[The efficacy of non-sreroidal anti-inflammatory drugs]. / Éffektivnost' nesteroidnykh protivovospalitel'nykh preparatov.

The paper presents current views on the efficacy of nonsteroidal anti-inflammatory drugs (NSAID). The authors analyze strengths and weaknesses of modern approaches and trends in the use of NSAID and highlight promising directions for clinical research of NSAIDs' efficacy.

[Spondyloarthritis: modern terminology and definitions].

Aim to identify outdated terms and make changes to the terminology of spondyloarthritis. MATERIALS AND METHODS: At the first stage of the work, the terms divided into two categories: "outdated" definitions and terms that need to be improved or unified. Subsequently, each member of the Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia (ExSpA) presented by its own definition of the designated term or agreed with the previous term. At the next stage, the existing definitions were put together. After discussion, experts left a term that scored at least 2/3 of the votes. The special opinion of experts was recorded, whose did not coincide with the majority opinion. An open vote was conducted, when defining an "outdated" term with the unanimous decision of all group members, this term was not recommended for further clinical use. RESULTS: The work carried out allowed us to identify a number of terms that are not recommended for use in clinical practice. Number of terms are defined, which should be used when discussing the problem of spondyloarthritis. CONCLUSION: The Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia suggests using or, accordingly, not using a number of terms and their definitions in clinical practice.

[Effectiveness of the tenoxicam in patients with ankylosing spondylitis]. / Éffektivnost' tenoksikama u bol'nykh s ankiloziruiushchim spondilitom.

AIM: To study the changes in pain syndrome and its characteristic in patients with ankylosing spondylitis (AS) who received tenoxicam after non-effective treatment with NSAIDs on the 'on-demand' basis. MATERIAL AND METHODS: Forty patients with AS, who had BASDAI ≥4.0 at baseline and after 52 weeks of NSAIDs on the 'on-demand' basis, were randomized into 2 groups: 30 patients were prescribed 20 mg of tenoxicam oraly per day, 10 patients continued previous therapy. The BASDAI, ASDAS indices were calculated in 52 and 56 weeks. RESULTS AND CONCLUSION: BASDAI and ASDAS indices decreased in patients treated with tenoxicam, the AS activity in patients with on-demand NSAID intake did not change. The change of the ineffective long-term NSAID intake in the 'on-demand' basis to permanent drug intake was associated with a rapid (within 4 weeks) decrease in the clinical activity of ankylosing spondylitis.

[The clinical diagnostic significance of auto antibodies to CD74 at axial spondylarthritis.]

The modern diagnostic approaches permit to diagnose axial spondylarthrosis (axSpA) at roentgenologic stage corresponding to ankylosing spondylitis (AS). While early diagnostic of non-roentgenologic axSpA (nr-axSpA) is still complicated. This situation conditions a need in searching new laboratory biomarkers for early diagnostic of spondylarthrosis, including auto-antibodies to antigen CD74 described recently. The purpose of study is to evaluate clinical diagnostic significance of auto-antibodies to antigen CD74 in case of axSpA. The technique of quantitative enzyme-linked immunosorbent assay was applied to measure content of auto-antibodies IgA to CD74 in samples of serum from 140 patients with axSpA: 68 with AS, 46 with nr-axSpA, 26 with psoriatic arthritis (PA) and 37 healthy representatives of control group with signs of axSpA totally clinically excluded. The average values of concentration of auto-antibodies IgA to CD74 in patients with axSpA and nr-axSpA made up to 3,5 ± 3,0 and 3,8 ± 2,9 U/ml correspondingly that reliably and significantly differed from patients with PA and healthy individuals - 2,1 ± 1,4 and 1,3 ± 1,4 U/ml correspondingly (p < 0,05). At threshold value of content of auto-antibodies IgA to CD74 higher than 2.0 U/ml in case of axSpA diagnostic sensitivity made up to 64.4%, specificity - 89.2%, risk factor of positive result - 5.9 whereas in patients with nr-axSpA at concentration 1.7 U/ml - 73,1%, 84% and 4,5 correspondingly. The auto-antibodies IgA to antigen CD74 are associated withaxSpA but not with PA that permits to use the given marker for diagnostic of axial spondylarthrosis and also in case of differential diagnostic between axSpA and PA.

Comorbidities in inflammatory joint and spine diseases in XXI century.

AIM: The evaluation the occurrence of comorbidities in patients with inflammatory diseases of the spine and joints and the assessment of the general changes in comorbidities at the beginning of the XXI century compared to previous period. MATERIALS AND METHODS: Comorbidity was analyzed in 245 patients with spondyloarthritis who participated in the scientific program PROGRESS. Validated comorbidity assessment indices were used in the study. The analysis of 96 sources of literary bases RISC and PubMed were used in literature analysis. The results of their own observation and literary search were compared. RESULTS: According to the patients' cards, an analysis of the structure of comorbidities was conducted in 221 patients: 207 (93.66%) patients with spondyloarthritis had two or more comorbidities. The most common diseases were diseases of gastrointestinal tract (60.6%) and cardiovascular pathology (58.3%), secondary osteoarthritis (60.2%). According to literature sources, most of the comorbidities and spondyloarthritis are interrelated pathogenetically and undergo a change in the profile of rheumatic and/or related diseases undergo simultaneous changes. The emergence of new diseases in the structure of comorbidity and new drugs requires the development of recommendations that take into account the presence of comorbidity in patients with a rheumatic diseases. CONCLUSION: Most patients with spondyloarthritis has comorbidity. The change in rheumatic and non-rheumatic diseases that occurs in the 21st century has a mutual influence, changing the profile of patients and determining the change in the tactics of their management.

[Efficiency of different celecoxib regimens in patients with active axial spondyloarthritis: Results of the 4-week pilot open-label comparative single-center study 'AIM']. / Éffektivnost' raznykh rezhimov primeneniia tselekoksiba u patsientov s aktivnym aksial'nym spondiloartritom: rezul'taty 4-nedel'nogo pilotnogo otkrytogo sravnitel'nogo odnotsentrovogo issledovaniia 'TsEL''.

AIM: To compare the efficiency and safety of two celecoxib regimens in the short-term treatment of patients with axial spondyloarthritis (axSpA). SUBJECTS AND METHODS: Examinations were made in 40 patients with axSpA (the 2009 ASAS criteria; age, 38.5±12.1 years; 29 (72.5%) men; axSpA duration, 6.67±5.8 years; BASDAI ≥4.0), who were randomly divided into two groups: 1) 20 patients who received celecoxib 400 mg/day for 30 days; 2) 20 patients who took celecoxib 600 mg/day for 7 days, then the drug was continued at a dose of 200 mg/day for 1 month. High-sensitivity C-reactive protein (CRP) was determined; back pain was assessed using a visual analog scale; ASDAS-CRP scores were calculated at baseline (day 0) and on days 8 and 30. RESULTS: On days 0, 8, and 30 of taking celecoxib 400 mg, the back pain scores were 6.0±3.01, 5.06±2.04, and 5.53±2.35; CRP levels, 24.13±21.46; 27.3±29.3%, and 13.1±21.3 mg/l; erythrocyte sedimentation rate (ESR), 15.25±14.36, 11.85±13.6, and 9.5±6.34 mm/h, respectively (p≥0.05 for all differences in all indicators relative to the baseline values). ASDAS was 3.34±1.02 at baseline, 2.74±1.14 on day 8, and 2.18±1.05 on day 30 (p=0.016 and p=0,000 for differences from the baseline values). In the patients using the dose de-escalation of celecoxib, the back pain scores were 4.95±1.6, 4.11±1.0, and 4.89±2.1 at baseline and on days 8 and 30, respectively (p=0.38 and p=0.065 for the differences from the baseline values); the CRP levels were 15.3±12.5, 12.1±10.8, and 7.5±4.5 mg/l, respectively (p=0.3 and p=0.001); ESR, 13.35±7.2, 15.7±11.6, and 15.16±8.9 mm/h (p≥0.05). At baseline and on days 8 and 30, ASDAS was 3.1±0.6, 2.22±0.7, and 3.47±0.56, respectively (p=0.02 and p=0.000). No differences were found in the rate of adverse events. CONCLUSION: Different regimens using nonsteroidal anti-inflammatory drugs demonstrated their feasibility, efficiency, and safety in AxSpA patients with high disease activity. The continuous use of celecoxib showed a gradual decrease in clinical and laboratory activity. The de-escalation dose of celecoxib achieved a permanent laboratory activity reduction and pain relief when using 600 mg celecoxib, and after reducing its dose to 200 mg/day, there was a decrease in laboratory disease activity without substantially changing the patients' functional activity. The safety of the comparable regimens was comparable.

[Changes in the serum concentrations of adhesion molecules and vascular endothelial growth factor in active ankylosing spondylitis patients taking amtolmetin guacil: Results of a 56-week prospective ореn-label controlled observational study]. / Izmenenie kontsentratsii molekul adgezii i faktora rosta éndoteliia sosudov v syvorotke krovi pri primenenii amtolmetina guatsila u patsientov s aktivnym ankiloziruiushchim spondilitom: rezul'taty 56-nedel'nogo prospektivnogo otkrytogo kontroliruemogo nabliudeniia.

AIM: To estimate changes in the concentrations of adhesion molecules and vascular endothelial growth factor A after 30-day additional use of amtolmetin guacil (AMG) in patients with active ankylosing spondylitis (AS) who were unresponsive to previous one-year treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). SUBJECTS AND METHODS: 20 patients with active AS who had not reached a BASDAI score <4.0 at week 52 of NSAID therapy and 10 healthy individuals matched for cardiovascular risk factors were examined. After 52 weeks of NSAID therapy, AMG was administered orally at 1200 mg/day to patients with AS for 30 days. The concentrations of adhesion molecules (sICAM-1 and sVCAM-1) and VEGF-A were measured. BASDAI and ASDAS scores and C-reactive protein (CRP) levels were determined in AS patients. The concentrations of adhesion molecules and VEGF-A were investigated in patients with AS at baseline, at 52 weeks after NSAID treatment start, and at 30 days following AMH initiation (at week 56) and in healthy individuals at baseline and at 30 days. RESULTS: The concentration of sICAM-1 in patients with AS was 987.0±217.39, 938.98±293.31, and 364.25±363.3 ng/ml at weeks 0, 52, and 56, respectively; that in healthy individuals was 769.25±189.32 and 740.05±225.76 ng/ml at baseline and at 30 days, respectively. The differences from the baseline concentration were significant in patients with AS (p<0.05) and insignificant in healthy subjects (p≥0.05); the differences between the concentrations in patients with AS and the controls were significant at baseline and at 52 weeks (p<0.05). The concentration of sVCAM-1 in patients with AS was 364.25±160.49, 325.34±245.1, and 319.1±248.73 ng/ml at weeks 0, 52 and 56, respectively; that in healthy individuals was 245.13±40.4 and 248.73±34.42 ng/ml, respectively (p<0.05 vs baseline values and values in healthy subjects). The level of VEGF-A in AS patients was not different from that in healthy individuals, but decreased during treatment. Correlations were found between the concentration of adhesion molecules and the level of CRP (p<0.01). CONCLUSION: Elevated concentrations of adhesion molecules have been found in AS patients compared with healthy individuals. The study has demonstrated that AMG treatment is efficient in treating patients with AS. NSAID/AMG treatment is associated with lower concentrations of adhesion molecules. Decreased CRP levels serve as predictors for reduced concentration of adhesion molecules. The level of VEGF-A at baseline did not differ from that in healthy subjects, but was decreased during treatment with NSAIDs.

[Stable high interleukin-17A concentration in patients with ankylosing spondylitis treated with tumor necrosis factor-α inhibitors during a year]. / Kontsentratsiia interleikina-17A ostaetsia stabil'no vysokoi u bol'nykh ankiloziruiushchim spondilitom, poluchaiushchikh ingibitory faktora nekroza opukholi α v techenie goda.

AIM: To assess changes in the concentration of interleukin-17A (IL-17A) in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor-α (TNFα) inhibitors during a year. SUBJECTS AND METHODS: Examinations were made in 30 patients (22 (73.3%) men) aged 38.35±9.19 years with AS (modified New-York criteria, BASDAI ≥4.0; AS duration, 11.4±9.6 years) and in 20 healthy individuals (12 (60%) men) aged 40.1±7.7 years) (a control group). All the patients were treated with infliximab (remicade, MSD) 5 mg/kg body weight during a year according to the recommended regimen. BASDAI and ASDAS were calculated; C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and TNFα and IL-17A concentrations were measured before and 52±2 weeks after TNFα inhibitors treatment. BASDAI/ASDAS improvement, ESR and CRP decreases; ASAS20/40 responses, ASAS partial remission, and an ASDAS improvement were estimated. RESULTS: In the patients with AS, the concentrations of TNFα and IL-17A were higher than those in the healthy individuals (p < 0.000). Twelve (40%) AS patients treated with TNFα inhibitors achieved ASAS partial remission. The average estimated back pain, ASDAS and BASDAI scores, and CRP and ESR substantially reduced (p<0.000 for all). The concentration of TNFα decreased from 17.8±7.6 to 7.3±3.2 pg/ml (p<0.000). The IL-17A level was 28.4±14.4 and 32.1±12.2 pg/ml before and after the treatment, respectively. The baseline level of IL-17A was lower in the patients with AS who had achieved remission than that in those who had not (p=0.01). CONCLUSION: The improvement due to one-year AS treatment with TNFα inhibitors is not associated with the reduction of IL-17A concentrations. In the patients who failed to achieve ASAS partial remission, the baseline and final serum concentrations of IL-17A were higher than in those who achieved the remission.

[Biomarkers of bone remodeling in ankylosing spondylitis patients using nonsteroidal anti-inflammatory drugs: results of an ETHICS research program]. / Biomarkery remodelirovaniia kosti u bol'nykh ankiloziruiushchim spondilitom, primeniaiushchikh nesteroidnye protivovospalitel'nye preparaty: rezul'taty nauchnoi programmy ÉTIKA.

AIM: To evaluate changes in the concentration of biomarkers for osteoproliferation and bone resorption in ankylosing spondylitis (AS) patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) in different regimens. SUBJECTS AND METHODS: Forty patients with AS (according to the modified New York criteria), who had BASDAI ≥ 4.0 at baseline and at 52 weeks of on-demand NSAID treatment were examined and randomized into 2 groups: 1) 30 patients who used continuously oral tenoxicam 20 mg daily (a study group); 2) 10 patients who continued previous therapy (a comparison group). BASDAI and ASDAS were calculated; the serum levels of C-reactive protein, C-terminal type I procollagen propeptide (PICP), and C-terminal telopeptide of type I collagen (CTX-I) were measured at baseline and at 52 and 56 weeks of treatment. A control group consisted of 19 healthy volunteers. RESULTS: The continuous use of NSAIDs (tenoxicam) decreased higher baseline BASDAI and ASDAS scores. There were no changes in the indicators of AS activity in the patients who took on-demand NSAIDs. Baseline CTX-I levels did not differ between the patients with AS and the healthy individuals; those declined during continuous intake of tenoxicam and remained unchanged during on-demand administration. In the patients with AS, baseline PICP levels exceeded those in the healthy individuals. In the tenoxicam-treated patients, the concentrations of PICP at baseline and at 52 and 56 weeks were 17.1±9.0, 16.8±9.9, and 13.29±6.7 ng/ml, respectively (p=0.0001 for differences between the baseline and week 56 levels); in the comparison group, PICP levels did not change statistically significantly (p≥0.05 for all intergroup comparisons). CONCLUSION: Changing the inefficient long-term on-demand use of NSAIDs to their continuous intake is associated with a rapid decrease in clinical AS activity (within 4 weeks) with a reduction in the higher baseline concentration of the marker for osteoproliferation and in the normal level of the marker for bone resorption.

[Antiinflammatory treatment in patients with chronic back pain]. / Protivovospalitel'naia terapiia pri khronicheskoi boli v spine.

Non-steroidal anti-inflammatory drugs (NSAIDs) are part of the treatment of patients with chronic nonspecific back pain (CBP). An analysis of the reasons for the absence of NSAIDs administration or cancellation of previously iniciated NSAIDs in patients with CBP was the goal of this study. MATERIAL AND METHODS: We analyzed the peculiarities of treatment of CBP in 250 patients at baseline and after 1 and 2 years. The features of drug therapy, the reasons for therapy cancellation were evaluated. RESULTS AND CONCLUSION: 52 (20.8%) of patients with CBP were not treated with NSAIDs, 38 (15.2%) recieved NSAIDs in 4 and > days per week, 44 (17.6%) - 3 and < days a week, 62 (24.8%) took NSAID in 7-14 day 2-5 times per year, 54 (21.6%) - in on-demand mode. Absence of NSAIDs administration in CBP was associated with older age, the presence of comorbidites, with non-alcoholic fatty liver disease and obesity. The cancelletion of previously initiated NSAID was equally associated with the resolution of pain and with the failure to respond to therapy, with the presence of obesity and with the intake of nonselective NSAIDs. Continuation of the initiated effective anti-inflammatory therapy was associated with the use of coxibs, complex treatment with the use of neirobion, with the presence of normal body weight, and with the achievement of a decrease in the severity of the pain syndrome even in the absence of its complete resolution. Increased adherence to treatment with NSAIDs in CBP patients can be achieved by increasing of its effectiveness through the use of NSAIDs (especially coxibs) with B group vitamins (B1, B6, B12), by normalizing of BMI and effectively controlling liver function.

[Efficacy and safety of intravenous methylprednisolone in the treatment of patients with active ankylosing spondylitis: results of a 12-week, prospective, open-label, pilot (METALL) study].

AIM: To evaluate the efficacy and safety of intravenous methylprednisolone (MP) 500 mg in patients with active ankylosing spondylitis (AS) and the inefficiency, intolerability of or contraindications to treatment with 2 or more non-steroidal anti-inflammatory drugs (NSAIDs). SUBJECTS AND METHODS: The investigation enrolled 20 patients (age, 35.35 ± 8.19 years) with a 10.2 ± 9.2 year history of AS who met the modified New York criteria) and had its activity defined as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 scores and an inadequate response to and intolerance of ≥ 2 NSAIDs; there were 13 (65%) men. MP was given in a single intravenous dose of 500 mg. The main efficiency criterion (primary study endpoint) was considered to be the number of patients who had achieved an ASAS20 response at week 2. Additional rating criteria (secondary endpoints) (improved BASDAI/ASDAS; decreased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels; the number of patients achieving ASAS20/40/5/6 responses and ASAS partial remission, and improved ASDAS) were calculated 2, 4, and 12 weeks after MP administration. Safety was monitored estimating the frequency of adverse events (AEs) and controlling vital functions and laboratory indicators. RESULTS: Nine (45%) patients achieved an ASAS40 response at week 2. ASDAS was 3.48 at baseline and 2.21 at week 2 (p < 0.0001). ASDAS clinical improvement was established in 11 (55%) patients at week 2. There were decreases in BASDAI from 6.6 to 3.7 at week 2, to 3.5 at week 4, and to 3.2 at week 12 (p < 0.001). CRP levels declined from 6.1 to 3.15 mg/l at week 2 (p < 0.05), to 2.85 mg/l at week 4 (p < 0.001), and to 4.6 mg/l at week 12 (p < 0.05). ESR was 6.5 mm/h at baseline, 5.5 mm/h at week 2 (p < 0.05), 6.0 mm/h at week 4, and 7.0 mm/h at week 12 (p > 0.05). A total of 13 AEs were recorded and no serious AEs were noted. CONCLUSION: Pulse therapy with MP 500 mg is safe and effective in the short-term treatment of patients with active AS who have achieved no benefits of NSAIDs.

[Efficiency and safety of different etoricoxib regimens in patients with axial spondyloarthritis, including ankylosing spondylitis].

AIM: To study the clinical and laboratory efficiency and safety of different etoricoxib (ET) regimens in patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis. SUBJECTS AND METHODS: Forty patients with high axSpA activity (Bath Ankylosing Disease Activity Index (BASDAI 4) were examined and randomized to 2 groups: 1) 30 patients who received ET 90 mg continuously every day; 2) 10 patients who took the drug in the same dose intermittently 1-3 times weekly. The activity of axSpA (BASDAI, Ankylosing Spondylitis Disease Activity Score (ASDAS), erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (hs-CRP)) was evaluated at baseline, 2 and 12 weeks; adverse events were recorded at baseline, 2, 6, and 12 weeks. The number of patients who had achieved an ASAS40 response at 2 and 12 weeks were taken into consideration. RESULTS At 12 weeks, the continuous administration group displayed decreases in BASDAI from 8 to 4, in ASDAS from 3.8 to 2.6, and in hs-CRP levels from 9.5 to 3.9 mg/l; the intermittent administration group exhibited decreases in BASDAI from 7.6 to 6.0, in ASDAS from 3.5 to 3.1, and hs-CRP from 8.8 to 4.5 mg/l (p<0.05). At this time, an AS40 response was achieved by 22 (73.3%) and 2 (20%) patients in Groups 1 and 2, respectively (p<0.05 for all). No serious adverse events were recorded. CONCLUSION: The efficacy of ET given in a daily dose of 90 mg was much higher than that of the drug used thrice or less weekly in the patients with axSpA.