The state of bone mineral density in men with ankylosing spondylitis and its relationship with the course of the disease.

Introduction: The aim of the study was to study the structural and functional state of bone tissue in men with ankylosing spondylitis (AS) and to assess its relationship with the course of the disease. Material and methods: A study was conducted with the participation of 105 men with AS aged from 22 to 59 years (average age was 40.7 ±0.8 years) with a duration of the disease of 8.7 ±0.5 years and 29 persons of the control group. Disease activity and the degree of functional limitations were determined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Activity Score correlated with C-reactive protein (ASDAS-CRP) and the Bath Ankylosing Spondylitis Functional Index (BASFI). Laboratory examination included determination of C-reactive protein (CRP). Bone mineral density (BMD) of the lumbar spine and femoral neck was determined by the method of dual-energy X-ray absorptiometry on the Hologic Discovery Wi device (S/N 87227). Results: In men with AS, a decrease in BMD (according to the Z-score and T-score) was found in 41.9%, while the percentage of patients with osteoporosis at the level of the femoral neck and lower back was 16.7%. Development of osteoproliferative changes was observed in 42 (40%) patients. Bone mass loss was associated with high activity of the inflammatory process according to ASDAS, BASDAI (r = -0.39, -0.65), and CRP (r = -0.28, -0.38) and low functional capacity according to BASFI (r = -0.27, -0.59), while syndesmophytosis had a reliable association with the age of the patients, the duration of the disease and low functional capacity. Low-energy fractures occurred in 11.4% of men with AS. The presence of fractures was associated with high disease activity (ASDAS, BASDAI, CRP) and was not related to the age of the patients or duration of the disease. Conclusions: A decrease in BMD and the development of fractures were closely associated with high activity of the inflammatory process and low functional capacity, while syndesmophytosis was related to the age of patients and the duration of the disease.

Vitamin D level in patients with systemic lupus erythematosus: its relationship to disease course and bone mineral density.

OBJECTIVE: To determine vitamin D levels in patients with SLE and evaluate their relationship to bone mineral density (BMD) and the disease course. METHODS: The study included 101 patients with SLE and 29 individuals in the control group. The study participants were tested for vitamin D level, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), interleukin (IL)-6, osteocalcin (OC) and collagen type I C-terminal telopeptide (CTX), and the dual-energy X-ray absorptiometry was provided to assess BMD in the lumbar spine and the hip. RESULTS: The mean serum vitamin D level was 18.98±0.88 ng/mL, and women had 25.42% lower vitamin D levels than men (p<0.05). There was no correlation between vitamin D levels and patient's age or disease course. There was a significant inverse correlation between vitamin D levels and cumulative dose of glucocorticoids (r=-0.26) and serum inflammatory markers, particularly CRP (r=-0.39), IL-6 (r=-0.37) and ESR (r=-0.15). Vitamin D level was associated with the bone turnover markers (BTMs). In women of reproductive age with vitamin D deficiency, BMD of the lumbar spine and the hip was 9.5-23.1% higher than in those with no vitamin deficiency, respectively, and the mean lumbar spine Z-score in women of reproductive age with vitamin D insufficiency and deficiency was significantly 2.0 and 2.9 times lower than in patients with normal vitamin D level. CONCLUSIONS: Hypovitaminosis D is quite common in patients with SLE and is associated with high inflammatory activity (SLE Disease Activity Index, ESR, CRP, IL-6), severity of organ damage (Damage Index), cumulative dose of glucocorticoids, BTM changes (decrease in OC, increase in CTX) and BMD decline. Vitamin D status was not associated with the patient's age or disease course.

LEVELS OF OSTEOCALCIN AND PROCOLLAGEN I N-TERMINAL PROPEPTIDE (PINP) IN MEN SUFFERING FROM ANKYLOSING SPONDYLITIS.

OBJECTIVE: The aim: To evaluate osteocalcin and PINP levels in men suffering from AS and to compare them with structural and functional state of bone tissue and clinical course of illness. PATIENTS AND METHODS: Materials and methods: The study included 82 patients suffering from AS with an average age of 40,9±0,9 years. Osteocalcin level was determined in 82 patients, and PINP level was determined in 79 patients. Control group included 22 apparently healthy persons. Disease activity was assessed through CRP level, ASDAS and BASDAI scores, while functional ability was assessed through the BASFI score. Osteocalcin and PINP levels were determined by immunoenzymatic method for the purpose of evaluating the metabolic state of bone tissue. RESULTS: Results: Average osteocalcin and PINP levels were not significantly different in patients suffering from AS and patients in the control group and did not show any significant correlation with ASDAS, BASDAI, BASFI and CRP scores. In patients with spinal ankylosis, average osteocalcin values (14,3 ng\ml) and PINP (747,2 pg\ml) were higher compared to patients with single syndesmophytes (11,0 ng\ml; 711,8 pg\ml) and patients without syndesmophytes (10,4 ng\ml; 537,7 pg\ml respectively). CONCLUSION: Conclusions: Osteocalcin and PINP levels are not related to age, disease duration, BMI, glucocorticoids load and inflammatory process activity, however, they are closely related to the presence of bone growths.

DISORDERS OF STRUCTURAL AND FUNCTIONAL STATE OF BONE TISSUE IN MEN WITH ANKYLOSING SPONDYLITIS, THEIR RELATION TO DISEASE COURSE.

OBJECTIVE: The aim: To study the structural and functional state of bone tissue in men with ankylosing spondylitis and to asses its relationship with the course of the disease. PATIENTS AND METHODS: Materials and methods: the study was conducted involving 105 men, aged 40.74 ± 0.87 years and 25 generally healthy individuals of the certain age and sex, who formed the control group. The functional ability was assessed by the BASFI index and the disease activity was calculated by ASDAS-CRP and BASDAI. Laboratory criteria for the activity of the inflammatory process were considered erythrocyte sedimentation rate and C-reactive protein. Bone mineral density of the lumbar spine and femoral neck was determined by dual energy X-ray absorptiometry. RESULTS: Results: osteoporosis and osteopenic syndrome were identified in men with ankylosing spondylitis in 27,7% and 29,5% consequently. Disorder of the structural and functional state of bone tissue was closely related to the total indicators of inflammatory activity in ASDAS-CRP (r = -0,36), BASDAI (r = -0,51), the functional index BASFI (r = -0,30), C-reactive protein (r = -0,30) and the cumulative dose of glucocorticoids (r = -0.32). The comparative analysis of densitometric parameters in groups of patients depending on the form of the disease has not shown statistically significant differences. CONCLUSION: Conclusions: The decrease in bone mineral density in patients with ankylosing spondylitis does not depend on age and duration of the disease, but is associated with the cumulative dose of glucocorticoids and high activity of the inflammatory process.

PECULIARITIES OF BONE MINERAL DENSITY IN WOMEN OF DIFFERENT REPRODUCTIVE AGE WITH SYSTEMIC LUPUS ERYTHEMATOSUS.

OBJECTIVE: The aim: To study the peculiarities of bone mineral density in the Ukrainian population of women of different reproductive age with systemic lupus erythematosus and to evaluate its connection with traditional and specific (typical for systemic lupus erythematosus) risk factors. PATIENTS AND METHODS: Materials and methods: A total of 91 women with systemic lupus erythematosus and 29 healthy individuals were examined. Along with the clinical study of the activity and severity of the disease, the serum levels of interleukin-6 were determined by the enzyme immunoassay. The peculiarities of bone mineral density were studied using dual-energy X-ray absorptiometry. The presence of fractures was evaluated by the X-ray method. RESULTS: Results: Patients with systemic lupus erythematosus frequently suffer from reduced bone mineral density. Reduced bone mineral density and the appearance of fragility fractures are associated with patients' age, disease duration, damage index, inflammatory activity, and cumulative dose of glucocorticoids. CONCLUSION: Conclusions: Progressive reduced bone mineral density in patients with systemic lupus erythematosus occurs not only during the aging process of a woman, but is also associatedwith a number of systemic lupus erythematosus - related osteoporosis risk factors.

Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial.

OBJECTIVE: To assess non-inferiority of s.c. to i.v. CT-P13 in RA. METHODS: Patients with active RA and inadequate response to MTX participated in this phase I/III double-blind study at 76 sites. Patients received CT-P13 i.v. 3 mg/kg [week (W) 0 and W2] before randomization (1:1) at W6 to CT-P13 s.c. via pre-filled syringe (PFS) 120 mg biweekly until W28, or CT-P13 i.v. 3 mg/kg every 8 weeks until W22. Randomization was stratified by country, W2 serum CRP and W6 body weight. From W30, all patients received CT-P13 s.c. In a usability sub-study, patients received CT-P13 s.c. via auto-injector (W46-54) then PFS (W56-64). The primary endpoint was change (decrease) from baseline in disease activity score in 28 joints (DAS28)-CRP at W22 (non-inferiority margin: -0.6). RESULTS: Of 357 patients enrolled, 343 were randomized to CT-P13 s.c. (n = 167) or CT-P13 i.v. (n = 176) at W6. The least-squares mean change (decrease) from baseline (standard error) in DAS28-CRP at W22 was 2.21 (0.22) for CT-P13 s.c. (n = 162) and 1.94 (0.21) for CT-P13 i.v. [n = 168; difference 0.27 (95% CI: 0.02, 0.52)], establishing non-inferiority. Efficacy findings were similar between arms at W54. Safety was similar between arms throughout: 92 (54.8%; CT-P13 s.c.) and 117 (66.9%; CT-P13 i.v.) patients experienced treatment-emergent adverse events (from W6). There were no treatment-related deaths or new safety findings. Usability was similar for CT-P13 s.c. via auto-injector or PFS. CONCLUSION: CT-P13 s.c. was non-inferior to CT-P13 i.v. in active RA. The convenience of s.c. administration could benefit patients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT03147248.

LEVEL OF HEPCIDINE IN PATIENTS WITH ANKYLOSING SPONDYLITIS, ASSOCIATION WITH ANEMIA AND THE SEVERITY OF THE DISEASE.

OBJECTIVE: The aim: To assess the level of hepcidin in patients with AS, to determine its connection to the disease and various forms of anemia. PATIENTS AND METHODS: Materials and methods: 118 patients with ankylosing spondylitis were examined and hematological, biochemical, immunologic indicators of the general parameters of hematopoiesis and ferrokinetics, plasma levels of CRP, IL-6 and hepcidin were determined. RESULTS: Results: It was found that high levels of hepcidin are found in 25% of patients with AS, 50% are limiting and only 25% are optimal. The serum levels of hepcidin in patients with AS are independent of the age, sex, and duration of the disease, but are closely associated with the activity (ESR, CRP, IL-6, BASDAI, and ASDAS levels) of the disease. Close pathogenetic connection of hepcidin with the formation of anemic syndrome was established. Patients with ACD were characterized by the highest levels of hepcidin. CONCLUSION: Conclusions: Hepcidin plays an important role in the pathogenesis of ACD in patients with AS and can be used as a diagnostic marker for differential diagnosis.

Anemia in patients with ankylosing spondylitis, association with the activity of the inflammatory process and the severity of the disease.

OBJECTIVE: The aim: To estimate the prevalence of anemia in patients with ankylosing spondylitis, major pathogenetic variants and their relationship with the activity of the inflammatoryprocess and the severity of the disease. PATIENTS AND METHODS: Materials and methods: 118 patients with ankylosing spondylitis participated in the study, which performed hematologic, biochemical, immunological studies with general haemopoiesis and ferrokinetics parameters, plasma levels of CRP and IL-6. RESULTS: Results: It was found that in Ukrainian population of patients with ankylosing spondylitis, 28.8% of patients has anemic syndrome. The anemia spectrum is represented by ACD (44.1%), ACD with iron deficiency (29.4%) and IDA (23.5%). It is shown that the severity of anemic syndrome increases with the increase of the stage of activity of the inflammatory process. The presence and severity of anemia are closely related to the severe course of the disease, evaluated by the BASDAI and ASDAS index, and laboratory markers of inflammation CRP and IL-6 of serum. CONCLUSION: Conclusions: The obtained data is promising for the search of effective means of correction of anemic syndrome in patients with ankylosing spondylitis.

THE EFFECT OF ATORVASTATINUM IN THE TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS.

OBJECTIVE: The aim: Was to evaluate the effect of 6-month pathogenetic treatment in combination with atorvastatinum on the endothelium function, lipid and adipokine levels, paroxonase activity and activity of inflammatory process in RA patients. PATIENTS AND METHODS: Materials and methods: The study included 55 patients with RA, dividing into two groups depending on the intended therapy. The first group included 33 patients with "traditional" treatment by methotrexate, glucocorticoids, and non-steroid anti-inflammatory drugs. The second group included 22 patients with "traditional" treatment and additionally prescribed of atorvastatinum 20 mg/day. The lipid profile, leptin, adipokine, paroxonase activity. C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) levels, FMDBA and IMT of carotid artery were determined in all participants of the study. Control parameters were recorded before the start, after 1 and 6 months of treatment. RESULTS: Results: The FMDBA has increased by 32% in the second group, compared by only 10.9% in the first group. The dynamics of IMT in the first group was also twice lower than in group with the additional use of atorvastatinum. The leptin levels in the second group significantly decreased by 27% and adiponectin levels increased by 12.8%, than in the first group - by 12.8% and by 7% respectively. The appointment of statins over 6 months resulted in DAS28, TNF-α, ESR and CRP reduction by 15%, 31%, 25% and 21.5% respectively. In the first group the dynamics of indicate rates ranged from 7.8% to 22.5%, and was significantly lower than in the second group. CONCLUSION: Conclusions: As a result of the study, it was found that the appointment of atorvastatinum 20 mg/day during 6 months not only reduces dyslipidemia, but also significantly reduces the inflammatory process and adipokine dysregulation, normalizes serum paraoxonase activity and improves the endothelium function.

The relationship between homocysteine level and vitamins B12, B9 and B6 status in patients with chronic kidney disease.

OBJECTIVE: Introduction: According to present knowledge, hyperhomocysteinemia is one of the risk factors of cardio-vascular pathology. Patients with chronic kidney disease are known to develop hyperhomocysteinemia more often than those in general population. Іmportant cause of hyperhomocysteinemia is the deficiency of vitamins В6, В9 and В12 that are involved in homocysteine metabolism. Vitamins deficiency, we believe, can be one of the causes of hyperhomocysteinemia in the patients with chronic renal failure. The aim: To analyze the plasma homocysteine level in patients with chronic kidney disease and its assosiation with the levels of vitamins B6, B9, B12 in Ukraine. PATIENTS AND METHODS: Materials and methods: The study involved 148 persons with different stagesis of chronic kidney disease who underwent immunoenzyme determination of total plasma homocysteine, B9, cobalamin and vitamin В6 status. RESULTS: Results: It was found that in ukrainian patient population with chronic kidney disease 58.7% of patients have hyperhomocysteinemia. Homocysteine level was shown to increase with the increase of chronic kidney disease stage. Supply of vitamins В6, В9 та В12 in the patients with chronic kidney disease was lower than in apparently healthy persons, but there was significant decrease of folic acid level proportionally to the increase of chronic kidney disease stage. There was close relationship between homocysteine level and folic acid status in the patients with chronic kidney disease, but it appeared to be independent on cobalamin and pyridoxin status. CONCLUSION: Conclusions: The obtained data are promising for finding effective means of correction of hyperhomocysteinemia in patients with chronic kidney disease by normalizing the vitamin status of such patients.

Long-Term Efficacy and Safety of Biosimilar CT-P10 Versus Innovator Rituximab in Rheumatoid Arthritis: 48-Week Results from a Randomized Phase III Trial.

OBJECTIVE: The aim of this study was to investigate long-term clinical outcomes of extended treatment with CT-P10, a rituximab biosimilar, compared with rituximab reference products sourced from the USA and the EU (US-RTX and EU-RTX) in rheumatoid arthritis (RA) for up to 48 weeks. METHODS: In this multinational, randomized, double-blind trial, adults with active RA received up to two courses of CT-P10, US-RTX, or EU-RTX alongside methotrexate. Efficacy endpoints included Disease Activity Score 28-joint count (DAS28) and American College of Rheumatology (ACR) response rates. Pharmacokinetics, pharmacodynamics, immunogenicity, and safety were also assessed. RESULTS: Of 372 patients randomized to the study drug, 330 (88.7%) completed the second treatment course. Mean change from baseline to week 48 in DAS28-C-reactive protein was comparable in the CT-P10 and combined rituximab (US-RTX and EU-RTX) groups (- 2.7 and - 2.6, respectively). ACR20, ACR50, and ACR70 response rates at week 48 indicated no differences between groups (80.6%, 55.4%, and 31.7% vs. 79.8%, 53.9%, and 33.7% in the CT-P10 and combined rituximab groups, respectively). Similar improvements in the Health Assessment Questionnaire Disability Index and all medical outcomes in the Short Form 36-Item Health Survey, including physical and mental health, were seen in all groups. At week 48, antidrug antibodies were detected in 4.9%, 9.4%, and 8.6% of patients in the CT-P10, US-RTX, and EU-RTX groups, respectively. CT-P10 and rituximab displayed similar pharmacokinetic, pharmacodynamic, and safety profiles. CONCLUSION: CT-P10 was similar to EU-RTX and US-RTX in terms of efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, and safety up to week 48. CLINICALTRIALS. GOV IDENTIFIER: NCT02149121.

A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study.

OBJECTIVES: To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. METHODS: Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5-25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. RESULTS: At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI -6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28-CRP, ACR-EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. CONCLUSIONS: CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. CLINICALTRIALS.GOV IDENTIFIER: NCT01217086.