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Headaches are a common, but under-recognized symptom of rheumatic diseases. They can result from intracranial (inflammation, thrombosis, etc.) or extracranial pathology, such as irritation, or degeneration of anatomically related structures such as the eyes, neck, and sinuses. In addition, patients with rheumatologic disorders have the same tendencies as the general population to develop primary headaches. While the latter are benign in nature, the former type of headaches may signal disease manifestation, progression, or complication. Information on headache syndromes related to rheumatologic disorders as well as understanding of underlying disease processes and mechanisms is important. This will help to improve diagnostics and treatment of rheumatic diseases.

Objective: to analyze the results of tofacitinib (TOFA) therapy in real clinical practice according to the All-Russian Arthritis Registry (OREL). Subjects and methods. The OREL Registry included 347 patients (286 (82%) women and 61 (18%) men) with rheumatoid arthritis (RA) who initiated TOFA therapy. The male:female ratio was 1:4.7. The patients’ median age at onset of the disease was 42 years; its duration was 8 years. Most of the patients included in the registry had extended- (n=171 (52%)) or late- (n=148 (45%)) stage of RA. Results and discussion. Prior to initiation of TOFA therapy, RA activity according to DAS28 was high and moderate in 91 (64.5%) and 40 (28.4%) patients, respectively; the median DAS28 value was 5.5 [4.6; 6.2]; SDAI – 30.5 [21.4; 42.9], and CDAI – 28.2 [20.0; 37.1]. The use of TOFA was accompanied by significant decrease of disease activity. After 12 weeks, high RA activity was persistent in 32 (22.7%) patients; the number of patients with moderate activity increased to 77 (54.6%), that of those with low activity rose to 15 (10.6%); remission was observed in 17 (12.1%) patients. 216 (62.6%) and 76 (22%) patients received TOFA as first- and second-line therapy, respectively. TOFA was most frequently prescribed when tumor necrosis factor-á inhibitors (19.6%), rituximab (7.8%), tocilizumab (4.3%), and abatacept (5.2%) were insufficiently effective or poorly tolerated. Conclusion. The results of using TOFA in real clinical practice may suggest that the drug has high efficacy in patients with RA. TOFA can be used at a dose of 5 or 10 mg twice daily as both alone and in combination with disease-modifying anti-rheumatic drugs. TOFA showed similar efficacy in patients who had earlier taken biological agents and in those who had not.

Background. Аnkylosing spondylitis (AS) is closely associated with inflammatory bowel disease (IBD). 5–10 % of patients with SpA eventually develop inflammatory bowel disease, with Crohn's disease being more common than ulcerative colitis. Colonoscopy is usually used to diagnose inflammatory bowel disease, but this procedure is invasive. FC is clinically used to detect IBD and correlates well with clinical, endoscopic, and histological indicators of disease activity in IBD.The aim. To evaluate the incidence of inflammatory bowel disease in patients with ankylosing spondylitis.Materials and methods. In the analysis were included 40 patients with ankylosing spondylitis, among them 26 (65.0 %) men, and 14 (35.0 %) women, the average age of patients was 41.2 ± 10.5, the duration of the disease was on average 13.0 ± 8.8 years. All patients were examined with ESR, CRP, esophagogastroduodenoscopy, colonoscopy and quantitative analysis of the fecal calprotectin levels using the method of lateral immunochromatography with the BUHLMANN Quantum Blue rapid test. Standart range: 100–1,800 µg/g.Results. All patients had a high disease activity, the average BASDAI was 5.2 ± 1.7, the average ASDAS CRP 3.8 ± 1.1. 35 (87.5 %) patients had calprotectin level more than 100 µg/g, the remaining 5 (12.5 %) patients less than 100 µg/g. 12 (30.0 %) patients had the calprotectin level more than 1,800 µg/g, 23 (57.5 %) from 101 to 1800 µg/g. All patients with FC levels more than 100 µg/g showed an increase CRP level (mean 28.4 mg/l) and ESR (mean 36.3 mm/h). IBD were diagnosed in 9 (22.5 %) cases: 5 (12.5 %) patients with Crohn's disease and 4 (10 %) patients with ulcerative colitis, in the remaining (77.5 %) cases there was no intestinal pathology.Conclusion. The results showed high frequency of IBD in patients with AS. Patients with high fecal calprotectin levels (more than 100 μg/g) had high disease activity (AS). In most cases, inflammatory bowel disease were diagnosed in patients AS with fecal calprotectin levels more than 100 µg/g.

Aim: To evaluate the effectiveness, safety and anti-destructive effect of anti-B-cell therapy (rituximab) in various combinations (RTM-mono, RTM + DMARD, RTM + GK) in patients with rheumatoid arthritis in real clinical practice.Materials and methods: Clinical and radiological evaluation of 110 patients with rheumatoid arthritis who received rituximab therapy (RTM) as monotherapy (group 1), in combination with methotrexate (group 2), leflunomide (group 3), and group 4 with other basic anti-inflammatory drugs.Results: When assessing at 48 weeks of treatment with these regimens, the achievement of remission and a low degree of activity was observed in 22.36% of patients. An X-ray evaluation showed the absence of progression in the total score in 60.9%. When assessing progression in the monotherapy group, there was no progression in 76.92%, in the group of PTM + MT – in 54.29%, in the group of PTM + LEF – 65.0%, in the group of other DMARDs – 50% of patients. When assessing the clinical effect in the group receiving GK – remission and a low degree of activity – 19.67% of patients, in the group without GK – 21.05%. Assessing the radiological dynamics, it was shown that in the group not receiving GK – inhibition by the total score occurred in 54.55%, receiving – 61.54%.Conclusion: This work has demonstrated the high therapeutic efficacy of RTM in real clinical practice. There were no significant differences in the degree of progression depending on the concomitant therapy of DMARDs or GK. In the treatment of RTM, inhibition of articular destruction is possible even against the background of clinical deterioration.

This article presents the results of international studies of abatacept efficacy and safety and searching for possible predictors of a good response to the therapy with this drug in real clinical practice.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by pathological activation of the innate and acquired immune response, the formation of antinuclear antibodies (ANA), and dysregulation of cytokine production. Objective: to study the relationship of ANA and cytokine profiles in patients with SLE using multiplex immune analysis (MIA) of these biomarkers. We examined 94 patients with SLE (SLICC diagnosis criteria, 2012) and 28 healthy donors. Profiles of ANA and cytokines in blood serum were determined on the basis of suspension microarray technology xMAP. In SLE, antibodies to dsDNA (52.1 %), nucleosomes (54.3 %) and SS-A/Ro (37.2 %), less often to Sm (28.7 %), RibP (14, 9 %), RNP-70 (13.8 %) and SS-B/La (11.7 %). Disease activity (SLEDAI-2K) positively correlated with the concentration of antibodies to dsDNA (r = 0.6), nucleosomes (r = 0.7), Sm (r = 0.4) and RibP (r = 0.3) (p < 0.05). In the sera of patients with SLE, an increase in the levels of IL-4, -6, -8, -12, GM-CSF, MCP-1, MIP-1β, RANTES and a decrease in the content of IL-1β, IL-1ra, IL-2, IL-9, IL-10, eotaxin, G-CSF, IFN-γ, MIP-1α, TNF-α, FGF, PDGF-BB, VEGF compared to donors (p < 0.05). An increase in the concentration of IP-10 and MCP-1 was associated with high disease activity (r = 0.4; r = 0.3; p < 0.05), hyperproduction of antibodies to dsDNA (r = 0.3), nucleosomes (r = 0.5), Sm (r = 0.5), SS-B/La (r = 0.3), RibP (r = 0.4) (p < 0.05) and antibodies to Sm (r = 0.3), SS-B/La (r = 0.3), RibP (r = 0.3) (p < 0.05), respectively.Conclusion: the formation of ANA and high activity of SLE are associated with the overexpression of chemokines IP-10 and MCP-1 induced by IFN.

Background: An important characteristic of immune pathology in rheumatoid arthritis (RA) is a B-cell tolerance defect, associated with autoantibodies production, and antigen-specific activation of Th-1 CD4+ T lymphocytes with an excess production of pro-inflammatory cytokines compared to anti-inflammatory ones. Pro-inflammatory cytokines contribute to the development of local inflammatory effects, induce bone destruction and pannus formation, and contribute to the development of autoimmune abnormalities and systemic manifestations. Anti-inflammatory cytokines are able to reduce the rate of joint destruction. There is evidence of the involvement of Th2 cytokines in the development of early RA. These facts suggest the need for a thorough investigation into the balance between the Th1 and Th2 types of immune response at different stages of the disease.Aim: To assess the importance of сytokine profiling in the evaluation of immune abnormalities in RA.Materials and methods: In this descriptive, controlled, retrospective study, we examined 118 patients with RA and 33 healthy donors as a control group. Serum IgM rheumatoid factor (RF) and C-reactive protein (CRP) levels were measured by immunonephelometry; anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) were determined by an enzyme immunoassay, cytokines levels with "xMAP" technique.Results: Serum cytokine levels vary depending on RA duration. The cytokine profile in early RA, unlike that in established RA with a duration of more than 6 months, is characterized by higher levels of pro-inflammatory (MIP-1α), Th1 (IFN-γ), and Th17 (IL-17) cytokines, colony-stimulating factors (IL-7, G-CSF), and chemokines (IL-8, IP-10) (p < 0.05 for all parameters). In established RA, the levels of pro-inflammatory (IL-1β, -6, -15, TNF-α), anti-inflammatory (IL-1ra, IL-10, IL-13, IL-5), Th1 (IL-2, IL-12), Th2 (IL-9) cytokines and colony-stimulating factors (G-CSF, GM-CSF) correlate with the concentrations of IgM RF and antibodies to citrullinated proteins (antiCCP, anti-MCV) (all p < 0.05). There was also а correlation between CRP and pro-inflammatory (IL-1β, IL-6, TNF-α), Th1 (IL-12), Th2 (IL-5, IL-9) cytokine levels and between DAS28 and pro-inflammatory cytokine (IL-6) and colony-stimulating factor (G-CSF) levels (all p < 0.05). Conclusion: In RA, cytokines, chemokines and colony-stimulating factors mirror the inflammatory activity of the disease. Changes in blood concentrations of cytokines enable to get an insight into the complex interplay of numerous mediators of innate and acquired immunity

Objective : to study the efficacy, immunogenicity, and safety of a 23-valent pneumococcal polysaccharide vaccine (PPSV-23) in patients with rheumatoid arthritis (RA) receiving disease-modifying antirheumatic drugs (DMARDs) and biologic agents (BAs) during a 5-year follow-up. Patients and methods. The investigation included 79 RA patients with a recent history of ≥2 episodes of lower respiratory tract infections (bronchitis, pneumonia). A single dose (0.5 ml) of PPSV-23 was administered subcutaneously during continued methotrexate/leflunomide therapy or 28–30 days before using TNF-α inhibitors. All the patients were followed up during the first year; 39 patients at 24 months (Visit 5), 13 at 36 months (Visit 6), 23 at 48 months (Visit 7), and 18 at 60 months (Visit 8). Results and discussion . RA patients receiving various therapies were noted to have a marked positive immune response to PPSV-23, which was manifested by a significant increase in the postimmunization response coefficient. Vaccination responses were recorded in 61% of the patients with RA. The level of postvaccination responses tended to decrease at the 4-year follow-up. Only one case of community-acquired pneumonia of unknown etiology was detected at 5 years of follow-up. Conclusion . The data obtained by the authors for the first time in the 5-year prospective study indicate the sufficient and long-term immunogenicity, high efficacy, and safety of PPSV-23 in RA patients treated with DMARDs and BAs. Further clinical trials are needed to clarify the influence of various factors on the efficacy and immunogenicity of PPSV-23 and on the degree of their correlation in patients with RA. Objective: to study the efficacy, immunogenicity, and safety of a 23-valent pneumococcal polysaccharide vaccine (PPSV-23) in patients with rheumatoid arthritis (RA) receiving disease-modifying antirheumatic drugs (DMARDs) and biologic agents (BAs) during a 5-year follow-up.Patients and methods. The investigation included 79 RA patients with a recent history of ≥2 episodes of lower respiratory tract infections (bronchitis, pneumonia). A single dose (0.5 ml) of PPSV-23 was administered subcutaneously during continued methotrexate/leflunomide therapy or 28–30 days before using TNF-α inhibitors. All the patients were followed up during the first year; 39 patients at 24 months (Visit 5), 13 at 36 months (Visit 6), 23 at 48 months (Visit 7), and 18 at 60 months (Visit 8).Results and discussion. RA patients receiving various therapies were noted to have a marked positive immune response to PPSV-23, which was manifested by a significant increase in the postimmunization response coefficient. Vaccination responses were recorded in 61% of the patients with RA. The level of postvaccination responses tended to decrease at the 4-year follow-up. Only one case of community-acquired pneumonia of unknown etiology was detected at 5 years of follow-up.Conclusion. The data obtained by the authors for the first time in the 5-year prospective study indicate the sufficient and long-term immunogenicity, high efficacy, and safety of PPSV-23 in RA patients treated with DMARDs and BAs. Further clinical trials are needed to clarify the influence of various factors on the efficacy and immunogenicity of PPSV-23 and on the degree of their correlation in patients with RA.

Rheumatoid arthritis (RA) is a disease with a high cardiovascular risk. The results of works on the impact of antirheumatic therapy on carotid artery (CA) intima-media thickness (IMT) are contradictory. Objective: to assess the time course of changes in CA IMT and CA atherosclerosis (CAA) in patients with early RA during treatment to target at a 18-month follow-up. Subjects and methods. The investigation enrolled patients with early RA (disease duration of less than 12 months), who had not previously taken disease-modifying antirheumatic drugs and glucocorticoids. Duplex scanning (DS) of the CA was performed with IMT measurement at baseline and at 18 months after treatment. Vascular atherosclerotic lesion was recorded when atherosclerotic plaque (ASP) was detected. Starting methotrexate (MTX) monotherapy was prescribed to all the patients, when it showed an insufficient effect at 3 months, a biological agent (BA), such as a tumor necrosis factor-α inhibitor or abatacept, was added. RA remission was noted in 31 (42%) patients at 18 months of treatment. Results and discussion. The investigation included 74 patients with early RA; whose median (Me) age was 56 years, all the patients had moderate or high disease activity (Me DAS28-ESR, 5.4). At baseline, there was increased CA IMT in 51.4% of cases and CAA in 55.4%. At 18 months of treatment, there were no significant IMT changes. New CA ASPs were recorded in 8 (24.2%) patients who had no CAA at the time of inclusion in the investigation (p < 0.05). Nineteen (46.3%) patients were recorded to have the progression that had been identified when including CAA as a considerable increase in the number of ASPs (p < 0.05). The risk of CAA progression was correlated inversely with the mean 18-month level of high-density lipoprotein cholesterol (HDL-Cmean) and directly with the mean concentration of C-reactive protein (CRPmean). There was no significant correlation between HDL-Cmean and CRPmean. The changes of CAA were unassociated with the value of DAS28-ESR, the achievement of RA remission, and antirheumatic therapy (MTX monotherapy, MTX + BA). Conclusion. CAA shows progress in patients with early RA despite they are treated to target. DAS28-ESR remission in RA and ongoing RA treatment option had no substantial impact on the course of CAA. HDL-Cmean and CRPmean are independent risk factors for progression of CAA.

Objective: to investigate the impact of antirheumatic therapy carried out according to the treat-to-target (T2T) principle on the time course of changes in NT-proBNP levels in patients with early rheumatoid arthritis (RA) over an 18- month follow-up period.Subjects and methods. The investigation enrolled 74 patients, comprising 56 (74%) women (median age, 54 years) with a reliable diagnosis of RA (ACR/AULAR criteria (2010)) (disease duration, 7 months); who were seropositive for IgM rheumatoid factor (87%) and/or anti-cyclic citrullinated peptide antibodies (100%) and had not previously taken disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids. All the patients started therapy with subcutaneous methotrexate (MTX), with escalation of the dose to 25-30 mg/week; in the absence of any effect after 3 months, biological agents (BAs) were added in 47 (71%) patients. Following 18 months, 44% of patients achieved RA remission; 51 patients (77%) received cardioprotective therapy. NT-proBNP levels were measured in 66 patients with early RA before and 18 months after treatment. The NT-proBNP value Results and discussion. During antirheumatic therapy, there was a decrease in the median level of NT-proBNP from 125 [65; 208] to 68 [33; 115] pg/ml (p < 0.05) and in the frequency of its elevated values from 49 to 21% (p < 0.02). In the patients with RA remission, there was a more pronounced decrease in the frequency of elevated NT-proBNP values (from 45 to 7%; p < 0.05), while in those who had not achieved RA remission, NT-proBNP values showed only a tendency to decrease (from 51 to 32%; p < 0.05). The level of NT-proBNP became normal in the patients who had achieved remission of RA during treatment. There was no progression of the existing chronic heart failure (CHF) or development of its new cases.Conclusion. A significant decrease in NT-proBNP levels was recorded during antirheumatic therapy performed according to the T2T strategy, especially when using a combination of MTX+BAs and achieving RA remission. Therapy with MTX and BAs did not lead to the worsening of CHF or to the development of its new cases in patients with early RA.

Objective: to compare the efficacy and safety of abatacept (ABC) in patients with different duration of rheumatoid arthritis (RA).Subjects and methods. The investigation enrolled 86 patients with previous inefficiency or intolerability of therapy with synthetic disease-modifying antirheumatic drugs (DMARDs), mainly with methotrexate, and/or biological agents (BAs), such as adalimumab, etanercept, rituximab, infliximab, certolizumab pegol, and tocilizumab. The patients were divided into 2 groups. Group 1 included 29 (34%) patients with early RA (< 2 years' disease duration); Group 2 consisted of 57 (66%) patients with long-term RA (> 2 years' disease duration). The patients' mean age was 49±13.4 years; most of them were women who had a high RA activity (the mean DAS28 value was 5.2±1.15), were seropositive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. All the patients underwent standard clinical and laboratory examinations. ABC was injected intravenously at a dose of 10 mg/kg according to the standard regimen. Every 3 months, disease activity was assessed with DAS28; functional status was evaluated with the Health Assessment Questionnaire (HAQ).Results and discussion. In the early and advanced RA patients, the mean DAS28 at baseline was 5.2±0.9 and 5.2±1.3, respectively. After 3 months of ABC treatment, it significantly decreased in both groups (p < 0.05). An improvement according to the criteria of the European League Against Rheumatism (EULAR) occurred in 76% of the early RA patients and in 74.5% of the advanced RA ones. Following 3 and 6 months of therapy, there were no significant differences between the two groups in the rate of a good response: the latter was obtained in 31 and 42% of early RA cases and in 25.5 and 40% of advanced RA cases, respectively. After 3 and 6 months, both groups showed a comparable number of those who did not respond to treatment (24 and 12.5% in the early RA group and 25.5 and 25% in the advanced RA group, respectively). During ABC therapy, both groups also displayed a significant decrease of HAQ disability index (DI) (p < 0.05). A total of 14 adverse events (AE) were recorded in 13 (15%) patients. The most common AE proved to be acute respiratory viral infections that were observed in 6 (7%) patients. Serious AE were seen in 3 (3.4%) patients. Conclusion. ABC therapy leads to decrease of RA activity in the majority of patients who have previously received ineffective therapy with DMARDs and BAs. There were no significant differences in good response rates according to the EULAR criteria between the advanced and early RA groups. Following 3 months of treatment, the decrease of HAQ DI was significantly more pronounced in the early RA group. AE were registered only in 15% of the patients. ABC has established itself as an effective drug that has a good safety profile and is able to occupy a niche in the therapy of both late and early RA.

The early administration of methotrexate (MTX) and the use of its high (by the rheumatology practice standards) doses contribute to the enhanced efficiency of therapy and the reduced severity of rheumatoid arthritis (RA). One of the important merits of MTX in the treatment of RA is the possibility of adjusting its dose and choosing its (oral or subcutaneous) administration routes, which makes it possible to individualize treatment. Particular emphasis has been recently placed just on a subcutaneous MTX formulation that creates prerequisites for substantially improving the efficiency of RA therapy. The paper gives the data of the REMARCA (Russian investigation of methotrexate and biologicals for early active arthritis) trial assessing the results of RA treatment in the use of the subcutaneous MTX dosage form as a first-line drug and in the elaboration of management tactics for this disease. Subjects and methods. The investigation included 191 patients (34 men and 157 women) with active RA; of whom 51.8% had very early RA (< 6 months' disease duration). 115 patients with RA completed a 24-month follow-up period; and their data were analyzed in more detail. Results and discussion. The findings may substantiate treatment policy based on the prescription of subcutaneous MTX (without previously administering its oral formulation) in patients with early RA and high disease activity, starting the drug at 15 mg/week and rapidly escalating with the highest tolerable doses during 4-8 weeks, which allows remission (or low disease activity) in the majority of patients without using glucocorticoids and biological agents.