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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.

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 (pConclusion. The presented data show that in certain clinical situations iIL6 can be highly effective in AS.

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.

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.

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.

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 Conclusion. Subcutaneous NTK at 120 mg dose demonstrated superior efficacy vs placebo, with fast onset of response and favorable safety profile when used in patients with ankylosing spondylitis.

The 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.

Aim to identify outdated terms and make changes to the terminology of spondyloarthritis.At the first stage of the work, the terms divided into two categories: "outdated" definitions and terms that need to be improved or unified. Subsequently, each member of the Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia (ExSpA) presented by its own definition of the designated term or agreed with the previous term. At the next stage, the existing definitions were put together. After discussion, experts left a term that scored at least 2/3 of the votes. The special opinion of experts was recorded, whose did not coincide with the majority opinion. An open vote was conducted, when defining an "outdated" term with the unanimous decision of all group members, this term was not recommended for further clinical use.The work carried out allowed us to identify a number of terms that are not recommended for use in clinical practice. Number of terms are defined, which should be used when discussing the problem of spondyloarthritis.The Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia suggests using or, accordingly, not using a number of terms and their definitions in clinical practice.Цель исследования: выявить устаревшие термины и внести изменения в терминологию, используемую при обсуждении проблемы спондилоартритов. Материалы и методы. На первом этапе работы собраны уже употребляемые термины, их разделили на две категории: «устаревшие» определения и термины, требующие доработки или унификации. В дальнейшем каждый член Экспертной группы по изучению спондилоартритов при Ассоциации ревматологов России (ЭкСпА) представлял свое определение обозначенного термина либо соглашался с прежним термином. На следующем этапе имевшиеся определения сводились воедино, после обсуждения оставляли термин, который набрал не менее 2/3 голосов, отдельно фиксировалось особое мнение экспертов, чье мнение не совпадало с мнением большинства. При определении «устаревшего» термина проводили открытое голосование, при единогласном решении всех членов группы этот термин не рекомендовался для дальнейшего клинического использования. Результаты. Проведенная работа позволила выделить ряд терминов, которые не рекомендованы к употреблению в современных условиях, даны определения и расшифровка целого ряда терминов, которые, напротив, целесообразно использовать при обсуждении проблемы спондилоартритов. Заключение. Экспертный совет по спондилоартритам при Ассоциации ревматологов России предлагает использовать или, соответственно, не использовать ряд терминов и их определения в повседневной клинической практике и при описании клинических и иных исследований.

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 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 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.

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.

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.

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.

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.

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.

To compare the clinical manifestations of ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nrAxSpA).A Moscow early spondyloarthritis cohort has now included 132 patients with axial spondyloarthritis, of whom 69 patients who have been followed up at least 12 months are to be involved in a preliminary analysis. The mean age at the time of inclusion in the study was 28.1±5.5 years; the mean disease duration was 24.7±15.8 months; 63 (91.3%) patients were HLA-B27 positive; 41 and 28 included patients were diagnosed with AS and nrAxSpA, respectively.Men were significantly more in the AS group than in the nrAxSpA group (58.5 and 32.1%, respectively; p=0.05). The patients of the two groups did not differ in main clinical parameters (the presence of arthritis and enthesitis), disease activity (BASDAI, ASDAS-CRP) and functional status (BASFI). All indicators of inflammatory activity decreased nearly 2-fold in both groups after 12 months of follow up. In 7 (25%) patients with nrAxSpA, radiologically detectable sacroiliitis (SI) developed over 12 months and the diagnosis of AS was verified. Among them, 2 (28.5%) patients had initially active SI detected by magnetic resonance imaging (MRI); 4 (57.1%) had chronic SI, and 1 (14.4%) had no pathological MRI changes.Due to the fact that the clinical manifestations of AS and nrAxSpA are comparable, it can be assumed that the latter is an early stage of AS.Цель исследования. Сопоставление клинических проявлений анкилозирующего спондилита (АС) и нерентгенологического аксиального спондилоартрита (нр-аксСпА). Материалы и методы. В московскую когорту КоРСар (Когорта Раннего Спондилоартрита) в настоящее время включены 132 больных аксиальным спондилоартритом (аксСпА), из которых в предварительный анализ вошли 69 больных, наблюдавшихся не менее 12 мес. Средний возраст на момент включения в исследование составил 28,1±5,5 года, средняя продолжительность заболевания - 24,7±15,8 мес, 63 (91,3%) больных позитивны по HLA-B27, 41 пациент включен с диагнозом АС, 28 - с нр-аксСпА. Результаты. В группе АС мужчин было достоверно больше, чем в группе с нр-аксСпА (58,5 и 32,1% соответственно; р=0,05). По основным клиническим параметрам (наличию артритов и энтезитов), активности болезни (согласно индексам BASDAI, ASDAS СРБ) и функциональному статусу (индекс BASFI) пациенты двух групп не различались. Через 12 мес наблюдения все показатели воспалительной активности уменьшились почти в 2 раза в обеих группах. У 7 (25%) пациентов с нр-аксСпА за 12 мес развился рентгенологически выявляемый сакроилиит и подтвержден диагноз АС. Изначально среди них у 2 (28,5%) человек имелись выявляемые при магнитно-резонансной томографии (МРТ) признаки активного СИ, у 4 (57,1%) - хронического СИ, а у 1 (14,4%) не выявлено патологических изменений по данным МРТ. Заключение. В связи с сопоставимостью клинических проявлений АС и нр-аксСпА можно предположить, что последний является ранней стадией АС.

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.

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 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.

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).

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.

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 Congress considered the issues pertinent to the latest approaches to therapy for axial spondyloarthritis (axSpA), as well as the problems associated with a search for axSpA-modifying anti-rheumatic drugs. Reports on the results of therapy with nonsteroidal anti-inflammatory drugs and biological agents (tumor necrosis factor- α and interleukin 17/23 inhibitors) were of the most relevance.

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.

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 paper provides guidelines for the use of tumor necrosis factor- α (TNF- α ) inhibitors in the treatment of patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis. It gives data on the efficacy of TNF- α inhibitors in patients with non-radiographic axSpA. By using international and Russian guidelines, the authors lay down indications for this therapy and criteria for evaluation of its efficiency and safety.

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.

As of now, magnetic resonance imaging (MRI) ranks high in the early diagnosis of inflammatory changes in the musculoskeletal system. The uniqueness of MRI is that this diagnostic technique can detect the signs of active and inactive inflammation at the pre-radiological stage of the disease, i.e. before the onset of radiological symptoms of sacroiliitis and the formation of spinal syndesmophytes. At the same time there is evidence that there is a temporary association between active inflammation and the development of radiological changes in the joints. The detection of bone marrow edema in the subchondral portions of bone tissue is of great importance not only for diagnosing the disease and verifying inflammatory activity, but also for predicting the development of chronic arthritis, choosing a treatment option, and evaluating the efficiency of performed therapy. Based on their long-term experience, the authors provided explanations of the MRI pattern of active and inactive chronic sacroiliitis and spondylitis, which can considerably facilitate the early diagnosis of injury to the sacroiliac joints and vertebral column in patients with ankylosing spondylitis.

Reactive arthritis (ReA) is one of the types of spondyloarthritis. According to the statistics reports by the Ministry of Health of Russia, the prevalence of ReA in 2013 was 42.8 per 100,000 adult population, 99, and 172.4 per 100,000 children aged 0–14 and 15–17 years, respectively. There is a wide scatter of ReA detection rates in both the federal districts and subjects of the Russian Federation, which may be associated with both the spread of sexually transmitted infections, asymptomatic trigger Chlamydia infection, and overdiagnosis of ReA.

Ankylosing spondylitis (AS) is a chronic progressive disease resulting in disability. Affecting mainly young and able-bodied people, AS considerably reduces the manpower of society. To date, it may be stated on the basis of the available data, that long-term therapy with tumor necrosis factor-α inhibitors makes it possible not only to improve clinical status, but also to restore working ability. This in turn can lead to the conclusion that the indirect costs associated with this disease can substantially reduce costly treatment-related medical losses of society as the patients return to active labor.

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.

Until recently there is no clarity in the nosological independence of non-radiographic axial spondyloarthritis (nraxSpA). Cohort studies can assist in solving this problem. In 2013, the V.A. Nasonova Research Institute of Rheumatology started to form a Cost and Resource utilization Study in Antiretroviral treated patients (CoRSaR) cohort to investigate the evolution of nr-axSpA and treatment policy for this condition. This communication deals with the preliminary results of a 12-month follow-up study of the CoRSaR cohort. Subjects and methods. The cohort was recruited from all consecutive patients with a < 5-year history of nr-axSpA who sought for medical advice and treatment. The patients were examined in accordance with the Ankylosing Spondylitis Assessments (ASAS) International Working Group guidelines at inclusion and after 12 months. A total of 94 patients with axSpA were enrolled; 54 patients out of them were included into a preliminary analysis of the evolution of axSpA; their mean age at inclusion was 27.1±5.5 years and the mean disease duration was 22.4±15.1 months; 49 (90.7%) patients were HLA-B27 positive. 31 of the 54 patients had ankylosing spondylitis(AS) and 23 had nr-axSpA. Results and discussion. The patients with AS and those with nr-axSpA showed virtually no difference in main clinical parameters, such as the presence of arthritis, enthesitis, BASDAI, ASDAS-CRP, and BASFI. By the end of the 12month follow-up, both groups virtually displayed almost a double reduction in all inflammatory markers but erythrocyte sedimentation rate. Nine (39%) patients with nr-axSpA developed radiographic sacroiliitis over 12 months and the diagnosis of AS was confirmed. Conclusion. 39% patients with nr-axSpA developed radiographic sacroiliitis at the 12-month follow-up. Nr-axSpA should be regarded as an early stage of AS.

The paper analyzes the main problems associated with randomized controlled studies in medical rehabilitation: patient selection; use of simulation devices as placebo; standardization of methods; blinding procedure. It presents methodological considerations for improving the quality of studies.

There is much evidence that ankylosing spondylitis (AS) is a disease that is also much older than early human civilizations and man as a whole. Until now, the Russia's earliest (14th c ntury) archaeological finding of such a patient remains a Volga Bulgaria inhabitant suffering with AS during his life. In the Republic of Tatarstan, at the site of an ancient Bulgar settlement appearing in the early ninth century, archaeologists have discovered an unusual grave: the deceased sitting with his back against the western wall of a tomb pitand having a bronze crosslet under his fingers. According to a historical source, it was the way of burying Christian hierarchs as pastors sitting on the altar and anticipating the great assize during which the destinies of human souls should be ruled. Anthropological analysis showed that the bones belonged to a 35–45-year-old man who was 158–163 cm tall. During the examination of the remains, attention was called to the following features of the spinal structure: ankylosis of the inferior cervical and superior thoracic vertebrae (СV–ThI) and inferior thoracic and lumbar spine (ThIV–LII) predominantly due to ossification of the anterior longitudinal ligament. Facet vertebral joints and costotransverse joints were also ankylosed at the same levels. The man's neck was fixed in a bent-over position with the head down, the chin touching the breast bone – the socalled soliciting posture. By and large, the vertebral changes are characteristic of late (X-ray stage III) spondylitis. Spinal and pelvic photos and X-films are given for demonstration. The studies conducted by historical scientists and forensic medical experts suggest that the found remains are most likely to belong to Christian Theodore nicknamed Jerusaleman, also further known as Holy Theodore philosopher Kamsky (Bulgarian), who was mentioned in the Nikon chronicle in 1323.

The paper summarizes the data of a randomized placebo-controlled phase 3 GO-RAISE trial of spondylitis (AS) patients receiving two different doses (50 and 100 mg) of golimumab (GLM), which evaluates its efficiency and safety and X-ray progression of changes in the axial skeleton. In AS patients, GLM therapy leads to a rapid long-lasting clinical and radiological response. The tolerability of long-term therapy with GLM generally complies with the safety profile of the entire class of tumor necrosis factor-р (TNF-р) inhibitors. The data of the GO-RAISE trial has substantiated once again the established fact that the high baseline level of C-reactive protein (CRP) and the presence of syndesmophytes are predictors for a rapider X-ray progression. At the same time, the results of the trial may question the recent assumptions that TNF-р suppression can exert a stimulating effect on the formation of new bone tissue with time. Further studies are to determine whether there is an association between the presence of syndesmophytes and elevated CRP levels and whether they have a combined effect on X-ray progression, and if so, whether the development of structural changes may be prevented with TNF-р inhibitors to be used at the earlier stages of the disease.

Uveitis is the inflammation of the uvea, which generally occurs in young people and may be accompanied by serious complications leading to disability. The review analyzes the data of Russian and foreign investigations on the pathogenesis of HLA-B27-associated uveitis occurring in different diseases from a group of seronegative spondyloarthritides (SpA) and also discusses current therapeutic approaches in this disease. Since the late 20th century, there has been rapid progress in studying the pathogenesis of HLA-B27-associated uveitis and in identifying the genetic factors predisposing to this pathology. Investigations of HLA-B27 antigen and its alleles are being continued. Tumor necrosis factor-α (TNF-α), the higher levels of which in blood, synovial fluid, and ocular fluid in rheumatic diseases has been proven in many works of both foreign and Russian scientists, is most studied among the inflammatory mediators. Due to the key role of this cytokine in the development of inflammation, drugs inhibiting TNF-α activity have been designed and successfully used in the past decade, which results in partial and occasionally stable remission.

Coxitis is one of the characteristic clinical manifestations of ankylosing spondylitis (AS). Hip joint (HJ) damage in AS is regarded as a poor prognostic factor and the early detection of coxitis is of great importance, as timely adequate therapy may reduce the risk of irreversible HJ changes. Coxitis may be diagnosed clinically and using different imaging techniques, each of which can characterize different aspects of damage of these joints. The lecture considers the clinical and instrumental diagnosis of coxitis in AS.

By the end of the first decade of the 21st century, spondyloarthritis studies have accumulated a certain number of terms that are obsolete, but used by physicians in their everyday speech, on the one hand, and a great variety of different definitions, on the other hand. In January 2014, the first organizational meeting of the Expert Group on Spondyloarthritis, Association of Rheumatologists of Russia, decided that its primary task should be to order the terminology used in this area. The authors primarily collected the terms, which had been already used in medical vocabulary, and then divided them into two categories: obsolete definitions and terms to be finalized and unified. This publication gives guidelines for using the medical terms relevant to spondyloarthritis and separately discusses how to correctly write the term sacroiliitis.

Diffuse idiopathic skeletal hyperostosis, or Forestier's disease (FD), is a rare non-inflammatory disease of the locomotor apparatus, which is associated with ligament and tendon ossification that gradually results in ankylosis. In a number of cases, the clinical and radiographic patterns of FD are similar to those of ankylosing spondylitis (AS), which requires a differential diagnosis. The paper describes two clinical cases demonstrating difficulties in the differential diagnosis of FD and AS.

To determine a neuropathic component of pain and define its causes in patients with rheumatoid arthritis (RA).One hundred and eighty-three patients with confirmed RA, mean age 46,5±11,7 years, RA duration from 3 month to 30 years, were studied. Rheumatology, neurological, using the DN4 questionnaire, examinations and stimulation electromyography were used. Results and сonclusion. Signs of neuropathic pain (NP) assessed with the DN4 were identified in 73 (43%) patients with RA. These patients were older, had longer RA duration as well as higher clinical stage of disease and reduced functional abilities. There were no correlation between NP and disease activity. Peripheral nervous system (PNS) lesions were seen in 96% patients with NP: sensory motor neuropathy (55%), tunnel syndrome (14%), mononeuropathy (19%) and their combinations (4%), cervical myelopathy (4%). PNS lesions is the main etiopathogenetic factor of peripheral NP in RA. This finding opens new perspectives for complex treatment, including group B vitamins, of chronic pain in RA.Цель исследования. Выявить нейропатический компонент боли и определить его причины у больных с ревматоидным артритом (РА). Материал и методы. Обследованы 183 пациента с достоверным РА, средний возраст 46,5±11,7 года, длительность РА от 3 мес до 30 лет. Проводились ревматологическое, неврологическое обследования с применением опросника DN4, стимуляционная электронейромиография. Результаты и заключение. Признаки нейропатической боли (НБ) по DN4 выявили у 73 (43%) пациентов с РА. Все эти пациенты имели более старший возраст, большую длительность, а также более высокую клиническую стадию заболевания и сниженные функциональные возможности. Связи НБ и активности заболевания получено не было. Поражение периферической нервной системы (ПНС) обнаружили у 96% пациентов с НБ: в виде сенсомоторной полинейропатии (55% случаев), туннельных синдромов (14%), мононейропатии (19%) и их сочетания (4%), шейной миелопатии (4%). Основным этиопатогенетическим фактором периферической НБ при РА является поражение ПНС. Этот факт открывает возможности комплексной терапии хронической боли при РА, в частности с применением витаминов группы В.

The article presents the differential diagnosis between mechanical and inflammatory lower back pain based on clinical and paraclinical evidence. The results of comparative studies of amtolmetinum guacilum (AMG) and celecoxib, as well the CORONA study of its efficacy and cardiovascular safety in ankylosing spondylitis, are also discussed.В статье представлена дифференциальная диагностика между механической и воспалительной болью в нижней части спины, основанная на клинических и параклинических признаках. Продемонстрированы результаты сравнительных исследований эффекта амтолметин гуацила (АМГ) с целекоксибом, а также результаты исследования КОРОНА по определению эффективности и кардиоваскулярной безопасности в лечении больных анкилозирующим спондилоартритом.