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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.

Hip joint inflammation (coxitis) occurs in almost half of patients with ankylosing spondylitis (AS) and often leads to early disability. A therapy for this condition has not yet been developed, although it is one of the indications for the initiation of biologic therapy in national recommendations. The review presents data from recent clinical trials on the use of biologics, focusing on the Russian national multicenter study of GO-COX in patients with AS with coxitis.Tumour necrosis factor-α inhibitors have been shown to be effective against inflammatory affection of the hip joint in patients with AS, and their administration over a two-year period inhibits the progression of coxitis.

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.

The link between the HLA-B27 gene and ankylosing spondylitis (AS) has been known for almost 50 years. During this time, it has been discovered that some of the clinical manifestations of the disease are uniformly associated with the disease in almost all populations, while the other part depends on the ethnicity of the patients. Unique associations characteristic only of certain ethnic groups are also periodically described. Objective: to analyze the clinical features of the inpatient population with AS in relation to their HLA-B27 status. Material and methods. Cross sectional study of 200 consecutive AS patients admitted to the rheumatology department of the V.A. Nasonova Research Institute of Rheumatology. All patients underwent standard clinical examination recommended for assessment of AS activity and functional status. The levels of transaminases, uric acid, urea, creatinine, interleukin (IL) 6 and IL17 in blood serum were also examined. Results and discussion. HLA-B27 was detected in 166 (83 %) of 200 patients with AS (in 89.8 % of men and in 73.2 % of women; p = 0.003). Among HLA-B27 positive patients with AS, 63.9 % were men, and among HLA-B27 negative patients, 35.3 % were men (p = 0.002). The mean age of AS onset was 5 years higher in HLA-B27-negative patients, and the disease was about 2 times less likely to occur in childhood in them. Syndesmophytes were detected in 25 % of HLA-B27 positive patients and in 15 % of patients who did not have this antigen (p > 0.05). Syndesmophytes were found in 31.1 % of HLA-B27 positive and 25 % of HLA-B27 negative men. 15 % of women with HLA-B27 and 9 % of women without this antigen had syndesmophytes (p = 0.022). Inflammatory bowel disease was more common in HLA-B27-negative patients, whereas uveitis and psoriasis were less common. Activity rates and incidence of arthritis and enthesitis were similar in HLA-B27 positive and negative patients. Serum concentration of IL17 was six times higher in HLA-B27 negative patients than in HLA-B27 positive patients (p = 0.012). Conclusion. In the Russia’s AS patient population there are associations with HLA-B27, characteristic for most ethnic groups (e. g., earlier onset of the disease) and associations not found in all ethnic groups (e. g., a more severe course, a higher incidence of arthritis and enthesitis). In addition, the concentration of IL17 in the blood serum of HLA-B27 negative patients was six times higher than that of HLA-B27 positive patients. This may indicate non-canonical mechanisms of pathogenesis of AS that develop in the absence of the HLA-B27 gene, which requires further research.

Coxitis is one of the characteristic clinical manifestations of ankylosing spondylitis (AS). Hip joint (HJ) involvement in AS is considered an un-favorable prognostic factor. Early detection of coxitis is of great importance, since with the timely initiation of adequate treatment, the risk of developing irreversible changes in HJ can be reduced.The lecture discusses the issues of clinical and instrumental diagnosis of coxitis in AS and presents an algorithm for its early detection developed by the authors.

The “Treat-to-target” (T2T) strategy for axial spondyloarthritis (axSpA) has made it possible to optimize therapy in most patients, but in some of them the treatment goals are not achieved.Objective: to analyze the clinical features of patients with ankylosing spondylitis (AS) with inefficacy of two or more biological disease modifying antirheumatic drugs (bDMARDs).Material and methods. From February 2020 to March 2022 458 patients with AS, who met the modified New York criteria of 1984, were admitted to V.A. Nasonova Research Institute of Rheumatology. From this group, 30 (6.6%) patients with high clinical disease activity and inefficacy of at least two bDMARDs were selected. The control group consisted of 139 (30.5%) patients with AS, who either had no history of bDMARDs use, or had previously received only one of them. All patients were examined in accordance with generally accepted methods and underwent a double expert control.Results and discussion. Men predominated in the main and control groups (67 and 60%, respectively). In patients of the main group, there was a higher laboratory activity of the disease, especially ESR (p=0.002), more often peripheral arthritis was detected. In both groups, there was a high incidence of coxitis (69.2 and 69.7%, respectively), while in the main group there were significantly more patients who underwent total joint arthroplasty, and the frequency of detected syndesmophytes was 2 times lower compared to the control. Differences in the features of AS onset were also established: in the main group, the disease often began with reactive arthritis (ReA), while in the control group, with inflammatory back pain.Conclusion. The T2T strategy in axSpA does not always lead to the achievement of the intended goals, and, according to our data, among inpatients with AS, the number of people with a history of inefficacy of two or more bDMARDs reaches 6%. In these patients, compared with the control, the following features of the disease can be distinguished: frequent onset with ReA, a significant incidence of peripheral arthritis and joint arthroplasty, and a higher ESR.

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is a concern for both doctors and patients. However, in axial spondyloarthritis (axSpA), NSAIDs are used not only as a symptomatic therapy, but also to prevent the progression of the disease. Therefore, in active axSpA, NSAIDs are recommended to be administered for a much longer period of time than it is indicated in the instructions for use of the drug. The article presents two clinical cases of long-term use of etoricoxib in active axSpA. In both cases, clinical efficacy and resolution of active osteitis in the sacroiliac joints, good tolerability of treatment were noted.

The 2019 coronavirus disease pandemic (COVID-19) is particularly challenging not only for doctors, but also for patients with inflammatory diseases, including spondyloarthritis. Although a large number of studies have been conducted over the past 2 years on the effect of COVID-19 on patients with rheumatic diseases, however, the conclusions from them are not always unambiguous. Given the growing number of cases of COVID-19 infection worldwide, there is a need to study the impact of individual diseases on its outcomes. The results of the study of COVID-19 in spondyloarthritis are limited to isolated reports of cases of the disease. Moreover, there is practically no literature devoted to the outcomes of COVID-19 exclusively in patients with axial spondyloarthritis. However, over the past few months, two large studies have been publishe d, in total, analyzing the outcomes of infection with SARS-CoV-2 in more than 14,000 patients with spondyloarthritis. The article discusses the results of these studies, the result of which is the conclusion that the presented data should convince both patients and doctors that axial spondyloarthritis and the therapy carried out for its treatment does not increase the risk of infection and does not aggravate the outcomes of COVID-19.

The review analyzes data on the course and outcomes of axial spondyloarthritis (axSpA) accumulated over the previous 2.5 years of the COVID-19 pandemic. The issues of clinical and immunological efficacy of vaccination against COVID-19 in this disease are considered. It was noted that the presence of axSpA, as well as treatment with tumor necrosis factor-á inhibitors and non-steroidal anti-inflammatory drugs, did not significantly increase the risk of COVID-19 infection and did not worsen its outcomes, apart from an increase in the incidence of venous thromboembolism. At the same time, it is assumed that anticytokine therapy for SpA may protect against severe COVID-19 course.The data presented suggest that the benefits of vaccination in SpA far outweigh the potential harms associated with the development of adverse events. It has been shown that in patients with SpA, vaccination does not affect the activity of the inflammatory process, and biologic disease modifying antirheumatic drugs have almost no significant effect on the post-vaccination response.

Spine involvement in ankylosing spondylitis (AS) resulting in limited mobility requires a search for accurate, quantitatively methods of assessment of the decline of its function and monitoring of its dynamics. One of the promising methods for assessing movements in the spine in AS is ultrasound examination (US).Objective: to determine the relationship between the mobility of the spine measured sonographically, and the activity and functional status of patients with AS.Patients and methods. Spinal ultrasound was performed in 15 patients (10 men and 5 women, mean age 40.8±11.4 years, mean duration of the disease 5.5±3.5 years) with a confirmed diagnosis of AS, admitted to the V.A. Nasonova Research Institute of Rheumatology from April to August 2019. All patients underwent a double examination (at baseline and after 2 weeks) according to a specially developed protocol.Results and discussion. A comparative analysis of the results of sonographic measurements of the distance between the spinous processes of the vertebrae of the studied spine segment at baseline and after 2 weeks revealed a tendency towards an increase in these parameters both in the initial position and during flexion. There was no relationship between age, body mass index, duration of the disease and the distance between the spinous processes in all parts of the spine measured by sonography in initial position and during flexion. Correlation analysis data indicate the presence of a correlation between an increase in the distance between the spinous processes in the cervical and lumbar spine and a decrease in ESR, and i increase in the distance between the spinous processes in the lumbar spine and level of CRP. A weak negative relationship was found between the BASDAI index and the mobility of the spine at the LIV–V level and between sonographic measurements in all segment of the spine and the BASMI index.Conclusion. The sonographic method of determining the mobility of the spine can be recommended in patients with AS, both for initial examination and during follow-up, but it can't substitute the BASMI metrological index. Further research is needed to confirm the findings.

Serum amyloid A protein A (SAA) is a normal serum protein (serving as a precursor of fibrillar tissue protein AA), synthesized in the liver and a rapidly responding marker of the acute phase of inflammation. A constant high concentration of SAA is one of the factors in the development of AA-amyloidosis. As a rule, secondary amyloidosis develops in patients with long-term and poorly controlled inflammatory diseases, including rheumatic diseases, one of which is ankylosing spondylitis (AS).Objective: to assess the level of SAA in AS patients and its relationship with indicators of disease activity.Patients and methods. The study included 124 patients with AS who met the modified New York 1984 criteria. The disease activity and functional status of patients were assessed according to the recommendations of Russian experts. SAA and CRP, ESR in blood serum were measured in all patients.Results and discussion. The median SAA concentration was 12.5 mg/L [4; 71.6]. Of 124 patients, 31% had SAA levels 5 mg/L. A strong correlation was found between the levels of SAA and CRP (r=0.80, p

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease with predominant involvement of the sacroiliac joints (SIJ) and/or the spine. Despite the fact that the prevalence of axSpA is almost the same in men and women, there is evidence of a delay in diagnosis and a more severe course of the disease in females. The available reports on the progression of structural changes in the SIJ in men and women with early axSpA are contradictory. Meanwhile, the analysis of radiographic progression in the SIJ has fundamental importance both for timely diagnosis and for assessing the effectiveness of therapy in axSpA. Such studies have not yet been carried out in the Russian Federation.Objective: to assess the radiographic progression of sacroiliitis (SI) over 3 years in men and women with early axSpA.Material and methods. The study included patients from the cohort of early axSpA CORSAR, formed at the V.A. Nasonova Research Institute of Rheumatology. Currently, it includes 175 patients with axSpA. We analyzed the data of 64 patients, followed for at least 3 years. To assess the radiographic progression of the disease at baseline and after 3 years, the sum of X-ray stages of SI in the left and right SIJ was determined (the total stage of SI). Progression was assessed by the change in the total stage of SI in the right and left SIJ (0-8) during the observation period. We also calculated the proportion of patients with deterioration (increase in the total stage of SI by at least 1 stage), with improvement (decrease in the total stage of SI by at least 1 stage) and without progression. In order to fully exclude the error in measuring the radiographic progression of SI, we counted patients with “net” progression, that is, the proportion of patients with improvement was subtracted from the proportion of patients with deterioration.Results. Among 64 patients with early axSpA, there were 37 (57.8%) men and 27 (42.2%) women. For 3 years, the median of the total stage SI in men was 0 [0; 1], in women - 0 [0; 2] (p>0.05). When assessing the progression of the total stage SI over 3 years, no significant differences were found between the number of men and women with improvement, with deterioration, “net” progression and without progression. Men with early axSpA showed a higher level of C-reactive protein (CRP) at baseline, women had higher BASDAI and ASDAS CRP values after 3 years. In 8% of patients, there was a regression of X-ray signs of SI.Conclusion. The radiographic progression of SI in patients with early axSpA does not depend on gender and disease activity. In some patients with early axSpA, reverse development of structural damage to the SIJ is possible.

Alopecia areata (АA) is an autoimmune multifactorial disease characterized by increased hair loss as a result of morphological and functional changes in hair follicles. АA is divided into four main forms, among which the most severe is the universal form (UA), in which complete hair loss is possible throughout the body. Alopecia in the practice of a rheumatologist can occur with some systemic diseases of the connective tissue, with the use of high doses of chemotherapy drugs and, more recently, with the use of inhibitors of tumor necrosis factors alpha (TNF-α). The article presents 3 clinical cases of the development of UA during therapy with TNF-α. Possible mechanisms are discussed, as well as the role of pro-inflammatory cytokines in the development of this condition.

Background. Recently, numerous studies have shown that TNFAIP3 gene polymorphisms have been associated with susceptibility to certain autoimmune inflammatory diseases, including systemic lupus erythematosus, scleroderma, rheumatoid arthritis and psoriasis. However, the results of studies devoted to the study of associations between TNFAIP3 gene polymorphisms and the risk of ankylosing spondylitis (AS) are ambiguous and few.The aim of the study was to study the possible association of hs10499194 polymorphism of the TNFAIP3 gene with a predisposition to AS and its clinical phenotypes.Material and methods. The rs10499194 S/T polymorphism of the TNFA1P3 gene was studied in two hundred patients with AS (130 men and 70 women). All patients were diagnosed with AS, according to the modified New York criteria, 1984 and high activity of the disease. Demographic and clinical-serological characteristics were studied in all patients. The average age of patients was 39.4±12.6 years; the average duration of the disease was 15.0±10.6 years. Out of 200 patients, 175 (87.5%) were seropositive for HLA-B27 antigen. Extra axial arthritis was detected in 125 (62.5%) patients, 148 (74.0%) had enthesitis, 137 (68.5%) had coxitis. The polymorphism rs10499194 of the TNFAIP3 gene was studied using an allelespecific polymerase chain reaction in real time (PCR-RV) using the Synthol kit.Results. The analysis of the frequencies of genotypes and alleles did not show significant differences with the control group. Stratification by sex, age, and clinical manifestations showed an association of the CT genotype with an increased risk of AS among men (OR=2.24; p=0.010), the TT genotype and the T allele with a high risk of predisposition to the development of extra axillary peripheral arthritis (OR=3.94; p=0.019 and OR=1.64; p=0.027 respectively). The BASDAI index was statistically significantly higher in carriers of the TT genotype compared to the CT genotype (p=0.002).Conclusion. The present study confirmed the association of the genetic polymorphism rs10499194 of the TNFAIP3 gene with AS. Stratification by gender and clinical manifestations showed an association of the CT genotype with an increased risk of AS among men, the TT genotype and the T allele with a high risk of predisposition to the development of extra axillary peripheral arthritis and a high BASDAI index in carriers of the TT genotype.

Ineffectiveness of interleukin 6 inhibitors (iIL6), tocilizumab (TCZ) and sarilimumab in ankylosing spondylitis (AS) was shown in randomized clinical trials. However, there is ample evidence that IL6 is actively involved in the pathogenesis of this disease. In addition, the efficacy of iIL6 in patients with secondary AA-amyloidosis was established.Objective: to analyze the results of TCZ administration in AS, complicated by secondary AA-amyloidosis.Patients and methods. The analysis included 6 patients with AS with secondary AA-amyloidosis. All patients were HLA-B27 positive male. The average age of patients was 44±9.2 years, the average age of the disease onset was 16.3±7.9 years, the average duration of AS was 26.0±7.5 years. All 6 patients had pathomorphologic confirmed secondary AA-amyloidosis: all had kidney affection, 5 patients also had gastrointestinal tract affection and 2 had heart affection. As a first biological drug TCZ was prescribed in 2 patients, and 4 patients had previously received one or more inhibitors of tumor necrosis factor α. The average duration of TCZ treatment was 27.6 [3.0; 36.0] months.Results and discussion. During TCZ therapy, the level of CRP (M±σ) significantly decreased: from 81.1±74.5 to 1.2±0.8 mg/L (p

The spectrum of bone lesions in axial spondyloarthritis is of great interest. With inflammation and mechanical influence concurrence in the background, both tissue gain and tissue loss in a particular bone area can occur simultaneously. Moreover, if vertebral bone mass loss, perhaps, can be easily explained by chronic systemic inflammation, the reason of its gain, observed in axial spondyloarthritis remains a mystery. It is unclear whether it is a consequence of enhanced recovery processes after injury, adaptation to altered mechanical stress, response to inflammatory cells activation or cytokines, produced by them, or changes in Wnt signaling pathways (for example). Whether these factors act individually or collectively is also unclear.

Objective. The aim of the investigation was to study the possible association of the rs7574865 polymorphism of the STAT4 gene with syndesmophytes (SMP) of the spine in patients with ankylosing spondylitis (AS).Subjects and methods. The study included a cohort of 100 patients, 79 men and 21 women with a diagnosis of AS.All patients were positive for the HLA-B27 antigen, had a mean age of 39.6±10.9 years and a mean disease duration of 60,4±28,4 months. The association of the rs7574865 polymorphism of the STAT4 gene with the SMP of the cervical, thoracic and lumbar spine was studied. For genotyping of the rs7574865 polymorphism, the method of allele-specific polymerase chain reaction in real time (RT-PCR) was used.Results. Spearman’s correlation analysis showed a statistically significant positive relationship between SMP in the thoracic spine and rs7574865 polymorphism of the STAT4 gene (r=0.23; p=0.022). The frequency of GT genotype carriers in the group of patients with thoracic spine trSMP(+) was statistically significantly lower than in the alternative group trSMP(–) (28.2% and 50.8%, respectively; p=0.025). Carriage of the GT genotype in patients with AS reduced the risk of trSMP(+) formation in the thoracic spine (OR=0.31) and this genotype was protective. No reliably significant association of the studied polymorphism with SMP of the cervical and lumbar spine was found. Patients with trSMP(+) were statistically significantly older in age, had a longer duration of the disease and a higher functional BASFI index compared with patients without trSMP(–).Conclusion. Genetic testing of the rs7574865 G/T polymorphism of the STAT4 gene in patients with AS opens up the possibility of using this polymorphism as a genetic marker-predictor – X-ray progression of structural changes in the thoracic spine.

Well-established and some little-known treatments of axial spondyloarthritis / ankylosing spondylitis (AS), which have appeared in recent years are discussed, also discussed are emerging trends for AS treatment.

If standard therapy with nonsteroidal anti-inflammatory drugs is ineffective, biological drugs are usually prescribed for patients with active ankylosing spondylitis. These medicines are purchased in Russia not under their trade names, but under their international non-proprietary ones. This leads to the fact that either originator drugs or their biosimilars are purchased from time to time. For this reason, without a patient' and his/her attending physician's knowledge, the originator drug is switched to its biosimilar, or vice versa. The paper describes two cases of multiple switches from an originator drug to its biosimilars, or vice versa, which are not clinically indicated. The results of analyzing these cases confirm the opinion that biosimilars may have a significantly different clinical efficacy from their originator drugs.

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.

The article provides data on the terminology and classification of spondyloarthritis (SpA) and highlights the current concept of axial SpA (axSpA). It gives the comparative characteristics of international cohorts of patients with axSpA. The review describes the role of magnetic resonance imaging and radiography in the diagnosis and study of the evolution of axSpA.

Family and twin studies have shown that ankylosing spondylitis (AS) has a hereditary nature that is based on a strong association with the leukocyte antigen HLA-B27. However, only 1–5% of HLA-B27 carriers develop AS, which indicates that there are other genetic markers involved in the formation of a predisposition to this disease. A number of genome-wide association studies have convincingly confirmed the role of the STAT4 gene. This gene encodes the protein – the signal transducer and activator of transcription (STAT) protein, which is a predisposing factor for the development of many autoimmune diseases. There are not so many studies of the relationship of STAT4 polymorphisms to the predisposition to AS, and there are no these studies regarding the Russian population.Objective: to study whether there is a possible association of STAT4 rs7574865 gene polymorphism with the predisposition to AS and to assess the activity of this disease using BASDAI and ASDAS scores in the Russian patient population.Patients and methods. A cohort of 203 individuals, including 100 patients (79 men and 21 women) with AS, and 103 healthy volunteers (a control group) was surveyed. Age, gender, duration, and specific features of AS onset, ESR, and CRP levels were assessed. BASDAI and ASDAS scores were calculated to evaluate disease activity.Results and discussion. There was a significant relationship between STAT4 polymorphism and C-reactive protein (CRP) levels and BASDAI and ASDAS-CRP scores. The TT genotype carriers had significantly higher mean activity indices compared to the GG (p=0.001) and GT (p=0.005) genotype carriers for CRP, BASDAI (p=0.0001 and p=0.009, respectively) and ASDAS-CRP (p=0.009 and p=0.001, respectively). High disease activity (BASDAI >4 and ASDAS-CRP >3.5) was also associated with the high frequency of the T allele (p=0.046 and p=0.004, respectively). The value of STAT4 rs7574865 gene polymorphism in the pathogenesis of autoimmune diseases is confirmed by a study in which the T allele in STAT4 rs7574865 enhances mRNA transcription and protein expression. Italian authors have shown that there is a relationship between the minor T allele of rs7574865 and the high risk of arthritis. We have previously established a relationship between the T allele and the predisposition to diffuse systemic scleroderma, interstitial lung damage, and elevated anti-topoisomerase I antibody levels.Conclusion. The present study has shown for the first time a significant association of STAT4 rs7574865 polymorphism with the main AS activity indicators: CRP levels, BASDAI and ASDAS-CRP scores. The studied polymorphism may be a new genetic marker for predicting the severity of AS.

Coxitis is one of the most common extra-axial manifestations of ankylosing spondylitis (AS). Most Russian studies consider hip joint (HJ) involvement in AS patients as a major factor of poor prognosis in this disease. All detected hip joint changes are characterized by one term «coxitis». Until recently, there has been no clarity on inflammation of which structures of HJ leads to its destruction. This problem can be solved by prospective studies. A start was made by the V.A. Nasonova Research Institute of Rheumatology on the study of the evolution of coxitis in AS in 2013. This communication is devoted to the results initially identified by various imaging techniques for detecting HJ changes.Objective: to study the characteristics of HJ injury in AS, which have been detected by different imaging techniques.Subjects and methods. The investigation enrolled 125 AS patients, including 84 men (a male/female ratio of 2:1). The mean age of the patients was 31.4±9.1 years; the mean age at disease onset – 24.6±4.4 years; the median duration of AS at the time of examination – 96 (12–444) months. The HLA-B27 antigen was present in the majority of patients (94%). AS activity defined by ASDAS-CRP and BASDAI was high; BASFI scores averaged 3.4±2.1. All the patients underwent the following instrumental examinations: plain pelvis radiography, HJ ultrasound and magnetic resonance imaging (MRI).Results and discussion. The clinical, ultrasound, and MRI signs of coxitis were found in 82, 75, and 88% of cases, respectively; coxitis was radiologically confirmed only in 50% of patients. This disease was diagnosed by several techniques in the vast majority of cases. The diagnosis of coxitis was based only on clinical signs in only three (2%) patients. In approximately every sixth (16%) patients with AS, who had clinical signs of coxitis, the latter was verified only by one of the instrumental techniques (ultrasonography, radiography, or MRI). Our findings demonstrated that more than half of patients had high coxitis activity, and more prolonged coxitis was responsible for higher X-ray HJ changes and functional limitations.Conclusion. Our study has showed that the instrumental techniques used to diagnose coxitis are not equivalent in evaluating HJ injury. To decide which of them is more effective in screening and predicting the course of coxitis, there is a need for further prospective investigations.

The review analyzes the foreign and Russian literature published in the past 30 years and devoted to the diagnosis and treatment of coxitis in ankylosing spondylitis (AS). The results of previous works have revealed the high rate of hip joint injury (HJI) in AS, but it is still unclear which diagnostic technique is the most sensitive for the early detection of coxitis. The latter has been shown to serve as one of the predictors of early disability in patients. The most studied treatment for coxitis is now HJI endoprosthesis, for which indications and contraindications have been clearly developed, while the question of drug therapy remains open.

The paper describes a case of a 36-year-old man with finger joint and bone damage that occurred a year and a half after severe frostbite.

The currently used methods for evaluating the progression of structural damages in early axial spondyloarthritis (axSpA) are little suitable to real practice since they require specially trained radiologists and increase a patient's exposure to radiation due to the need for radiography of three regions of the axial skeleton. In addition, the first radiological bone changes in the sacroiliac joints (SIJ) appear only many years after the onset of the disease, the overlying spine areas are involved in the pathological process. Objective: to develop a method for evaluating the radiographic progression of sacroiliitis (SI) in early axSpA for real clinical practice. Subjects and methods. The investigation enrolled patients from the early spondyloarthritis cohort (ESAC) formed at the V.A. Nasonova Research Institute of Rheumatology. The current ESAC comprised 164 patients; the analysis included 68 patients who had been followed up for at least 2 years and had plain pelvic bone films at the inclusion in the cohort and at 2-year follow-up. To evaluate disease progression, the investigators used the sum of radiographic SI stages in the left and right SIJs (the summary stage of radiographic SI (ssrSI), which was calculated at baseline and at 2-year follow-up. A formula for determining the rate of radiographic progression was derived. Results and discussion. At baseline and at 2-year follow-up, the median ssrSI difference (ΔssrSI) in 68 patients was 0 [0; 1.0]. During the study period, almost 60% of the patients had no progression of ssrSI, i.e. ΔssrSI was 0 in these patients, 1 and 2 scores in 12 (18%) and 13 (19%) patients, respectively, and there were singly cases, in which this figure was equal to 3, 4 and 7. The mean value of ssrSI was 3.5±1.6 at baseline and increased by 0.8, reaching 4.3±1.5 at 2 years (p = 0.006). Before included into the investigation, the patients had a progression rate of 1.75 during 1 year, which decreased to 0.4 per year in the active follow-up period. At the time of inclusion in the study, 40 (58.8%) of the 68 patients had ankylosing spondylitis (AS), and at 2 years their number increased to 51 (75.0%); i.e. 11 (39%) patients were observed to have progression of non-radiographic axSpA to AS. Conclusion. The proposed procedure to calculate ssrSI is easily feasible in real practice; it fails to lead to additional radiation exposure, is economically feasible, and allows one to monitor the rate of progression of axSpA in the early stage of the disease.

Objective: to evaluate the safety and effectiveness of vaccination with trivalent split virion influenza vaccine in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), estimate the effect of vaccination on rheumatoid disorder (RD) activity and influenza and influenzalike illnesses morbidity.Materials and methods. The study included 86 patients (58 females and 28 males aged 22–82 years) with RDs (52 patients with RA and 34 patients with AS), as well as 40 subjects without RD (control group). At the time of study inclusion, all patients were receiving drug therapy. Duration of RD varied from 2 months to 46 years. The Vaxigrip vaccine containing the currents trains of the flu virus for 2016–2017 season or 2017–2018 season was administered subcutaneously as 1 dose (0.5 ml) with continuing antirheumatic therapy. The main control stages were visits 1, 3, and 6 months after vaccination. During the visits, standard clinical and labtests, clinical examination with disease activity evaluation were performed.Results. In 98 patients, vaccination tolerability was high, no post vaccination reactions were observed. In 20 cases, pain, swelling, and hyperemia of the skin 2 cm in diameter at the point of vaccination were observed; in 8 cases, low-grade fever, myalgia, discomfort, headache were observed. No RD flares or development of new autoimmune disorders were diagnosed during the follow-up period. No cases of influenza or influenza-like illnesses were registered during the follow-up period.Conclusion. The obtained data demonstrate high tolerability, clinical effectiveness of trivalent split virion influenza vaccine in patients with RA and AS.

Objective: to compare the impact of continuous or on-demand use of nonsteroidal anti-inflammatory drugs (NSAIDs) on the activity and radiographic progression of early axial spondyloarthritis (axSpA).Subjects and methods. The investigation enrolled patients from the early spondyloarthritis cohort who met the 2009 Assessment of Spondyloarthritis International Society (ASAS) criteria for axSpA. This analysis included 68 patients who had been followed up for at least 24 months. The mean age at the time of inclusion in the investigation was 28.5±5.8 years; the mean disease duration was 24.1±15.4 months; 63 (92.6%) patients were HLA-B27-positive. The patients were divided into two groups: 1) 35 patients used NSAIDs at maximum therapeutic doses continuously during the follow-up period; 2) 33 patients received these drugs on-demand, depending on the presence and severity of back pain.Results and discussion. After 2-year follow-up, the median stage of radiographic sacroiliitis (SI) in Group 1 was unchanged and remained equal to 4; that in Group 2 in this period significantly increased from 3 to 4 scores (p < 0.05). At baseline, the patient groups did not differ in C-reactive protein (CRP) levels, the Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP), and the Bath Ankylosing Spondylitis Functional Index (BASFI); however, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was higher in Group 1 (p < 0.05). The number of patients with active SI, as evidenced by magnetic resonance imaging (MRI), and the degree of its severity did not differ significantly between groups. After 2 years, all the patients retained low disease activity according to ASDAS-CRP, BASDAI, and CRP levels; and these measures did not differ significantly between groups either; the BASFI became higher in Group 1. MRI findings indicated that the number of patients with active SI decreased, but no differences were found between the groups.Conclusion. In patients with early axSpA, the continuous intake of NSAIDs can slow radiographic progression to a greater extent than their on-demand use.

Objective: to clarify pregnancy outcomes in patients with ankylosing spondylitis (AS) and its course during pregnancy on the basis of a retrospective analysis.Subjects and methods. The paper presents the results of Stage 1 of a Russian pilot study of the impact of pregnancy on AS activity, parity, and pregnancy outcomes in these patients. The basis for Stage 1 is the results of a retrospective analysis of the data of a questionnaire survey of 204 women with AS, during which they answered 19 questions regarding the presence of pregnancies and their outcomes, the reasons for the lack of pregnancies, and a subjective assessment of their health status during gestation. The respondents’ mean age was 32.0±5.8 years; the mean disease duration was 107.2±73.5 months.Results and discussion. 84 (41.1%) women did not have pregnancies; the reasons for the lack of pregnancies were associated with AS (fear of the teratogenic effect of taken drugs; a child’ inheritance of the disease) in 48.8% of the cases, with infertility in 9.5%, and with non-medical reasons in 41.7%. A total of 120 (58.9%) women had 248 pregnancies; of whom 136 patients had the latter before and 112 – after the onset of AC. In AS versus a healthy life period, there were lower abortion rates at a woman’s will (8.9 and 35.3%, respectively; p < 0.01), more pregnancies that resulted in childbirth (75.9 and 52.2%, respectively; p < 0.01), and higher surgical delivery rates (43.5 and 28.2%, respectively; p < 0.05). The premature birth rate after the onset of AC was 13.0%. The newborn infants born before the onset of AS in mothers did not differ from those born after the onset of AS in mothers in weight and Apgar scores. Half of the respondents reported that their health status was improved in any trimester of pregnancy (slightly more often in the first trimester; but the difference was statistically insignificant). However, almost 70.0% of the respondents noted their worse health status during pregnancy, the severity of AS symptoms increased with a gestational period.Conclusion. The reason for the lack of pregnancies in almost half of the patients with AS is associated with their subjective fear of the negative impact of the disease and therapy on a child’s future health. In AS versus a healthy life period, surgical deliveries are performed more frequently. The neonatal outcomes of pregnancies do not differ before and after the onset of AS.

Etanercept (ETC), a soluble tumor necrosis factor-α (TNF-α) receptor, was registered for the treatment of spondyloarthritis in the Russian Federation in 2009. By now, results of prolonged treatment with this drug have been obtained in patients with ankylosing spondylitis (AS).Objective: to evaluate the efficiency and tolerability of long-term therapy with ETC in patients with AS.Subjects and methods. The follow-up included 60 patients with a documented diagnosis of AS (the 1984 New York criteria) and/or axial spondyloarthritis (the 2009 ASAS criteria), high activity (BASDAI >4), who received long-term (at least a year) regular therapy with subcutaneous ETC 50 mg weekly. Its effect was evaluated using the ASAS criteria.Results and discussion. ETC was the first TNF-α inhibitor used in 29 (48%) patients, including 22 (76%) patients who achieved partial remission; 7 (24%) patients who showed ASAS40 improvement. One patient was observed to have hepatotoxicity (alanine aminotransferase elevation to 72 U/l), therefore the drug was discontinued. 31 (52%) patients were switched to ETC after infliximab (n=24) or adalimumab (n=7) due to their poor tolerance and/or loss of effect. At the same time, ETC became the second anti-TNF-α drug in 21 (35%) patients and the third one in 10 (17%). During the therapy, 21 (68%) patients switched to ETC were noted to have ASAS40 improvement; 9 (29%) patients had partial remission. The insufficient effect of the drug was observed only in one patient (3%), in whom ETC was the third TNF-α inhibitor. The tolerability of ETC was generally satisfactory after switching from anti-TNF-α monoclonal antibodies (mAbs). Three patients developed de novo psoriasis that required therapy discontinuation in one patient; another male patient developed uveitis for the first time. In one female patient with AS associated with Crohn’s disease with loss of mAb effect, ETC became the third anti-TNF-α drug, during therapy with which there was no exacerbation of Crohn’s disease. The drug was well tolerated and highly effective in 8 patients, in whom ETC treatment was initiated at the age of 60 years and older: 6 (75%) achieved partial remission, 2 (25%) had ASAS40 improvement. Nine patients with previous and/or latent tuberculosis had no exacerbation of this disease during ETC therapy.Conclusion. During regular therapy with ETC, more than half of patients (52%) achieved partial remission according to the ASAS criteria, while this was more frequently achieved when the drug was used for the first time (76%) than when mAbs were switched to ETC (29%). Discontinuation of the latter due to adverse events was required only in 2 (3%) patients.

The paper gives the definition of remission in axial spondyloarthritides (axSpA), which has been developed by the Spondyloarthritis Study Group of Experts. The work used the Delphi technique. At stage 1, based on the analysis of the data available in the literature and on their own clinical experiences, the experts proposed some variants of the definition of remission and ways of its evaluation in patients with axSpA. At Stage 2, the definitions that had received at least 80% of the votes via anonymous voting were selected and adopted without further discussion. Those that had received an equal number of votes were reconsidered and additionally discussed; then there was repeat voting, by choosing the final definition. As a result of their discussion, the experts formulated the definitions of clinical laboratory and magnetic resonance imaging (MRI) remissions. They proposed the following remissions in axSpA: drug and drug-free, clinical laboratory, and MRI remissions, as well as a remission in the presence and absence of structural changes in the locomotor system, as evidenced by imaging techniques. Criteria for clinical laboratory remission and basic tools for its evaluation that can be used in real clinical practice and researches have been elaborated.

Telemedicine, including mobile applications for patients, is progressing rapidly now. However, patients with axial spondyloarthritis (axSpA) still have no applications that can be used to monitor their health status independently and to contact their physician remotely. Objective: to develop and test an «ASpine» mobile application for smartphones in real clinical practice. Material and methods. The draft «ASpine» mobile application has two parts: a mobile application for patient and a personal computer program used by a rheumatologist to monitor disease activity in patients. The patient part of «ASpine» consists in filling out the BASDAI and BASFI questionnaires and monitoring how recommendations for daily exercise therapy and medications are fulfilled. There is also an opportunity for constant contact with the physician through the mobile application. The patients from the Moscow cohort CoESAr (Cohort of Early SpondyloArthritis) which was made up at the V.A. Nasonova Research Institute of Rheumatology in 2013 and is being formed to the present time took part in mobile application testing. Results and discussion. The mean scores of BASDAI at inclusion and after 12-month follow-up were 3.3±1.7 and 2.1±1.7 (p > 0.5) and those of BASFI were 1.6±1.3 and 1.3±1.2, respectively (p > 0.5). To analyze the health status of 35 patients, one doctor requires 1 min daily if there are no reports of their worse health. It takes an average of 5–8 min to make a decision if the patient reports the occurrence of any symptom or an adverse reaction. The findings can lead to the conclusion that the «ASpine» mobile application allows patients to independently monitor disease activity, to store medical records, and to contact their physician remotely. Continuous monitoring of the patient's condition makes it possible to maintain low disease activity or remission for a long time.

The paper gives recommendations for the drug therapy of axial spondyloarthritides, which have been developed by the Spondyloarthritis Study Group of Experts. The recommendations describe the patient management tactic in the most common clinical situations, which is aimed at maximizing the efficacy and safety of treatment.

The communication briefly presents the updated version of treat-to- target (T2T) recommendations for spondyloarthritides.

Involvement of the aorta and heart valves in ankylosing spondylitis (AS) is a manifestation of the systemic inflammatory process. Data on the frequency, clinical significance, and evolution of these manifestations are controversial.Objective: to estimate the time course of echocardiographic (EchoCG) changes in the aorta and heart valves from the results of a prospective follow-up study of patients with AS.Subjects and methods. In 2008 to 2015, the V.A. Nasonova Research Institute of Rheumatology followed up 45 patients (35 men and 10 women) with documented AS that was consistent with the modified New York criteria and the original EchoCG changes in the aorta and heart valves. All the patients underwent transthoracic echocardiography at baseline and after 1–5 years. At baseline, there was aortic root dilatation (>37 mm) in 15 patients, thickening of the aortic walls and aortic valve (AV) cusps in 21 and 32 patients, respectively, as well as thickening of the mitral valve (MV) cusps in 15, and valve prostheses in 5 patients (2 had AV and MV prostheses). Aortic regurgitation (AR) was recorded in 19 patients (grades 1–2 AR in 15 patients and grades 3–4 in 4 patients); grades 1–2 mitral regurgitation (MR) was seen in 20 patients. Ten patients had subaortic pectinate thickening (SPT) in the aortomitral junction area. Of the 45 patients, 16 took biological agents (BA); 29 received traditional therapy, including 14 patients who used nonsteroidal anti-inflammatory drugs, 11 and 4 patients had sulfasalazine and methotrexate, respectively.Results and discussion.Repeated examinations revealed negative changes in 27 (60%) of the 45 patients. Progressive aortic dilatation (1 to 6 mm) was found in 12 (80%) of the 15 patients; dilatation appeared during follow-up in 2 patients. Fourteen patients were noted to have negative valve changes: the emergence of cusp thickening in the valves (that in AV and MV in 9 and 4 patients, respectively; both in 1 patient). Four patients underwent valve replacement: 3 and 1 patients underwent AV and MV replacements, respectively. Ten of the 19 patients were observed to have AR progression by 2 grades in 2 (10.5%) patients and by one grade in 8 (42.0%) patients. MR progression by one grade was noted in 6 (30.0%) of the 20 people. A negative correlation was found between BA therapy and aortic dilation progression (r = -0.329; p = 0.03). SPT appeared in 3 patients. Of the 10 patients who had a baseline SPT, its reduction (8 to 3.5 mm) was seen in one patient; complete regression was identified in two patients; all received BAs. Thus, pathological changes in the aorta and heart valves in AS are progressive in most patients. SPT may regress, which reflects apparently a reduction in the severity of active inflammation of the aortic root. Active anti-inflammatory treatment may play a protective role in the progression of aortic dilatation.

The paper gives the recommendations for the assessment of disease activity and functional status in patients with ankylosing spondylitis in clinical practice, which have been developed by experts, by taking into account international and Russian experience in managing these patients.

Ankylosing spondylitis (AS) is a systemic inflammatory disease involving not only the skeleton, but also other organs. The data on the frequency and clinical significance of extraskeletal manifestations are contradictory. Objective: to assess the frequency and severity of extraskeletal manifestations (ESMs) of AS in the authors' own clinical practice. Subjects and methods. 452 patients (363 men and 89 women) with AS fulfilling the 1984 relevant New York criteria were examined at the V.A. Nasonova Research Institute of Rheumatology in 2005 and 2014. The patients' median age was 31.5 [24; 41] years; median disease onset age, 19 [15; 23] years; disease duration, 11 [7; 18] years; HLA B27 was identified in 442 (97.7%) patients. In addition to standard laboratory and instrumental examinations, transthoracic echocardiography was performed in 172 patients. Rehberg's test, IgA test, histological examination of subcutaneous fat tissue or duodenal mucosa for amyloid, and renal ultrasound were made if there were urinary abnormalities and elevated creatinine levels. If indicated, there were consultations by an ophthalmologist with an appropriate instrumental examination (with evidence of uveitis in the history), a dermatologist, a nephrologist, an urologist, a gastroenterologist, and a endoscopist. Uveitis, cardiac involvement (conduction disturbance, aortic and valvular changes), inflammatory bowel disease (IBD), glomerulonephritis, and psoriasis were borne in mind as ESMs. The absolute number and percentage of patients having any ESM over the follow-up period were estimated. The number of exacerbations per year and that of complications were taken into account when evaluating uveitis; the magnitude of valvular regurgitation and the presence of prosthetic valves and a pacemaker were considered when assessing cardiac damage; the total body surface area (BSA) and the psoriasis areas and severity index (PASI) were estimated in psoriasis; the presence and stage of chronic kidney disease (CKD) and/or macrohematuria were kept in mind in nephropathy; when evaluating IBD, the Harvey–Bradshaw index (HBI) was determined on the basis of a stool frequency, the presence of blood in the stool, abdominal pain, and general well-being. Results and discussion. ESMs were detected in 218 (48%) of the 452 patients. Uveitis was present in 140 (30%) patients; in one-fourth of them, it relapsed frequently: three or more exacerbations per year and more than 10 during the disease; 41 (29%) patients had uveitis complications accompanied by visual impairment. Cardiac conduction disturbance was revealed in 61 (13%) patients. Five of them underwent pacemaker implantation. 71 (41.2%) patients were found to have aortic and valvular changes, including aortic root dilatation/thickening in 60 (34.8%) patients and aortic/mitral valve leaflet thickening in 63 (36.6%). Grades 3 and 4 valvular regurgitation was noted in 10 (5.8%) patients; valve replacement was carried out in 9 (5.2%) cases. Nephritis was diagnosed in 16 (3.5%) patients, 4 of them had Stage 2 or above of CKD. Psoriasis was present in 17 (3.7%) patients; 2 of them had severe psoriasis (BSA >10%). IBD (ulcerative colitis or Crohn's disease) was diagnosed in 16 (3.5%) patients, including 4 who showed a severe course. 79 (36%) patients were observed to have a concurrence of two or more ESMs; that of uveitis and heart disease was most commonly seen. Conclusion. ESMs are observed in nearly half (48%) of the patients with AS and can be concurrent; the most common ESMs of AS are uveitis, aortic root and heart valve lesions, and cardiac conduction disturbance. ESMs worsen the course and prognosis of AS.

The article summarizes the data of two randomized controlled trials (RCTs) Phase III MEASURE 1 and MEASURE 2 investigating the efficacy and safety of secukinumab (SEC) in treating ankylosing spondylitis (AS) and compares the data with the results obtained from Russian patients with active AS, who were enrolled in these RCTs.Subjects and methods. Among 590 patients included in the MEASURE 1 and MEASURE 2 trials, the Russian group totaled 107 patients: 44 and 29 patients took SEC in the MEASURE 1 and MEASURE 2 trials, respectively; 34 patients had placebo in the two trials.Results and discussion. A retrospective analysis of the results for the Russian patient group showed that the efficacy of SEC in treating AS was fully similar to that demonstrated in the entire MEASURE 1 and MEASURE 2 group cohort. At 1 to 16 weeks of SEC therapy, the MEASURE 1 trial Russian patients displayed a rapid clinical improvement in 52.6% (p = 0.043); and in the SEC 150- and 75-mg groups, ASAS20 improvement was achieved by 64% (p = 0.0015), respectively. The SEC 150-mg group in the MEASURE 2 trial exhibited an ASAS20 response in 66.7% of cases (p = 0.0063). The clinical response at 16 weeks in the patients randomized at baseline into SEC treatment groups was sustained for 52 weeks. The proportion of patients achieving ASAS20 response at 52 weeks was 63.2 and 68% in the MEASURE 1 trial (in the SEC 150- and 75-mg groups, respectively) and 73.3% in the MEASURE 2 trial (the SEC 150-mg group). At 52 weeks, ASAS40 reponse was achieved by 52.6% of the patients in the MEASURE 1 trial and by 60% of those in the MEASURE 2 trial (the SEC 150-mg group). In the MEASURE 1 trial, ASAS 5/6 response rates at 16 weeks were 42.1 and 52.0% in the SEC 150- and 75-mg groups (p = 0.0249 and p = 0.0013, respectively). In the MEASURE 2 trial, the proportion of the SEC 150-mg group patients achieving ASAS 5/6 response was 53.3% (p=0.0135). After 52 weeks, these rates were 57.9, 52, and 73.3%, respectively. The adverse reactions observed in both the placebo-controlled and later follow-up periods and in the Russian patient cohort suggest that SEC has an acceptable safety profile and good tolerability in patients with AC.

The paper briefly discusses the history of spondyloarthritis (SpA) from the article published by J. Moll et al. in 1974 to the present day. The discussion of the recent SpA concept proposed by the Assessment of SpondyloArthritis International Society (ASAS), which divides this group of diseases into axial and peripheral types, by elaborating the appropriate criteria, holds a special position. This division could rapidly introduce the principles of early diagnosis of axial SpA on the one hand; however, it hinders their investigation as a genetically and clinically associated spectrum of diseases on the other hand.

The paper analyzes two matching-adjusted indirect comparison-based investigations of the efficacy of adalimumab (ADA) and secukinumab (SCM) in active ankylosing spondylitis, which have been recently reported at the EULAR Congress (London, 2016). One study sponsored by AbbVie was conducted to determine the short-term (16-week) comparative clinical and economic efficacy of the test drugs and the other was supported by Novartis to reveal long-term (52-week), only clinical efficacy. Both studies have shown that the short-term efficacy ofADAand SCM is practically similar; however, the latter has a better long-term clinical efficacy. A pharmacoeconomic analysis of both drugs used during the first 12 weeks has demonstrated some advantage ofADA.

The paper presents the results of recent studies of the efficacy of golimumab (GLM) in the treatment of uveitis in patients with ankylosing spondylitis (AS). The data obtained in these studies suggest that GLM is highly effective in relieving and preventing uveitis attacks. However, all the given studies have a number of disadvantages; primarily they have included a limited number of patients. Further prospective randomized clinical trials with large sample sizes are required to evaluate the efficacy and safety of GLM for the treatment of uveitis in patients with spondyloarthritis.

At present, there are a number of unsolved problems associated with unawareness of the causes and ways to prevent the inefficacy of tumor necrosis factor-α inhibitors.Objective: to study the causes of secondary inefficacy of infliximab (INF), by analyzing its concentrations and antidrug antibody levels in the serum of ankylosing spondylitis (AS) patients receiving long INF, as well as a possibility to overcome its secondary inefficacy through plasmapheresis.Subjects and methods. 54 patients with active AS (BASDAI > 4) underwent regular long-term (1-to-10-year) treatment with INF 5 mg/kg according to the standard scheme. During the therapy blood samples were taken before a regular INF infusion to quantify the levels of antibodies to the drug and its concentration. According to the efficiency of the drug, two groups were formed: 1) 27 (50%) patients with INF inefficacy (an exacerbation occurred 2–4 weeks after infusion); 2) 27 patients with drug efficacy. The levels of anti-double stranded DNA antibodies and antinuclear factor were estimated in 27 patients to investigate a relationship between the immunogenicity of INF and the presence of autoantibodies in its secondary inefficacy. A plasmapheresis session was carried out in 5 patients before a regular IFN infusion.Results and discussion. Anti-INF antibodies were found in 28 (52%) patients, these being more common in the patients with drug inefficacy than in the others (67 and 37%, respectively; p < 0.05). In the patients with INF inefficacy, anti-INF antibody levels were significantly higher than in those with preserved drug effect (18.33 and 4.67 U/ml, respectively; р < 0.05). Moreover, the serum concentration of INF was not significantly different in these groups (1.6 and 2.96 μg/ml). There was an inverse correlation between INF concentrations and anti-INF antibodies (r = -0.7; p < 0.05). The level of autoantibodies did not correlate with that of anti-INF antibodies. Following plasmapheresis, the level of anti-INF antibodies dropped in all the patients and the concentration of the drug increased in only three of the five patients; in two of them anti-INF antibody levels were initially low (p < 0.05). Plasmapheresis promoted a short-term restoration of INF efficacy no matter what the baseline level of anti-INF antibodies. Conclusion. The secondary inefficacy of INF may be associated with not only the emergence of its neutralizing antibodies and the reduction in serum drug concentration, but also with other yet unknown causes. There is a need for further investigation of the causes of secondary INF insufficiency and methods for its overcoming.

The rate of osteoporosis (OP) and the mechanism of its development in patients with ankylosing spondylitis (AS) and other spondyloarthrititides (SpA) have not been sufficiently investigated. Steady-state inflammatory disease activity is anticipated to be the leading factor of OP in AS.Objective: to investigate lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) in patients with early axial SpA (axSpA) and to reveal its association with inflammatory disease activity.Subjects and methods. A total of 150 patients (59 men and 91 women) aged 18 to 45 years with inflammatory back pain for ≥3 months and ≤5 years were examined. The diagnosis of axSpA was established in accordance with the 2009 ASAS criteria. BASDAI and ASDAS-CRP were used to assess activity and functional status was evaluated with BASFI. The examination included determination of HLA-B27, X-ray of the pelvis and LS, magnetic resonance imaging (MRI) of the sacroiliac joints, LS, and hip joints (in the presence of clinical signs of their involvement), and densitometry of LS (LI–IV) and FN. By taking into account the patients’ young age, the Z score was used to estimate BMD. The Z-score -2 SD or lower in at the least one of the regions examined is considered to be diminished BMD. Results and discussion. The median Z-score was -0.7 [-1.3; -0.2] SD for FN and -0.9 [-1.6; -0.6] SD for LS. Reduced BMD in at the least one of the regions examined was diagnosed in 27 (18.0%) patients. There was lower BMD in LS in 21 (14.0%) patients and in FN in 8 (5.3%). Two (1.3%) patients were diagnosed as having osteopenia in the two examined regions. There was no association between diminished BMD and age, gender, disease activity assessed with BASDAI, ASDAS-СRP, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). An association was found between inflammatory LS changes, as evidenced by MRI (MRI spondylitis), and reduced BMD in at least one of the examined regions. MRI spondylitis was detected in 27 (18.0%) patients. Decreased BMD in any of the examined skeletal regions was seen in 9 (33.3%) of the 27 patients having MRI spondylitis; the remaining 18 (66.7%) patients had normal BMD values. In the absence of MRI spondylitis, osteopenia was identified in 18 (14.6%) patients; normal BMD values were noted in 105 (85.4%); p = 0.03). There was also a relationship between the presence of MRI spondylitis and diminished BMD in the same region. LS osteopenia was found in 7 (25.9%) patients with MRI spondylitis and LS BMD remained within the normal range in 20 (74.1%). In the absence of MRI spondylitis, LS osteopenia was observed in 14 (11.4%) patients and LS BMD was normal in 109 (88.6%) (p < 0.05).Conclusion. There was an association between inflammatory LS changes, as evidenced by MRI, and reduced BMD in the same region. Our findings confirm the hypothesis that bone mass loss in the vertebral bodies in early axSpA results from local inflammation.

The paper briefly describes the history of spondyloarthritis studies from the works of the outstanding Russian neurologist V.M. Bekhterev up to the present time. Special emphasis is laid on the results of the representatives of the scientific school of Professor E.R. Agababova, an organizer of the first laboratory of spondyloarthritis in Russia. The major areas of the investigations that are currently under way in Russia are shown.

Relapsing uveitis is a serious problem for patients with ankylosing spondylitis (AS). Tumor necrosis factor-α inhibitors significantly reduce the frequency of uveitis attacks in AS patients, but they are not always available. In this connection, it is appropriate to evaluate the effect of traditional disease-modifying antirheumatic drugs on the course of uveitis in AS.Objective: to compare the frequency of uveitis attacks in AS during combined therapy using sulfasalazine (SULF) and nonsteroidal anti-inflammatory drugs (NSAIDs) versus monotherapy with NSAIDs.Subjects and methods. A total of 111 patients with significant AS who had at least one uveitis attack during the disease were examined. 49 subjects received combined therapy including SULF 2 grams daily and NSAIDs for at least 1 year. Six of the 49 patients were noted to have frequently relapsing uveitis (above 3 episodes yearly); 43 had no more than 3 ones per year. The remaining 62 patients took NSAIDs only throughout the follow-up period. Nine of them had an average of 3 uveitis attacks per year; 53 had no more than 3 ones per year. Out of the 49 patients receiving combined therapy with NSAIDs and SULF, 23 took NSAIDs only at least 1 year before SULF use; 10 of them were observed to have frequent relapses in that period and 13 had three or fewer episodes.Results and discussion. The entire group showed an average of 2.06±2.04 uveitis attacks per year during monotherapy with NSAIDs and 1.41±1.83 attacks yearly during combined therapy with NSAIDs and SULF (p = 0.08). Among the patients with less than 3 uveitis attacks per year, the mean number of episodes was significantly fewer during combined therapy than during NSAID monotherapy: 0.99±0.87 and 1.37±0.91, respectively (p = 0.04). Among those with frequently relapsing uveitis (more than 3 attacks per year), the mean number of episodes yearly was not significantly different during NSAID monotherapy and combined therapy: 5.7±2.5 and 5.5±2.7, respectively (p = 0.9). In a subgroup of patients receiving sequentially NSAID monotherapy and combined therapy with NSADs and SULF, 13 patients with three or fewer baseline attacks per year displayed a significant reduction in the frequency of episodes from 1.92±0.96 to 0.4±0.44 (p = 0.00003). During combined therapy versus monotherapy, 10 patients with frequently relapsing uveitis (over 3 episodes yearly) exhibited an insignificant reduction in the number of relapses from 5.9±3.02 to 5.33±1.1 (p = 0.6).Conclusion. Combined therapy with SULF and NSAIDs does not substantially affect the frequency of uveitis episodes in AS patients with frequently relapsing uveitis (above 3 attacks per year), but significantly reduces the number of episodes among patients with its mild course (less than 3 attacks yearly).

Guidelines for the treatment of ankylosing spondylitis (AS) lack muscle relaxants. At the same time, the latter are used for combined therapy using nonsteroidal anti-inflammatory drugs (NSAIDs) in 53.1% of patients in an outpatient setting. No clear recommendations make the administration of these agents uncontrolled, on the one hand, and substantially restrict therapeutic possibilities, on the other.Objective: to investigate the short-term effect and safety of using tolperisone hydrochloride (THC, Mydocalm®) in patients with AS during group therapeutic exercise (TE).Subjects and methods. The investigation included 40 patients aged over 18 years with a valid diagnosis of AS who had been treated at the Clinic of the V.A. Nasonova Research Institute of Rheumatology and agreed to participate in the study. All the patients were randomized in a 1:1 ratio into two groups: 1) 20 patients used NSAIDs in combination with TE; 2) 20 patients received NSAIDs, TE, and THC 450 mg/day. The groups were matched for age, gender, disease duration, and functional impairments. Before and after completion of the investigation, the investigators estimated BASDAI, BASFI, patient-rated numerical pain rating scale (NPRS), patient-rated TE performance scores (NPRS, where 0 (very effective), 10 (ineffective), THC tolerance monitoring (consideration of adverse events). Spinal motility was evaluated using BASMI and chest excursion measurement.Results and discussion. During TE, both groups showed a significant increase in the volume of movements (p < 0.03), when measuring chest excursion and carrying out modified Schober's test, a decrease in BASDAI (p < 0.01) and BASFI (p < 0.009), as well as a reduction in patient-rated overall disease activity assessment (p < 0.02) as compared to the baseline values. At the same time the modified Schober test revealed that the increase in motility was significantly higher in Group 2 than in Group 1 (p < 0.05). During the follow-up, the patient-rated evaluation of TE efficiency remained significantly unchanged in Group 1 whereas at the end of the study it significantly increased in Group 2 as compared to the baseline values (p < 0.01). There were no significant differences between the groups in the time course of changes in BASDAI and BASFI. When performing the BASMI tests, there was an intensive increment in the volume of movements after the third TE lesson. The increment occurred saltatorily in Group 1, but more rapidly and evenly in Group 2. No serious adverse events were recorded in Group 2 during the investigation. Conclusion. Incorporation of THC into the treatment of patients with AS contributes to the enhanced efficiency of TE. There is a need for further investigations to study the use of muscle relaxants, including THC, in AS in order to elaborate recommendations on how to administer this class of drugs for this disease.

The paper gives the draft guidelines elaborated by the Expert Spondyloarthritis Diagnosis and Treatment Group by order of the Association of Rheumatologists of Russia. The guidelines include the essentials of how to use nonsteroidal anti-inflammatory drugs in axial spondyloarthrititides, including ankylosing spondylitis, contain instructions for how long they should be administered, and describe possible patient management tactics in the most common clinical situations and a preferential algorithm for evaluating the efficiency and safety of treatment.

The literature virtually lacks the results of investigations aimed to study the clinical picture of ankylosing spondylitis (AS) in the real practice of rheumatologists in Russia. At the same time, these investigations may give information on not only the epidemiological aspects of the disease, but also a variety of its clinical presentation, its social importance, allow evaluation of the efficiency of therapy, and plan a system of further health care costs.Subjects and methods. In early 2015, the cross-sectional multicenter non-interventional trial EPICA2 was conducted to refine the clinical picture of AS in the real practice of a rheumatologist. The trial involved 402 patients with AS from 10 centers of Russia. The patients were examined using the international standards accepted for this disease. Results and discussion. 180 out of the 402 patients were treated in hospital; the others were examined during outpatient visits. The patients' mean age was 40.8±11.5 years; there were 292 (72.6%) men; 82.6% were HLA-B27 positive. The average age of onset was 27.6 years; the interval between symptom onset and diagnosis was 85.2 months. The rheumatologists established the diagnosis in 87.3% of the cases. BASDAI and BASFI averaged 4.3±2.1 and 4.1±1.8, respectively. At the trial, there was peripheral arthritis in 33.1% of the patients, enthesitis in 37.1%, and dactylitis in 1.2%. Joint endoprosthesis was carried out in 4.7% of the patients. The most common comorbidities were hypertension (25.1%), gastric ulcer (9.7%), coronary heart disease (4.0%), and diabetes mellitus (3.0%).Conclusion. AS is diagnosed in real practice more than 7 years after its onset mainly by rheumatologists.The delay of the diagnosis is mostly associated with the fact that specialists of other medical specialties are unaware of the clinical presentation of the disease. The examined group of patients with AS shows a relatively high activity and obvious functional impairments, which is primarily related to the specific features of patient selection in this trial.

The European League Against Rheumatism (EULAR) Congress (EULAR-15) was held in Rome on 10–13 June 2015. One of the most important aspects of the Congress was the problem of spondyloarthritis (SpA). Reports on the pathogenesis of SpA, including a relationship between the inflammatory processes and the mechanisms of bone proliferation, occupied a prominent place in the program of the Congress. The fundamental importance of proinflammatory cytokines, such as interleukin 17 (IL17)/IL23, for SpA was the subject of wide speculation. As in previous years, many reports were dedicated to the early diagnosis of SpA, the comparison of different SpA classification criteria, and the progression of non-radiographic axial SpA to ankylosing spondylitis. Much time was devoted to the results of the latest studies visualizing sacroiliitis and spondylitis.

Therapy for ankylosing spondylitis (AS) is a challenge for a physician, primarily because of a small number of therapeutic alternatives. Interleukin-17 (IL17), a novel promising therapeutic target, has been recently disclosed. The first representative of the new group of drugs – anti-IL17A monoclonal antibodies (secukinumab) has emerged, which allows expanding therapeutic opportunities for this disease. Trials have shown that secukinumab is effective in treating AS, has low immunogenicity and its safety profile does not virtually differ from that of placebo.