Certolizumab pegol (CZP) is a new drug from the group of tumor necrosis factor a inhibitors. The efficacy and safety CZP in the treatment of rheumatoid arthritis (RA) have been studied in the international 52-week RAPID-1 and 24-week RAPID-2 clinical trials that studied the use of CZP in combination with methotrexate (MTX) in patients with active RA unresponsive to MTX. The study populations of the RAPID 1 and RAPID 2 trials constituted the major portion of Russian patients (11.8 and 18.4%, respectively), including that in the prolonged open-labeled phases. The results of using CZP in Russian patients in the RAPID trials showed that they displayed a highly stable response to treatment and a rapidly developing clinical effect, that a therapy response could be predicted in the first 12 weeks, and that the incidence of local postinjection reactions was low.

Objective: to evaluate the clinical efficiency of tocilizumab (TCZ) from the DAS 28, SDAI, and CDAI indices and to estimate remission rates from the European League Against Rheumatism (EULAR) criteria, and the new remission criteria proposed by the EULAR and the American College of Rheumatology (ACR) in 2011. Subjects and methods. Forty-two patients with rheumatoid arthritis (RA) who had received 6 infusions of TCZ in an intravenous dose of 8 mg/kg at a 4-week interval during stable therapy with disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids were examined. The EULAR criteria based on changes in the DAS 28 index and the SDAI and CDAI activity indices were used to evaluate the efficiency of TCZ therapy. Disease remission was assessed by the EULAR criteria and the new 2011 EULAR/ACR remission criteria. Results. The baseline values (median and interquartile range: 25-75th percentiles) were 6.44 (5.87-7.04) for DAS 28; 45 (36.2-57) for SDAI; and 41.5 (32-53) for CDAI. At week 2 of TCZ therapy, there was a reduction in the levels of DAS 28 to 4.86 (4.28-5.29) and at week 4, there were decreases in SDAI to 22.6 (19.4-29.3) and CDAI to 21.9 (19.3-30), which remained until week 24 (p < 0.01). By week 24 of TCZ therapy, according to the EULAR criteria, 35 and 7 patients were observed to have good and moderate effects, respectively. By week 24, 30 (71%), 13 (31%), and 14 (33%) patients achieved remission according to DAS 28, SDAI, and CDAI, respectively; low DAS 28 (2.6-3.2), SDAI (3.3-11), and CDAI (2.8-10) disease activity was observed in 5 (12%), 21 (50%), and 20 (47.6%) patients, respectively; high SDAI and CDAI activities remained in 2 (4.8%) patients. Remission was observed in 10 (24%) patients according to the 2011 criteria. Conclusion. The obtained results of the 24-week study suggest that TCZ therapy is highly effective according to the changes in DAS 28, SDAI, CDAI activity indices and to the new 2011 EULAR/ACR remission criteria in severe RA resistant to the standard treatment with DMARDs.

Objective: to study the comparative efficacy of the genetically engineered biological agents infliximab (INF) and adalimumab (ADA) in patients with ankylosing spondylitis (AS). Subjects and methods. The study included 86 patients with active AS who had failed to achieve remission with the maximal tolerated doses of nonsteroidal anti-inflammatory drugs, sulfasalazine, methotrexate, and glucocorticoids. The patients were divided into 2 groups: 1) 53 patients (mean age 35±9 years, disease duration 13.9±7.5 years) took INF; 2) 33 patients (mean age 35±12 years; disease duration 9.1±6.7 years) received ADA. Therapeutic effectiveness was evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI) scores, ASsessments in Ankylosing Spondylitis (ASAS) remission criteria, vertebral index changes, laboratory parameters, and HLA-B27 typing. INF was administered at a dose of 3—5 mg/kg body weight (300—400 mg) at 0, 2, and 6 weeks and then every 8 weeks, ADA was given in a dose of 40 mg once every 2 weeks. Therapeutic effectiveness was evaluated every 12 weeks. Results. At 48 weeks of therapy, there was a 50% decrease in BASDAI scores in 64 and 60% of the patients in the INF and ADA groups, respectively. ASDAS dropped in 69% and reached its minimal value in 51% in the INF group; those in the ADA group were 54 and 66%, respectively. The mean BASFI score was almost halved in both INF and ADA groups; its low score was recorded in 67 and 60%, respectively. Both groups showed a significant increase in the spine range of motion after 12 weeks of therapy. By the end of the study, there was a significant improvement of locomotion (BASMI) as compared to the baseline values: from 19.4±8.1 to 13.6±4.8 and from 17.3±6.2 to 15.9±7.3, respectively. According to the ASAS criteria, partial remission was achieved in 69% of the patients receiving INF and in 75% of those taking ADA. There were marked positive laboratory changes. The INF and ADA groups displayed decreases in erythrocyte sedimentation rate (ESR) from 37.7±18.9 to 19.0±16.8 and from 38.3±16.5 to 17.8±18.5, respectively (p<0.001 in both groups) and C-reactive protein (CRP) from 39.8+37.2 to 7.8±24.0 (p < 0.001) and from 23.2±21.2 to 1.0±2.5 (p > 0.13), respectively; and an increase in hemoglobin from 125.9±18.8 to 137.5±20.4 (p < 0.001) and from 129.7±16.2 to 146.3±11.5 (p > 0.10), respectively. Adverse reactions (AR) were found in 37 and 33% in the IFN and ADA groups, respectively. The most common AR (elevated hepatic enzymes) was seen in 11 and 9% in Groups 1 and 2, respectively. Serious ARs that caused to discontinue the use of a drug were observed in only 1 patient receiving INF. In Group 1, 3% of the patients were found to have a lower therapeutic effectiveness requiring that the biological drug be changed for ADA. Conclusion. BASDAI and BASMI scores indicated a more marked clinical response to INF therapy. Both groups showed a rapid decrease in acute-phase inflammatory markers, such as ESR and CRP, and elevated hemoglobin just in the early periods of therapy. Functional improvement in locomotion (in spondylitis, peripheral arthritis) was achieved in both groups. The genetically engineered biological agents were well tolerated.

Objective: to assess the prevalence and risk factors of arterial hypertension (AH) in young and middle-aged patients with rheumatoid arthritis (RA). Subjects and methods. Two hundred and twenty-two patients with RA (34% with early RA) who had no concomitant symptoms of cardiovascular disease were examined. Their mean age was 47±9.7 years (15% were males); 60% of the patients were seropositive for rheumatoid factor (RF); a mean DAS 28 score was 5.77±1.1; a mean HAQ-DI score, 1.58±0.7. Logistic regression models were used to study associations between AH and risk factors adjusting for age and sex. Results. AH was found in 153 (69.4%) patients with RA (55% with early RA). Elevated blood pressure was first documented in 56.3% patients after RA onset. Age (odds ratio [OR] 2.06; 95% confidence interval [CI] 1.51—2.81), RF seropositivity (OR = 3.05; 95% CI 1.67—5.57), abdominal obesity (OR = 3.82, 95% CI 1.89—7.71), body mass index (BMI) (OR = 1.15; 95% CI 1.07—1.24), and long-term prednisolone use (OR = 1.17; 95% CI 1.03—1.33) were associated with AH in RA. In early RA, RF seropositivity (OR = 4.62; 95% CI 1.67—12.82), RF titer (OR = 1.43, 95% CI 1.04—1.96), DAS 28 swollen joints (OR = 1.14; 95% CI 1.03—1.27), DAS 28 (OR = 1.64, 95% CI 1.001—2.67), HAQ-DI (OR = 3.14, 95% CI 1.19—8.25) and BMI (OR = 1.14; 95% CI 1.01 — 1.29) were associated with AH. Conclusion. AH is very common in patients with RA, including those with early RA. In more than half of cases, AH develops in the presence of RA and associated with traditional risk factors, RF, and long-term prednisolone intake. The contribution of RA characteristics to the development of AH is more apparent in early RA. The findings suggest that there is a need for the early diagnosis and effective treatment of AH in RA with adequate RA activity control.

Objective: to consider clinical practice problems in the differential diagnosis of different types of plasma cell dyscrasias (PCD). Subjects and methods. Fourteen patients (8 men and 6 women) aged 52±12 years, in whom rheumatic diseases (RD) were ruled out and who were diagnosed as having primary PCD: different types of myeloma in 7 patients, myeloma + AL-amyloidosis in 2, AL-amyloidosis in 3, and Waldenstrom’s macroglobulinemia in 2, were examined. Results and discussion. The most common maldiagnosed RDs in patients with PCD were seronegative rheumatoid arthritis (RA), systemic lupus erythematosus, Sjogren’s disease, and different forms of vasculitis. The most frequent masks of RD were kidney (78%) and osteoarticular system (64%) lesions, vascular disorders (36%), peripheral polyneuropathies (36%), and enlarged salivary glands with xerostomia (28.5%). Serum and urine immunochemical study should be performed in all patients who have clinical manifestations of seropositive RA, spondyloarthritis, intensive bone pain syndrome, ulceronecrotic vasculitis, enlarged submandibular salivary glands with macroglossia in the absence of markers of autoimmune disease for the timely diagnosis of PCD and the exclusion of RD. The paper estimates the sensitivity and specificity of main methods used to diagnose different types of PCD.

Objective: to study the clinical picture of ankylosing spondylitis (AS), the association of its manifestations with the degree of disability in the real practice of a rheumatologist in Russia. Subjects and methods. The investigation enrolled 464 patients with AS, who had consecutively visited rheumatologists for 4 months in 24 cities and towns of the Russian Federation. A specially designed clinical card was filled out for all patients. Later on, the diagnosis of the disease was verified at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, according to the 1984 modified New York criteria and pelvic survey X-ray films were assessed by two independent experts in a blind fashion. Results. The valid diagnosis of AS was confirmed in 330 (71.1%) out of all 464 patients included into the study; their mean age was 39.7±10.2 years; the mean duration of disease was 14.6±2.6 years; 86% were men and 14% were women. About half (47%) of the patients had peripheral arthritis and 56% had clinical signs of coxitis. The mean BASDAI and BASFI scores were 4.8±2.1 and 4.3±2.6, respectively. 61% of the patients had a BASDAI score of >4.0. Uveitis was the most common extravertebral manifestation (22%). One third of the patients did not work because of health reasons; 45% of the patients changed their work activities due to disease. Conclusion. In Russia, AS is characterized by its high activity, frequent involvement of hip joints and poor functional status in the patients on average 15 years after the onset of the disease. Loss of working capacity was observed in one-third of the patients. In the country, AS is diagnosed very late, on average 9 years after the disease onset.

Objective: to study the mechanism for the involvement of ТGFβ1 T(861-20)C in bone resorption in postmenopausal osteoporosis (OP). Material and methods. DNA from 158 postmenopausal women and patients with OP and from 89 healthy age-matched women was examined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (PCR-RFLP) analysis. Bone mineral density (BMD) was estimated by dual-energy X-ray absorptiometry. Standard biochemical protocols were used to detect alkaline phosphatase activity and calcium and phosphorus levels in serum. Total RNA was isolated from the peripheral blood of 32 patients with OP and 39 healthy donors and used for real-time PCR study. Results. No significant differences were found in the frequency of individual alleles and genotypes between the OP group and control donors. The minor T allele frequency was 0.27. There was a significant correlation of ТGFβ1 T(861-20)C polymorphism with low lumbar spine BMD (r=0.18; p=0.025) in Russian patients with OP. Age-adjusted (Z-score) BMD in CC genotype carriers turned to be significantly lower than that in CT and TT genotype carriers. This was accompanied by lower ТGFβ1 gene expression in the peripheral blood of CC genotype carriers (n=10) as compared to the combined group of carriers of two other genotypes (n=22) in the OP group (p=0.03). No changes in ТGFβ1 gene expression were seen in healthy women who were CC genotype carriers (n=18) as compared to the combined representatives of two other genotypes (n=21). Overall, the OP group exhibited significantly lower ТGFβ1 gene expression than the healthy controls (p=0.04). Conclusion. The association of ТGFβ1 (861-20)CC genotype with lower lumbar spine BMD in patients with OP is attended by decreased ТGFβ1 gene expression. Therefore, ТGFβ1 T(861-20)C polymorphism may be a predictor for the development of OP and the more severe form of the disease may be expected in (861-20)CC genotype carriers.

Objective: to study the prevalence of borderline psychic disorders (BPD) in rheumatoid arthritis (RA) patients with different clinical manifestations. Subjects and methods. The study enrolled 192 patients having a valid diagnosis of RA. All the patients underwent clinical, laboratory, and X-ray studies; the questionnaire for the assessment and detection of neurotic states (K.K. Yakhin and D.M. Mendelevich, 1978) and the Health Assessment Questionnaire were filled out. Results. BPDs were identified in 123 (64.1%) patients. BPDs were more often diagnosed in patients with seropositive RA (p<0.05). The incidence of BPD tended to rise with an increase in the activity of RA, radiographic stage, pain intensity according to the visual analogue scale, in the duration of morning stiffness and the number of tender joints (p>0.05). The detection rate for BPD did not depend on the systemic manifestations of RA, number of swollen joints, laboratory parameters of RA activity. The frequency of BPD increased with worsening function (p<0.05) and with the longer duration of the articular syndrome (p<0.05). Conclusion. An examination of patients with RA showed the high frequency of BPD (64.1%), the presence of which correlated with joint dysfunction and the duration of the articular syndrome.

Objective: to develop an education program for patients with rheumatoid arthritis (RA) and to evaluate its efficiency. Subjects and methods. The study included 43 patients with RA: 23 study group patients were trained according to an education program (Rheumatoid Arthritis Health School), 20 patients formed a control group. The education program consisted of 4 daily 90-min studies. The MDHAQ (R798—NP2) questionnaire was used to determine DAS 28, HAQ, RAPID 3 scores at baseline and following 6 months. Results. Six months after education, the study group showed reductions in DAS 28 by 1.33+0.26 scores (р < 0.05), HAQ by 0.91±0.54 (55.2%; р < 0.01), and RAPID 3 by 5.96±0.92 (49.9%; р < 0.01), anxiety level by 0.86±0.32 (54.4%; р < 0.05), depression by 0.87±0.61 (53.4%; р < 0.05), fatigability by 3.39±1.17 (47.5%; р < 0.05); sleep improved by 0.81±0.36 scores (54.7%; р < 0.05). Six months following education program participation, there was significantly more frequently a good DAS 28 response to treatment according to the EULAR criteria (52.2% versus 30.0% in the control group; р < 0.05), and the number of patients who reported health improvement increased by 8.5 times (р < 0.01). The changes in the control group were less pronounced, which determined statistically significant differences between the groups in most indicators (р < 0.05). Conclusion. The education program improves functional capacities and psychological status, assists in controlling the disease activity, and enhances the quality of life in patients with RA.