to its subsequent lines with an increasing clinical disease activity. TCZ can be a second- and third-line drug when the effect of therapy with other BAs escapes.

The basis of the clinical picture of adult-onset Still's disease is a triad of symptoms, includingfever, arthralgia/arthritis, and characteristic rash called «Still rash». The first line of therapy includes glucocorticoids, synthetic disease-modifying anti-rheumatic drugs; biological agents, such as tumor necrosis factor a inhibitors and interleukin-6 and interleukin-1 inhibitors, are used in standard therapy-resistant cases.

The article is devoted to medical activity of the sons of the outstanding Russian clinician and scientist Sergey Petrovich Botkin (1832-1889) — Evgeny Sergeevich Botkin (1865-1918) and Sergey Sergeevich Botkin (1859-1910). Sergey Petrovich Botkin is the founder of the first in Russia and one of the largest scientific therapeutic schools. Among the doctors who were trained in the clinic of the Military medical Academy in the years of work of Sergei Petrovich Botkin, were his sons, however, traditionally in the publications on the scientific clinical school of Sergei Petrovich Botkin, their names are not mentioned among his students. The authors made an attempt to trace the stages of the life of the sons of Sergei Petrovich Botkin, in particular, study and work in the Military medical Academy, scientific training abroad, medical activities in medical institutions of St. Petersburg and organization of medical care as part of the red cross during the Russian-Japanese war (1904-1905). The work of Yevgeny Botkin as a court physician of the family of the last Russian Emperor Nicholas II is considered separately. The article reveals the influence of the person S.P. Botkin and his closest disciples on E.S. Botkin and S.S. Botkin, as well as the continuity of clinical views and research of S.P. Botkin and his sons. The authors emphasize the similarity of ethical principles of medical activity, which guided Sergey Petrovich Botkin and his sons. The materials presented in the article confirm that the sons of Sergey Petrovich Botkin — Evgeny Sergeevich Botkin and Sergey Sergeevich Botkin — belong to his scientific clinical school.

The review presents the data available in the literature on the use of the lupus band test (LBT) for systemic lupus erythematosus (SLE). LBT is a direct immunofluorescence method used to detect immunoglobulins and complement factors in the dermoepidermal junction of skin biopsy specimens. LBT may be applied as one of the diagnostic tests for early diagnosis of SLE in patients without skin manifestations and in those of incomplete SLE. Like the results of other laboratory tests, those of LBT may be taken into account when establishing a final diagnosis only in conjunction with other clinical, immunological and instrumental data.

Febuxostat is a non-purine selective inhibitor of isoforms of xanthine oxidoreductase (XOR), the effect of which is aimed at lowering the level of serum uric acid (UA). Febuxostat is a more potent inhibitor of XOR than allopurinol, as confirmed by that target UA levels have been achieved more frequently with febuxostat than with allopurinol, particularly in patients with high serum urate concentrations. The pharmacokinetic properties of febuxostat are not dependent on renal clearance, which distinguishes it from allopurinol and may benefit patients with chronic kidney disease. A number of studies are being conducted to further evaluate the cardiovascular safety of febuxostat and its possible positive effects in preserving renal function. Of importance is the fact that febuxostat does not require dose adjustment in elderly patients.

The absence of a current emergency care system for rheumatic patients makes the solution of this problem relevant. Objective: to create and test a health care system for patients with acute articular syndrome (AAS) and to analyze the distribution of patients according to the profile of hospitalization. Subjects and methods. The practice of providing medical care to patients with AAS was studied using the materials of the I.I. Dzhanelidze Research Institute of Emergency Care (RI of EC) in 2008 to 2015. The causes of hospital admissions were analyzed by taking into account the verified nosological diagnosis. Results and discussion. The incidence of AAS in the general flow of patients referred for hospitalization was analyzed; the most frequent causes of AAS were determined. Trends in the referral of rheumatic patients to inpatient and outpatient treatment were analyzed separately. The decrease in the proportion of rheumatic patients in need of inpatient treatment from 76.7 to 50.8% during the study allows optimization of the costs of the health care system. Conclusion. The presented concept of providing medical care to patients with AAS has proven its effectiveness as a result of its testing at the RI of EC from 2008 to the present time. This concept can be recommended for its introduction in other subjects of the Russian Federation.

Objective: to assess the long-term safety and efficiency of tocilizumab (TCZ) therapy in patients with early rheumatoid arthritis (RA) of moderate and high activity, who have completed the basic WA19926 study, as well as the rate of sustained drug-free remission.Subjects and methods. A long-term open-label multicenter Phase III extension study (ML28124) was conducted using a group of 49 patients (36 (73.5%) women and 13 (26.5%) men; mean age 53.3±10.8 years) with early RA of moderate and high activity. All the patients received an intravenous infusion of TCZ 8 mg/kg every 4 weeks for 104 weeks (a total of 27 infusions). The safety assessment criteria were the rate and severity of all adverse events (AE), serious AE (SAE), and AE of particular interest; the rate of AE causing drug dosage changes or withdrawal from the study; the frequency of clinically significant laboratory abnormalities. The analysis of efficiency (secondary end points) included changes of DAS8, which was calculated using erythrocyte sedimentation rate (ESR) (DAS28-ESR) and SDAI, the of tender joint count (TJC) and swollen joint count (SJC); the number of patients who had achieved drug-free remission; and the time to a RA exacerbation in patients who had achieved non-drug remission.Results and discussion. The total rate of AE was found to be 69.4%; that of SAE was 10.2%; SAE were 6.9% of the the total number of AE; AE of particular interest were 17.2% of the total number of AE. More than one-third (35.6%) of the AE caused drug dose changes or therapy discontinuation or complete cessation. The laboratory clinically significant abnormalities included those in complete blood cell counts (blood alanine aminotransferase, aspartate aminotransferase, total and direct bilirubin, creatinine, and glucose). The evaluation efficiency analysis showed that the main disease activity measures (DAS28-ESR, SDAI, SJC, and TJC) decreased at 104-week follow-up versus at baseline. The rate of drug-free remission was 71.4%; that of recurrence was 40.0% (the median time to recurrence was 23 weeks). The findings suggest that the safety profile of TCZ is acceptable in the long-term treatment of early RA and correspond to earlier results.

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.

Objective: to determine the efficiency and safety of therapy with tofacitinib (TOFA) in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) after insufficient previous therapy in real clinical practice.Subjects and methods. The investigation enrolled a total of 33 patients with RA who met the 1987 American College of Rheumatology (ACR) and/or the 2010 ACR/European League Against Rheumatism (EULAR) criteria. All the patients received TOFA 5–10 mg administered orally twice daily in combination with MTX; 30 patients took TOFA 10 mg/day and 3 patients had TOFA 20 mg/day. Every 6 weeks, the patients were examined by a rheumatologist and laboratory-instrumental tests. RA activity changes were assessed with DAS28-CRP, SDAI, and CDAI.Results and discussion. Results were assessed at weeks 12, 54, and 114. A significant decrease in DAS28-CRP, SDAI, and CDAI values was noted just at 12-week follow-up; at week 54, the mean values of these indices were 3.7±1.0, 14.9±8.8, and 13.4±9.0, respectively. There was a substantial decline in the levels of rheumatoid factor in 27% of the patients; while one third of them had a 60% decrease in its level and four patients achieved a negative seroconversion. Neither serious adverse events (AEs) no AEs that had not previously been described in the literature were observed during the follow-up study. Nine non-serious AEs were recorded in 8 (25.0%) patients.Conclusion. The investigation shows that TOFA makes it possible to control the activity of the inflammatory process and, with its sufficient safety and generally good tolerance, to achieve low RA activity in 49% of cases, including patients with multidrug resistance. The high efficacy of TOFA and, in particular, its combination with MTX used in patients with refractory RA give grounds for wider use of this drug, as confirmed by our investigation.

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, spine, and entheses, which is associated with psoriasis. The pathological process is localized mainly in the tissues of the locomotor system and leads to the development of erosive arthritis and intra-articular osteolysis. PsA occurs in 5–7% of patients with moderate psoriasis. Despite advances in the treatment of psoriasis and PsA with diseasemodifying antirheumatic drugs (DMARDs) and biological agents (BAs), the problems associated with immunogenicity, infectious complications, and secondary inefficiency have not been fully solved. These factors have motivated the search for novel targeted synthetic drugs (signaling pathway inhibitors). This group of drugs includes apremilast, a phosphodiesterase 4 inhibitor. Recent data of controlled studies suggest that the drug is effective and safe in treating psoriasis and PsA. Prospects for the use of apremilast in PsA are associated with the possibility to use the drug in patients because of the inefficacy of DMARDs or BAs and with the ability to maintain long-term (more than 3-year) remission and to reduce the manifestations of enthesitis and dactylitis.

Febuxostat, a selective inhibitor of isoforms xantinoxydoreductase, it is an alternative to a limited number of medications to reduce urates levels applied in recent decades. Inhibition of xantinoxydoreductase by febuxostat more is more powder and effective than by allopurinol, as evidenced by more frequent achievement of target urate level in the blood serum, especially in patients with high urates concentration. Unlike allopurinol pharmacokinetic properties febuxostat do not depend to a large extent on renal clearance, which is important for patients with chronic renal disease. A few studies conducted further evaluation of the febuxostat safety for the cardiovascular system and its potential positive impact on renal function. It is also important that elderly patients didn’t require correction doses of the drug.

Gout is a fairly common rheumatic disease, the significance of which becomes an increasingly important interdisciplinary problem. It is known that about 2.5% of men over the age of 30 and women over the age of 50 suffer from gout. By the age of 80 y.o. the disease is registered already in 9% of men and 6% women. The increased incidence, high comorbidity, and low compliance of patients with gout put new questions when the adequate complex therapy is sought.Despite the fact that the treatment of this disease is well known and widely discussed in the literature, it’s possible to achieve remission of gout only in very rare cases. In the literature, there is evidence that less than ½ of patients with gout get ordinary therapy, while often drugs are prescribed in doses not sufficient to obtain the effect [1].

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.

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease (ARD) associated with the production of broad-spectrum antibodies, the detection of which is of important diagnostic and prognostic values. The problems of RA diagnosis are associated with the limited sensitivity of currently used serological markers.Objective: to evaluate the diagnostic informative value of autoantibodies against different post-translationally modified (PTM) vimentin peptides in patients with RA and other ARDs.Patients and methods. The frequency of autoantibodies against different isoforms of vimentin was estimated in 144 patients with RA, in 36 patients with other ARDs (ankylosing spondylitis and scleroderma systematica), and in 25 patients of a control group, who had no rheumatic diseases. Antibodies against different PTM vimentin peptides obtained using citrullination, carbamylation/homocitrullination, and acetylation were determined. Anti-citrullinated vimentin (anti-CitVim) peptide, anti-carbamylated vimentin (anti-CarVim) peptide, and anti-acetylated vimentin (anti-AcVim) peptide autoantibodies of IgG and IgA classes were estimated in the serum by enzyme immunoassay.Results. The results of the study showed that IgG and IgA anti-CitVim had the maximum area under the ROC curve (AUC) (0.859 and 0.855, respectively). A slightly smaller AUC was seen in IgG anti-CarVim (0.85), IgG anti-AcVim (0.784), and IgA anti-AcVim (0.651). The diagnostic sensitivity and diagnostic specificity were 66.2 and 96.77% for IgG anti-CitVim, 60.56 and 91.94% for IgA anti-CitVim, 91.55 and 53.23% for IgG anti-CarVim, 63.38 and 93.55% for IgG anti-AcVim, and 49.3 and 70.97%, IgA anti-AcVim, respectively. Positivity for IgG anti-CitVim, IgG anti-CarVim, and IgG anti-AcVim, and anti-IgA CitVim was significantly more frequently detected in patients with RA than in those with other ARDs and in the control group (p

The Russian biotechnological company «BIOCAD» has designed a chimeric monoclonal antibody against CD20 (BCD-020, Acellbia®) that is a biosimilar of rituximab (RTM; MabThera®, F. Hoffmann-La Roche Ltd., Switzerland). In recent years, there has been evidence that RTM can be used at lower doses than those given in the standard recommendations and instructions for the use of this drug. This serves as the basis for the BCD-020-4/ALTERRA (ALTErnative Rituximab regimen in Rheumatoid Arthritis) trial, the objective of which was to investigate the efficiency and safety of using Acellbia® (at a dose of 600 mg twice at a 2-week interval) as the first biological agent (BA) for methotrexate (MTX)-resistant active rheumatoid arthritis (RA). The investigation enrolled 159 patients aged 18 to 80 years with active RA. After 24 weeks 65.7 and 29.4% of patients achieved 20% improvement by the American College of Rheumatology (ACR) criteria in the Acellbia® + MTX and placebo (PL) + MTX groups, respectively (p

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, spine, and entheses, which is associated with psoriasis. The pathological process is localized mainly in the tissues of the locomotor system and leads to the development of erosive arthritis, intra-articular osteolysis, and spondyloarthritis. Nonsteroidal anti-inflammatory drugs, glucocorticoids, disease-modifying antirheumatic drugs (DMARDs), biological agents (BAs), and targeted synthetic drugs (or signaling pathway blockers) are used to treat PsA. The latter group of drugs includes apremilast, a phosphodiesterase 4 inhibitor. Recent data of controlled studies suggest that apremilast is effective and safe in treating psoriasis and PsA. Prospects for the use of apremilast in PsA are associated with the possibility of giving the drug to patients because of the inefficacy of DMARDs or BAs.

Anti-heterogeneous nuclear ribonucleoprotein (RNP) autoantibodies (AAbs) are encountered in many autoimmune rheumatic diseases (ARDs). The potential diagnostic value of the RA33 AAb complex consisting of RNP A2 and alternative domains of the splicing proteins RNP B1 and RNP B2 is now of interest to rheumatologists. Subjects and methods. The authors studied the frequency of anti-RNP B1 AAbs in 300 patients with systemic ARDs, including those with rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjö gren's syndrome (SS) and in 53 people without ARDs, who constituted a control group. Serum anti-RNP B1 AAbs were assessed by enzyme immunoassay. Results and discussion. The frequency of anti-RNP B1 AAbs in patients with ARDs was much higher than that in the control group: 170/300 (56.6%) and 8/53 (13%) patients, respectively. Anti-RNP B1 AAbs were detected in 78.5% (113/144) of the patients with RA; 40.3% (23/57) of those with AS, in 67.5% (27/40) of those with SSc, in 36.4% (16/44) of those with SLE, and in 13.3% (2/15) of those with SS. The diagnostic sensitivity of the marker for RA was 78.5%, its diagnostic specificity was 84.9%; the likelihood ratio of positive and negative results was 5.24 and 0.24, respectively. In the patients with RA, the level of anti-RNP B1 AAbs significantly correlated with that of C-reactive protein and erythrocyte sedimentation rate, while in those with SSc the detection of anti-RNP B1 AAbs was related to the rigidity of the vascular wall and the presence of hypertension. The frequency of anti-RNP B1 AAbs among the RA patients seronegative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies was 15.4%. Conclusion. Anti-RNP B1 AAs are a useful laboratory marker (with the upper limit of the normal range being 3.3 U/ml), but are of limited value in the diagnosis of RA. Anti-RNP B1 AAbs may be regarded as an additional diagnostic marker for RA.