munosorbent assay. HLA DRB1, DQA1 and DQB1 genotype was determined using commercial sequence-spec... more munosorbent assay. HLA DRB1, DQA1 and DQB1 genotype was determined using commercial sequence-specific oligonucleotide kit. Statistical analysis was performed using Pearson Chi 2 , Fisher exact test, or Spearman correlation. Results: The median age at diagnosis was 43±13,28 years (range: 18-70), 48 patients exhibited myositis (98%), 35 ILD (73%), 43 arthritis (88%), 32 Raynaud's phenomen (65%), 21 fever (43%), 16 mechanic's hand (33%), 27 skin rash (55%) and 6 dysphagia (12%). We could detect significant correlation between the initial anti-Jo-1 titer and the first CK (R=0,328; p=0,003) and CRP (R=0,374; p=0,016) level. Furthermore anti-Jo1 levels during disease course had significant correlation to the corresponding CK (R=0,497; p<0.001), and CRP (R=0,325; p<0.001) level. The most frequent antibody besides anti-Jo-1 was anti-SSA (28/49; 57%). The anti-Jo-1+/SSA+ population had younger age at the diagnosis (36,12±11,08 vs. 47,22±12,87; p=0,004), lower rate of ILD (53% vs. 81%; p=0,039), but higher maintaining steroid (methylprednisolone) dose (9,53 mg vs. 3,7 mg; p=0,031) compared to the Jo-1+/SSA-group. Higher (≥8 mg) maintaining steroid therapy was associated with higher initiating CRP (36,34 vs. 17,84 mg/l; p=0,014) ESR (33,87 vs. 19,81 mm/h; p=0,032) level and higher presence of fever (67% vs. 37%; p=0,038) at diagnosis but not with initiating CK (p=0,374), LDH (p=0,224) level or ILD presence (p=1). 68,96% of the patients were HLA DRB1*03 positive, where the CK level at diagnosis was significantly lower compared to the HLA DRB1*03 negative patients (2816,30 vs. 5969,44 U/l; p=0.04). 58.62% of the patients were positive for HLA DQA1*0501-DQB1*0201 haplotype, but no significant correlation was found regarding to any clinical or laboratory features. Conclusions: Our results confirm previously reported data from other centers considering the clinical features of anti-Jo1 positive patients. HLA DRB1*03 positivity was associated with lower CK level but has no influence on clinical or serological features. It seems that anti-Jo1 level might reflect disease activity; ESR, CRP levels, associated fever and anti-SSA positivity at the diagnosis could be considered as prognostic markers.
RF, anti-citrullinated protein antibodies, and disease activity measures for SpA and RA were asse... more RF, anti-citrullinated protein antibodies, and disease activity measures for SpA and RA were assessed. The rheumatologic Scores and periodontal condition were evaluated by two experienced and calibrated periodontists and rheumatologist. The groups were compared with Kruskal Wallis, Mann-Whitney U and Wilcoxon test's test and a paired t-test. The chi-square test was used to evaluate periodontal variables and SpA disease activity. The institutional Ethics Committee approved the study. Results: 79 SpA patients with the following subtypes were included: Ankylosing Spondylitis (AS) (19), undifferentiated SpA (46), and reactive arthritis (ReA) (14). SpA patients had a considerable frequency of periodontitis (55.7%). Of them, 39.2% were classified as moderate and 2.5% as severe periodontal condition. No differences was found in frequency of periodontal condition between subtypes. SpA patients showed lower levels of insertion loss compared to RA patients and the control group (p<0.05). A significant association was observed in microbiological variables of SpA patients. The frequency of (P gingivalis) in the control group was 51.9% compared to 30% in SpA (p=0.015), especially in those with good response to NSAIDS (p= <0.05). Significant associations between the severity of periodontal involvement in RA patients was observed. 63.8% of RA patients had moderate severity disease (49.2%) and severe periodontitis (13.6%) (p=0.035) but not in SpA group. There were not association between disease activity measures in SpA, periodontal and severity condition. Conclusions: As compared to RA and healthy controls, periodontal condition in SpA patients was similar. Lower grades of severity and bacterial load were found. This suggests that an interdisciplinary treatment between periodontists and rheumatologists may help to modulate periodontal condition and prevent systemic impact References:
Background: Iguratimod (IGU) is a small-molecule antirheumatic drug that was approved in Japan in... more Background: Iguratimod (IGU) is a small-molecule antirheumatic drug that was approved in Japan in September 2012. IGU suppressed tumor necrosis factoralpha-induced production of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein 1 via inhibition of nuclear factor kappa B activation in cultured human synovial cells and human acute monocytic leukemia cells. IGU also reduced immunoglobulin production by acting directly on human B lymphocytes without affecting B lymphocyte proliferation. Recently, an increased release of extracellular adenosine and a decreased production of lymphotoxins such as ammonia and superoxide have been shown to be involved in the anti-inflammatory mechanisms of methotrexate. Thus, the combination of MTX and IGU may have synergic efficacy for rheumatoid arthritis (RA) treatment. Objectives: To evaluate the clinical efficacy of add-on IGU in patients with Japanese active RA who had shown inadequate responses to MTX therapy from initiation to 52-week. Methods: Patients with a diagnosis of RA according to the 2010 ACR/EULAR criteria who had been unresponsive to MTX therapy (DAS>3.2 or CDAI>10), and who had been prescribed add-on IGU from Tsurumai Biologics Communication Registry (TBCR)-plus between November 2012 and September 2013 were enrolled. The final study cohort of 41 patients received continuous IGU therapy more than 52 weeks. We reviewed the methods about the improvement of CRP, MMP3, DAS28-ESR and CDAI which was an index of disease activity of RA using Wilcoxon signed-rank test and the rate of remission patients at Week24, 52. Results: The group of patients included 6 males and 35 females. The mean age was 63.0±11.0 years old; the disease duration was 8.0±8.6 years and the methotrexate dose was 9.8±4.2 mg/week. Clinical findings related to RA were as follows: mean tender joint count, 5.2±5.
A highly polymorphic microsatellite (CA) n-marker (CAct685) previously isolated from human chromo... more A highly polymorphic microsatellite (CA) n-marker (CAct685) previously isolated from human chromosome 19 cosmid library was localized near GPI in 19q13.1. For the fine localization of this marker, the hybridization with chromosome 19-specific cosmid libraries assembled in contigs was used. Polymorphism analysis of the marker in 12 populations of Russia and neighboring countries showed 14 alleles containing from 16 to 30 repeat units. Populations belonging to Indo-European, Uralic and Altaic linguistic families demonstrated a great similarity in allele frequency profiles. Differences between these populations were lower for CAct685 than for classical markers. Allele distribution of CAct685 in a Chukchi population belonging to the Chukchi-Kamchatkan linguistic family differs from those in all other populations, that may be typical for Mongoloid population or reflect an ethnic history of Chukchi as a small population. Thus use of the CAct685 marker seems to be effective for analysis of distant peoples.
Long-Term Use of Nonsteroidal Antiinflammatory Drugs and the Risk of Colorectal Adenomas
Digestion, 2000
Aims: Previous studies have suggested that the regular use of NSAIDs reduces the risk of colorect... more Aims: Previous studies have suggested that the regular use of NSAIDs reduces the risk of colorectal adenomas. The aim of this study was to examine this association while taking possible confounding factors into account. Methods: The intake of drugs including NSAID intake during the last 20 years was assessed by means of a case-control study in 184 cases and matched hospital and community controls. Results: Overall, there were few individuals with a relevant drug intake for more than 5 years. NSAID intake for more than five years was associated with decreased risk in comparison with both control groups. The RR was 0.20 (0.04–1.04) compared with hospital and 0.21 (0.04–0.99) compared with population controls, the latter association being statistically significant. Subgroup analysis by type of drug revealed a significant protective effect only for long-term aspirin intake in relation to hospital controls, the RR being 0.09 (0.01–0.82). Conclusion: Our data support the hypothesis that t...
Serum amyloid A protein A (SAA) is a normal serum protein (serving as a precursor of fibrillar ti... more Serum amyloid A protein A (SAA) is a normal serum protein (serving as a precursor of fibrillar tissue protein AA), synthesized in the liver and a rapidly responding marker of the acute phase of inflammation. A constant high concentration of SAA is one of the factors in the development of AA-amyloidosis. As a rule, secondary amyloidosis develops in patients with long-term and poorly controlled inflammatory diseases, including rheumatic diseases, one of which is ankylosing spondylitis (AS).Objective: to assess the level of SAA in AS patients and its relationship with indicators of disease activity.Patients and methods. The study included 124 patients with AS who met the modified New York 1984 criteria. The disease activity and functional status of patients were assessed according to the recommendations of Russian experts. SAA and CRP, ESR in blood serum were measured in all patients.Results and discussion. The median SAA concentration was 12.5 mg/L [4; 71.6]. Of 124 patients, 31% had ...
The review analyzes data on the course and outcomes of axial spondyloarthritis (axSpA) accumulate... more The review analyzes data on the course and outcomes of axial spondyloarthritis (axSpA) accumulated over the previous 2.5 years of the COVID-19 pandemic. The issues of clinical and immunological efficacy of vaccination against COVID-19 in this disease are considered. It was noted that the presence of axSpA, as well as treatment with tumor necrosis factor-á inhibitors and non-steroidal anti-inflammatory drugs, did not significantly increase the risk of COVID-19 infection and did not worsen its outcomes, apart from an increase in the incidence of venous thromboembolism. At the same time, it is assumed that anticytokine therapy for SpA may protect against severe COVID-19 course.The data presented suggest that the benefits of vaccination in SpA far outweigh the potential harms associated with the development of adverse events. It has been shown that in patients with SpA, vaccination does not affect the activity of the inflammatory process, and biologic disease modifying antirheumatic dru...
Currently, the problem of reactive arthritis (ReA) remains important. This is due to the sufficie... more Currently, the problem of reactive arthritis (ReA) remains important. This is due to the sufficiently high prevalence of the disease. The analysis of epidemiological data allows us to put forward a number of possible reasons explaining the different frequency of ReA in certain regions of the Russian Federation and in other countries. The article details the clinical picture of the disease, analyzes the significance of various laboratory techniques aimed at identifying the causative agent of ReA. The main approaches to the therapy of ReA, including the use of antimicrobial drugs, are described.
BackgroundThe main goal of “T2T” strategy for spondyloarthritis (SpA) is to achieve clinical remi... more BackgroundThe main goal of “T2T” strategy for spondyloarthritis (SpA) is to achieve clinical remission or inactive disease. In 2001, the ASAS formulated criteria for partial remission [1], and the Russian Expert Group for Study of SpA (ExSpA) in 2018 identified clinical-laboratory remission (absence of clinical manifestations of the disease that persists for 6 months with normal values of CRP and ESR), MRI remission and complete remission (a combination of clinical-laboratory and MRI remission) [2].Objectivesto compare the ASAS criteria for partial remission and the clinical-laboratory remission in patients with early axial SpA (axSpA) at 3rd year of follow-up.MethodsThe study included patients with early axSpA (ASAS criteria 2009 with inflammation back pain duration less than 5 years) from the CORSAR cohort (Early SpondyloArthritis Cohort), formed at the V.A. Nasonova Research Institute of Rheumatology. The cohort includes 175 patients with axSpA. The analysis included 66 patient...
BackgroundThe main goal of “T2T” strategy for spondyloarthritis (SpA) is to achieve clinical remi... more BackgroundThe main goal of “T2T” strategy for spondyloarthritis (SpA) is to achieve clinical remission or inactive disease. In 2001, the ASAS formulated criteria for partial remission [1], and the Russian Expert Group for Study of SpA (ExSpA) in 2018 identified clinical-laboratory remission (absence of clinical manifestations of the disease that persists for 6 months with normal values of CRP and ESR) [2].Objectivesto analyze the therapy in patients with early axial spondyloarthritis who achieved the ASAS partial remission and the clinical-laboratory remission at the 3rd year of follow-up.MethodsThe study included patients with early axSpA (ASAS criteria 2009 with inflammation back pain duration less than 5 years) from the CORSAR cohort (Cohort of Early SpondyloArthritis), formed at the V.A. Nasonova Research Institute of Rheumatology. The cohort includes 175 patients with axSpA. The analysis included 66 patients followed for at least 3 years, of which 37 (56%) were men. The avera...
ABSTRACTSpondyloarthritis (SpA) comprises a number of inflammatory rheumatic diseases with overla... more ABSTRACTSpondyloarthritis (SpA) comprises a number of inflammatory rheumatic diseases with overlapping clinical manifestations. Strong association with several HLA-I alleles and T cell infiltration into an inflamed joint suggest involvement of T cells in SpA pathogenesis. In this study, we performed high-throughput T cell repertoire profiling of synovial fluid (SF) and peripheral blood (PB) samples collected from a large cohort of SpA patients. We showed that synovial fluid is enriched with expanded T cell clones that are shared between patients with similar HLA genotypes and persist during recurrent synovitis. Using the recently published algorithm we discovered antigen-driven CD8+ clonal groups associated with risk HLA-B*27 or HLA-B*38 alleles. These clonal groups were enriched in SF and had higher frequency in PB of SpA patients vs healthy donors, suggesting their relevance to joint inflammation. Several of the identified groups were shared among patients with ankylosing spondyli...
Ankylosing spondylitis is a chronic systemic inflammatory disease. Inflammation and high levels o... more Ankylosing spondylitis is a chronic systemic inflammatory disease. Inflammation and high levels of serum amyloid A (SAA) protein are predisposing factors for secondary AA amyloidosis. The role of SAA1 gene polymorphisms in AS is not well understood.To investigate the association of SAA1 gene polymorphism -13T/C (rs12218) with ankylosing spondylitis and to evaluate the influence of this polymorphism on SAA protein concentration.123 AS patients (72 males, 51 females; age - M (SD) 37.51 (12.77) years; disease duration - 14.28 (11.22) years; BASDAI – 5.59 (1.13); B27-positive - 111 (90.2%) pts) and 95 gender, age matched healthy individuals (control group) were included in this study. SAA1 gene polymorphism -13T/C was genotyped using allele-specific RT-PCR assay. SAA protein concentration was measured using nephelometry in AS patients.The distribution of genotypes TT, TC and CC differed statistically between AS and control groups (24.4%, 56.1%, 19.5% and 41.1%, 44.2%, 14.7% respectively...
Клиническая эффективность и переносимость мелокса (мелоксикама) при хронических заболеваниях суставов
Objective. To study efficacy and safety of Iwo doses of melox (meloxicam) in pts with rheumatoid ... more Objective. To study efficacy and safety of Iwo doses of melox (meloxicam) in pts with rheumatoid arthritis (RA) and osteoarthritis (OA). Material and methods. An open uncontrolled study of melox was performed on 20 pts with chronic rheumatic diseases: 10 with RA and 10 with OA, 18 female and 2 male, mean age respectively 57,5±11,1 and 65,0±7,6 years, mean duration of the disease - 11,1 ±9,9 and 5,6±6,2 years. 90% of RA pis had 2nd activity degree and 1I-IV stage of the disease. 6 pts of OA group had gonarthritis and 4 - coxarthri- tis, 7 pts had 11 and 3 - 111 radiological stage according to Kellgren classification. The drug was administered orally during 4 weeks. Initial dose was 7,5 mg/day. In case of insufficient efficacy it was increased till 15 mg/day in 5 days. Results. All 20 pts completed 4-weeks study. There were no adverse events leading to withdrawal of melox. In 10 pts dose was increased from 7,5 to 15 mg/day - 2 with OA and 8 with RA. According to opinion of pts and inv...
Almost half of patients with axial spondyloarthritis (axSpA) in Russia have hip joint lesions (HJ... more Almost half of patients with axial spondyloarthritis (axSpA) in Russia have hip joint lesions (HJ), but only in 7% of cases it becomes so severe and requires arthroplasty. The causes and rates of progression of coxitis have not been studied.To assess the relationship between disease activity and the sonographic synovitis of the hip joint with the progression of X-ray coxitis in patients with axSpA with a 2-year follow-up.The study included 77 patients (mean age 28 ± 5.92 years) with axSpA (ASAS criteria 2009), who were followed up for at least 2 years. Among them, AS (mNY criteria, 1984) had 66 (86%) patients, and nonradiographic axSpA - 11 (14%). The median duration of the disease was 30 [3–60] months, BASDAI - 4.5 [3.2; 5.9], BASFI - 2.4 [0.9; 4.8]. All patients underwent clinical examination, X-ray and ultrasound investigation of the hip joint during the monitoring period. For ultrasound, coxitis was considered an increase in the cervical-capsular distance (CCD) of more than 7 mm...
However, a case-control study with a larger population is necessary to determine whether patients... more However, a case-control study with a larger population is necessary to determine whether patients with RA express more shame and guilt than their peers without RA.
Background: Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease primari... more Background: Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease primarily affecting the sacroiliac joints and spine, causing pain, stiffness and loss of mobility and function. These manifestations can severely impair patients' quality of life (QoL). 1 Dual neutralisation of IL-17F in addition to IL-17A has been shown to reduce inflammation to a greater extent than inhibition of IL-17A alone in disease-relevant cell models. 2 Results previously reported from this Phase 2b study (NCT02963506) demonstrated that, during the 12-week double-blind treatment period, bimekizumab provided substantial clinical improvements in disease outcome measures, including Assessment of SpondyloArthritis international Society 40% (ASAS40), in patients with active AS. 3 Objectives: To assess the impact of bimekizumab on patient-reported and QoL outcomes at Week 12 in patients with active AS. Methods: In this 48-week Phase 2b study (double blind to Week 12 then dose blind to Week 48), 303 patients with active AS (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] !4; spinal pain !4 [0-10 numerical rating scale]), fulfilling the modified New York criteria, were randomised 1:1:1:1:1 to receive subcutaneous bimekizumab 16mg, 64mg, 160mg, 320mg or placebo Q4W for 12 weeks. Prior exposure to one anti-TNF therapy was permitted. Secondary and other endpoints included: BASDAI, !50% improvement in BASDAI (BASDAI 50), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life (ASQoL) and Patient's Global Assessment of Disease Activity (PGADA) at Week 12. Safety was also assessed. Results: Overall, 297 (98.0%) patients completed the 12-week double-blind period. Baseline scores on patient-reported and QoL outcomes were similar across treatment groups (Table). At Week 12, BASDAI 50 was achieved by 23.7-47.5% of bimekizumab-treated patients versus 11.9% receiving placebo. All bimekizumab doses were associated with greater reductions in individual BASDAI components, including: fatigue (range:-1.6 to-2.5 vs-0.8); neck, back or hip pain (-2.0 to-3.3 vs-1.2); discomfort due to tenderness to touch or pressure (-1.6 to-3.0 vs-1.1); level of morning stiffness (-2.5 to-3.5 vs-1.2) and duration of morning stiffness (-1.7 to-3.3 vs-1.4) (Table). Compared with placebo, greater reductions from baseline were also achieved with bimekizumab for BASFI (-1.4 to-2.2 vs-0.6), ASQoL (-2.3 to-4.6 vs-1.3) and PGADA (-1.9 to-3.3 vs-1.0). The overall incidence of treatment-emergent adverse events was 89/243 (36.6%) for bimekizumab-treated patients versus 23/60 (38.3%) for placebo; the majority were of mild or moderate intensity. No unexpected safety findings were observed. Conclusion: Dual neutralisation of IL-17A and IL-17F with bimekizumab was associated with improvements in patient-reported and QoL outcomes including pain, fatigue and tenderness in patients with active AS after 12 weeks of treatment. No new safety findings were observed versus previous studies of bimekizumab. 3,4
serum levels of cholesterol, LDL cholesterol and atherogenic index only showed association with r... more serum levels of cholesterol, LDL cholesterol and atherogenic index only showed association with reclassification in controls. The effect of each factor associated with reclassification in patients and controls was compared by the addition of interaction factors in the regression model. In this sense, age (beta coef 2.74 [IC95% 1.34-5.62] in controls vs. beta coef 0.63 (95% CI 0.40-0.99) in patients, interaction p=0.001) and serum LDL cholesterol levels (beta coef 1.03 [IC95% 1.02-1.04] vs. beta coef 1.00 [0.99-1.01], interaction p=0.002), cholesterol and atherogenic index, showed a greater effect in controls than in patients. The reclassification in patients with a-SpA was associated with a higher ASDAS-PCR (2.2 ± 1.0 VS. 2.5 ± 1.0, p=0.041), BASFI (3 [1-5] vs. 4 [2-7], p=0.000) and BASMI scores (2 [1-4] vs. 4 [2-5], p=0.000). However, these differences were lost when they were analyzed adjusting for CV risk factors. Conclusion: Patients with a-SpA are more likely to be reclassified into very high-risk after carotid ultrasound compared to controls. Traditional CV risk factors have less effect on this reclassification in patients than in controls. The activity, functionality and metrology scores of the a-SpA have a univariate positive relationship with this reclassification.
Spondyloarthritis – clinical aspects (other than treatment), 2018
Results: Data from 23 patients were analysed during the 52 weeks observational period. Mean age w... more Results: Data from 23 patients were analysed during the 52 weeks observational period. Mean age was 54.7 years, 60% of the patients were female. Mean DAS28 at baseline was 4.26, mean BSA 9%, whereas mean values for SJC were 5.9 and TJC 11.4 using 66/68 joint count. All patients were negative for ACPA and rheumatoid factor. ROC analysis revealed that a DACT cutoff of 4.55 at baseline, indicating moderate expression of fluorescence intensities in context of disease activity, shows a predictive quality to LDA achievement at W52 with 80% specificity, 78% sensitivity and likelihood ratios of 3.89 (LQ+) and 0.28 (LQ-). The corresponding AUC value is 0.717 (95%CI=[0.393, 1]; p=0.146). Compared to clinical disease measurements such as baseline DAS28, TJC or SJC, the DACT at BL is more discriminative to identify patients who attain LDA at W52. Conclusions: This interim analysis of the XPLORE study shows promising data for the use of FOI as possible imaging biomarker for disease activity measure and prediction of response in PsA-patients newly treated with antiTNF-therapy: Baseline values evaluated using the automated computer-based reading of the fluorescence intensities with a cutoff of 4.55 are predictive for later achievement of DAS28 low-disease activity or remission within the treatment course. Data will be verified in a larger cohort of the XPLORE study.
munosorbent assay. HLA DRB1, DQA1 and DQB1 genotype was determined using commercial sequence-spec... more munosorbent assay. HLA DRB1, DQA1 and DQB1 genotype was determined using commercial sequence-specific oligonucleotide kit. Statistical analysis was performed using Pearson Chi 2 , Fisher exact test, or Spearman correlation. Results: The median age at diagnosis was 43±13,28 years (range: 18-70), 48 patients exhibited myositis (98%), 35 ILD (73%), 43 arthritis (88%), 32 Raynaud's phenomen (65%), 21 fever (43%), 16 mechanic's hand (33%), 27 skin rash (55%) and 6 dysphagia (12%). We could detect significant correlation between the initial anti-Jo-1 titer and the first CK (R=0,328; p=0,003) and CRP (R=0,374; p=0,016) level. Furthermore anti-Jo1 levels during disease course had significant correlation to the corresponding CK (R=0,497; p<0.001), and CRP (R=0,325; p<0.001) level. The most frequent antibody besides anti-Jo-1 was anti-SSA (28/49; 57%). The anti-Jo-1+/SSA+ population had younger age at the diagnosis (36,12±11,08 vs. 47,22±12,87; p=0,004), lower rate of ILD (53% vs. 81%; p=0,039), but higher maintaining steroid (methylprednisolone) dose (9,53 mg vs. 3,7 mg; p=0,031) compared to the Jo-1+/SSA-group. Higher (≥8 mg) maintaining steroid therapy was associated with higher initiating CRP (36,34 vs. 17,84 mg/l; p=0,014) ESR (33,87 vs. 19,81 mm/h; p=0,032) level and higher presence of fever (67% vs. 37%; p=0,038) at diagnosis but not with initiating CK (p=0,374), LDH (p=0,224) level or ILD presence (p=1). 68,96% of the patients were HLA DRB1*03 positive, where the CK level at diagnosis was significantly lower compared to the HLA DRB1*03 negative patients (2816,30 vs. 5969,44 U/l; p=0.04). 58.62% of the patients were positive for HLA DQA1*0501-DQB1*0201 haplotype, but no significant correlation was found regarding to any clinical or laboratory features. Conclusions: Our results confirm previously reported data from other centers considering the clinical features of anti-Jo1 positive patients. HLA DRB1*03 positivity was associated with lower CK level but has no influence on clinical or serological features. It seems that anti-Jo1 level might reflect disease activity; ESR, CRP levels, associated fever and anti-SSA positivity at the diagnosis could be considered as prognostic markers.
RF, anti-citrullinated protein antibodies, and disease activity measures for SpA and RA were asse... more RF, anti-citrullinated protein antibodies, and disease activity measures for SpA and RA were assessed. The rheumatologic Scores and periodontal condition were evaluated by two experienced and calibrated periodontists and rheumatologist. The groups were compared with Kruskal Wallis, Mann-Whitney U and Wilcoxon test's test and a paired t-test. The chi-square test was used to evaluate periodontal variables and SpA disease activity. The institutional Ethics Committee approved the study. Results: 79 SpA patients with the following subtypes were included: Ankylosing Spondylitis (AS) (19), undifferentiated SpA (46), and reactive arthritis (ReA) (14). SpA patients had a considerable frequency of periodontitis (55.7%). Of them, 39.2% were classified as moderate and 2.5% as severe periodontal condition. No differences was found in frequency of periodontal condition between subtypes. SpA patients showed lower levels of insertion loss compared to RA patients and the control group (p<0.05). A significant association was observed in microbiological variables of SpA patients. The frequency of (P gingivalis) in the control group was 51.9% compared to 30% in SpA (p=0.015), especially in those with good response to NSAIDS (p= <0.05). Significant associations between the severity of periodontal involvement in RA patients was observed. 63.8% of RA patients had moderate severity disease (49.2%) and severe periodontitis (13.6%) (p=0.035) but not in SpA group. There were not association between disease activity measures in SpA, periodontal and severity condition. Conclusions: As compared to RA and healthy controls, periodontal condition in SpA patients was similar. Lower grades of severity and bacterial load were found. This suggests that an interdisciplinary treatment between periodontists and rheumatologists may help to modulate periodontal condition and prevent systemic impact References:
Background: Iguratimod (IGU) is a small-molecule antirheumatic drug that was approved in Japan in... more Background: Iguratimod (IGU) is a small-molecule antirheumatic drug that was approved in Japan in September 2012. IGU suppressed tumor necrosis factoralpha-induced production of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein 1 via inhibition of nuclear factor kappa B activation in cultured human synovial cells and human acute monocytic leukemia cells. IGU also reduced immunoglobulin production by acting directly on human B lymphocytes without affecting B lymphocyte proliferation. Recently, an increased release of extracellular adenosine and a decreased production of lymphotoxins such as ammonia and superoxide have been shown to be involved in the anti-inflammatory mechanisms of methotrexate. Thus, the combination of MTX and IGU may have synergic efficacy for rheumatoid arthritis (RA) treatment. Objectives: To evaluate the clinical efficacy of add-on IGU in patients with Japanese active RA who had shown inadequate responses to MTX therapy from initiation to 52-week. Methods: Patients with a diagnosis of RA according to the 2010 ACR/EULAR criteria who had been unresponsive to MTX therapy (DAS>3.2 or CDAI>10), and who had been prescribed add-on IGU from Tsurumai Biologics Communication Registry (TBCR)-plus between November 2012 and September 2013 were enrolled. The final study cohort of 41 patients received continuous IGU therapy more than 52 weeks. We reviewed the methods about the improvement of CRP, MMP3, DAS28-ESR and CDAI which was an index of disease activity of RA using Wilcoxon signed-rank test and the rate of remission patients at Week24, 52. Results: The group of patients included 6 males and 35 females. The mean age was 63.0±11.0 years old; the disease duration was 8.0±8.6 years and the methotrexate dose was 9.8±4.2 mg/week. Clinical findings related to RA were as follows: mean tender joint count, 5.2±5.
A highly polymorphic microsatellite (CA) n-marker (CAct685) previously isolated from human chromo... more A highly polymorphic microsatellite (CA) n-marker (CAct685) previously isolated from human chromosome 19 cosmid library was localized near GPI in 19q13.1. For the fine localization of this marker, the hybridization with chromosome 19-specific cosmid libraries assembled in contigs was used. Polymorphism analysis of the marker in 12 populations of Russia and neighboring countries showed 14 alleles containing from 16 to 30 repeat units. Populations belonging to Indo-European, Uralic and Altaic linguistic families demonstrated a great similarity in allele frequency profiles. Differences between these populations were lower for CAct685 than for classical markers. Allele distribution of CAct685 in a Chukchi population belonging to the Chukchi-Kamchatkan linguistic family differs from those in all other populations, that may be typical for Mongoloid population or reflect an ethnic history of Chukchi as a small population. Thus use of the CAct685 marker seems to be effective for analysis of distant peoples.
Long-Term Use of Nonsteroidal Antiinflammatory Drugs and the Risk of Colorectal Adenomas
Digestion, 2000
Aims: Previous studies have suggested that the regular use of NSAIDs reduces the risk of colorect... more Aims: Previous studies have suggested that the regular use of NSAIDs reduces the risk of colorectal adenomas. The aim of this study was to examine this association while taking possible confounding factors into account. Methods: The intake of drugs including NSAID intake during the last 20 years was assessed by means of a case-control study in 184 cases and matched hospital and community controls. Results: Overall, there were few individuals with a relevant drug intake for more than 5 years. NSAID intake for more than five years was associated with decreased risk in comparison with both control groups. The RR was 0.20 (0.04–1.04) compared with hospital and 0.21 (0.04–0.99) compared with population controls, the latter association being statistically significant. Subgroup analysis by type of drug revealed a significant protective effect only for long-term aspirin intake in relation to hospital controls, the RR being 0.09 (0.01–0.82). Conclusion: Our data support the hypothesis that t...
Serum amyloid A protein A (SAA) is a normal serum protein (serving as a precursor of fibrillar ti... more Serum amyloid A protein A (SAA) is a normal serum protein (serving as a precursor of fibrillar tissue protein AA), synthesized in the liver and a rapidly responding marker of the acute phase of inflammation. A constant high concentration of SAA is one of the factors in the development of AA-amyloidosis. As a rule, secondary amyloidosis develops in patients with long-term and poorly controlled inflammatory diseases, including rheumatic diseases, one of which is ankylosing spondylitis (AS).Objective: to assess the level of SAA in AS patients and its relationship with indicators of disease activity.Patients and methods. The study included 124 patients with AS who met the modified New York 1984 criteria. The disease activity and functional status of patients were assessed according to the recommendations of Russian experts. SAA and CRP, ESR in blood serum were measured in all patients.Results and discussion. The median SAA concentration was 12.5 mg/L [4; 71.6]. Of 124 patients, 31% had ...
The review analyzes data on the course and outcomes of axial spondyloarthritis (axSpA) accumulate... more The review analyzes data on the course and outcomes of axial spondyloarthritis (axSpA) accumulated over the previous 2.5 years of the COVID-19 pandemic. The issues of clinical and immunological efficacy of vaccination against COVID-19 in this disease are considered. It was noted that the presence of axSpA, as well as treatment with tumor necrosis factor-á inhibitors and non-steroidal anti-inflammatory drugs, did not significantly increase the risk of COVID-19 infection and did not worsen its outcomes, apart from an increase in the incidence of venous thromboembolism. At the same time, it is assumed that anticytokine therapy for SpA may protect against severe COVID-19 course.The data presented suggest that the benefits of vaccination in SpA far outweigh the potential harms associated with the development of adverse events. It has been shown that in patients with SpA, vaccination does not affect the activity of the inflammatory process, and biologic disease modifying antirheumatic dru...
Currently, the problem of reactive arthritis (ReA) remains important. This is due to the sufficie... more Currently, the problem of reactive arthritis (ReA) remains important. This is due to the sufficiently high prevalence of the disease. The analysis of epidemiological data allows us to put forward a number of possible reasons explaining the different frequency of ReA in certain regions of the Russian Federation and in other countries. The article details the clinical picture of the disease, analyzes the significance of various laboratory techniques aimed at identifying the causative agent of ReA. The main approaches to the therapy of ReA, including the use of antimicrobial drugs, are described.
BackgroundThe main goal of “T2T” strategy for spondyloarthritis (SpA) is to achieve clinical remi... more BackgroundThe main goal of “T2T” strategy for spondyloarthritis (SpA) is to achieve clinical remission or inactive disease. In 2001, the ASAS formulated criteria for partial remission [1], and the Russian Expert Group for Study of SpA (ExSpA) in 2018 identified clinical-laboratory remission (absence of clinical manifestations of the disease that persists for 6 months with normal values of CRP and ESR), MRI remission and complete remission (a combination of clinical-laboratory and MRI remission) [2].Objectivesto compare the ASAS criteria for partial remission and the clinical-laboratory remission in patients with early axial SpA (axSpA) at 3rd year of follow-up.MethodsThe study included patients with early axSpA (ASAS criteria 2009 with inflammation back pain duration less than 5 years) from the CORSAR cohort (Early SpondyloArthritis Cohort), formed at the V.A. Nasonova Research Institute of Rheumatology. The cohort includes 175 patients with axSpA. The analysis included 66 patient...
BackgroundThe main goal of “T2T” strategy for spondyloarthritis (SpA) is to achieve clinical remi... more BackgroundThe main goal of “T2T” strategy for spondyloarthritis (SpA) is to achieve clinical remission or inactive disease. In 2001, the ASAS formulated criteria for partial remission [1], and the Russian Expert Group for Study of SpA (ExSpA) in 2018 identified clinical-laboratory remission (absence of clinical manifestations of the disease that persists for 6 months with normal values of CRP and ESR) [2].Objectivesto analyze the therapy in patients with early axial spondyloarthritis who achieved the ASAS partial remission and the clinical-laboratory remission at the 3rd year of follow-up.MethodsThe study included patients with early axSpA (ASAS criteria 2009 with inflammation back pain duration less than 5 years) from the CORSAR cohort (Cohort of Early SpondyloArthritis), formed at the V.A. Nasonova Research Institute of Rheumatology. The cohort includes 175 patients with axSpA. The analysis included 66 patients followed for at least 3 years, of which 37 (56%) were men. The avera...
ABSTRACTSpondyloarthritis (SpA) comprises a number of inflammatory rheumatic diseases with overla... more ABSTRACTSpondyloarthritis (SpA) comprises a number of inflammatory rheumatic diseases with overlapping clinical manifestations. Strong association with several HLA-I alleles and T cell infiltration into an inflamed joint suggest involvement of T cells in SpA pathogenesis. In this study, we performed high-throughput T cell repertoire profiling of synovial fluid (SF) and peripheral blood (PB) samples collected from a large cohort of SpA patients. We showed that synovial fluid is enriched with expanded T cell clones that are shared between patients with similar HLA genotypes and persist during recurrent synovitis. Using the recently published algorithm we discovered antigen-driven CD8+ clonal groups associated with risk HLA-B*27 or HLA-B*38 alleles. These clonal groups were enriched in SF and had higher frequency in PB of SpA patients vs healthy donors, suggesting their relevance to joint inflammation. Several of the identified groups were shared among patients with ankylosing spondyli...
Ankylosing spondylitis is a chronic systemic inflammatory disease. Inflammation and high levels o... more Ankylosing spondylitis is a chronic systemic inflammatory disease. Inflammation and high levels of serum amyloid A (SAA) protein are predisposing factors for secondary AA amyloidosis. The role of SAA1 gene polymorphisms in AS is not well understood.To investigate the association of SAA1 gene polymorphism -13T/C (rs12218) with ankylosing spondylitis and to evaluate the influence of this polymorphism on SAA protein concentration.123 AS patients (72 males, 51 females; age - M (SD) 37.51 (12.77) years; disease duration - 14.28 (11.22) years; BASDAI – 5.59 (1.13); B27-positive - 111 (90.2%) pts) and 95 gender, age matched healthy individuals (control group) were included in this study. SAA1 gene polymorphism -13T/C was genotyped using allele-specific RT-PCR assay. SAA protein concentration was measured using nephelometry in AS patients.The distribution of genotypes TT, TC and CC differed statistically between AS and control groups (24.4%, 56.1%, 19.5% and 41.1%, 44.2%, 14.7% respectively...
Клиническая эффективность и переносимость мелокса (мелоксикама) при хронических заболеваниях суставов
Objective. To study efficacy and safety of Iwo doses of melox (meloxicam) in pts with rheumatoid ... more Objective. To study efficacy and safety of Iwo doses of melox (meloxicam) in pts with rheumatoid arthritis (RA) and osteoarthritis (OA). Material and methods. An open uncontrolled study of melox was performed on 20 pts with chronic rheumatic diseases: 10 with RA and 10 with OA, 18 female and 2 male, mean age respectively 57,5±11,1 and 65,0±7,6 years, mean duration of the disease - 11,1 ±9,9 and 5,6±6,2 years. 90% of RA pis had 2nd activity degree and 1I-IV stage of the disease. 6 pts of OA group had gonarthritis and 4 - coxarthri- tis, 7 pts had 11 and 3 - 111 radiological stage according to Kellgren classification. The drug was administered orally during 4 weeks. Initial dose was 7,5 mg/day. In case of insufficient efficacy it was increased till 15 mg/day in 5 days. Results. All 20 pts completed 4-weeks study. There were no adverse events leading to withdrawal of melox. In 10 pts dose was increased from 7,5 to 15 mg/day - 2 with OA and 8 with RA. According to opinion of pts and inv...
Almost half of patients with axial spondyloarthritis (axSpA) in Russia have hip joint lesions (HJ... more Almost half of patients with axial spondyloarthritis (axSpA) in Russia have hip joint lesions (HJ), but only in 7% of cases it becomes so severe and requires arthroplasty. The causes and rates of progression of coxitis have not been studied.To assess the relationship between disease activity and the sonographic synovitis of the hip joint with the progression of X-ray coxitis in patients with axSpA with a 2-year follow-up.The study included 77 patients (mean age 28 ± 5.92 years) with axSpA (ASAS criteria 2009), who were followed up for at least 2 years. Among them, AS (mNY criteria, 1984) had 66 (86%) patients, and nonradiographic axSpA - 11 (14%). The median duration of the disease was 30 [3–60] months, BASDAI - 4.5 [3.2; 5.9], BASFI - 2.4 [0.9; 4.8]. All patients underwent clinical examination, X-ray and ultrasound investigation of the hip joint during the monitoring period. For ultrasound, coxitis was considered an increase in the cervical-capsular distance (CCD) of more than 7 mm...
However, a case-control study with a larger population is necessary to determine whether patients... more However, a case-control study with a larger population is necessary to determine whether patients with RA express more shame and guilt than their peers without RA.
Background: Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease primari... more Background: Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease primarily affecting the sacroiliac joints and spine, causing pain, stiffness and loss of mobility and function. These manifestations can severely impair patients' quality of life (QoL). 1 Dual neutralisation of IL-17F in addition to IL-17A has been shown to reduce inflammation to a greater extent than inhibition of IL-17A alone in disease-relevant cell models. 2 Results previously reported from this Phase 2b study (NCT02963506) demonstrated that, during the 12-week double-blind treatment period, bimekizumab provided substantial clinical improvements in disease outcome measures, including Assessment of SpondyloArthritis international Society 40% (ASAS40), in patients with active AS. 3 Objectives: To assess the impact of bimekizumab on patient-reported and QoL outcomes at Week 12 in patients with active AS. Methods: In this 48-week Phase 2b study (double blind to Week 12 then dose blind to Week 48), 303 patients with active AS (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] !4; spinal pain !4 [0-10 numerical rating scale]), fulfilling the modified New York criteria, were randomised 1:1:1:1:1 to receive subcutaneous bimekizumab 16mg, 64mg, 160mg, 320mg or placebo Q4W for 12 weeks. Prior exposure to one anti-TNF therapy was permitted. Secondary and other endpoints included: BASDAI, !50% improvement in BASDAI (BASDAI 50), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life (ASQoL) and Patient's Global Assessment of Disease Activity (PGADA) at Week 12. Safety was also assessed. Results: Overall, 297 (98.0%) patients completed the 12-week double-blind period. Baseline scores on patient-reported and QoL outcomes were similar across treatment groups (Table). At Week 12, BASDAI 50 was achieved by 23.7-47.5% of bimekizumab-treated patients versus 11.9% receiving placebo. All bimekizumab doses were associated with greater reductions in individual BASDAI components, including: fatigue (range:-1.6 to-2.5 vs-0.8); neck, back or hip pain (-2.0 to-3.3 vs-1.2); discomfort due to tenderness to touch or pressure (-1.6 to-3.0 vs-1.1); level of morning stiffness (-2.5 to-3.5 vs-1.2) and duration of morning stiffness (-1.7 to-3.3 vs-1.4) (Table). Compared with placebo, greater reductions from baseline were also achieved with bimekizumab for BASFI (-1.4 to-2.2 vs-0.6), ASQoL (-2.3 to-4.6 vs-1.3) and PGADA (-1.9 to-3.3 vs-1.0). The overall incidence of treatment-emergent adverse events was 89/243 (36.6%) for bimekizumab-treated patients versus 23/60 (38.3%) for placebo; the majority were of mild or moderate intensity. No unexpected safety findings were observed. Conclusion: Dual neutralisation of IL-17A and IL-17F with bimekizumab was associated with improvements in patient-reported and QoL outcomes including pain, fatigue and tenderness in patients with active AS after 12 weeks of treatment. No new safety findings were observed versus previous studies of bimekizumab. 3,4
serum levels of cholesterol, LDL cholesterol and atherogenic index only showed association with r... more serum levels of cholesterol, LDL cholesterol and atherogenic index only showed association with reclassification in controls. The effect of each factor associated with reclassification in patients and controls was compared by the addition of interaction factors in the regression model. In this sense, age (beta coef 2.74 [IC95% 1.34-5.62] in controls vs. beta coef 0.63 (95% CI 0.40-0.99) in patients, interaction p=0.001) and serum LDL cholesterol levels (beta coef 1.03 [IC95% 1.02-1.04] vs. beta coef 1.00 [0.99-1.01], interaction p=0.002), cholesterol and atherogenic index, showed a greater effect in controls than in patients. The reclassification in patients with a-SpA was associated with a higher ASDAS-PCR (2.2 ± 1.0 VS. 2.5 ± 1.0, p=0.041), BASFI (3 [1-5] vs. 4 [2-7], p=0.000) and BASMI scores (2 [1-4] vs. 4 [2-5], p=0.000). However, these differences were lost when they were analyzed adjusting for CV risk factors. Conclusion: Patients with a-SpA are more likely to be reclassified into very high-risk after carotid ultrasound compared to controls. Traditional CV risk factors have less effect on this reclassification in patients than in controls. The activity, functionality and metrology scores of the a-SpA have a univariate positive relationship with this reclassification.
Spondyloarthritis – clinical aspects (other than treatment), 2018
Results: Data from 23 patients were analysed during the 52 weeks observational period. Mean age w... more Results: Data from 23 patients were analysed during the 52 weeks observational period. Mean age was 54.7 years, 60% of the patients were female. Mean DAS28 at baseline was 4.26, mean BSA 9%, whereas mean values for SJC were 5.9 and TJC 11.4 using 66/68 joint count. All patients were negative for ACPA and rheumatoid factor. ROC analysis revealed that a DACT cutoff of 4.55 at baseline, indicating moderate expression of fluorescence intensities in context of disease activity, shows a predictive quality to LDA achievement at W52 with 80% specificity, 78% sensitivity and likelihood ratios of 3.89 (LQ+) and 0.28 (LQ-). The corresponding AUC value is 0.717 (95%CI=[0.393, 1]; p=0.146). Compared to clinical disease measurements such as baseline DAS28, TJC or SJC, the DACT at BL is more discriminative to identify patients who attain LDA at W52. Conclusions: This interim analysis of the XPLORE study shows promising data for the use of FOI as possible imaging biomarker for disease activity measure and prediction of response in PsA-patients newly treated with antiTNF-therapy: Baseline values evaluated using the automated computer-based reading of the fluorescence intensities with a cutoff of 4.55 are predictive for later achievement of DAS28 low-disease activity or remission within the treatment course. Data will be verified in a larger cohort of the XPLORE study.
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