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Modern Rheumatology Journal

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Vol 14, No 2 (2020)
View or download the full issue PDF (Russian)
https://doi.org/10.14412/1996-7012-2020-2

LECTURES

7-13 1216
Abstract
Assessing the status of a patient with rheumatoid arthritis allows one to obtain information necessary to choose appropriate management tactics for the patient. The use of quantitative methods in routine practice to determine inflammatory activity is the basis for the development of standardized patient management recommendations and provides a substantial improvement in the quality of health care. At the same time, the accumulated experience suggests that the existing summary indices do not always allow one to correctly determine disease activity. The paper discusses factors that can corrupt the result of assessment of inflammatory activity, as well as approaches to eliminating possible errors.
14-19 2241
Abstract
The lecture covers main approaches to differential diagnosis in rheumatic diseases. It highlights the key questions that should be answered at the primary examination of the patient. The most important signs that can identify severe, sometimes urgent nonrheumatic diseases are presented. The author describes pain of different patterns and intensity and the most common variants of acute or chronic onset of mono-, oligo-, or polyarthritis. The 2016 European League Against Rheumatism (EULAR) definition of arthralgia suspicious for the development of rheumatoid arthritis is given. The lecture presents the signs indicating the inflammatory nature of back pain in cases of suspected spondyloarthritis (SpA), as well as a two-step diagnostic strategy for axial SpA. Attention is paid to the semiotics of joint damage and extra-articular manifestations in various rheumatic diseases. A brief algorithm for a differential diagnostic search for joint pain is given.

ORIGINAL INVESTIGATIONS

20-26 845
Abstract

Objective: to evaluate the effect of the rituximab (RTM) biosimilar Acellbia on the peripheral blood levels of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, and CD4+CD25+CD127- lymphocytes in patients with rheumatoid arthritis (RA).
Patients and methods. Examinations were made in 20 RA patients who received 2 RTM infusions at a total dose of 1200 mg. The levels of C-reactive protein, IgM rheumatoid factor, IgG, IgM, and IgA were measured by a nephelometric method. The relative and absolute contents of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, CD4+CD25+CD127- T regulatory cells (Tregs) were estimated by multicolor flow cytofluorometry.
Results and discussion. At week 24 of RTM therapy, there was a good/satisfactory effect according to EULAR criteria in 17 (85%) patients; DAS28 remission in 4 (20%), and SDAI remission in 2 (10%). The use of RTM was accompanied by a significant increase in the relative content of CD4+CD25+CD127- T lymphocytes, the median of which at weeks 12 and 24 after therapy initiation increased from 6.8 [5.2; 7.6]% to 7.3 [6.1; 8.3] and 6.97 [6.4; 8.2]%, respectively (p<0.05). The absolute peripheral blood count of Tregs tended to increase at weeks 12 after the first infusion of the drug (up to 0.05 [0.04; 0.075] ⋅ 109 /l; p=0.05). At week 24 follow-up, the patients who achieved SDAI remission/low disease activity had significantly higher baseline relative Tregs levels (7.35 [6.8; 7.97]% than those with the moderate activity of the pathological process (5.8 [4.3; 7.22] %; p<0.05).
Conclusion. The use of the RTM biosimilar is accompanied by the development of complete depletion of CD19+ lymphocytes and by an increase in CD3+ and CD3+CD4+ lymphocytes and Tregs. The larger baseline number of CD4+CD25+CD127- lymphocytes is associated with the higher efficiency of RTM therapy.

27-34 1921
Abstract

Objective: to study of the relationship between psychological factors and indicators of rheumatoid arthritis (RA) disease activity in patients who have been followed up for a long time after initiation of treat-to-target therapy.
Patients and methods. The investigation enrolled 38 RA patients (29 women and 9 men) aged 33 to 80 years (mean age, 56.5±12.5 years) with a mean disease duration of 6.0±0.9 years. All the patients underwent clinical examination; the following parameters were recorded: patient global assessment; physician’s global assessment; pain visual analogue scale (VAS), by measuring in millimeters; number of painful joints (NPJ), and number of swollen joints (NSJ). The investigators determined functional status with the Health Assessment Questionnaire (HAQ), quality of life with the 36-Item Short Form Health Survey questionnaire (SF-36), the nature of pain by the painDETECT questionnaire (PDQ), and the presence of anxiety and depression with the Hospital Anxiety and Depression Scale (HADS). The patients also filled out the Resilience (Res) Questionnaire (RQ) and the General Self-Efficacy ((GSE) Scale. Disease activity was evaluated by DAS28, CDAI, and RAPID3 scores. Results and discussion. RA disease activity was high in 4 patients, moderate in 21, and low in 9, and 4 patients had DAS28 remission. The average scores of RQ, its individual components, and GSE scale were comparable with the corresponding population scores for this age group. The patients who had RQ scores below the average group ones were noted to have significantly higher scores of patient global assessment; physician’s global assessment, NPJ, NSJ, CDAI, and RAPID3 than in those who had moderate and higher RQ scores. The similar trend was traced for individual Res components, such as involvement (INV), control (CONT), and risk acceptance (RA). However, the revealed differences in these indicators failed to reach statistical significance. There was no correlation between the measures of inflammatory activity and the result of GSE. The patients with subclinical and clinical anxiety and depression had significantly lower RQ, INV, and CONT scores than those who did not have anxiety or depression, whereas RA and GSE did not differ significantly in these groups. There was a significant positive correlation of Res, INV, and CONT with the quality of life, as assessed by SF-36. The findings suggest that low RQ scores can decrease the efficiency of the therapy performed (due to the patient’s poor compliance), on the one hand, and can corrupt the result of inflammatory activity assessment (due to the impact on a patient’s perception of his/her illness), on the other hand.
Conclusion. The findings may suggest that there is a need to assess the psychological status of a patient when determining the level of RA disease activity.

35-40 1040
Abstract

Objective: to investigate joint damage and laboratory and instrumental features in Löfgren's syndrome (LS) in patients referred to the Rheumatology Center.
Patients and methods. The five-year investigation enrolled 142 patients of both sexes (31 men and 111 women; mean age, 39.3±11.1 years) with erythema nodosum (EN) accompanied by polyarthralgias or arthritis. All the patients underwent comprehensive clinical, laboratory and instrumental examinations, including joint ultrasound and chest computed tomography.
Results and discussion. Disseminated EN that was correlated with the level of CRP was detected in 96% of cases (p=0.006; r=0.38). The signs of joint damage with predominantly periarticular changes in the ankle joints were observed in 124 (87%) patients. There was a relationship of the duration of the articular syndrome to that of inflammatory changes in subcutaneous tissue and to the number of nodules (p=0.02; r=0.45). The level of CRP had a significant direct correlation with the number of nodules (p=0.008; r=0.29) and the severity of the articular syndrome (p=0.003; r=0.29). Elevated levels of angiotensin-converting enzyme were found in 97 (78%) patients. Joint damage was significantly more frequently combined with X-ray Stage I sarcoidosis (Sr) (p=0.03). The Stage II Sr showed a male preponderance (p=0.04) and a 4.8-fold increase in the merging of subcutaneous nodes into conglomerates (p=0.002).
Conclusion. Joint damage may be one of the first signs of LS, which requires that physicians of various specialties should coordinate their actions to timely diagnose, assess activity, and choose an adequate therapeutic approach.

41-44 4378
Abstract

According to statistics from the Ministry of Health of Russia, the incidence of reactive arthropathies varies significantly by region and year. In ICD-10, reactive arthropathies include reactive urogenic arthritis (M02.3), other reactive arthropathies (M02.8), and reactive arthropathies, unspecified (M02.9). Information on reactive arthritis (ReA) cannot be extracted from these data.
Objective: to specify the number of patients with ReA among inpatients with reactive arthropathies.
Patients and methods. A retrospective analysis of 224 case histories was made in the patients treated at the V.A. Nasonova Research Institute of Rheumatology Clinic in 2009–2018 and discharged with Codes M02.3, M02.8, and M02.9.
Results and discussion. Nineteen out of the 224 patients were diagnosed with reactive urogenic arthritis (M02.3), 128 had reactive arthropathies (M02.8), and 77 had reactive arthropathies, unspecified (M02.9). All the 19 patients with this diagnosis met the criteria for reactive urogenic arthritis. Among the 128 patients with reactive arthropathies, 77 met the ReA criteria, 8 of them were found to have reactive urogenic arthritis, since the clinical picture had a triad consisting of arthritis, urogenic or enterocolitic infection, and conjunctivitis. Twenty-five out of the 77 patients discharged with Code M02.9 met the criteria for certain ReA and 6 did those for possible ReA. Thus, the diagnosis fitted the criteria for ReA in only half (56.7%) of the patients with reactive arthropathies.
Conclusion. The performed investigation revealed that clinicians paid insufficient attention to the diagnosis of ReA and that statisticians did this to the coding of reactive arthropathies.

45-51 4915
Abstract

Fibromyalgia (FM) is a condition characterized by generalized pain syndrome and by the presence of fatigue, cognitive impairment, affective and multiple somatic symptoms. Pain syndrome can have national, ethnic, gender, and age characteristics.
Objective: to evaluate the features of the course of FM in a large industrial center of the Russian Federation and to present its phenotypic options.
Patients and methods. The investigation enrolled 92 FM patients (8 men, 84 women) aged 18 to 86 years (mean age, 50.5 years). The diagnosis was established according to the 2016 ACR criteria. Account was taken of data on disease duration, occupation, sport training loads, previous therapy, pain intensity, and somatic symptoms according to the 2010 ACR diagnostic criteria and on general health assessment in the patients. All the patients completed the hospital anxiety and depression scale (HADS).
Results and discussion. The most significant somatic symptoms in the clinical picture of FM were shown to be muscle pain and muscle weakness, the manifestations of irritable bowel syndrome and fatigue; moreover, the prevalence of many symptoms in people over 60 years of age was lower than that in younger patients. Female gender was an additional risk factor for increases in pain and cognitive impairment. The presence of concomitant depression verified by HADS was associated with a substantial deterioration of the clinical manifestations of FM. At the same time, professional activities and sports were found to be protective factors against a number of symptoms of FM. It was hypothesized that there were several FM phenotypes (anxious, anxiety-depressive, egocentric, and vascular ones).
Conclusion. The authors have demonstrated the features of the course of FM in a large industrial center of the Russian Federation and identified various disease phenotypes, which can be useful for determining the treatment policy for patients.

52-56 1023
Abstract

Osteoarthritis (OA) is a chronic rheumatic disease that is characterized by pain and articular cartilage degradation. Pain in OA is a main clinical symptom that limits working capacity and is one of the indications for joint replacement. However, 10-40% of patients with OA also continue to experience painful sensations after surgery.
Objective: to develop a method for searching for biomarkers to predict the dynamics of pain in the postoperative period and to determine the feasibility of arthroplasty on the basis of a retrospective analysis of relative blood gene expression prior to surgery.
Patients and methods. The investigators tested the blood taken from 53 OA patients (mean age, 56.5±8.9 years) before knee arthroplasty and from 26 healthy donors (mean age, 55±8.3 years). Total RNA was isolated from blood and after reverse transcription into complementary DNA was used to measure the level of relative gene expression in real-time polymerase chain reaction.
Results and discussion. A retrospective analysis of the expression of genes associated with central sensitization in 53 patients with OA before arthroplasty showed that the data on the expression of tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and transforming growth factor β1 were uninformative due to their high blood expression in all the patients. The high gene expression of cathepsin S (in 17% of the patients) and cathepsin K (in 21%) and the low gene expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) (in 31%) may indicate that postoperative pain can be persistent. In contrast, no post-arthroplasty pain can be expected in 43% OA patients with low caspase 3 expression and in 23% of those with low MMP-9 one.
Conclusion. Analysis of pre-arthroplasty blood gene expression in patients with OA seems to be a promising approach to predicting the dynamics of pain after surgical treatment.

 

57-61 1649
Abstract

Objective: to estimate the incidence of diabetes mellitus (DM) in patients with rheumatoid arthritis (RA) in the Republic of Karelia and to analyze the types of carbohydrate metabolism disorders.
Patients and methods. The investigation enrolled 889 patients aged 18 years and older with RA treated in the Rheumatology Department, V.A. Baranov Republican Hospital (Petrozavodsk), in 2000 to 2019. Among them, there were 709 (79.8%) women and 180 (20.2%) men; the median age was 59 [52; 66] years; the median duration of RA was 6.5 [1.75; 13] years. Most patients were found to have positive rheumatoid factor (68.3%), the second and more advanced radiological stages (90.6%), and moderate and high RA disease activity (84.8%). Methotrexate as a mainstay disease-modifying anti-rheumatic drug was taken by 68.2%; biological agents and glucocorticoids (GCs) were used in 4.8 and 3.3%, respectively. The incidence of DM and its types and risk factors (RFs) were analyzed.
Results and discussion. DM was recorded in 67 (7.5%) RA patients (55 women and 12 men; the median age was 62 [56; 66] years). Among these patients, 9 (1.0%) patients with RA were observed to have type 1 DM, 50 (5.6%) and 8 (0.9%) patients had steroid-induced DM (SIDM), and type 2 DM, respectively. In 55.5% of cases, type 1 DM was represented by latent autoimmune diabetes in adults (LADA), which is of late onset. SIDM was detected in 75% of patients over 60 years of age who had RFs for type 2 DM. In this study, the incidence of type 2 DM in RA patients exceeded official figures in the general population of the Russian Federation, but was close to the predicted prevalence rates of type 2 DM. Patients with RA and type 2 DM had major RFs, such as age over 45 years, hypertension, overweight or obesity; moreover, 60% of patients were found to have a combination of these factors.
Conclusion. RA patients showed a higher incidence rate of carbohydrate disorders of different types; the number of cases of type 1 DM and type 2 DM among the examined patients with RA exceeded that in the regional DM registries in the general population in the Republic of Karelia. It seems advisable to screen for carbohydrate disorders in patients with RA, especially in the presence of RFs for type 2 DM and during systemic therapy with GCs.

62-68 1835
Abstract

Studying the factors leading to a pathological change in the cardiac structure in patients with rheumatoid arthritis (RA) can contribute to improvement in early diagnosis and to prevention of premature mortality from cardiovascular events.
Objective. To study the types of left ventricular (LV) remodeling in patients with RA, by taking into account traditional cardiovascular risk factors, and to assess the clinical and immunological features of RA and the impact of drug therapy.
Patients and methods. The investigation enrolled 74 RA patients who underwent assessment of echocardiography findings, by determining the type of LV remodeling, traditional cardiovascular risk factors, clinical and immunological features of the disease, as well as the current drug therapy.
Results and discussion. Eccentric LV hypertrophy (ELVH) (n=33 (44.59%)) and concentric LV hypertrophy (CLVH) (n=34 (45.95%)) occurred at almost the same frequency among the pathological types of LV remodeling in patients with RA. Higher DAS28 values (p<0.0001) were noted in ELVH than in CLVH. There were also positive correlations of EHLH with ESR and CRP level (r= 0.51, p<0.0001; r=0.48, p=0.0001, respectively). The higher values of systolic blood pressure (p=0.0002), body mass index (p=0.01), patient age (p=0.0001), and the incidence of dyslipidemia (p= 0.008) were established in CVLH than in ELVH. LV diastolic dysfunction (DD) was detected much more frequently in RA patients with CLVH than in those with ELVH (p=0.01). The DD parameters (peak A, E/A) correlated with the degree (r=0.5, p<0.0001; r=-0.5. p<0.0001) and stage of hypertension (r=0.54, p<0.0001; r=-0.48, p=0.0001, respectively), as well as with peak A and traditional risk factors, such as patient age (r=0.52, p<0.0001), and high-density lipoprotein cholesterol levels (r=-0.48, p=0.0001).
Conclusion. Most patients with RA had signs of LV hypertrophy; moreover, ELVH was closely linked with disease activity, whereas CLVH was related to the traditional risk factors.

69-75 1324
Abstract

Janus kinase (JK) inhibitors block the intracellular signaling pathways that are responsible for the synthesis of proinflammatory cytokines and mediators, which in turn cause the activation of pain receptors and central sensitization (CS). It is suggested that JK inhibitors can rapidly eliminate pain and reduce the severity of CS.
Objective: to evaluate the effect of the JK inhibitor tofacitinib (TOFA) on the intensity of pain and the signs of CS in patients with active rheumatoid arthritis (RA) at 7 and 28 days after therapy initiation.
Patients and methods. A study group consisted of 39 patients (79.5% female) (mean age 50.9±11.1 years) with RA (DAS28 5.8±0.6). Of these, 89.7% were seropositive for rheumatoid factor; 82.0% took methotrexate and 18.0% received leflunomide. All the patients were prescribed TOFA 5 mg twice daily due to the inefficacy or intolerance of biological agents. The investigators estimated pain intensity using a Brief Pain Inventory (BPI), rated the presence of a neuropathic pain component (NPC) with the PainDETECT questionnaire, and assessed the signs of CS with the Central Sensitization Inventory (CSI) during the first 4 weeks after TOFA administration.
Results and discussion. The patients initially experienced moderate or severe pain (the mean scores of 5.33±2.51 on the numerical rating scale (NRS) included in BPI); 53.8% had signs of CS (CSI scores of ≥40); 17.9% had signs of a NPC (PainDETECT scores of >18). Already on day 7 after the start of TOFA administration, there was a statistically significant decrease in the mean NRS pain intensity scores to 4.06±2.2 (p=0.01) and by 29.4±17.9%, as shown by the patient's assessment of the analgesic effect of therapy (BPI), as well as the severity of CS, namely a decrease in the mean NRS pain score to 35.9±11.2 (p=0.01). On 28 days, the effect became better: there was a reduction in the level of NRS pain to 2.32±1.57 (p<0.001), in pain according to the patient's assessment of the analgesic effect of therapy to 43.6±29.6%; in the median PainDETECT score to 2.5 [0; 8.7] (p<0.001); and in CSI scores to an average of 26.4±13.9 (p <0.001). No serious adverse reactions were noted.
TOFA has a rapid analgesic effect, which allows it to be considered as a chooser for pathogenetic therapy in patients with active RA and severe pain, especially in the presence of CS signs and secondary fibromyalgia. Undoubtedly, large-scale, long-term controlled studies with a wider range of estimated parameters are required to clarify the therapeutic potential of TOFA in this patient category. The limitation of this investigation was its open observer design pattern.
Conclusion. The use of the JK inhibitor TOFA can achieve a rapid analgesic effect, inter alia due to its effect on CS and NPC.

76-83 4286
Abstract

Glycosaminoglycan-peptide complex (GPC) is a popular injectable extended-release symptomatic agent (ERSA) in Russia for the treatment of osteoarthritis (OA). To date, no large-scale studies of GPC used in real clinical practice have been conducted in our country.
Objective: to evaluate the efficacy and safety of GPC in the treatment of OA in real clinical practice.
Patients and methods. A multicenter observational non-interventional study was performed to evaluate the efficacy of GPC (Rumalon® , a cycle of intramuscular injections thrice weekly; a total of 25 injections). A study group consisted of 2,955 patients (75.4% female) aged 61.4±11.8 years) with knee and hip OA, and generalized OA (GOA) with the previous inefficacy of oral ERSAs, moderate/severe pain, and the need for regular use of nonsteroidal anti-inflammatory drugs (NSAIDs). 414 (14%) patients received a GPC and diacerein combination 100 mg/day. The investigators assessed the dynamics of pain during movement and at rest, functional disorders (on a numeric rating scale (NRS) of 0–10), as well as the need for NSAIDs at 12 weeks after starting the GPC cycle.
Results and discussion. 98.5% of the patients completed their GPC treatment cycle. The therapy decreased the intensity of pain at rest from 4 [3; 5] to 1 [0; 2] and during movement from 6 [5; 7] to 2 [1; 3] and reduced the severity of functional disorders from 5 [4; 6] to 1 [0; 3]. The number of patients with a good response to therapy (a≥50% decrease in symptom severity) for pain at rest and during movement was 55.6 and 53.5%, respectively; and for functional disorders was 50.8%. 68.1% of patients stopped taking NSAIDs. The GPC and diacerein combination was more effective than GPC monotherapy: the number of patients with a ≥50% decrease in movement pain was 62.8 and 54.3%, respectively (p <0.001). GPC was well tolerated. During treatment, there were skin allergic reactions (0.3%), moderate injection-site pain (0.37%), and adverse reactions (ARs) related to the gastrointestinal tract (8%) and cardiovascular system (6%) (which were likely to be caused by NSAIDs). There were no serious ARs that were life-threatening and required hospitalization.
Conclusion. GPC allows successful control of the main symptoms of knee and hip OA and GOA, by reducing pain, and those of functional disorders, and the need for NSAIDs. The GPC and diacerein combination is more effective than GPC monotherapy. GPC therapy is well tolerated and very rarely causes ARs.

84-89 913
Abstract

Objective: to assess bone mineral density (BMD) and the incidence of osteoporosis (OP) and sarcopenia (SP) in women suffering from rheumatoid arthritis (RA).
Patients and methods. Eighty-one women (mean age, 59.0±8.1 years) with a reliable diagnosis of RA were examined. The women underwent the following studies: a survey using a special questionnaire; tests to measure the functional status of muscles, including those to determine their strength; as well as dual-energy X-ray absorptiometry of the axial skeleton and whole body.
Results and discussion. According to the EWGSOP2 criteria, 20 (24.7%) female patients were diagnosed with SP, 24 (29.6%) had OP, and 39 (48.2%) had osteopenia. OP in female patients with and without SP occurred in 35.0 and 27.9% of cases, respectively (p>0.05). BMD in the femoral neck and in the proximal femur as a whole was significantly lower in the presence of SP than in its absence (p=0.0006 and p=0.0061, respectively). The frequency of falls was significantly higher in the female patients with SP than in those without SP (p=0.028). The major osteoporotic and hip fracture probabilities calculated according to the FRAX ® algorithm was higher in the patients with SP than in those without SP (p=0.041 and p=0.033, respectively). There were positive correlations of BMD with body mass index, appendicular muscle mass, appendicular muscle index, hand strength, shoulder circumference, and the serum levels of calcium, creatinine and uric acid, as well as negative correlations with age, postmenopausal length, and RA duration.
Conclusion. OP and SP are common RA complications that increase the risk of falls and fractures.

90-96 750
Abstract

Analysis of the results of clinical trials should be based on the use of objective parameters that allow for assessing the significance of the data obtained for real medical practice. These parameters include Minimal Clinically Important Improvement (MCII) and Patient Acceptable Symptom State (PASS).
Objective: to determine the approximate value of the parameters MCII and PASS on the basis of data from the PARACELS (Regular Piascledine and Artrosilene Administration for osteoarthritis (OA): Expediency of the Unified Treatment Regimen) study.
Patients and methods. A study group consisted of 6,448 patients (70.9% female, 29.1% male) (mean age, 57.8±10.2 years) with knee OA and moderate or severe pain of ≥40 mm on a 100-mm visual analogue scale (VAS). All the patients took during 12 weeks avocado/soybean unsaponifiables 300 mg/day and a nonsteroidal anti-inflammatory drug (ketoprofen lysine salt) 320 mg/day, which was prescribed at the beginning of treatment for 10–14 days and then could be used on demand with more pain to come. Pain intensity was measured using the 100-mm VAS. Patient satisfaction with treatment results was also studied with a point scale, where 0 is worsening or no effect, while 5 is an excellent effect. The dynamics of pain was compared and treatment results were assessed by patients.
Results and discussion. After 12 weeks, most patients showed a substantial improvement: a mean pain intensity reduction of 77.7±29.6%. A satisfactory treatment result estimate (that can be considered as a surrogate measure of MCII) corresponded to an average pain reduction of 32.0±11.7 mm on VAS (a 47.3% improvement compared to the baseline level). A good treatment result estimate (that can be considered as a surrogate measure of PASS) corresponded to an average pain reduction of 41.0±13.3 mm on VAS (a 62.9% improvement compared to the baseline level).
Conclusion. The PARACELS study has shown that in Russian patients receiving analgesic therapy, MCII can correspond to a pain reduction of >30 mm on VAS (>40% of the baseline level), PASS can do to its reduction of >40 mm on VAS (>60% of the baseline level).

97-103 2474
Abstract

The 2018 national guidelines for the management of gout provide a consistent scheme for urate-lowering drugs; however, the possibility of achieving uric acid (UA) targets in its use has not been studied.
Objective: to evaluate the effectiveness and safety of the urate-lowering therapy algorithm presented in the national guidelines for the management of gout.
Patients and methods. This investigation was a prospective single-center study. It has been currently included 54 patients (91% males) with gout. The follow-up period is not less than 12 weeks of continuous use of allopurinol or febuxostat (Azurix) at the final dose.
After the initiation of urate-lowering therapy, allopurinol 100 mg/day was prescribed, followed by dose titration to achieve the UA target that was defined as <360 or <300 μmol/L in patients with severe tophaceous gout. The maximum dose was 900 mg/day; it was 300 mg/day when the glomerular filtration rate was <60 ml/min/1.73 m2 . Patients with the inefficacy of allopurinol and/or the presence of its associated adverse reactions (ARs) were prescribed febuxostat 80 mg/day; the dose was increased to 120 mg/day as needed.
For the prevention of acute arthritis attacks, all the patients received a nonsteroidal anti-inflammatory drug (NSAID) at the minimum therapeutic doses or colchicine 0.5 mg/day, and if these drugs were contraindicated, a glucocorticoid (GC) 7.5 mg/day, as calculated with reference to prednisone, was taken.
The probability of achieving the serum UA target (<360 or 300 μmol/L) was assessed in patients with chronic tophaceous gout.
Results and discussion. 12 weeks after therapy initiation, the UA target could be achieved in 39/50 (79%) patients. The target levels <360 and 360 μmol/L were recorded in 15/21 (71%) and 24/33 (73%), respectively. The UA level <360 μmol/L was noted to decrease in a total of 92% of cases. Febuxostat was given to 41 patients: to 27 (66%) due to the inefficacy of allopurinol and to 14 (34%) due to its ARs. As a result, the UA target was achieved in 30 (73%) patients, and there was a decrease in the UA level <360 μmol/L in 35 (85%).
ARs were seen only in 3 febuxostat-treated patients, including 2 patients with previous allopurinol-induced ARs.
For the prevention of arthritis attacks, 10 (19%) patients took NSAIDs, 41 (75%) received colchicine, and 3 (6%) used GC. There were no refusals to receive urate-lowering and preventive anti-inflammatory therapies.
Conclusion. The proposed treatment regimen allows for achieving the serum UA target in 79% of patients and its decrease <360 μmol/L in 92%. Treatment with febuxostat (Azurix) is associated with its good tolerance, including in the patients who could not use allopurinol because of AR. Preventive anti-inflammatory therapy is likely to improve adherence to urate-lowering therapy.

CLINICAL OBSERVATIONS

104-109 889
Abstract
The paper discusses prospects for prescribing tumor necrosis factor-α (TNF-α) inhibitor biosimilars, their interchangeability with original drugs for inflammatory joint diseases. It describes clinical cases when original infliximab is replaced with its biosimilar Flammagis for ankylosing spondylitis. The authors emphasize that it is difficult to predict the interchangeability of original TNF-α inhibitors and biosimilars in rheumatology, and this is confirmed by the above clinical cases. They also indicate that the optimal use of biosimilars requires a constant cooperation of rheumatologists, pharmacologists, and regulatory authorities, which is aimed at protecting the rights of a patient in order to ensure safe, effective and high-quality care. It is concluded that it is advisable to conduct further investigations to develop a special pharmacovigilance system in this area.

REVIEWS

110-116 21167
Abstract

Currently, the infection caused by the new coronavirus COVID-19 is considered by the global community as an emergency of international concern. Rheumatologists are particularly concerned about this problem, since patients with immune-mediated inflammatory rheumatic diseases (IMIRDs) are at higher risk for infectious diseases and receive immunosuppressive treatment. The use of disease-modifying antirheumatic drugs and biological agents increases the incidence of serious infections, but insufficient/no monitoring of IMIRD activity is an even greater risk factor for infectious complications. In addition, the role of vaccination mainly against influenza and pneumococcal infection is substantially increasing in modern conditions, since the risk of death from respiratory tract infections is quite high in patients with IMIRDs, which is very important in the context of the current COVID-19 pandemic.
The paper presents an update on the incidence of viral infections in patients with IMIRDs and also discusses whether antirheumatic drugs can be used to treat COVID-19.

117-122 999
Abstract

The processes that vary in nature and underlie the pathogenesis of malignant neoplasms (MNs) and immune-mediated inflammatory rheumatic diseases (RDs) share just the same some common features. Thus, many early-stage neoplasias can mask autoimmune diseases, requiring that physicians of various specialties should comply with the principle of cancer alertness. When specific cancer treatments (immunotherapy, cytostatic therapy, radiotherapy) are performed, there may be certain rheumatic syndromes (arthritis, myalgia, serositis, etc.) that require a differential diagnosis. At the same time, the course of a number of RDs (rheumatoid arthritis, Sjögren's syndrome, and polymyositis) can be accompanied by the development of MNs, which is relevant for real clinical practice and calls for further investigation.
The community of etiological factors and a genetic predisposition in the development of RDs and MNs remain to be of no less importance. At the same time, therapists should pay attention to the presence of rheumatic masks in many MNs, which undoubtedly prolongs the time between onset of the first symptoms and correct diagnosis.

123-130 880
Abstract
The paper provides a review of the data available in the literature on the relationship of pain to the risk of OA progression. Network analyses and numerous studies, including those conducted at the V.A. Nasonova Research Institute of Rheumatology, have confirmed that pain syndrome is one of the significant predictors of knee OA progression. The major class of medications for OA pain includes nonsteroidal anti-inflammatory drugs. The paper gives data on the efficacy of meloxicam in OA patients, which is widely used in both Russia and other countries of the world. Meloxicam is characterized by a good safety profile in the gastrointestinal tract, cardiovascular and renal systems. It is the drug of choice in patients with musculoskeletal diseases, in particular OA. Good results in severe pain syndrome have been shown by a step-by-step regimen of meloxicam when the injection formulation of the drug is used in the first days of treatment, and then, to consolidate what has been gained from therapy, its oral dosage form is administered in terms of concomitant diseases.
131-137 3220
Abstract
The paper deals with an update on biologically active additives (BAAs) and emphasizes their role in normalizing and/or improving the functional status of organs and systems, including the gastrointestinal tract microflora, in reducing the risk of diseases, etc. It gives data on the consumption and turnover of BAAs, definitions and classifications of this group of substances, the basic documents governing the control of their production and promotion in different countries and in Russia. Undenatured type II collagen (UC-II® ) that is made from the chicken sternal cartilage and is a component of Sustaflex is considered as an example of the BAA that is compliant with good medical practice regulations. The therapeutic properties of UC-II® have been confirmed in clinical trials. The paper describes the mechanism of action of the BAA, evidence for its efficacy and safety, and the possibility of its administration for the prevention and combination treatment of knee osteoarthritis (OA) and its use as an alternative treatment for OA.


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ISSN 1996-7012 (Print)
ISSN 2310-158X (Online)