Psoriasis (Ps), psoriatic arthritis (PsA), and inflammatory bowel diseases (IBDs) are characterized by a progressive course and frequently lead to disability; therefore, their early diagnosis with the assessment of a clinical phenotype and unfavorable prognostic factors and the timely initiation of therapy are important tasks. The paper provides the experts agreed opinion on the definition of the early stage of Ps, PsA, and IBDs, the goals of therapy and main unfavorable prognostic factors for the course of these diseases and gives the rationale for the early use of biological agents in patients with immune-mediated inflammatory diseases.

Objective: to study the clinical characteristics of PsA and working capacity in patients included in the All-Russian PsA Registry.

Patients and methods. The investigation enrolled 614 patients aged 19–84 years with psoriasis from 39 subjects the Russian Federation, who were followed up in the All-Russian PsA Registry. On the basis of the assessment of demographic data, the spectrum of comorbidities, the degree of activity of the underlying disease according to Disease Activity Index for PsA (DAPSA) and Disease Activity in 28 joints (DAS28), clinical, functional, and social indicators were analyzed in the patients. The investigators studied information on the patients employment, working capacity, and disability, by assessing the group of the latter. The health status and the presence and severity of functional impairment in the patients were analyzed using the Health Assessment Questionnaire (HAQ), while their working efficiency was estimated according to the Workers Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP questionnaire), by calculating the following parameters: absenteeism, presenteeism, an overall decrease in labor productivity, and impairment in daily functional activity.

Results and discussion. The analysis of the All-Russian PsA Registry showed that most of them were of working age (30 to 59 years); 48.4% had concomitant diseases. Data on DAPSA changes were obtained in 349 patients, who were recorded to have mainly moderate (34.7%) or high (42.7%) disease activity, multiple dactylitides and enthesitides, and limited joint function. The registry reflects information on the social status of 521 patients: employed (61.2%) and unemployed (22.1%) persons, pensioners (15.2%), and students (1.5%). More than one third (37.1%) of patients with PsA had disability, mainly of Group III. The changes in the HAQ disability index were assessed in 326 patients; mild, moderate, and severe functional impairments were observed in 36, 26.4, and 3.7%, respectively. Absenteeism was detected in less than one third of patients with PsA, presenteeism was found in about half; there was an overall decrease in labor productivity in more than 60% and daily activity impairment in 68.8%. Statistically significant direct moderate correlations were established between the indicators of PsA activity (DAPSA and DAS28) and the level of productivity impairment in the patients; this was mostly related to an overall decline in labor productivity and to a decrease in daily activity.

Conclusion. The data obtained from real clinical practice suggest that half of the PsA patients had high disease activity and a third had severe functional impairment, which led to a lower quality of life and to disability. The overall decrease in labor productivity and daily activity, which was detected in more than half of the patients, was associated with high PsA activity. The follow-up in the All-Russian PsA Registry, regular anti-inflammatory therapy with disease-modifying antirheumatic drugs and biological agents can improve the clinical and functional status and, consequently, working capacity in patients with PsA.

Objective: to assess the relationship of the clinical characteristics and laboratory inflammatory markers to the ultrasound signs of synovitis and enthesitis in patients with psoriatic arthritis (PsA).

Patients and methods. Examinations were made in 63 patients diagnosed with PsA according to the 2006 Classification Criteria for Psoriatic Arthritis (CASPAR) criteria. Among the patients, the majority were females (54.2%); the mean age was 42.9±10.3 years; the median (Me) PsA duration was 7 [3; 10] years; Me Disease Activity in Psoriatic Arthritis (DAPSA) was 16.5 [11.6; 25] years.
All the patients underwent estimation of tender joint count, swollen joint count, tender entheseal count, inter alia using the Leeds Enthesitis Index (LEI), Maastricht Ankylosing Spondylitis Enthesis Score (MASES), and Spondyloarthritis Research Consortium of Canada (SPARCC). The investigators determined PsA activity by DAPSA and the prevalence and severity of psoriasis by the Psoriasis Area and Severity Index (PASI) and also estimated erythrocyte sedimentation rate (ESR) and high-sensitivity CRP (hs-CRP) levels. Ultrasonography was used to assess bilateral upper and lower limb joints, by calculating joint counts (JC) with synovitis signs (SJC), as well as tendon and ligament entheses (a total number of 54 in one patient), by determining the presence of vascularized enthesis count (VEC) and structurally changed enthesis count (SCEC) and using the ultrasound indices (Glasgow Ultrasound Enthesitis Scoring System (GUESS), Belgrade Ultrasound Enthesitis Score (BUSES), Madrid Sonography Enthesitis Index (MASEI), Sonographic Enthesitis Index (SEI)).

Results and discussion. There were no significant differences in the frequency of damage to the upper (15.7%) and lower (19.3%) limb joints (p>0.05), whereas inflammation in the entheses of the lower limbs (23.2%) was significantly more common than that in the upper limbs (15.3%) (p<0.01). A weak relationship was established between SPARCC and SEI (r=0.276; p<0.05). A positive correlation was found between VEC and hs-CRP levels (r=0.323, p=0.01), ESR (r=0.332, p<0.01). Ultrasound imaging showed that SJC (p<0.01), enthesitis count (p<0.01), and SCEC (p<0.05) increased with age. The relationship between SCEC and GUESS (r=0.724; p<0.01) and that between the VEC and BUSES (r=0.562, p<0.01) proved to be more pronounced.

Conclusion. Ultrasound imaging indicates that the entheses of the lower limbs are more frequently affected in patients with PsA. There is no relationship between DAPSA and ultrasound inflammatory changes in the joints and extra-articular structures. A strong relationship is established between enthesiseal structural and inflammatory changes and GUESS and BUSES, respectively, which allows one to recommend the use of these indices for assessing enthesitis in PsA. Entheseal vascularization associated with inflammatory markers (hs-CRP, ESR) (p<0.05) is a manifestation of PsA activity regardless of age and DAPSA.

 

Objective: to determine a set of signs that are prognostically significant for identifying a high-risk axial skeletal lesion in early psoriatic arthritis (ePsA).

Patients and methods. Examinations were made in 95 patients (47 men and 48 women) with peripheral arthritis lasting for ≤2 years, who met the 2006 Classification Criteria for Psoriatic Arthritis (CASPAR). The clinical characteristics of the patients were presented in our previously published work. In all the patients, a standard examination was made and the signs of inflammatory back pain (IBP) were identified according to the Assessment of SpondyloArthritis International Society (ASAS) criteria, the presence of human leukocyte antigen B27 (HLA-B27) was determined, and pelvic bone X-ray was done; regardless of whether they had IBP, 79 patients underwent magnetic resonance imaging (MRI) of the sacroiliac joints using a low-field Signa Ovation 0.35 T. Sacroiliitis (SI) diagnosed based on radiography (rSI) was considered reliable if there were bilateral changes corresponding to at least Stage II or unilateral changes corresponding to at least Stage III according to the Kellgren system. SI diagnosed based on MRI (MRI-SI) was regarded as active when osteitis was detected in the STIR mode in the bones adjacent to the joint on at least two slices or in the presence of two signals in a slice. X-ray and MRI results were assessed by an independent radiologist. The extent of a skin lesion was determined from the body surface area (BSA): the extent was regarded insignificant, moderate, and significant with involvements of <3%, 3–10%, and >10%, respectively.
The patients were divided into two groups. Group 1 included 65 (68.4%) patients with the manifestations of axial PsA (axPSA): IBP, and/or rSI, and/or MRI-SI; Group 2 consisted of 30 (31.6%) patients without axial manifestations, only with peripheral PsA (pPsA). Multivariate stepwise discriminant analysis was used to identify a group of signs that were most characteristic of axPsA.

Results and discussion. Comparative analysis of the two groups showed that there were more males among patients with axPsA than among those with pPsA (39 (60%) and 8 (26.7%), respectively) (p=0.003). HLA-B27 positivity was also more often detected in patients with axPSA than in those with pPsA (30 (46.6%) and 7 (23.3%) patients, respectively) (p=0.02). In the axPSA group, there were significantly more individuals with moderate and high DAS, high CRP levels, and a more severe skin lesion (BSA >3%).
The investigators obtained the following discriminant classification rule associated with axPSA: 1.566 (if CRP is >5 mg/L) + 0.957 (if HLA-B27 is positive) + 0.986 (if BSA is >3%) + 1.845 (if DAS is moderate or high) + 0.6 (if the sex is male) >3.751 (p=0.0025). The sensitivity and specificity of the model were 68% and 73%, respectively.

Conclusion. The combination of signs, such as male sex, HLA-B27 positivity, high or moderate DAS, CRP >5 mg/L, the extent of skin lesions according to BSA >3%, is prognostically significant for identifying high-risk axial skeletal lesion in ePSA. The proposed mathematical model can be used to screen patients for the early diagnosis of an axial lesion in ePSA.

Currently, the causes of extra-axial and extra-skeletal manifestations of ankylosing spondylitis (AS) and the possible impact of genetic aspects on its course and clinical features remain unresolved.

Objective: to investigate the association of the polymorphic markers rs10050860 and rs17482078 in the ERAP1 gene and rs11209026 in the IL23R gene with the development and clinical manifestations of AS.

Patients and methods. An allele-specific polymerase chain reaction assay was carried out to assess the alleles and corresponding genotypes of ERAP1 and IL23R gene polymorphisms in 70 patients (49 men and 21 women; mean age, 38 [31; 49] years) with AS and in 20 healthy donors. The activity indices, ESR, CRP, and extra-axial and extra-skeletal manifestations of AS were assessed in patients at the time of the investigation and in their history.

Results and discussion. The results of genotyping showed a significant association of the studied markers with AS. The carriage of the C/T genotype of the polymorphic markers rs10050860 and rs17482078 in the ERAP1 gene was associated with the history of peripheral arthritis (p=0.029) and the presence of incomplete right bundle branch block (IRBBB) (p=0.003 and p=0.006); the carriage of the G/A genotype of the marker rs11209026 in the IL23R gene was significantly associated with psoriasis (p=0.017) and IRBBB (p=0.03) in patients with AS.

Conclusion. The polymorphic markers of the ERAP1 and IL23R genes are associated with the risk of developing AS in this sample of patients. There is a significant correlation between the studied polymorphisms and some clinical manifestations of AS, which can be considered as a predictor of a more severe disease course.

Renal AA amyloidosis is the most severe type of renal pathology in patients with ankylosing spondylitis (AS). The characteristic symptoms of AA amyloidosis in rheumatic diseases do not often occur for years, making it difficult to diagnose it early and to start adequate therapy.

Objective: to identify the clinical features of AS complicated by secondary AA amyloidosis.

Patients and methods. The investigation enrolled 9 patients with AS (according to the 1984 modified New York criteria) and histologically confirmed secondary AA amyloidosis (Group 1). A comparison group included 216 AS patients without amyloidosis (Group 2).

Results and discussion. In Group 1 patients, the age at the onset of AS was significantly less and the disease duration was 4 times longer than those in Group 2. All the patients with AA amyloidosis had enthesitis and arthritis, including those of the hip joints. The scores of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), and the acute phase inflammation index CRP were higher in Group 1 than in Group 2.

Conclusion. The clinical feature of AS complicated by secondary AA-amyloidosis is the long duration of the disease and the high frequency of juvenile onset, non-axial manifestations (arthritis, coxitis and enteritis), as well as the high activity of systemic inflammation.

Objective: to analyze the data available in the literature on the efficacy and safety of ixekizumab (IXE) and adalimumab (ADA) via their direct comparisons in the treatment of psoriatic arthritis (PsA).

Patients and methods. The results of the SPIRIT H2H study were analyzed, the aim of which was to investigate the potential superiority of IXE to ADA for arthritis and skin manifestations in a group of patients with active PsA, stable plaque psoriasis with an inadequate response to synthetic disease-modifying antirheumatic drugs (sDMARDs) who had not previously received biological agents (BAs).
Design: a 52-week multicenter, randomized, parallel-group study. The patients were randomized 1:1 to open IXE or ADA administration groups for 52 weeks. This review presents the data obtained at 24-week follow-up.
Of the 684 screened patients, 566 (82.7%) were included in the study; moreover, the distribution of the patients was equal between the ADA (n=283) and IXE (n=283) groups. At 6 months, 269 (95%) patients in the ADA group and 262 (93%) in the IXE one continued to participate in the study. Efficacy analysis was made based on the achievement of the primary endpoint that was considered to be related to the relative number of patients, who had simultaneously achieved improvements in the joints and skin according to the ACR50 and PASI100 criteria.

Results and discussion. At 24 weeks, the proportion of patients who had simultaneously achieved ACR50 and PASI100 responses was significantly higher in the IXE group (36%) than in the ADA one (28%) (p=0.036). It was found that the IXE group was not inferior to the ADA one in terms of ACR50 response rates (in 51% (IXE) and 47% (ADA) patients) and was superior in achieving PASI100 response rates (in 60% (IXE) and 47% (ADA) patients) (p=0.001). The IXE group was recorded to have a higher response than the ADA group and in terms of other manifestations of the disease: the severity of skin and nail psoriasis, enthesitis, remission achievement, minimal and very low disease activity, and improved quality of life. Comparable effectiveness was noted for the effect of the drugs on dactylitis, as well as for the simultaneous achievement of remission and low disease activity in psoriatic arthritis according DAPSA. Serious adverse events (SAEs) were recorded in 8.5% (ADA) and 3.5% (IXE) patients.
The safety and tolerability of both BAs corresponded to their previously presented safety profile. The findings were also confirmed at 52-week follow-up, presented at the Meetings of the American College of Rheumatology in November 2019 and the European League Against Rheumatism in June 2020, and published in the leading journals of rheumatology.

Conclusion. The first randomized placebo-controlled study (SPIRIT H2H) directly comparing the two BAs with different mechanisms of action demonstrated the advantage of IXE over ADA in simultaneously reducing the activity of arthritis and psoriasis and showed their comparable efficacy comparable efficacy regarding joint symptoms. The use of IXE versus ADA was accompanied by the more frequent achievement of a combined endpoint related to the signs of joint and skin damages in patients with PSA, as well as by the quantitatively lower frequency of SAEs in patients with active PSA who had failed previous sDMARD therapy. The findings are of great importance for clinical practice from the point of view of the reasonable choice of a treatment strategy in these patients.

Objective: to analyze the structural features of the internal picture of the disease (IPD in patients with systemic lupus erythematosus (SLE) and its ratio with quality of life (QOL) as an indicator of adaptation to the disease.

Patients and methods. The investigation enrolled 51 patients with SLE. Comparison groups included patients differing in the psychological parameter – the perception of the existing disease as a threat to life and health: Group 1 (n=17) regarded their disease as a moderate threat to life and well-being; Group 2 (n=34) considered it as a severe threat.

Results and discussion. Comparative analysis of the cognitive level of IPD revealed statistically significant differences between the patients of Groups 1 and 2 in the following scales: «course of the disease» (p<0.001), «personal control» (p<0.001), «treatment control» (p<0.001), «understandability of the disease» (p<0.001), «emotional response to the disease» (p<0.005), and «overall level of disease threats» (p<0.001). It turned out that Group 1 patients better understood the features of the course and manifestation of the disease, were more confident in the efficiency and importance of the treatment prescribed, as well as in their own capabilities to improve their health status. Group 2 patients were more inclined to try to cope with the existing negative experiences, by avoiding the problem.

Conclusion. IPD can be different in patients with SLE. The perception of illness as a severe threat negatively affects the efficiency of therapy, mental well-being, social activity, and ultimately QOL. The findings can be used to develop programs for psychological support of patients with rheumatic diseases, in particular those with SLE.

Osteoarthritis (OA) is the most common joint disease. Searching for new treatment methods and regimens for OA is relevant.

Objective: to evaluate the efficiency and safety of therapy with a symptomatic sustained-release drug (Alflutop) in combination with intra-articular hyaluronic acid (HA) injection versus monotherapy with HA in patients with knee OA in routine clinical practice.

Patients and methods. A post-registration open-labeled prospective comparative randomized study was conducted to assess the results of treatment in 76 patients (31 men and 45 women; mean age, 49.3±8.5 years; body mass index, 28.4±0.8 kg/m2 ) in two clinical centers in Yekaterinburg and Perm. The patients were randomized into two equal groups, were homogeneous in terms of gender, the frequency of comorbidities, and vital signs (blood pressure, heart rate, and respiratory rate).
Group 1 patients received Alflutop as 1-ml daily intramuscular injections (a total of 20 injections) + 2 ml of 1% intraarticular (IA) HA solution injections three times at 1-week intervals; Group 2 patients were given 2 ml of 1% intraarticular HA solution injections three times at 1-week intervals. As an additional therapy, the use of meloxicam 7.5–15 mg/day was permitted, and, if non-steroidal anti-inflammatory drugs were contraindicated, paracetamol 1–3 g/day might be used.

Results and discussion. During treatment, both groups of patients showed improvement (compared to the baseline levels). At the same time, evaluating the intergroup values revealed clear differences: a more pronounced decrease in all WOMAC indicators in Group 1 patients: pain scores, 2 [1; 3] vs. 4 [2; 5] in Group 2 (p<0.001); stiffness, 1 [0; 2] vs. 2 [1; 4] (p<0.001); functional insufficiency, 8 [3; 12] vs. 15.5 [12; 20] (p<0.001); and total WOMAC scores, 12 [7; 13] vs. 21.5 [15; 28] (p<0.001). Pain-intensity assessment using the visual analogue scale also showed the more pronounced positive effect of the combination therapy in Group 1 (p<0.001).
Alflutop used in combination with HA was shown to be more preferable than HA monotherapy, which was confirmed by the results achieved for all WOMAC indicators. At 6 months, by the last visit, there were pronounced positive changes in all the analyzed parameters in both groups. At the same time, the most significant changes were recorded in the Alflutop + HA group than in the HA group (p<0.001). Perhaps, the mechanism in exhibiting the found synergistic effect of these drugs lies in their different effect on the pathogenesis of the disease. However, further study of this issue is required in multicenter randomized controlled trials.
The good safety of the drugs was confirmed: not a single adverse event was revealed.

Conclusion. The patients receiving the combination therapy with Alflutop + HA had the best treatment results in all the parameters assessed.

Objective: to assess pain dynamics, daily functional activity of joints, quality of life, and treatment satisfaction in patients with knee and hip osteoarthritis (KOA and HOA), who long take a combined glucosamine (GA) and chondroitin sulfate (CS) drug in routine clinical practice.

Patients and methods: An interim analysis of data from an open multicenter prospective non-interventional study that is being conducted in the Russian Federation was carried out. The study included patients with Kellgren–Lawrence Stages I–III KOA or HOA, who were treated with a combined GA and CS drug (Theraflex^®). The interim analysis was based on the data obtained at 16–24 weeks of treatment (Visit 2) in 542 patients (50% of the total sample).

Results and discussion. A study group included patients with KOA (n=399) or HOA (n=143) from 43 centers in Russia. At visit 2, the KOA/HOA patients showed positive changes in all subscales of the Knee disability and Osteoarthritis Outcome Score (KOOS/Hip disability and Osteoarthritis Outcome Score (HOOS) questionnaires compared to the baseline level. The proportion of patients with a ≥20% increase in different subscale scores ranged from 42.6 to 67.4% for KOA and from 47.6 to 66.4% for HOA.
Most (89.1%) patients took Theraflex^® for ≥3 months. 76,1% of patients were satisfied with treatment efficiency. Adverse events (AEs) related to treatment were recorded in 16 (3.0%) patients and included mainly gastrointestinal tract disorders in 12 (2.2%) cases.

Conclusion. The results obtained at 16–24 weeks of Theraflex^® treatment are indicative of a decrease in the frequency and intensity of pain and other symptoms of OA, as well as increases in joint functional activity and quality of life in patients with KOA or HOA after the first cycle of therapy. The majority of the patients were satisfied with the treatment. The incidence of drug-related AEs was low, while their nature was consistent with information on the drug's side effects.

Objective: to evaluate the efficiency and the safety of treatment with injectable chondroitin sulfate (ICS) in combination with dosed physical exercise (exercise therapy (ET)) for hand osteoarthritis (HOA).

Patients and methods. A study group consisted of 68 patients with HOA; the diagnosis of which was established in accordance with the 1991 American College of Rheumatology (ACR) criteria. The investigators identified two groups: 1) 36 women and 4 men; mean age, 62.2±3.4 years (a study group); 2) 20 women and 8 men; mean age, 61.7±6.5 years (a control group). Group 1 patients received treatment with 25 intramuscular ICS (Chondroguard) injections per cycle and underwent ET under the guidance of a trainer. In the first 3–5 days, the patients could take nonsteroidal anti-inflammatory drugs (NSAIDs). Group 2 patients were prescribed a magnetic therapy cycle (alternating pulsed magnetic field, 15–20-minute hand exposure, a total of 10 sessions). They could also take NSAIDs within the first 3–5 days. A visual analogue scale (VAS, mm) was used to analyze hand pain severity over time: at baseline, at 3 weeks, and at 3 months after the start of treatment.

Results and discussion. The dynamics of VAS joint pain was statistically more significant in Group 1 than in Group 2: 69.1±2.83 and 71.1±2.15 mm at baseline; 42.6±1.16 and 57.14±1.96 mm at 3 weeks (p<0.05), and 36.4±2.96 and 62.8±3.26 mm at 3 months (p<0.001). Similarly, Group 1 versus Group 2 showed a greater improvement in indicators, such as a decrease in the duration of morning stiffness in the hands and an increase in their grip strength. No adverse reactions requiring discontinuation of treatment or special therapy were noted in both groups.

Conclusion. The investigation showed the advantage of ICS used in combination with ET over magnetotherapy in the treatment of patients with HOA.

Objective: to assess the relationship between bone mineral density (BMD) and the muscular apparatus in male patients with coronary heart disease (CHD).

Patients and methods. The investigation enrolled 79 male patients (median age, 63 [57; 66] years) with an established diagnosis of CHD verified by coronary angiography.
Muscle mass was assessed by multispiral computed tomography, by determining the axial muscle tissue area (cm2 ) at the level of L_III. Muscle strength was measured with a wrist dynamometer. Muscle function was examined using the tests of the Short Physical Performance Battery (SPPB). BMD at the neck and proximal femur as a whole and at the lumbar spine was measured by dual energy X-ray absorptiometry.
For comparative analysis, the patients were divided into three groups (EWGSOP, 2010). Group 1 included 31 patients without sarcopenia; Group 2 consisted of 21 patients with presarcopenia; and Group 3 comprised 27 patients with sarcopenia.

Results and discussion. Osteopenic syndrome was diagnosed in 34 (43%) patients: osteopenia and osteoporosis in 31 (39%) and 3 (4%) patients, respectively. Normal BMD values were observed in 45 (57%) men. The prevalence of osteopenic syndrome was significantly higher in the patients with sarcopenia than in those with presarcopenia (p=0.050) and was comparable to that in men without sarcopenia (p>0.050). BMD at the neck and proximal femur as a whole was significantly lower in the patients with sarcopenia than in those without sarcopenia or with presarcopenia (p<0.050). There was a direct correlation between BMD and the characteristics of muscle mass and muscle strength. Regression analysis showed that the total skeletal muscle area at the level of L_III had a significant direct impact on BMD at the neck and proximal femur as a whole, and the reverse – walking speed.

Conclusion. The relationship between the characteristics of the muscular apparatus and BMD requires further investigation.

The paper characterizes the basic principles of a treat-to-target (T2T) strategy for spondyloarthritis, including psoriatic arthritis (PsA). The data from observational cohort studies suggest that inadequate therapy for PsA increases the risk of structural progression. The results, obtained in the international randomized controlled Tight Control of Psoriatic Arthritis (TICOPA) trial and the Russian open-label observational REMARCA study, have justified the necessity of using the T2T strategy for early-stage PsA. The authors have analyzed their own results of a 6-year follow-up study of a patient with early PsA, in whom the T2T strategy was used.

Axial spondyloarthritis (axSpA) is an immune-mediated inflammatory disease that affects predominantly the sacroiliac joints and spine. The main goal of axSpA therapy is to slow down and prevent structural damages that become a main cause of disability in able-bodied patients. Timely diagnosis and early prescription of biological agents can slow down the progression of the disease. The paper presents the experience in using the tumor necrosis factor-α inhibitor certolizumab pegol (CP) in a young female patient with early axSpA, who receives the drug within the framework of a model for clinical statistical groups (CSG) in the Kaliningrad Region. The high efficiency of CP and the possibility of using the latter within the CSG tariffs allow the drug to be prescribed for early-stage axSpA. The absence of an Fc-fragment in the molecular structure of CP provides additional opportunities for reproductive-aged female patients who can use the drug during the planning stage, pregnancy, and lactation.

The paper is devoted to the assessment of the R92Q (p.Arg121Gln) mutation/polymorphism in the TNFRSF1A gene associated with the monogenic autoinflammatory disease – Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS). It gives data on the frequency of this gene in the general population, which is 1.3% and significantly exceeds the incidence of TRAPS. The authors describe the variants of phenotypes associated with its mutation from asymptomatic carriage to the development of a severe systemic autoinflammatory state with persistent febrile fever and a significant increase in the level of acute-phase inflammatory markers that do not respond to standard antirheumatic therapy. They present a clinical case of the high efficiency of the anti-interleukin 1β monoclonal antibody canakinumab in a female patient with a severe TRAPS phenotype, who had the R92Q mutation and hormonal dependence. Canakinumab therapy led to complete relief from all manifestations of the disease and to discontinuation of glucocorticoids. The authors conclude that the decision to prescribe therapy with biological agents should be made on the basis of the clinical severity of the disease rather than a variant of the mutation that caused it.

Programmed immunoadsorption (IA) with regeneration of adsoption columns is a promising and safe technique to treat lupus nephritis (LN) in case of ineffective immunosuppressive therapy and its severe adverse reactions. This technique makes it possible to control disease activity, to maintain kidney function, and to ensure a normal quality of life. Due to the reusability of IA columns, it is possible to remove any required amount of IgG and to reduce the cost of an extracorporeal procedure.

The paper describes a clinical case of 3-year prolonged IA in a female patient with systemic lupus erythematosus (SLE) and LN with the insufficient efficacy of drug therapy and related complications. Seventy IA sessions were performed during a follow-up period. Combined treatment with glucocorticoids, cytotoxic drugs, and IA resulted in improved clinical and laboratory parameters, lower SLE activity according to SELENA-SLEDAI scores, and better quality of life according to the SF-36 scale. No adverse reactions were recorded during IA sessions.

The emergence of updated American College of Rheumatology (ACR) guidelines for the management of gout may serve as a prerequisite for revising the draft Russian Federal Clinical Guidelines (FCGs). Despite some differences, it should be noted that both guidelines are similar in key points concerning the principles of drug correction of hyperuricemia, indications for prescription and algorithms for the use of specific medicaments. The proximity of positions can be also traced in the need for the priority use of xanthine oxidase inhibitors (allopurinol and febuxostat) for urate-lowering therapy (ULT), which is aimed at implementing the target principle of gout management – the strict, constant control of serum levels of uric acid (its value should not exceed 6 mg/dl, or 360 μmol/l). The practical results of ULT in accordance with the basic principles outlined in the FCG have been published earlier.

The paper highlights the relationship between HLA-B27-associated uveitis and spondyloarthritis (SpA). It presents the genetic aspects of inflammation of the eyes and musculoskeletal system, the role of the HLA-B27 histocompatibility antigen, and the contribution of other genes to the development of uveitis and spondylitis. The authors characterize the general pathogenetic mechanisms of the development of these diseases: the importance of factors of innate immunity, proinflammatory cytokines in the initiation of inflammation of the eyes and joints. The detection rate of SpA is analyzed in various forms of uveitis; the predictors of SpA development are identified in the patients. An algorithm is presented, which makes it possible to timely diagnose SpA in the presence of acute anterior uveitis. HLA-B27, inflammation in the ocular anterior chamber, unilateral alternating eye lesions, an acute recurrent course, and uveitis onset at the age of less than 30 years are singled out as the most significant signs associated with SpA in patients with uveitis. The features of the course and the frequency of complications in uveitis with and without SpA are compared. It is shown that exacerbations of uveitis and associated complications occur statistically significantly more frequently in SpA. There is evidence for the need for a close interaction between ophthalmologists and rheumatologists in the management of patients with uveitis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line medications for ankylosing spondylitis (AS); their action is associated with blockade of the enzyme cyclooxygenase 2 and with a mediated decrease in the synthesis of prostaglandins (PGs). However, PGs play an important role in regulating the functions of the female reproductive system. The paper presents an update on the participation of PG in folliculogenesis, ovulation, implantation, and development of the embryo, and labor activity. Based on experimental and clinical findings, the authors discuss whether due to inhibition of the synthesis of PGs, NSAIDs are able to cause ovulation failure, including luteinized unovulated follicle syndrome and spontaneous abortions. Further investigation is justified to determine the most optimal NSAID therapy regimens when planning pregnancy and during gestation in women with AS.

Early osteoarthritis (OA) is a poorly studied problem, the importance of which is due to both the prevalence of OA in the population and the high medical and economic costs of treatment and rehabilitation in patients with this disease. The accumulating data indicate that the earlier active management of patients with OA may lead to a better long-term prognosis; to date, however, the very formulation of the concept of «early osteoarthritis», as well as the holistic clinical diagnostic criteria of the disease, have not been fully formulated. The paper considers the problem associated with the elaboration of approaches to diagnosing early OA with clinical, laboratory, and modern instrumental examinations.

Rheumatoid arthritis (RA) is characterized by a progressive course with the formation of joint deformities and the development of severe functional disorders. The most favorable conditions for changing the course of the disease emerge in the first months after its onset. Methotrexate (MTX) occupies a leading position in the treatment of RA. There is a need to develop tools that will be able to predict the efficacy and tolerability of MTX at the earliest stages of RA treatment. The concentration of active metabolites of MTX is considered as a potential biomarker that enables one to predict what response to therapy with this drug will be.

The paper analyzes the most relevant works devoted to the study of the concentration of active MTX metabolites polyglutamates (MTX PGs) in patients with RA. It is shown that the presented studies do not cover all the possibilities of therapeutic drug monitoring, in particular the determination of the levels of MTX PGs in mononuclear cells over time. Further investigation is needed to develop an objective approach to prescribing MTX in RA patients.

The curation of patients with gout involves the mandatory prescription of pathogenetic therapy with urate-lowering drugs, among which xanthine oxidase inhibitors, such as allopurinol and febuxostat, are most widely used. According to various national and international guidelines, allopurinol is the first line drug for gout. However, there is a large cohort of patients, in whom the use of febuxostat is not only justified, but is also preferable. First of all, these are patients who are intolerant to allopurinol and at a high risk of severe skin reactions. There is a high risk of mortality and a low probability of achieving the target uric acid level when allopurinol is prescribed for patients with diminished renal function. Taking into account the fact that febuxostat has a pronounced nephroprotective effect, prescribing the drug in these patients will be a more effective way to achieve normouricemia. At the same time, the presence of cardiovascular diseases, although this requires additional caution when choosing therapy, should not be a reason for refusal to take febuxostat, since the results of many studies not only have failed to confirm a higher risk for cardiovascular events during therapy with this drug, but also have shown that it has cardioprotective properties.