Modern facilities of pharmacological correction of hyperuricemia in rheumatic diseases: management of difficult clinical cases

The article presents clinical cases of management of patients with low compliance with treatment, suffering from rheumatic diseases and disorders of purine metabolism.Cases report 1. The first patient with advanced gout, after taking 100 mg of allopurinol, developed undesirable effects: sore throat, change in voice, cough, and therefore treatment was discontinued. After six months without therapy, the condition worsened and, in self-medication, the patient resumed taking allopurinol at a dose of 300 mg per day, which, as expected, resulted in a resumption of the allergic reaction and a serious exacerbation of gouty arthritis. In order to stop continuous relapses of arthritis, it became necessary to prescribe glucocorticoids. After stabilization of the state, constant administration of febucostat with positive clinical and laboratory dynamics was recommended.Cases report 2. The second patient with rheumatoid arthritis (RA) developed analgesic nephropathy, secondary hyperuricemia, and typical gouty attacks in the background of high activity of the underlying disease, existing kidney pathology and inappropriate use of non-steroidal anti-inflammatory drugs (NSAIDs). Frequent exacerbations of arthritis prompted the patient to finally see a rheumatologist. The adjusted therapy made it possible to reduce RA activity, reach the recommended level of uric acid, and reduce the drug load on the kidneys with almost complete withdrawal of NSAIDs. Thus, in modern conditions, rheumatologists have in reserve all the necessary means for the pharmacological correction of hyperuricemia, even in difficult clinical cases. Febucostat is the drug of choice for correcting uric acid levels in case of intolerance to allopurinol, as well as in the development of secondary gout against the background of renal failure. In addition, it should be noted that the effectiveness of the treatment of rheumatic diseases largely depends on the patient’s compliance. To increase adherence to therapy, regular patient schools are recommended

Clinical significance of collchicine in pharmacotherapy of cardiovascular pathology in patients with hyperuricemia in rheumatic diseases

For a long time, there has been scientific debate about the appropriateness of prescribing drugs to lower the level of uric acid in patients without clinical manifestations of gout. Long-term hyperuricemia is known to be the cause of gout and gouty arthritis. However, an increased level of uric acid is often found in a number of other diseases (metabolic syndrome, kidney disease, cardiovascular disease, psoriasis). Clinical evidence suggests that uric acid-lowering therapy slows the progression of cardiovascular disease and chronic kidney disease. And, if in rheumatological practice this issue still remains a subject of discussion, then the cardiological community by 2019 has clearly defined the indications for starting urate-lowering therapy. The Consensus on the Management of Patients with Hyperuricemia and High Cardiovascular Risk strongly recommends that the practitioner prescribe drugs to control hyperuricemia in hypertensive patients. The need to control the level of uric acid is reflected in the relevant sections of the Clinical Guidelines for the Management of Patients with Arterial Hypertension, 2020. This article provides a review of the literature on the etiology, pathophysiology, pharmacotherapy of hyperuricemia in patients with cardiovascular and rheumatic diseases. A separate section is devoted to scientific studies of the effects of colchicine in advanced therapy for CVD and RD. A clinical case of observation of a patient with newly diagnosed psoriatic arthritis, hyperuricemia, high cardiovascular risk is presented. The peculiarity of this clinical case is the onset of the disease after orthopedic surgery on the knee joints, high comorbidity and poor tolerance of standard basic therapy. The use of colchicine stabilized the patient’s condition. Thus, in clinical practice, it is necessary to take into account the role of hyperuricemia in the pathogenesis of inflammation in cardiovascular pathology. Colchicine may be the drug of choice for patients with hyperuricemia at high cardiovascular risk

Body composition and serum fetuin-A levels in patients with rheumatoid arthritis

Background. Rheumatoid cachexia is a pathological condition which appears in patients with rheumatoid arthritis with low fat-free mass and normal or high body mass index. Bone mass loss is one of the components of rheumatoid cachexia. Fetuin-A, a major noncollagen protein of bone tissue, regulates bone remodeling. Aim of the study was to investigate the prevalence of rheumatoid cachexia and the association of serum fetuin-A level with body composition components in patients with rheumatoid arthritis. Material and methods. 110 patients (8 male and 102 female) with rheumatoid arthritis were enrolled in our study. Serum fetuin-A level was determined by ELISA. Dual-energy X-ray absorptiometry with Total Body program was performed. The diagnosis of rheumatoid cachexia was based on the next criteria: fat-free mass index less than 10th percentiles with fat mass index above 25th percentiles. Results and discussion. We observed rheumatoid cachexia in 25 patients (22,7 %). According to the literature, such patients have an increased risk of developing metabolic syndrome, arterial hypertension and mortality. Positive significant (p < 0,05) correlations were observed between serum fetuin-A levels and right and left lower limb, trunk, gynoid region, both lower limbs and total body bone mass. No statistically significant relationships with other indicators were identified. Fetuin-A negative dynamic in patients with rheumatoid arthritis may be accompanied by the loss of bone mass, which requires the improvement of therapeutic approach. Conclusions. Almost a quarter of patients with rheumatoid arthritis have rheumatic cachexia. Positive correlation between serum fetuin-A levels and lower limbs, trunk, gynoid region and total body bone mass was observed

SERUM FETUIN-A LEVELS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is the second most common rheumatic disease. In recent decades, there has been an active search for and study of biologically active substances involved in the pathogenesis of RA, which can serve as a starting point in designing new drugs for targeted therapy of this disease. The hepatokine fetuin-A (FA) is one of these substances.Objective: to investigate serum FA levels in patients with RA.Subjects and methods. The investigation enrolled 110 patients with RA. All the patients underwent the following set of studies: general blood test and determination of the serum levels of C-reactive protein (CRP), serum FA, rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP) antibodies, cartilage degradation products (CartiLaps), and urine creatinine. A control group consisted of 30 apparently healthy individuals whose serum FA level was determined in order to obtain reference values.Results and discussion. The normal FA level varied from 653.55 to 972.19 μg/ml. All the patients with RA were divided into two groups: 1) 23 patients with a low FA level (<653.55 μg/ml) and 2) 87 patients with a normal FA levels (≥653.55 μg/ml). The groups differed significantly in anti-CCP antibody concentrations, disease activity, radiological stages, functional classes, and the presence of complications. Patients with lower FA levels were noted to have increased CRP concentrations, erythrocyte sedimentation rate, and CartiLaps/urine creatinine ratio. The mean FA concentration was considerably and significantly lower in patients with higher DAS28 scores. Conclusion. Our investigation has revealed that there is a relationship between the levels of FA and the individual clinical manifestations of RA. The lower FA level is associated with higher disease activity and the aggressive phenotype of RA (the presence of anti-CCP antibodies, radiological stages III and IV, extra-articular manifestations and complications)

The Comparative Efficacy and Safety of Long- and Short-Term Continuous Use of Non-Steroidal Anti-Inflammatory Drugs for the Treatment of Knee Osteoarthritis

Objective. To compare the efficacy and tolerability of long-term and short-term continuous NSAIDs in patients with knee osteoarthritis with insufficient efficacy “on demand” NSAIDs and SYSADOA.Study design. 12-week, prospective, comparative, randomized, single-center study.Materials and Methods. 180 patients with primary knee osteoarthritis aged 40 to 85 years with insufficient efficacy of “on demand” NSAIDs and SYSADOA were examined. Anti-inflammatory drugs were recommended for everyone: 56 people took Naproxen (31.11%), 63 — Etoricoxib (35%), 61 — Ketoprofen (33.89%). Patients were randomized into two groups: 1st group — with 8-week continuous intake of NSAIDs, 2nd group — with a 2-week continuous course of NSAIDs.Results. There was a positive dynamics of pain syndrome according to VAS and decrease in the level of the WOMAC index in both groups after 2 weeks of therapy. The pain level (VAS) and WOMAC indices in 1st group achieved after 8 weeks significantly differed from the ones after 2 weeks of therapy (VAS dynamics —10.93±2.43 mm, t = 42.64; p<0.001). In both groups we noted gradual significant increase in the average pain level according to VAS and WOMAC indices after NSAIDs cancellation. However, there was better control of pain in 1st group with long-term NSAID than in 2nd one. Safety profile of drug therapy was similar in both groups.Conclusion. The long-term 8-week use of NSAIDs in patients with knee osteoarthritis with insufficient efficacy “on demand” NSAIDs and SYSADOA provides better dynamics of the pain syndrome than with 2-week therapy. After treatment is canceled longer prior NSAID therapy contributes to better control of the pain syndrome. Continuous use of NSAIDs demonstrated good tolerance and safety, did not require dose reduction and/or discontinuation of therapy. Thus, anti-inflammatory therapy of osteoarthritis in this group of patients may be prescribed for a longer period with continuous use of NSAIDs

The ten-year probability of fractures with the FRAX tool: which threshold for intervention to be used and how?

Objective: to analyze the clinical and organizational feasibility of using different intervention thresholds for the Russian population.Subjects and methods. The probability of fractures using the Russian FRAX model was calculated on a sample of 3,866 postmenopausal female residents from 6 cities of the Russian Federation. Different intervention thresholds, including fixed (20% for major fractures and 3% for hip fractures), age-dependent (European and Russian) ones, as well as alternative models, were analyzed. The proportion of women to be treated was estimated using different intervention thresholds.Results and discussion. The analysis of the effectiveness of the thresholds showed that the European threshold was the least appropriate one for the formed sample, since more than half (53.6%) of the women to be treated using the threshold, while the vast majority (90%) of the patients were in the younger age groups (50—54 years). There were very similar results of the effectiveness analysis of the fixed threshold (according to the USA National Osteoporosis Foundation — NOF) recommendations and that of the age-dependent threshold for Russia (in the context of the national clinical recommendations). Using the NOF approach in our sample could identify 47.8% of the postmenopausal women to be treated for osteoporosis. Their proportion rose from 29.6% of the patients aged 50—54 years to 80.6% of those aged 85 years and older. The alternative analyses of age-dependent thresholds showed great effectiveness when the fracture was considered not as a risk factor for future fractures, but as a clinical disease manifestation that was sufficient to recommend that the patient should be treated without FRAX counting. However, with their use, the proportion of older people to be treated remains not high enough. In this connection, there remains a need to search for the more adequate application of the existing intervention threshold or to develop a new, for example, hybrid variant of the age-dependent threshold