In the past decade, rheumatology has shown clear progress in the practical introduction of biological agents (BAs) and targeted sintetic anti-inflammatory agents. At the same time, the use of these agents is associated with an increasing risk for infections of different origin and sites, including opportunistic infections (invasive my-coses, Pneumocystis pneumonia, etc.), as well as an increased risk for reactivation of latent infections, primarily tuberculosis (TB). In addition, there are cases of severe infections (pneumonia, sepsis, bacterial arthritis, skin and soft tissue lesions, etc.), including those with a fatal out-come. The review analyzes the literature data (mainly in the last 5 years) regarding the frequency and localization of infections in rheumatologic patients treated with BAs. It characterizes the significance of various infections (TB, pneumonia, chronic viral hepatitis, herpesvirus infection, etc.) in the tactics of following up these patients. The authors emphasize the need for the more widespread use of various vaccines (especially those against influenza and pneumococcal infection) in patients with autoimmune inflammatory rheumatic diseases.

Russian and international clinical recommendations postulate the possibility of withdrawal of biological agents in patients with rheumatoid arthritis (RA) after the achievement of clinical remission. But it is not clear what would be the results of implementation of these recommendations in clinical practice.

Patients and methods. In REMARCA (Russian invEstigation of MethotrexAte and biologicals for eaRly aCtive Arthritis) trial 78 patients (66 females, 12 males, median age 53 years, duration of disease 7 months at inclusion), who were resistant to high doses of subcutaneous (SC) methotrexate (MTX), were treated by combination therapy with SC MT and biologics (adalimumab, certolizumab or abatacept). Patients were investigated every 3 months using DAS28-ESR, SDAI, CDAI indices as disease activity measures.

Results. 30 (38.5%) patients (from 78) continued combination therapy. In 47 (60.3%) after achievement of remission or low disease activity (LDA) the therapy was modified to one of two options: 1) in 21 (26.9%) patients doses of biologics were tapered, in some cases to zero; 2) in 26 (33.3%) patients single-step discontinuation of biologics was performed. After 6 months among 47 patients with modification of therapy 27 (57.4%) maintained remission or LDA, in 20 (42.6%) deterioration observed, including 6 (12.8%) patients who lost remission but remained in LDA, and 14 (29.8%) flared (activity increased to moderate or high levels). First modification option was significantly superior to second option regarding the maintaining remission or LDA.

Conclusion. In terms of maximum preservation of the results, optimal modification of treatment strategy is the tapering of the dose by the gradual increase in the period between injections of biologics, at least 12 months after reaching the state LDA or clinical remission. 

Objective: to assess liver function changes in patients with spondyloarthritis (SpA) taking NSAIDs regularly over a long period.

Patients and methods. The data obtained during a 10-year PROGRESS prospective single-center cohort study of functional status, activity, and comorbidity (including gastrointestinal tract diseases) in patients with SpA were analyzed. The data of 363 SpA patients receiving NSAIDs regularly over a long period and followed up for 10 years were also explored. The changes that had occurred over a decade in the liver enzyme levels, the number of discontinued NSAID treatments because of a persistent increase in liver enzyme levels, and the number of prescriptions of hepatoprotective agents were analyzed.

Results. For 10 years, 18 patients with SpA discontinued their NSAID intake due to elevated liver enzyme levels (≥3 times greater than the reference value); during that time, the same increase in enzyme levels was observed in 2 healthy individuals (χ2 =1.39; p=0.2). In the patients with SpA as compared to the healthy individuals, the relative risk of abnormal liver function was 1.19 (95% CI, 1.009–1.405); odds ratio was 2.9 (95% CI, 0.65–12.95). There was no increased risk for discontinuation of some NSAIDs, including nimesulide (χ2 =0.03, p=0.85), the frequency of using hepatoprotective drugs was proved to be highest for diclofenac sodium, ibuprofen, nimesulide, and ketoprofen.

Conclusion. The regular long-term (as long as 10 years) use of NSAIDs to treat SpA is associated with treatment discontinuation because of elevated enzyme levels in every 10 patients. The maximum rate of discontinuation of NSAIDs due to a persistent increase in liver enzyme levels is observed 6–8 years after their regular use, so long-term NSAID therapy requires continuous monitoring of hepatic safety. The longterm intake of nimesulide, as compared with other NSAIDs, is shown to be unassociated with the higher rate of its discontinuation because of worse liver function. Hepatoprotectors are less frequently prescribed to patients taking nimesulide than to those receiving diclofenac sodium or ibuprofen and more frequently to patients using meloxicam. In most cases, prescribing hepatoprotective agents to patients receiving NSAIDs does not require discontinuation of anti-inflammatory therapy. 

Objective: to investigate the impact of the selectivity and half-life of nonsteroidal anti-inflammatory drugs (NSAIDs) on the development of subclinical kidney injury (SKI). A standard physical examination was made.

Patients and methods. The study included 80 patients with a verified rheumatoid arthritis (RA) diagnosis. The patients filled in a specially designed questionnaire to explore a history of drug use. As markers of SKI, the investigators determined the concentrations of albumin, α1-microglobulin (α1-MG), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in urine. A control group consisted of 20 apparently healthy individuals matched for age and gender.

Results. 80 patients suffering from RA received drug therapy. Of them, 82.5% and 87.5% took NSAIDs and disease-modifying antirheumatic drugs, respectively. The levels of SKI markers were compared in three groups of the examinees: 1) NSAID-treated patients; 2) NSAID-untreated patients; 3) a control group. There were statistically significant differences between all the groups (p<0.05). Comparison of the levels of SKI markers revealed no statistically significant difference in the groups receiving selective cyclooxygenase-2 (COX-2) inhibitors (n=18.6%), in those taking nonselective ones (n=68.6%), and the control group. Comparison of the levels of SKI markers demonstrated significantly higher >< 0.05). Comparison of the levels of SKI markers revealed no statistically significant difference in the groups receiving selective cyclooxygenase-2 (COX-2) inhibitors (n=18.6%), in those taking nonselective ones (n=68.6%), and the control group. Comparison of the levels of SKI markers demonstrated significantly higher α1-MG levels in the long-acting NSAID groups (n=8.6%) than in the short-acting NSAID group (n=80%). ALT, ALP, and microalbuminuria showed a similar trend that failed to reach statistical significance.

Conclusion: NSAIDs remain a group of medications with a certain nephrotoxic effect. At the same time, the design of selective COX-2 inhibitors has failed to solve the problem of nephrotoxicity. NSAIDs with long half-lives are characterized by greater nephrotoxicity. The available data provide preconditions for the more differentiated use of NSAIDs, particularly in patients with RA.

To optimize treatment for musculoskeletal pain (MSP) is a topical medical and social problem. A meeting of experts was held inMoscowin June 2015 to discuss the possibility of forming an interdisciplinary approach and elaborating a unified MSP treatment algorithm based on the com prehensive pathogenetically justified use of different classes of medicines. The Analgesic Treatment Using a Systemic Algorithm (ATUSA) trial is a retrospective observational study of the effectiveness of this approach in clinical practice.

Objective: to investigate the efficiency of combination treatment for MSP in real clinical practice.

Patients and methods. A study group consisted of 3304 patients (women (54.3%) and men (45.7%); mean age 48.9±14.6 years) with osteoarthritis, nonspecific back pain, and rheumatic juxta-articular soft tissue pathology who had visited their doctors for acute/subacute MSP. Treatment was performed in accordance with the following algorithm: the first appointment was a nonsteroidal anti-inflammatory drug (NSAID), such as aceclofenac), in case of contraindications, paracetamol and/or tramadol + a topical NSAID, in case of indications, muscle relaxants. The therapeutic efficiency was monitored every 7 days (a total of 4 visits); during each visit, therapy could be changed: switching to another NSAID, local administration of glucocorticoids (GC), as well as antidepressants or anticonvulsants. The dynamics of pain (a 0–10 pain intensity numeric rating scale), the number of patients in whom MSP had been resolved completely, as well as treatment satisfaction were taken into account to assess the results of treatment.

Results. The first appointment in 97.5% of the patients was NSAIDs, mainly aceclofenac (93.7%), that was used in combination with a muscle relaxant in 67.7%. By Visit 4, there was a reduction in MSP from 6.9±1.5–2.2±1.3 scores. MSP was completely resolved in 77.0% of the patients. The vast majority (88.4%) of the patients rated their treatment outcome as good or excellent. There was a need for switching to another NSAID in 8.1% of cases, local administration of GC in 1.9%; use of an antidepressant or an anticonvulsant in 1.5%, and hospitalization in 0.25%. Adverse reactions were noted in 2.2% of the patients.

Conclusion. The application of the treatment algorithm based on a pathogenetic approach ensures effective and relatively safe relief of MSP in most patients. 

Objective: to study the course and outcomes of lipodermatosclerosis (LDS) as a variant of lobular panniculitis.

Patients and methods. Examinations were made in 38 patients (37 women and one man) aged 54±13 years who had been diagnosed with LDS lasting 2 weeks to 20 years and followed up at the V.A. Nasonova Research Institute of Rheumatology in 2009–2016. In addition to general clinical examination, the patients underwent immunological studies and lower extremity venous Doppler ultrasonography (DUSG). Outcomes were assessed as a significant improvement (complete regression of indurations), an improvement (regression of indurations was achieved, but there was one recurrence of LDS in the follow-up period), a slight improvement (regression of indurations was achieved, but there was more than one recurrence of LDS, which needed to change treatment policy), no effect of the therapy (no regression of indurations was achieved), and deterioration of health.

Results. The 38 patients with LDS were noted to have subcutaneous fat inflammation in the leg (100%) and asymmetric inflammation (55%) on its medial surface (92%). If the body mass index (BMI) was normal, LDS regressed more rapidly (p=0.04). During the entire follow-up period, 16 (42%) patients were observed to have recurrent LDS; the median time to recurrence was 3 [1; 6] months. The development of a recurrence was associated with node merging into conglomerates [odds ratio (OR), 4.33; 95% confidence interval (CI), 1.05–17.8; p=0.037] and with the use of hydroxychloroquine (HCQ) agents at a dose <400 mg/day (OR, 5.25; 95% CI, 1.26–21.96; p=0.019). Regression of indurations was achieved in 39.5% of cases, the likelihood of its development was higher when the duration of LDS was ≤3 months before therapy initiation (OR, 14.67; 95% CI, 1.5–139.8; p=0.006) and in the absence of perforating vein valve incompetence, as evidenced by DUSG (OR, 4.1; 95% CI, 1.0–17.0; p=0.045).

Conclusion. In the study group, LDS was more common in middle-aged women with increased BMI and chronic venous insufficiency. The elevated clinical and laboratory parameters of inflammatory activity were not typical of LDS. Higher BMI values contributed to a longer regression of indurations. Recurrences were more frequently observed after stress and due to non-compliance with prescribed therapy. Node merging into conglomerates and use of HCQ< 400 mg/day for ≥6 months after therapy initiation are risk factors of recurrent LDS. The likelihood of regression of indurations was higher in patients, in whom the duration of the underlying disease was ≤3 months before therapy initiation and perforator vein valve incompetence was absent, as evidenced by DUSC. 

Patients and methods. The investigation included 103 psoriatic patients (47 men, 56 women; mean age, 44±13.69 years) with different clinical forms of Ps (mean duration, 10.7±10.2 years). Before being examined by a dermatologist, all the patients completed a Psoriasis Epidemiology Screening Tool (mPEST) questionnaire: its score of ≥3 was indicative of the presence of PsA and that of<3 showed its absence. All the patients were examined by a rheumatologist to confirm or exclude the diagnosis of PsA and underwent standard clinical and instrumental evaluations. The CASPAR criteria were considered to be a gold standard of PsA diagnosis.

Results and discussion. According to the mPEST questionnaire data, 60 (58.2%) of the 103 patients had a mPEST of ≥3 that was an indication for suspected PsA diagnosis. The CASPAR criteria confirmed the diagnosis of PsA in 47 (45.6%) of them. 43 (41.7%) of the 103 patients had a mPEST score of <3 showing a low probability of having PsA. At the same time, PSA according to the CASPAR criteria was absent in 29 (28.2%) of them.

Conclusion. For the diagnosis of PsA in patients with Ps, it is insufficient to use only the mPEST questionnaire due to the large number of underdiagnosed and overdiagnosed cases of the disease. All patients must be examined by a rheumatologist in accordance with the rheumatologic standard and the CASPAR criteria. 

Objective: to reveal the characteristic symptoms and syndromes of early-stage psoriatic arthritis (ePsA), which are pivotal to its early diagnosis.

Patients and methods. Fifty-one patients with a PsA duration of less than 2 years (mean 12 months) were examined. The diagnosis of PsA was established on the basis of the conventional CASPAR criteria and the Russian criteria developed by the expert method. The conventional current criteria, including the number of tender and swollen joints, DAS28, values of acute-phase indicators, were used to detect inflammatory activity. Skin syndrome was evaluated using the Psoriasis Area and Severity Index (PASI). X-ray study of the hands, distal and proximal feet, pelvis, and other involved joints and MRI of the distal hands/feet were performed. The Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and reduced GUESS were used to assess enthesopathy.

Results. The types of articular syndrome in ePsA were identified in accordance of the duration of the disease. The authors determined the characteristic features of arthritis, spondylitis, enthesitis, and dactylitis, their diagnostic value and associations with other manifestations in the first 2 years of PsA. There was a relationship of dermatitis and psoriatic onychopathy to the clinical picture of articular syndrome.

Conclusion. ePsA is characterized by marked heterogeneity of articular syndrome with predominantly mono/oligoarthritic and polyarthritic articular syndrome. The significant signs are enthesitis and dactylitis, which serve as risk factors for the unfavorable course of the disease. 

To date there have been no results of a direct comparison of the efficiency of using tumor necrosis factor-α inhibitors, secukinumab (SCM) and adalimumab (ADA) in particular, to treat psoriatic arthritis (PsA). This suggests that there is a need to apply the Matching-Adjusted Indirect Comparison (MAIC) method that will be able to choose a treatment option for PsA. Objective: to compare the efficacy of SCM andADAby using the MAIC method in patients with active PsA.

Patients and methods. The results of usingADAin the Adalimumab Effectiveness in Psoriatic Trial (ADEPT), a randomized clinical trial (RCT), and SCM in the FUTURE 2 RCT were compared according to theAmericanCollegeof Rheumatology (ACR) and Psoriatic Area and Severity Index (PASI) criteria. The analysis based on the MAIC principles included aggregated data on 151 patients with active PsA from the ADEPT RCT and 189 patients from the FUTURE 2 RCT.

Results. At 16 weeks, ACR20/50/70 responses were observed in 74.4/50.1/18.5% of the patients treated with SCM 150 mg, in 65.5/50.1/50.1% of those treated with SCM 300 mg, and in 55.6/32.5/20.5% of those receivingADA, respectively. Both doses of SCM had a significant advantage over the dose ofADAaccording to ACR20 and ACR50 responses. A PASI75 response forADAand SCM 150/300 mg was observed in 60.9 and 59.5/64.1% of the patients; and a PASI90 response was seen in 39.1 and 47.7/40.8% of the patients, respectively. At 24 weeks of treatment, ACR20, ACR50, and HAQ-DI responses in patients receiving SCM 150 and 300 mg were significantly higher than in PsA patients takingADA. No statistically significant differences were observed in ACR70 response rates. The ratio of ACR20 and ACR50 indicators was similar after 48 weeks of treatment initiation. Assessment of the dynamics of psoriasis yielded similar results.

Conclusion. Patients with active PsA demonstrated the advantage of therapy with SCM 150 and 300 mg over that withADA. There was a greater improvement in quality of life in patients with PSA treated with SCM. 

The paper analyzes two matching-adjusted indirect comparison-based investigations of the efficacy of adalimumab (ADA) and secukinumab (SCM) in active ankylosing spondylitis, which have been recently reported at the EULAR Congress (London, 2016). One study sponsored by AbbVie was conducted to determine the short-term (16-week) comparative clinical and economic efficacy of the test drugs and the other was supported by Novartis to reveal long-term (52-week), only clinical efficacy. Both studies have shown that the short-term efficacy ofADAand SCM is practically similar; however, the latter has a better long-term clinical efficacy. A pharmacoeconomic analysis of both drugs used during the first 12 weeks has demonstrated some advantage ofADA. 

Joint involvement in syphilis has been considered as casuistry in recent years. At the same time, the high incidence of primary syphilis and the notified cases of late neurosyphilis may suggest that joint involvement in this disease is by no means always verified. Traditionally there are two forms of syphilitic arthritis: primary synovial (involving the articular membranes and sac) and primary bone (involving the articular bones and cartilages) ones. The paper describes the authors' clinical case of the primary bone form of articular syphilis in a 34-year-old man. 

Inflammation is the most important element in the pathogenesis of major human diseases. It determines the fundamental value of anti-inflammatory therapy in the modern concept of targeted pathogenetic treatment. The rational choice of anti-inflammatory drugs and the design of new promising agents are inconceivable without clear knowledge of the characteristics of development of an inflammatory response. Eicosanoids, the metabolites of polyunsaturated fatty acids, play a key role in the process of inflammation. These substances have diverse and frequently antagonistic biological effects, which is determined by their chemical structure and specific features of receptors with which they interact. Some of them (prostaglandins, leukotrienes, auxins, and hepoxilins) are potential mediators of inflammation and pain; others (lipoxins, epoxyeicosatrienoic acid derivatives, resolvins, protectins, maresins, and endocannabinoids) have anti-inflammatory and cytoprotective activities, contributing to the resolution of the inflammatory response. This review describes considers the main classes of eicosanoids, their metabolism, effects, and clinical significance, as well as the possibilities of pharmacological interventions in their synthesis or interaction with receptors. 

The authors have analyzed the literature dealing with studies of the efficiency and safety of stem cell transplantation (SCT) in patients with ankylosing spondylitis (AS) through the electronic resources Pubmed and Medline by using the keywords «bone marrow transplantation», «hematopoietic stem cell transplantation», «ankylosing spondylitis», «autoimmune diseases», and «sacroiliac joint biopsy». The paper describes four cases of SCT in AS patients, including transplantation that was carried out in one patient with lymphoma concurrent with AS, in two AS patients without blood cancers, and in one patient with AS concurrent with myeloid leukemia. Drug-free remission was achieved in 3 cases: lymphoma concurrent with AS (n=1), AS concurrent with myeloid leukemia (n=1), and AS without comorbidities (n=1). In addition to an improvement in the course of AS, there were also two cases with clinical presentations of AS after SCT. The given cases show that SCT can be basically used to induce drug-free remission in patients with severe forms of standard therapy-resistant AS. However, the introduction of SCT in clinical practice needs to adjust the technique to the specific features of AS patients. 

The paper discusses the problem of phenotyping of knee osteoarthritis (OA). It is assumed that that existing differences between clinical recommendations of different years, as the inadequate efficiency of their practical application, may be associated with the clinical features of individual OA phenotypes. It is of great importance in selecting individual therapeutic approaches in these patients. The place of Hylan G-F20 inthe treatment algorithm for knee OA is considered, by taking into account different types of the disease. 

Prevention of gastrointestinal tract (GIT) complications is the most important element for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin (LDA). Proton pump inhibitors (PPIs) have long been the only medication to prevent these complications. However, PPIs are only effective in preventing and treating upper GIT diseases (NSAID gastropathy) rather than small intestinal injury (NSAID enteropathy). Rebamipide has emerged as a novel agent to protect the gastrointestinal mucosa today. The effect of the drug differs from that of PPIs: it is a typical gastroand enteroprotector that enhances the synthesis of endogenous prostaglandins and possesses a significant anti-inflammatory potential. Rebamipide has long been widely used by doctors inJapan,South Korea, andChinaas an effective and safe agent for the treatment of many diseases of the digestive system. There is a strong evidence base for the efficacy of rebamipide in preventing and treating NSAID gastropathy and NSAID enteropathy (including LDA-induced injuries). Controlled studies have found that the drug is not inferior to the classic gastroprotective agent misoprostol, significantly outperforming the latter in its tolerability. This review describes the mechanism of action of rebamipide and main clinical trials of its therapeutic effect in NSAID gastropathy and NSAID enteropathy. 

The paper reviews the literature dealing with juvenile idiopathic arthritis (JIA) prognosis, patient physical activity, its role in the development of functional problems that cause limited vital activity and reduced quality of life, as well as the efficiency of physical exercises (exercise therapy (ET)) in the treatment of this disease. It stresses the relationship between physical developmental delay in patients with JIA and the occurrence of psychological and social problems. There are data of publications about the need for physical loads for patients with various rheumatic diseases, as well as for adults. Special attention is paid to the good endurance of ET that is identified by a number of authors as an additional treatment for JIA patients, which improves their functional status, but fails to affect the course and outcome of the disease. The author analyzes survey papers on the multidisciplinary rehabilitation of children, adolescents in particular, and the importance of science-based propaganda of active lifestyle. By having analyzed the literature, the author concludes that it is expedient to include ET into standard treatment for patients with JIA.