Immunogenicity, the characteristic property of proteins affecting an immune response, shows up in the formation of anti-drug antibodies (ADA) and/or immune complexes. The paper discusses whether immunogenicity has an impact on the efficacy and safety of TNF-α inhibitors (TNF-αI) in different rheumatic diseases. It provides evidence that immunogenicity has an impact and no impact on the pharmacodynamics and pharmacokinetics of the drugs. It also demonstrates the detection rate of ADA when using different biological agents (BAs) in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, and Crohn's disease. The impact of TNF-αI change, concurrent methotrexate (MT) therapy, and treatment intervals on immunogenicity is characterized. A combination of TNF-αI and MT versus BA monotherapy is shown to diminish immunogenicity; moreover, the use of therapeutic doses of MT as compared to its low weekly doses (2.5–5 mg) could reduce to a greater degree the rate of anti-TNF-αI antibody formation. Randomized controlled trials have demonstrated that the presence or absence of ADA affects the rate of adverse reactions (ARs) (due to infusion or injectable therapy) than the change in TNF-αI efficacy. This is confirmed by the data of real clinical practice (BA registers from different countries), which show that there is no significant difference in the duration of treatment with different TNF-αI; therapy with the latter in the presence of ADA was shorter mainly because of ARs rather than its inefficiency. ADA detecting methods and the complexity of their interpretation are depicted.

The present-day views of the immunogenicity of biological agents (BAs) used to in the treatment of psoriasis and psoriatic arthritis are analyzed. The immunogenicity of these medicaments is noted to depend on their molecular structure, individual patient characteristics, and used treatment regimens. As this takes place, the primary structure of the drug and its posttranslation modifications during manufacture are key factors. It is pointed out that a number of antigenic structures may give rise to the body's BA antibodies – murine epitopes, idiotopes, and allotropes, neoantigens forming in the coupling area of hybrid proteins, nonlinear epitopes present in the aggregated preparations. BAs that tend to form large immune complexes with these antibodies are most immunogenic. The antibodies to most BAs, except drugs based on soluble tumor necrosis factor-α receptors (etanercept), are neutralizing, i.e. they affect the efficiency of therapy, particularly when used over a long period of time.

The results of trials evaluating the impact of antibodies to BAs on their clinical value are considered. It is believed that immunogenicity is itself of great importance in respect to the occurrence of the escape phenomenon of a response to BA therapy and to its safety. Attention is drawn to immunogenicity diagnostic problems; at the same it is noted that none of the used laboratory diagnostic techniques can reveal individual BA antibody forms and isotypes. It is concluded that there is a need for further investigations to standardize optimal methods for diagnosing neutralizing antibodies, to elaborate criteria for predicting a response to therapy in terms of an immunogenicity factor, and to reveal pathogenetic mechanisms responsible for the production of antibodies to BAs. The design of novel medicaments with minimal immunogenicity will depend on whether these mechanisms are common to all drugs or specific.

The review considers the specific features of golimumab (GLM), a representative of a group of tumor necrosis factor-α inhibitors primarily by comparing its immunogenicity parameters with other drugs in this group (infliximab, adalimumab, certolizumab pegol, etanercept). Despite its fundamental similarity with other biologicals from a category of monoclonal antibodies, GLM is shown to be characterized by a significantly lower detection rate for antibodies to the drug and by its high serum concentration stabilities and a sustained clinical response.

The paper gives the clinical guidelines for the laboratory diagnosis of rheumatic diseases (RDs) elaborated by the Association of Rheumatologists of Russia in terms of the international requirements for methodology of a system search and assessment of the quality of evidence. The main goal of the laboratory diagnosis of RDs is to obtain objective information on the presence and pattern of immunopathological changes in a patient, which is an important tool for the early diagnosis, assessment of activity and severity of the disease, and its prediction, and efficiency of performed therapy. The clinical informative value of laboratory studies is determined by calculating their diagnostic sensitivity and specificity and the likelihood ratio for positive and negative results. Serological antibody detection tests hold a central position in the laboratory diagnosis of RDs. The main diagnostic laboratory markers of the latter are antinuclear antibodies, rheumatoid factor, anticitrullinated protein antibodies, antineutrophil cytoplasmic antibodies, and antiphospholipid antibodies. The positive results of autoantibody detection include diagnostic criteria for systemic autoimmune RDs, are used to assess the activity and prognosis of these diseases, play an important role in the diagnosis of earlystage RD, permit identification of individual clinical and laboratory RD subtypes, and serve as predictors for RDs in the absence of its symptoms. Standard autoantibody profiles were elaborated; a list of primary (screening), secondary (confirming), and additional serological tests were made out to diagnose systemic autoimmune RDs. The important laboratory markers of RDs are acutephase indicators (erythrocyte sedimentation rate, C-reactive protein, etc.) that can assess the inflammatory activity of the disease, its progression pattern, and prognosis during the chronic inflammatory process, as well as therapeutic efficiency. Other laboratory biomarkers (immunoglobulins, immune complexes, cryoglobulins, complement components, cytokines, endothelial activation markers, lymphocyte subpopulations, genetic markers, bone and cartilage tissue metabolic parameters, etc.) are of less clinical value than autoantibodies and acute inflammatory phase parameters in diagnosing RD.

The paper gives data on the prevalence of osteoarthritis (OA) and the rate of comorbidities in this disease. It discusses problems of adequate and safe therapy in these patients. The basic provisions of the 2015 clinical guidelines for the rational use of nonsteroidal antiinflammatory drugs (NSAIDs), as well as assessment of risk factors for NSAID-related complications are presented. The place of symptomatic slow-acting drugs for OA (SYSАDOA) and a clash of opinions as to their efficacy among different national or international communities of specialists are discussed. The 2014 ESCEO International Committee guidelines for the management of OA patients, which confirm the necessity of prescribing SYSDOA as initial treatment, are presented. The properties and function of synovial fluid in health and OA are depicted. Clinical and experimental findings have shown that, by improving the lubricating properties of synovial fluid, exogenous hyaluronon has many anticatabolic and anabolic effects and affects pathogenetically significant factors in OA. The results of randomized clinical trials (RCTs) comparing hyaluronans of different molecular weight are given. There are data of RCTs on the clinical efficacy and structuremodifying activity of hylan G-F 20 and on its significant pain relief in OA patients. The paper demonstrates benefits in surviving the analgesic effect of hylan G-F 20 versus intraarticular administration of glucocorticoids.

The paper presents the basic principles on the use of imaging studies in the diagnosis and management of juvenile idiopathic arthritis (JIA), which have been elaborated by the European League Against Rheumatism (EULAR) jointly with the Pediatric Rheumatology European Society (PreS). These principles will render certain assistance to practitioners in diagnosing and treating patients with JIA. Undoubtedly, there have been no answers to many questions so far. This primarily applies to the necessity of understanding the standards for the possibility to interpret the pathological process, to harmonize the respective MRI protocols, to identify bone marrow edema, erosions, and synovitis, and to determine the suitability of these or those examinations in order to reveal changes in individual joints. There are considerable conceptual differences in approaches to diagnostic techniques in adults and children. The EULAR-PReS experts assume that some studies may be impracticable or economically inaccessible and this may hinder their introduction into clinical practice. However, most techniques, including ultrasonography, are quite affordable. The practical application of these techniques certainly requires a high professionalism of specialists in functional diagnosis and other instrumental studies.

Adherence to treatment with antiosteoporotic drugs is one of the most important factors contributing to their efficacy during longterm therapy. The adherence is assessed by two main lines: firstly, how long a drug is taken and, secondly, whether its dosage regimen is adhered.

Subjects and methods. The paper gives the data of a 12-month prospective follow-up study of 40 women with postmenopausal osteoporosis (OP) who initiated treatment with the biological agent denosumab.

Results and discussion. After the 12-month follow-up, the significant bone mineral density increase was 4.9% in the lumbar spine, 3.2% in the femoral neck, and 3.0% in the total hip. The previous administration of other antiosteoporotic drugs did not lower the efficiency of denosumab therapy. There were no cases of osteoporotic fractures during 1-year follow-up. 95% of the patients received two denosumab injections (an annual cycle); moreover, 90% of the women were noted to adhere to the dosage regimen. Age, marital status, level of education, time taken to reach the clinic, parental femoral fractures, a history of fractures, duration of OP, and previous therapy had no impact on treatment adherence during 12 months.

Conclusion. The one-year prospective follow-up study of the outpatients demonstrated that denosumab was an effective and safe agent for the treatment of patients with postmenopausal OP and its dosage regimen implying its rare subcutaneous administration (twice yearly) ensured the high patient adherence to therapy.

Objective: to evaluate the efficacy and tolerability of the combined symptomatic slow-acting combined agent Theraflex in gonarthrosis patients untreated with nonsteroidal antiinflammatory drugs (NSAIDs).

Patients and methods. The investigation enrolled 84 patients (78 women and 6 men) aged 55.23±7.36 years with knee arthritis lasting 6.2±0.98 years who were blindly randomized into 2 groups. A study group took Theraflex (chondroitin sulfate 400 mg and glucosamine sulfate 500 mg) with or without acetaminophen. A comparison group received acetaminophen only. At baseline and 3 and 6 months after treatment, the investigators assessed changes in the magnitude of osteoarthritis (OA) using WOMAC and Lequen's indices, evaluated the therapeutic efficiency rated by a patient and a physician according to the visual analogue scale, and took into account adverse reactions (AR).

Results. All the patients taking Theraflex for 6 months showed a positive effect in substantially lowering WOMAC and Lequen's indices and reducing pain and needs for analgesics as compared to both the values at baseline and those obtained in the patients receiving acetaminophen only.

Conclusion. In osteoarthritis patients untreated with NSAIDs, Theraflex treatment was associated with a reduction in pain syndrome and stiffness and with better function and lower needs for analgesics. Six-month Theraflex therapy did not cause serious ARs, as well as in patients having controlled gastrointestinal and renal diseases and hypertension

Therapy with intravenous human immunoglobulin (IVIG) was and continues to remain essential for a number of diseases. At the same time the evidence base for IVIG use is extremely small in rheumatology. Clinical experience shows that IVIG is effective in treating thrombocytopenic purpura, Guillain–Barre syndrome, and chronic inflammatory demyelinating polyneuropathy, which develop in the presence of rheumatic diseases, such as systemic lupus erythematosus, inflammatory myopathies, and antineutrophil cytoplasmic antibody-associated vasculitides. The review considers indications for the use of IVIG, its dosage regimen, benefits, and adverse reactions and analyzes the Russian and foreign literature on this issue.

Pain associated with rheumatic diseases of juxta-articular soft tissues (RDJAST) of the pelvis and lower extremity is a frequent reason for seeking advice from general practitioners and rheumatologists. However, the true cause of painful sensations is often overlooked by a physician and the patient is long and frequently treated unsuccessfully for lumbago, coxarthrosis, or gonarthrosis.

The complexities of topical diagnosis are largely associated with the fact that instrumental methods virtually always determine these or those degenerative changes in the lumbar spine and hip joint (HJ), which formally supports the presence of nonspecific low back pain and coxarthrosis. Differential diagnosis can be made between these conditions if their clinical features are considered, by discriminating symptoms, such as pains in the back or buttock, and those located predominantly in the hip and groin area.

The most known forms of RDJAST of the pelvis and HJ may include trochanteritis, hip abductor and adductor syndromes, iliopectineal bursitis, and ischial tuberosity bursitis.

This review briefly describes the major forms of RDJAST of the mentioned area, their clinical manifestations, and topical diagnostic techniques. It also considers main therapeutic approaches: the administration of nonsteroidal antiinflammatory drugs, local injections of glucocorticoids and plateletrich plasma, and physiotherapy.

Osteoarthritis (OA) usually affects certain joint groups selectively and the hand joints (HJ) are one of its classical locations. Hand OA is widespread in the population. In their practice rheumatologists encounter HJ injury in OA in 38% of cases. It is conventional to identify three main types of hand OA. These are 1) interphalangeal OA that may or may not be accompanied by nodulation; 2) first carpometacarpal OA; and 3) erosive OA. At the same time, the rate of clinical forms ranges from 2.0 to 6.2%; it is 4.7 to 20.4% in the elderly. Nonsteroidal antiinflammatory drugs (NSAIDs) are most commonly used to relieve pain that is the main manifestation of the disease. The risk for NSAID-related adverse gastrointestinal (GI) events is substantially reduced by the drugs that exert their effects mainly on cyclooxygenase 2. These include nimesulide in particular. Undesirable GI effects may be also considerably minimized by using NSAIDs that have both their gastroprotective and antiinflammatory activities. By suppressing pain and inflammatory changes, the recently designed NSAID amtolmetin guacil simultaneously exerts a protective effect on the GI mucosa, by elevating its nitric oxide levels.

The review deals with current pharmacological approaches to treating psoriatic arthritis (PsA). It gives data on the prevalence of psoriasis and psoriatic joint injury that is a common cause of early patient disability. Approaches to evaluating the efficacy of drugs are given on the basis of developed and used criteria with regard to the standardized assessment of the dynamics of joint injury in rheumatic diseases and PSA in particular. The review gives brief information on the mechanism of drug actions and the results of clinical trials evaluating the efficacy and safety of different medicaments in PsA. It also covers the experience in using nonsteroidal antiinflammatory drugs, glucocorticoids, synthetic diseasemodifying antirheumatic drugs (methotrexate, cyclosporine, leflunomide, sulfasalazine), and also a promising group of biologicals. Particular emphasis is placed on the results of using tumor necrosis factor inhibitors (etanercept, infliximab, golimumab, certolizumab pegol, adalimumab), interleukin inhibitors (ustekinumab, brodalumab), and phosphodiesterase 4 inhibitors (apremilast).

Neonatal lupus (NL) is a syndrome diagnosed in neonatal infants, whose mothers frequently suffer from autoimmune rheumatic diseases, manifested by two major signs: skin lesion and cardiac lesion. The paper gives data from the history of a description of the syndrome, as well as current ideas on its pathogenesis, considers both typical and rarer clinical manifestations of the disease, and presents approaches to NL therapy and prevention.

Uveitis is the inflammation of the uvea, which generally occurs in young people and may be accompanied by serious complications leading to disability. The review analyzes the data of Russian and foreign investigations on the pathogenesis of HLA-B27-associated uveitis occurring in different diseases from a group of seronegative spondyloarthritides (SpA) and also discusses current therapeutic approaches in this disease.

Since the late 20th century, there has been rapid progress in studying the pathogenesis of HLA-B27-associated uveitis and in identifying the genetic factors predisposing to this pathology. Investigations of HLA-B27 antigen and its alleles are being continued. Tumor necrosis factor-α (TNF-α), the higher levels of which in blood, synovial fluid, and ocular fluid in rheumatic diseases has been proven in many works of both foreign and Russian scientists, is most studied among the inflammatory mediators. Due to the key role of this cytokine in the development of inflammation, drugs inhibiting TNF-α activity have been designed and successfully used in the past decade, which results in partial and occasionally stable remission.

В первом номере журнала «Современная ревматология» за 2015 г. была опубликована статья И.З. Гайдуковой, А.И. Акуловой, А.В. Апаркиной, А.П. Реброва «Диагностика спондилоартрита: нужны ли нам новые критерии?». В ответ на публикацию статьи в третьем номере журнала вышли комментарии профессора Ш.Ф. Эрдеса.