The results of studies conducted over the past two decades were used to elaborate EULAR recommendations for the management of rheumatoid arthritis (RA); the updated recommendations have recently been published.

In accordance with these recommendations, the tactics in management of each patient is determined by the disease activity. This indicator determines the frequency of examination for the patient, selection of an anti-rheumatic drug, and the need for therapy correction. Methotrexate is recommended to patients with active RA (high or moderate activity) naÏve to disease-modifying anti-rheumatic drugs (DMARDs). Another DMARD can be used for patients with lower activity of RA. Therapy effectiveness is evaluated as soon as 3 months after its prescription.

Clinical improvement (decrease in RA activity from high to moderate) needs to be achieved by this time. However, the aim of therapy is to achieve low disease activity or remission (that needs to be achieved earlier than 6 month after the therapy was started) rather than clinical improvement only. If the maximum dose of a drug results neither in clinical improvement after 3 months nor in low activity after 6 months, the therapy should be corrected. EULAR experts recommend using the overall score that includes joint score indices (DAS28, SDAI or CDAI) to assess the level of RA activity. 

The problem of comorbid infections (CI) in modern rheumatology remains important. The reasons behind it include the presence of an autoimmune rheumatic disease and the need to use immunosuppressant drugs. We discuss some problems of CI under EULAR recommendations (2013) for the management of rheumatoid arthritis (RA). The incidence rates of comorbid infections in patients treated with different disease- modifying anti-rheumatic and biological drugs are analyzed. The significance of measures for preventing CI in management of RA patients is demonstrated. The significance of vaccination (first of all, with anti-influenza and pneumococcal vaccines) of RA patients to reduce the incidence rate of lower respiratory tract infections and the risk of infection-related mortality is emphasized. Vaccination is recommended even if suboptimal outcome is expected. 

The role of glucocorticoids (GCs) in the current strategy of treating rheumatoid arthritis (RA) according to the EULAR 2013 recommendation is discussed. The main studies focused on GCs since they started to be used to treat RA are reviewed. The difficulties, advantages, and draw- backs of using GCs to treat RA, as well as possibilities to affect progression of destruction in small joints of the hands and feet, are discussed.

Since new data have recently been obtained, EULAR recommendations 2013 for the management of RA patients states the following for GCs: «The use low doses of GCs (combined with one or several disease-modifying anti-rheumatic drugs) should be considered as a component of the treatment strategy during the first six months of the disease». It is particularly emphasized that GCs should be abandoned as soon as it is pos- sible from the clinical viewpoint. The term «low dose of GC» means prednisolone prescribed at a dose ≤7.5 mg/day. 

Tumor necrosis factor (TNF) α inhibitors are the most commonly used agents to treat rheumatoid arthritis (RA) and other inflammatory arthropathies. Five drugs belonging to the family of TNFα inhibitors have been certified in Russia for treating RA: infliximab (INF), adali- mumab (ADA), golimumab, certolizumab pegol, and etanercept (ETN). These drugs have different compositions. ETN does not belong to the family of monoclonal antibodies (mAbs) and has a different mechanism of action. It is a dimeric molecule of synthetic fusion protein contain- ing TNF receptor and bound to the Fc-fragment of human Ig1. ETN can inhibit both TNFα and lymphotoxin α. ETN contains only the pro- tein identical to human protein.

All TNFα inhibitors exhibit a virtually identical anti-inflammatory activity. The data from the registries show that the risk of discontinuation of therapy with TNFα during the first 2–3 years is appreciably high; there is a trend toward increased frequency of therapy discontinuation because of loss of effectiveness. It was found that the risk of therapy discontinuation because of insufficient effectiveness and adverse events (AEs) is minimal for ETN and maximal for INF. The structure of biological drugs (which also affects their immunogenicity) has the key neg- ative effect on maintaining the response to therapy and frequency of AEs. However, since ETN is a fusion molecule and contains less poten- tially immunogenic epitopes compared to mAbs, the frequency of detecting anti-drug antibodies (ADAbs) is appreciably lower.

The fact that ETN has a lower immunogenicity can be used to explain the significantly lower probability of discontinuing therapy using this drug as compared to INF and ADA. The risk that the need to increase the dose because of gradual loss of effectiveness of therapy with ADA and INF, was 4.9- and 28-fold higher, respectively, as compared to ETN.

Therapeutic algorithms make it possible to control therapy with TGFα inhibitors (development of ADAbs, blood concentration of drug), as well as to switch to using another biological drug. Currently, the main method for preventing ADAb formation is to strictly follow the recommenda- tions for using biological drugs in combination of disease-modifying anti-rheumatic drugs (first of all, with methotrexate). TNFα inhibitors hav- ing the lowest immunogenicity (ETN, etc.) are advisable to be used in this case. 

Laboratory examination is an integral part of managing patients with systemic lupus erythematosus (SLE). A number of laboratory tests need to be conducted to verify the diagnosis; some indicators attest to the development of a concomitant pathology (development of comorbid conditions and therapeutic aggravation). The monitoring of individual laboratory tests makes it possible to assess the effectiveness of therapy or indicates that it needs to be enhanced in some cases. Furthermore, some parameters are considered to be prognostic factors of treatment outcome. The article reports on the range and frequency of laboratory errors in SLE patients. The role of laboratory tests in diagnosis and assessment of disease prognosis is discussed. The relationship between clinical and laboratory manifestations and the mechanisms for preventing laboratory errors are studied. The international guidelines for monitoring SLE patients are presented.

Proper range of examination of SLE patients and interpretation of the results ensures timely diagnosis (sometimes at the early stage) and allows one to avoid a hyperdiagnosis, to timely prescribe adequate therapy, and prevent its complications. 

Raynaud’s phenomenon (RP) is a common condition that predominantly occurs among women. The onset age in most cases is under 30 years. The phenomenon was first described by M. Raynaud over 150 years ago. Primary (Raynaud’s disease) and secondary RP were subsequently distinguished. Pathophysiology of RP has not been fully elucidated yet; RP seems to be a multifactor disease. A pronounced vasospasm in response to stimuli is believed to be caused by disruption in the central and local mechanisms of regulation of vascular tonus. Vascular endothe- lial, intravascular, and neuronal disorders are the key ones among these factors. Structural changes in vessels that can be observed by nailfold capillaroscopy play a significant role in pathophysiology of secondary RP. The key step in the diagnosis of RP is identifying its clinical variant, since secondary RP may be a sign or a premonitory symptom of certain autoimmune, hematologic, endocrine, neoplastic, and other disorders. Secondary RP is most frequently observed in patients with systemic rheumatoid diseases. Therapy of secondary RP provides no satisfactory out- comes, since there is no complete conception about the pathophysiological mechanisms of its development. Different groups of drugs are cur- rently used to treat RP, including calcium channels blockers, phosphodiesterase type 5 inhibitors, endothelin receptor antagonists, etc.

This review focuses on pathogenesis, the algorithm of early and differential diagnosis of RP, and current approaches to therapy based on the analysis of the published and our own data. 

We report the results of a pilot study on physician awareness of modern diagnostic methods and drug therapy of osteoporosis (OP) and the use of this knowledge in daily practice.
A pilot survey among physicians demonstrated that experts (rheumatologists, endocrinologists, etc.) have a high level of awareness of the OP problem and successfully use this knowledge in daily practice (modern diagnosis, prevention, and treatment methods). They widely prescribe original drugs and certain generics that were shown to be effective in post-marketing surveillance.

Limitations of the study: 1) only physicians dealing with diagnosis and treatment of OP were surveyed; hence, the conclusions of this study are valid only for this group of physicians; 2) only physicians working in large cities who can use modern diagnosis methods (densitometry; determination of bone turnover markers) participated in the study; 3) Prolia medication, which has been used in Russia since 2013, was not taken into account in the questionnaire. 

Methotrexate or leflunomide is recommended to be used as the first synthetic disease-modifying anti-rheumatic drug to treat rheumatoid arthri- tis (RA). In 2011, ELAFRA (leflunomide, Haupt Pharma Munster GmbH, Germany; license LP-000804 registered October 3, 2011) was cer- tified and approved in Russia.
This surveillance study was aimed at assessing the effectiveness and tolerability of ELAFRA in RA patients in real-life clinical practice.

Material and Methods. The study involved patients corresponding to the 1987 RA classification criteria, with varying disease duration. The patients were monitored at 33 Russian medical institutions in March–December 2013. According to the drug label, ELAFRA was prescribed at a dose of 10 mg/day during the first 3 days and subsequently at a dose of 20 mg/day. In case of adverse effects (AEs), the daily dose was recommended to be reduced to 10 mg. The patients were examined before the drug was prescribed; as well as 1, 3, 6 months after therapy was started. The number of painful swollen joints and pain intensity according to the Visual Analog Scale (VAS) were assessed. The patients were subjected to laboratory exam- ination (blood test; ESR test; C-reactive protein (CRP) test). RA activity was determined using the DAS28 index. AEs were identified. The data on 99 patients (87 females and 12 males; mean age: 51.1±11.1 years; mean disease duration 74.9±65.7 months) were used for sta- tistical analysis. Disease activity was moderate in 9 patients and high in 90 patients.

Results. Six-month therapy with ELAFRA reduced the mean number of swollen joints from 13.7 to 5.1 and the number of painful joints, from 14.9 to 9.5. VAS pain intensity decreased from 62.7 to 29.6 mm; ESR decreased from 38.8 to 22.18 mm/h; SRP, from 24.9 to 13.0. Low and moderate RA activity according to DAS28 and CDAI indices after treatment was observed in 63 and 46 patients, respectively. No serious AEs have been revealed; non-serious AEs were reported for 8 patients. The drug therapy was cancelled in only 3 patients: because of an AE; because of insufficient effectiveness; and because of personal reasons in one patient.

Conclusion. The results indicate that ELAFRA drug is characterized by good clinical effectiveness and tolerability. 

Therapy with biological agents (biologics) over the past few years has become an important part of the strategy of medical treatment of patients with rheumatoid arthritis who respond insufficiently to the disease modifying anti-inflammatory drugs. The possibility to predict response to biologics is of special importance. Factors associated with good response to TNF-inhibitors are very different: age, liver and kidney function, body mass index, concomitant therapy, immunogenicity, the presence of ACPA and the rheumatoid factor, the cytokine profile, genetics, smoking, previous therapy by biologics etc. Another factor that significantly affects the long-term prognosis of biologic therapy is the primary response to treatment. Inhibitors of TNF-α as a whole is characterized by the development of the most marked clinical response within the first 12–24 weeks of treatment that can sustain for 12 months or more. Certolizumab pegol is characterized by rapid development of marked clinical response to treatment against disease activity and function with maintaining consistent improvement over the years, and the prognosis can be determined in most patients by the response to therapy in the first 12 weeks. We present a clinical case. 

Modern concepts of the role of angiogenesis in pathogenesis of psoriasis and psoriatic arthritis (PsA) are analyzed. The features of cell-mediated and humoral immune responses resulting in proliferation of synovial membrane and vessel overgrowth in patients with this pathology are discussed. A number of angiogenesis mediators, pro-angiogenic cytokines, growth factors, matrix metalloproteinases, etc. are shown to be involved in progression of neovascularization. The role of tumor necrosis factor α as a key therapeutic target for treatment of psoriasis and PsA is emphasized. Drugs inhibiting some stages of angiogenesis, which are either used in clinical practice or are being developed, are discussed. 

The data on pathogenetically significant parameters that are involved in pain perception in fibromyalgia (FM) patients (increased sensitivity or density of dopamine receptors D2, enhanced pain signal due to the elevated substance P level or insufficient modification of the pain signal caused by low serotonin level; allodynia phenomenon; and the psychosomatic component) are reported.

New classification criteria of FM and assessment of severity of the symptoms included in these criteria are presented. The changes that have taken place in therapy of FM pain over the past decade are demonstrated: less frequent use of peripheral analgesics, tricyclic antidepressants; more frequent use of serotonin reuptake inhibitors (duloxetine, milnacipran) and pregabalin. The effectiveness and fair pain tolerability of pregabalin are demonstrated. The effectiveness and tolerability of duloxetine, milnacipran, and pregabalin are compared using the data of 17 randomized controlled trials. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the main component of symptomatic treatment of patients with rheumatic disorders. The use of these drugs reduces the intensity of the most unpleasant symptoms and improves patients’ quality of life. Unfortunately, NSAID therapy is limited by the risk of dangerous gastric and cardiovascular complications. Researchers all over the world are involved in designing new drugs belonging to this family that would be characterized by increased safety. These drugs include coxibs (selective cyclooxygenase-2 (COX-2) inhibitors), combination drugs containing NSAIDs and gastroprotector agents (misoprostol, H2 blockers, proton pump inhibitors), COX2/LOG2 (lipoxygenase 2) inhibitors, and COX-inhibiting nitric oxide donors (CINODs). However, all these drugs proved to have serious drawbacks. Some of them are being actively used; launching of other drugs has been stopped at the stage of clinical trials; while the others were abandoned because of inadequate efficacy/tolerability ratio.

A new representative of improved NSAIDs, amtolmetin guacil (AMG), was synthesized from tolmetin, a nonselective NSAID. As opposed to tolmetin, AMG has a number of gastroprotective properties. The most important one is that it increases NO concentration in the mucous membrane of the gastrointestinal tract. The pharmacological features of AMG are discussed; the data obtained during pre-clinical and clinical trials are reported. 

The typical X-ray symptoms of psoriatic arthritis (PsA) in joints of hands and distal sections of feet (asymmetric lesions; isolated lesion of distal interphalangeal joints (DIJ) of hands with no changes in other small joints of hands; axial lesion of three joints in a single finger; transverse lesion of joints of the hand at the same level; destruction of distal phalanges; narrowing of the distal epiphysis of hand finger phalanges and metacarpal bones; cup-shaped deformity of the proximal portion of hand finger phalanges and narrowing of distal epiphysis; osseous ankyloses; multiple osteolytic lesions and destruction of bone epiphysis and joint deformities; inflammatory changes in the sacroiliac joints; and typical degenerative changes in the spine) are described. It is especially important to know X-ray manifestations of PsA when there are no typical cutaneous manifestations of psoriasis. 

Nonspecific low back pain (NLBP) is one of the most common rheumatic disorders; it is responsible for the greatest number of patients seeking medical advice. Unfortunately, there is neither a generally acknowledged viewpoint on the nature of this pathology nor a unified conception of its treatment in Russia. The unreasonably wide use of expensive instrumental diagnostic methods and treatment options that have unconfirmed and disputable efficiency is a serious problem in managing NLBP patients.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been and remain basic medications used to treat NLBP. Their therapeutic potential has been proved in a large number of well-designed clinical trials and it is beyond any doubt. At the same time, there are new NLBP pharma- cotherapies, such as epidural injection of tumor necrosis factor-α inhibitors, the use of nerve growth factor inhibitors and nociceptive system dysfunction-affecting drugs.

This paper considers the main groups of drugs (NSAIDs, paracetamol, opioids, myorelaxants, antidepressants and anticonvulsants, glucocor- ticoids, local anesthetics, and genetically engineered biological agents) that have found application or tested in NLBP and gives general data on their efficacy and tolerability. 

Osteoarthritis (OA) is a common disorder, seen most often in older patients. The main clinical symptom is pain in the knee and hip joints. Nonsteroidal anti-inflammatory drugs are used to arrest pain taking into account the effect they have on somatic diseases and the cartilage tis- sue. Diacerein is one of the drugs exhibiting a pathogenetic effect in OA patients: it inhibits proinflammatory cytokines, tumor necrosis factor and interleukin 1. The effectiveness and safety of the generic drug arthrocare were demonstrated in foreign and Russian studies. 

Glucocorticoid-induced osteoporosis (GIO) is the most common cause of secondary osteoporosis (OP) and a main cause of drug-induced OP. Fractures of the skeleton are registered in 30–50% of patients who have taken oral glucocorticoids (GCs) for a long time, during which the frac- tures develop with the use of any daily GC dose and with higher bone mineral density (BMD) than in postmenopausal OP.
In patients who have taken oral GCs long or in high daily doses, decrease of BMD and low bone tissue quality leading to fractures are largely associated with the reduction of bone formation. This gives proof to the administration of antiosteoporotic agents that enhance the formation of bone during its remodeling. Teriparatide, a recombinant human parathyroid hormone, enhances osteoblast function, decreases the apoptosis of osteoblasts and osteocytes, increases the differentiation of osteoblast precursors, and can prevent the negative effect of exogenous GCs on bone. According to clinical trials results, teriparatide treatment increases BMD and reduces the risk of vertebral fractures in patients who have taken oral GCs long. In accordance of the clinical recommendations for the diagnosis, prevention, and treatment of GIO, which have been developed by the Russian Osteoporosis Association jointly with the Association of Rheumatologists of Russia and the Russian Respiratory Society, teriparatide is the drug of first choice for the treatment of GIO in men and women at high risk for fractures (with the history of fragility fractures or having high FRAX 10-year absolute fracture risk). Teriparatide may be prescribed in case of previous antiosteoporotic treatment failure (new fractures occurring during treatment and/or continuing to decrease BMD), as well as when other drugs to treat OP are intolerable or when there are contraindications to their use.