FRONTIERS
The incidence of major rheumatic diseases was analyzed inRussia's adult population in 2012–2013 on the basis of the statistical reports of the Ministry of Health ofRussia(Form No. 12).
Among the adult population ofRussia, the overall incidence of acute rheumatic fever (ARF) decreased by 11.6% (from 1666 to 1474 cases). No case of ARF was registered in 11 of the 83 subjects of the Federation in 2013. The inci- dence rates per 100,000 adult population compared toRussia's ones were higher in theRepublicofIngushetia(21.0%), theChechen Republic(13.2%), and the Chukotka Autonomous District (26.2%). All cases of ARF were first notified. The overall incidence rates of chronic rheumatic heart diseases amongRussia's adult population tend to reduce slightly [by 5.3% (from 182,286 to 172,687 cases)].
In the period in question, the total number of patients with musculoskeletal diseases (MSD) slightly rose. The bulk of rheumatic patients from the MSD group are more than 4 million patients with osteoarthritis (OA), half of them (2,454,563) being those who are older than able-bodied age. The incidence of OA tends to increase in all Federal Districts (FD). The most common joint inflammatory diseases are rheumatoid arthritis (RA) (286,000 cases), spondylopathies (90,000 cases), and osteoporosis (152,000 cases). The incidence rates of MSD per 100,000 adult population are higher in the North-Western (19,397.7), Volga (16,552.6), and Siberian (16,133.4) FD thanRussia's mean rate (14,205.5). There were somewhat higher incidence rates of RA per 100,000 population in 2013 than in 2012 (241.4 and 245.6, respectively). The rates in the North-Western, Ural, Far Eastern, and Volga FDs are higher than the mean Russian ones.
In 2011, the rubric of «Ankylosing spondylitis» (AS) was replaced by that of «Spondylopathies» that, besides AS (ICD-10 M45), encompasses other inflammatory spondylopathies (M46), including infectious one, which does not allow single out the spinal inflammatory diseases under a rheumatologist's competence. InRussia, there were 39,800 patients with AS in 2010 and as many as 89,000 patients with spondylopathies in 2013.
The incidence of systemic connective tissue diseases (SCTD) remains rather stable. Unfortunately, SCTDs include different nosological entities (sys- temic lupus erythematosus, systemic sclerosis, systemic vasculitides, etc.), which cannot refine trends in the incidence of specific diseases.
In a number of the Federation's subjects, the incidence rate of reactive arthritis (ReA) is higher thanRussia's mean one. It is not inconceivable that not only arthropathies caused by prior enteric and urogenital infection are taken as ReA, leading to the hyperdiagnosis of ReA.
The incidence of osteoporosis varies in FDs: from 226.5 per 100,000 adult population in the Siberian FD to52.0 inthe Southern FD, which is most likely to be associated with the fact that an instrumental examination cannot be made in patients to detect this pathology.
ORIGINAL RESEARCH
Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, vertebral column, and entesises, which is associated with psoriasis. T helper type 17 cells (Th-17) play a leading role in the development of inflammation in psoriasis and PsA so different biologicals affecting interleukins (IL) 17 and 23 are being intensively investigated. Randomized, placebo-controlled Phase III PSUMMIT 1 (NCT01009086, EudraCT 2009-012264-14) and PSUMMIT 2 (NCT01077362, EudraCT 2009-012265-60) studies were undertaken to evaluate the efficiency and tolerability of ustekinumab (UST) treatment in PsA patients.
Subjects and methods. The PSUMMIT 1 study covered 152 Russian patients with active PsA (≥5 tender and ≥5 swollen joints; C-reactive protein ≥3 mg/l) who were randomly (using the dynamic centralized randomization method on the basis of an interactive vocal response algorithm) divided into three groups (at a 1:1:1 ratio): 1) subcutaneous UST 45 mg; 2) UST 90 mg; 3) placebo (PL) at baseline, 4 weeks later, and then every 12 weeks). After 16 weeks the patients showing a less than 5% reduction in the number of tender and swollen joints were given UST 45 mg (if they belonged to the PL group) or 90 mg (if they were in the UST 45-mg group). The PL-receiving patients were given UST 45 mg at weeks 24 and 28 and then every 12 weeks. The treatment duration was 2 years. A therapeutic response was estimated by theAmericanCollege of Rheumatology (ACR) response criteria. The PSUMMIT 2 study enrolled 40 Russian patients who had previously received or were currently receiving disease-modifying anti-rheumatic drugs and/or nonsteroidal anti-inflammatory drugs and tumor necrosis factor-α inhibitors. The patients were randomized to the groups of those receiving UST 45 mg or 90 mg or PL at baseline and at week 4, then once every 12 weeks. The last dose of UST was given at week 40. The follow-up lasted until week 60.
Results and discussion. In the PSUMMIT 1 study, 24-week administration of UST 45 mg and 90 mg significantly more frequently ensured a 20% improvement according to the ACR criteria than that of PL (39.2; 44.0, and 15.7%, respectively; p < 0.01); the therapeutic response persisted until week52. In the PSUMMIT 2, following 24 weeks, the UST 45-mg and 90-mg groups considerably more often showed a 20% improvement according to the ACR criteria than the PL group (64.3, 57.1, and 16.7%, respectively; p < 0.01); the therapeutic response persisted until week 52. Among 150 Russian patients taking UST, on the average, for 45.1 weeks in the PSUMMIT 1 study, 62 (41.3%) were observed to have adverse events (AE) that were serious in 6 (4.0%). Among 40 PsA patients who participated in the PSUMMIT 2 study inRussia, AEs were seen in a total of 25 (62.5%) patients, serious AEs being absent.
Conclusion. The results of the PSUMMIT 1 and PSUMMIT studies in the Russian population indicated that UST treatment contributed to a significant reduction of PS symptoms and exhibited a good tolerability.
Current therapy for rheumatoid arthritis (RA) should not only suppress inflammation, but should also prevent local and generalized bone mineral density (BMD) loss. The drug of choice to treat secondary osteoporosis (OP) is denosumab, a monoclonal antibody, which binds RANKL, inhibiting the interaction with its receptor, which tends to reduce osteoclast activity and bone resorption.
Objective: to evaluate the effect of denosumab on BMD in the axial and peripheral skeleton of RA patients with OP. Subjects and methods. 52 postmenopausal women with RA and OP received subcutaneous denosumab 60 mg at baseline and after 6 months. BMD was measured at baseline and after 12 months, by dual-energy X-ray absorptiometry at three sites: lumbar spine, femoral neck, and distal forearm.
Results. The patients’ mean age was 58.4±6.4 years; the mean RA duration was 19.0±10.9 years. All the patients received anti-inflammatory therapy, including 30 (57.7%) patients who took glucocorticoids (GC). Preand
post-treatment BMD in the lumbar spine was 0.814±0.101 and 0.848±0.103 g/cm2 (р < 0.001), in the femoral neck – 0.629±0.089 and 0.641±0.090 g/cm2 (p = 0.02), in the distal forearm – 0.497±0.094 and 0.502±0.091 g/cm2 (р = 0.34) respectively. Regardless of the administration of GC, stabilization or significant positive changes were noted in all the skeletal regions under study
Conclusion. Therapy with subcutaneous denosumab 60 mg twice a year at an injection interval of 6 months could significantly increase BMD in the lumbar spine and femoral neck and stabilize it in the distal forearm in RA patients with OP irrespective of the use of GC.
Ankylosing spondylitis (AS) is characterized by considerable variation in the rate of development of structural changes in the vertebral column and joints. As of now, the clinical and laboratory predictors of progression of undifferentiated axial spondyloarthritis (SpA) to AS have not been adequately explored.
Objective: to study the clinical features of early axial SpA in view of radiographic changes in the sacroiliac and hip joints and spinal column.
Subjects and methods. The rate of different clinical syndromes of axial SpA was analyzed in 162 patients. The study included less than 35-year-old patients with a 2-to-5-year history of axial SpA that was first diagnosed according to the 2009 ASAS criteria, by excluding psoriatic and reactive arthritis and inflammatory bowel diseaserelated arthritis.
Results and discussion. The examinees were diagnosed with undifferentiated SpA (52.5%), advanced AS (43.2%), and late AS (in the presence of syndesmophytes) (4.3%). 38.3% of patients had peripheral arthritis (PA), 8.6% – dactylitis, 28.4% – enthesitis , and 4.9% – uveitis. The patients with advanced AS had higher C-reactive protein (CRP) levels (38.7 [22.3; 45.8]) and lower rates of PA (27%) than those with undifferentiated axial SpA (14.4 [4.2;
18.6] mg/l and 48%, respectively; p < 0.05). The patients with late AS had more commonly enthesitis (71.4%) and HLA-B27 (100%) than those with undifferentiated axial SpA (31.4 and 78.8%) and those with advanced AS (22.3 and 81.4%, respectively; p < 0.05). Radiographic narrowing of the hip joint space was accompanied by increases in the rate of enthesitis up to 56.2% and HLA-B27 up to 93.7% (the remaining patients exhibited 24.6 and 79.5% increases, respectively (p < 0.05).
Conclusion. High CRP levels, presence of enthesitis and HLA-B27 may be regarded as predictors for rapid progression of structural changes in patients with early axial SpA.
Objective: to study the integral stiffness of the arterial system in patients with systemic lupus erythematosus (SLE) and its relationship to vasoactive regulatory endothelial function.
Subjects and methods. The investigation included 51 patients with SLE, including 45 (88%) women and 6 (12%) men at the age of 17 to 52 years (mean age 34±8.3 years). A control group consisted of 31 healthy volunteers aged 22 to 47 years (mean age 31±5.65 years). Among them, there were 23 (74%) women and 8 (26%) men. The ultrasound method described by D. Celermajer et al. and modified by the authors of this article was used to evaluate endothelial function. The cardiovascular system model developed by A.E. Teregulov was employed to calculate volumetric elasticity coefficient (VEC), mean blood pressure (BP), total peripheral vascular resistance (TPVR), and VEC/TPVR ratio.
Results and discussion. In the patients with SLE, the stiffness of the arterial system was significantly higher than that in the control subjects (p < 0.001). According to the results of a reactive hyperemia test, the patients with SLE were divided into two subgroups: 1) 20 (39%) patients with a normal response of the brachial artery; 2) 31 (61%) patients with endothelial dysfunction. The values of arterial system stiffness and TPVR were independent of endothelial function, SLE activity, and kidney involvement. Patients with disease duration more than 5 years had higher VEC (p = 0.049) and VEC/TPVR ratio (p = 0.044) than those with a shorter history of SLE. The stiffness of the arterial system was higher in hypertensive patients (p = 0.049) whereas VEC/TPVR ratios were unrelated to BP values. Thus, as compared with the control subjects, the patients with SLE had significantly higher integral arterial system stiffness that in these patients depended on arterial lesion, disease duration and BP. In SLE patients, endothelial dysfunction did not affect the formation of arterial system stiffness either.
Objective: to study the pattern and rate of comorbid diseases in patients with rheumatoid arthritis (RA) in the Saratov Region.
Subjects and methods. The investigation enrolled 328 RA patients treated at the Rheumatology Unit, Saratov Regional Clinical Hospital, in 2011 to 2013. RA was diagnosed using the 1987 ACR criteria and the 2010 ACR/EULAR ones. The investigation included the patients receiving disease-modifying antirheumatic drugs (DMARD) at a stable dose for 3 months or longer. A questionnaire survey and objective examination were made in the patients; data from their medical records were taken into account.
Results and discussion. Comorbidities were identified in 86.6% of the patients; 57.9% had a concurrence of two or more comorbid conditions. Osteoarthritis, hypertension, and coronary heart disease were detected in 50.7, 57.7, and 30.9% of the RA patients, respectively. Out of the inflammatory diseases, gastrointestinal tract lesion was most common (80.3%); urinary tract infections were slightly less common (19.7%).
Conclusion. The high rate of comorbidity was noted in patients with RA. The pattern of comorbidities shows a preponderance of hypertension and osteoarthritis and an exacerbation of gastrointestinal and urinary tract diseases frequently makes the choice of DMARD difficult.
Rheumatoid arthritis (RA) is a chronic disease that may affect women of childbearing age. The occurrence of their pregnancy is frequently accompanied by the lower activity of RA and its exacerbation may occur postpartum. Regular disease activity monitoring during pregnancy and postpartum is a necessary condition for adequate therapy correction in this category of patients.
Objective: to determine an optimal method to assess RA activity during pregnancy and postpartum
Subjects and methods. Thirty-two pregnancies were prospectively followed up during each trimester and within 12 months postpartum in 29 women with RA (according to the 1987 ACR criteria) who had been examined at the V.A. Nasonova Research Institute of Rheumatology from February 2011 to August 2014.
Results. Comparison of different methods to assess RA activity demonstrated that DAS28-ESR shows overrated estimates due to a physiological ESR elevation during pregnancy. CDAI and SDAI are greatly affected by a patient's subjective assessment of his/her health, which may be overestimated during pregnancy and in the first month after giving birth. DAS28-CRP(3) recommended in the world literature to assess RA activity in pregnant women showed the same changes as DAS28-CRP(4). The latter is widespread in international studies and has been validated in a large number of patients. Thus, DAS28-CRP(4) may be considered optimal to monitor RA activity during pregnancy and postpartum.
Objective: to compare the efficiency and safety of four treatment regimens using methotrexate (MT), leflunomide (LEF), and a combination of MT and glucocorticoids (GC) for early rheumatoid arthritis (RA) (disease duration <2 years).
Subjects and methods. 141 patients with early RA (of them there were 122 women; mean age 51 years; mean disease duration 7.8 months; mean DAS28 6.0) were randomized to 4 treatment groups: 1) MT 10–20 mg/week (n = 35); 2) MT 10–20 mg/week + oral GC equivalent to 10 mg/day of prednisolone (n = 34); 3) MT 10–20 mg/week + oral CG + single intravenous administration of methylprednisolone (MP) 1000 mg at baseline (n = 35); 4) LEF 20 mg/day (n = 37). The patients were matched for main clinical and demographic characteristics. The duration of treatment was 1 year. Its efficiency was evaluated according to the European League Against Rheumatism (EULAR) criteria.
Results. 125 patients completed one-year treatment. At this time, 11.4% of the patients achieved remission (DAS28 <2.6) in the MT group, 37.5% in the MT+GC group, 29.4% in the MT+GC+MP group, and 16.2% in the LEF group. Adverse events, mainly of mild intensity, were recorded in 9 patients in each MT group. A total of 7 patients had to discontinue treatment because of its inefficiency.
Conclusion. All the four therapy regimens demonstrated a significant efficiency in patients with early RA; the total remission rate was 24%. The combination of MT and GC produced the most pronounced effect. The tolerability of treatment was good in all groups.
Diacerein (DR) is widely used to treat osteoarthritis (OA) and belongs to a group of symptomatic slow-acting drugs for OA (SYSADOA). One of the major benefits of this drug is a low risk of serious adverse events(AE). However,Russiahas not conducted its own large-scale trials of the safety of DR despite its popularity.
Objective: to estimate the frequency of AE of DR (Diaflex®, Romfarm) in real clinical practice.
Subjects and methods. The use of DR was retrospectively analyzed in 3479 patients (60.4% women and 39.6% men; mean age 57.6±12.6 years) with OA and back pain. DR was used in a dose of 100 mg/day; treatment results were assessed following 30 days. The patients received combination therapy: in addition to DR, 62.6% took nonsteroidal anti-inflammatory drugs, as well as myorelaxants, local glucocorticoid injections, other SYSADOA, etc. The efficiency of therapy (visual analogue scale (VAS) pain changes and treatment satisfaction), and the frequency and nature of AE were assessed.
Results. Combination therapy using DR was effective in the majority of patients: VAS pain intensity decreased from 71.2±17.5 to 22.6±16.3 mm; 76% of the patients rated their treatment results as good or excellent. Major AE involved the gastrointestinal tract; obvious gastralgia, nausea, and a sensation of heaviness were observed in only 1.7, 1.8, and 2.4% of the patients, respectively. There were frequent stools: 5.91±1.9 defecation episodes per week at baseline; 7.3±2.8 episodes per week after 30 days of DR administration (p < 0.001). Only 30 (0.86%) patients developed marked diarrhea. There was a considerable (more than two-fold higher than the upper reference limits) increase in alanine aminotransferase and aspartate aminotransferase (ALT/AST) levels in only 20 (0.57%) patients.
Conclusion. Combination treatment using DR is effective in reducing pain in patients with OA and low back pain. DR is well tolerated and rarely causes serious AE. Marked diarrhea and significantly elevated ALT/AST levels are seen in less than 1% of the patients takingPOSTGRADUATE PROGRAM OF CONTINUING MEDICAL EDUCATION
Ankylosing spondylitis (AS) is a disease whose main clinical manifestation is an inflammatory lesion in the axial skeleton with its gradual ankylosing. The peak incidence of AS occurs at a young age; and, if there is no timely adequate therapy, its disability rates are virtually as high as 50% ten years after disease onset, which determines the social importance of this disease The diagnosis of AS is based on its characteristic clinical presentation and the compulsory detection of sacroiliitis on pelvic radiography. However, the existing reports of the X-ray stages of sacroiliac joint injuries in the literature provide little evidence and frequently misinterpret radiographic changes. Based on their long-term experience, the authors give expanded explanations of the standard X-ray stages of sacroiliitis and other radiographic signs that can make a diagnostic search in AS easier.
PROGRESS IN RHEUMATOLOGY IN THE XXI CENTURY
Mast cells are an integral component of the pathogenetic chain of immune inflammation in the body's tissues in different diseases. The mechanisms underlying the proinflammatory effects of mast cells remain inadequately investigated. Their study may contribute to the optimization of therapy for different diseases, including chronic arthritis.
REVIEW
The review analyzes trials dealing with the safety of golimumab (GLM) used in rheumatology. This drug was the latest
Contact: Galina Lukina;
Поступила 12.05.14
tumor necrosis factor α (TNF-α) inhibitor introduced into clinical practice and therefore the estimation of its tolerability is particularly relevant. The data obtained in large-scale clinical trials suggest that GLM has a good safety profile. The most common adverse events (AE) were infections, more often mild. The rate of infections was higher with the use of GLM 100 mg than with that of 50 mg. The overall cancer rate did not increase during a follow-up of less than 160 weeks. However, the rate of lymphomas in patients receiving GLM 100 mg proved to be higher than in those taking GLM 50 mg, in the general population, and in the placebo group in particular. AE were evenly distributed among patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. Overall, the findings are in agreement with the data on the safety of previously used TNF-α inhibitors. No fundamentally new AE have been encountered. It is necessary to accumulate data on the use of GLM in real clinical practice, which will be able to more objectively define its place in the current therapy of rheumatic diseases.
PEDIATRIC RHEUMATOLOGY
DISCUSSION
Objective: to estimate the rehabilitation or palliative care needs of patients with spondyloarthritis (SpA) and to determine the specific features of palliative care in them.
Subjects and methods. The literature on the investigated problem was analyzed using the electronic resources of Pubmed, Medline, and E-library. The authors obtained data based on the prospective follow-up of 182 patients with SpA in January 2010 to March 2014 (PROGRESS study). The degree of axial skeletal immobility (Bath Ankylosing Spondylitis Metrology Index (BASMI)) was estimated; the presence of irreversible organ changes (uveitis-induced visual loss, chronic renal failure due to amyloidosis, etc.), and X-ray changes of the joints and spine were specified. The number of people with varying degrees of disability and that of those needing surgery were taken into account.
Results. The investigation showed that mobility changes and disability might progress rapidly in patients with SpA: in 2010 to 2014, the number of disable patients with SpA increased from 20.5 to 48.9%. In 2014, more than one third (37.8%) of the patients needed rehabilitation and orthopedic correction; 5 (2.74%) patients had IV functional class and required nursing and palliative care.
Conclusion. SpA is a chronic disease that can lead to a rapid functional impairment. Chronic pain, loss of mobility, vision deterioration, amyloidosis, and other causes show the need for palliative care in some patients with SpA. Special tools for evaluating the health status of patients with SpA should be elaborated to determine whether the patient needs rehabilitation and palliative care.
ISSN 1995-4492 (Online)
