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Objective: to assess whether the modified combined glucocorticoid (GC) toxicity index (MCGTI) can be used to analyze adverse reactions (ARs) to GCs administered in the management of rheumatoid arthritis (RA). Subjects and methods . The investigation enrolled 71 RA patients (57 females, 14 males; mean age, 51.7+15.2 years). All the patients met the ACR/EULAR classification criteria and took GCs (the median duration of GC treatment duration was 7.1 [0.9; 12.0] years). In addition to the standard clinical, laboratory, and instrumental indicators, the daily and cumulative doses of GCs (in prednisolone equivalent) and MCGTI were analyzed. Results and discussion . The value of MCGTI statistically significantly correlated with treatment duration (r=0.411), age (r=0.384), and the cumulative dose of GCs (r=0.361), but did not correlate with their maximum dose (r=0.06). A ROC analysis showed that the critical level of the cumulative dose of GCs in relation to MCGTI was 17,337.5 mg. Conclusion. MCGTI correlates with cumulative dose (making it possible to establish its critical level), treatment duration, and age, which is the basis for further study of whether this can be applied in clinical practice to evaluate, predict, and prevent ARs.

The paper discusses data on the high frequency of non-indicated use of proton pump inhibitors and on the manifestations of potential harms of their use.

The review gives an update on adult-onset Still’s disease: on its causes, the specific features of its pathogenesis, diagnosis, clinical presentations (with identification of subtypes), and treatment with consideration for the nature of the course of the disease and life-threatening complications.

Rheumatoid arthritis (RA) is an immune inflammatory (autoimmune) rheumatic disease of unknown etiology, which is characterized by chronic erosive arthritis and systemic damage to the viscera, and leads to early disability and reduced survival in patients. For its diagnosis, it is currently recommended to use the 2010 ACR/EULAR classification criteria for RA, which should be applied in clinical trials to identify at least one swollen joint, i.e. the presence of arthritis; therefore, the problem of extra-articular manifestations of RA is apparent to stay in the background.

The paper discusses the possible causes of the problems related to pharmacovigilance.

The article presents the provisions of the Erice Declaration on the safety of medicines and discusses the need for their transformation into the XXI century.

Objective: to evaluate the safety and efficiency of monotherapy with methotrexate (MTX) solution for subcutaneous injection (SC MTX), by using the estimated dosing, in patients with rheumatoid arthritis (RA). Subjects and methods . A 12-month prospective controlled study enrolled 106 patients with early RA who were given SC MTX was conducted at the V.A. Nasonova Research Institute of Rheumatology in the framework of the REMARCA (Russian invEstigation of MethotrexAte and biologicals for eaRly aCtive Arthritis) program. Results and discussion. 12-month SC MTX monotherapy could achieve the treatment goal (remission or low disease activity) in 68% of the patients with active RA who did not need biological agents (BAs). In 36% of the patients, the treatment caused adverse reactions (ARs) that were the basis for its complete discontinuation in 8%. The therapeutic effect of SC MTX depended on body mass index (BMI) and was more pronounced in patients with its normal values (≤25 kg/m2) than in those with overweight or obesity. The incidence of ARs did not depend on the duration of the disease and the weight of a patient receiving SC MTX. Addition of BAs to SC MTX monotherapy did not lead to an increase in the frequency of ARs. In early RA, the effect was better when SC MTX was used in combination with lowdose oral glucocorticoids. The findings showed the expediency of intensively using SC MTX at the doses calculated per 1 m2 of the body surface, the dependence of therapeutic action and the independence of the frequency and severity of ARs from the patient’s BMI.

The paper discusses the issues of imperfect 1987 American College of Rheumatology (ACR) and the 2010 ACR/European League Against Rheumatology (EULAR) rheumatoid arthritis classification criteria and justifies the need for their correction.

The early administration of methotrexate (MTX) and the use of its high (by the rheumatology practice standards) doses contribute to the enhanced efficiency of therapy and the reduced severity of rheumatoid arthritis (RA). One of the important merits of MTX in the treatment of RA is the possibility of adjusting its dose and choosing its (oral or subcutaneous) administration routes, which makes it possible to individualize treatment. Particular emphasis has been recently placed just on a subcutaneous MTX formulation that creates prerequisites for substantially improving the efficiency of RA therapy. The paper gives the data of the REMARCA (Russian investigation of methotrexate and biologicals for early active arthritis) trial assessing the results of RA treatment in the use of the subcutaneous MTX dosage form as a first-line drug and in the elaboration of management tactics for this disease. Subjects and methods. The investigation included 191 patients (34 men and 157 women) with active RA; of whom 51.8% had very early RA (< 6 months' disease duration). 115 patients with RA completed a 24-month follow-up period; and their data were analyzed in more detail. Results and discussion. The findings may substantiate treatment policy based on the prescription of subcutaneous MTX (without previously administering its oral formulation) in patients with early RA and high disease activity, starting the drug at 15 mg/week and rapidly escalating with the highest tolerable doses during 4-8 weeks, which allows remission (or low disease activity) in the majority of patients without using glucocorticoids and biological agents.

The past two decades have been marked by the design of a great variety of innovative biological agents, the clinical introduction of which could substantially improve the results of treatment for rheumatic diseases. At the same time, there are a larger number of reports on their administration-associated adverse events, often paradoxical ones (these drugs indicated in many autoimmune processes may induce similar autoimmune processes).

Objective: to investigate the immunogenicity and safety of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatic diseases (RD). Subjects and methods. The prospective open-label comparative study enrolled 133 people (102 (76.7%) women and 31 (23.3%) men) aged 23 to 76 years, including 79 patients with rheumatoid arthritis (RA), 16 with systemic sclerosis, and 7 with dermatomyositis/polymyositis, as well as 31 subjects without systemic inflammatory RD (a control group), who had a recent history of at least two cases of lower respiratory tract infections (bronchitis, pneumonia). At their inclusion, all the patients with RD were receiving ant-inflammatory therapy, including 52 taking methotrexate (MT), 14 – leflunomide (LEF), and 13 – MT + tumor necrosis factor-α (TNF-α) inhibitors. The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France) was administered in a single dose of 0.5 ml subcutaneously during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patients and conventional laboratory studies were performed during control visits (1, 3, and 12 months after vaccination). The serum levels of anti-pneumococcal capsular polysaccharide antibodies were measured in 102 patients by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, United Kingdom). Results and discussion. No clinical and radiological symptoms of pneumonia were recorded in any case during the follow-up period of 12 months. The patients with RD and the control group showed a significant, more than double increase in anti-pneumococcal antibodies 12 months following vaccination. Vaccination was well tolerated: 90 (68%) patients displayed no adverse events; 37 (28%) had pain, cutaneous swelling and hyperemia up to 2 cm in diameter at the site of injection for vaccination;6 (4%) had low-grade fever. There were no episodes of a RD exacerbation or any new autoimmune disorders during the follow-up period. Conclusion. The findings were suggestive of the sufficient immunogenicity and good tolerability of 23-valent pneumococcal vaccine in patients with RD.

The paper discusses whether patients' spontaneous reporting on adverse drug reactions is appropriate and possible.

The paper discusses the results of the long-term PRECISION study specially designed for the prospective comparative evaluation primarily of the cardiovascular safety of celecoxib, ibuprofen, and naproxen, which are long used for the treatment of pain in patients with arthritis.

Objective: to investigate the immunogenicity, safety, and clinical efficacy of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatoid arthritis (RA) during a two-year follow-up study.Subjects and methods. The prospective open-label comparative study enrolled 110 people, of them there were 81 (73.6%) women and 29 (26.4%) men at the age of 23 to 76 years, including 79 patients with RA, as well as 31 subjects without systemic inflammatory rheumatic diseases (RD) (a control group). The group of RA patients exhibited a predominance of middle-aged women who had > 3 years’ disease duration and a moderate inflammatory activity (the mean value of DAS28, 4.32). 52 patients received methotrexate (MTX), 14 had Leflunomide (LEF), and 13 were treated with tumor necrosis factor-α (TNF-α) inhibitors + MTX.The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France) was administered in a single dose of 0.5 ml subcutaneously during continuous MTX or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patient and conventional clinical and laboratory studies were performed during control visits (1, 3, 12, and 24 months after vaccination). Clinical effectiveness and safety were evaluated in all the patients included in the study. The serum levels of anti-pneumococcal capsular polysaccharide antibodies (Ab) were measured in 72 patients with RA and in 30 individuals in the control group during a 12-month follow-up study, including in 25 patients with RA for a 24-month follow-up study by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, Birmingham, United Kingdom). Along with this, the post-immunization response coefficient was calculated for each patient as the ratio of postvaccination Ab levels during Visits 2, 3, 4, and 5 to the baseline Ab level.Results and discussion. No clinical and radiological symptoms of pneumonia were recorded in any case during the follow-up period. The patients with RA and the control group showed a more than double significant increase of anti-pneumococcal Ab level during 3 months following vaccination. Despite the decrease in their concentration by month 12, the latter remained at the appropriate level and significantly increased at 24-month follow-up. Vaccination was well tolerated. A favorable course of the postvaccinal period was noted in all cases. There were no adverse reactions to vaccination in 72 (65%) patients; 38 (35%) patients were noted to have pain, skin swelling and hyperemia up to 2 cm in diameter at the site of injection, as well as low-grade fever. There were no episodes of a RD exacerbation or any new autoimmune disorders during the follow-up period.Conclusion. The findings were suggestive of the sufficient immunogenicity and good tolerability of 23-valent pneumococcal vaccine in patients with RD during the two-year follow-up period.

The review deals with the prediction of the therapeutic effect of methotrexate in rheumatoid arthritis, by determining its level in the red blood cells.

When treating rheumatoid arthritis (RA), it is important not only to suppress inflammation, but also to prevent local and generalized bone loss, particularly in patients receiving glucocorticoids (GC). Denosumab is a fully human monoclonal antibody that binds receptor activator of nuclear factor kappa B ligand (RANKL), prevents its interaction with receptor on osteoclasts, reduces their activity, and inhibits bone resorption. Objective: to evaluate the effect of 12-month therapy with denosumab on bone mineral density (BMD) of the axial and peripheral skeleton and destructive changes in the hand and foot joints of RA patients receiving GC. Subjects and methods. Fifty-two postmenopausal women with RA concurrent with osteoporosis received subcutaneous denosumab 60 mg twice: at baseline and 6 months later. BMD was measured before drug administration and after 12 months of a follow-up, by applying dual-energy X-ray absorptiometry of three sections: the lumbar spine (LI–IV), femoral neck (FN), and distal forearm (DF). Radiographic changes in the hand and foot joints were assessed using the Sharp method modified by van der Heijde (SVH) at baseline and 12 months later. Results and discussion . The patients’ mean age was 58.4±6.4 years; the mean RA duration – 19.0±10.9 years. Antiinflammatory therapy was performed in all the patients, including 30 (57.7%) who received GC. The mean BMD during follow-up increased from 0.814±0.101 to 0.848±0.103 g/cm2 in LI–IV (p

The paper historically considers whether it is appropriate to use the term (concept) “drug-induced disease”.

To introduce treat-to-target recommendations is an important task of modern rheumatology; however, there is still a diversity of serious problems relating to a scientific rationale and a clinical one for this strategy and to the possibilities of its implementation in real clinical practice, in the rheumatology service of the Russian Federation in particular, by taking into account the specific features of funding for high-tech medical care. Objective: to determine the efficiency and safety of combined therapy with subcutaneous methotrexate (MT) and biological agents (BA) when using the treat-to-target strategy in patients with active early and extended-stage rheumatoid arthritis (RA) who have risk factors for a poor prognosis. Subjects and methods. The results of the REMARCA ( R ussian Inv E stigation of M ethotrex A te and biologicals in ea R ly a C tive inflammatory A rthritis) trial of 130 patients followed up for 12 months or more were given. There was a female preponderance; mean age 48.9±13.9 years, rheumatoid factor positivity (86.9%); anti-cyclic citrullinated peptide antibody positivity (89.2%). Seventy patients formed a subgroup of early RA (disease duration ≤6 months (mean 4.17±1.39 months)); 60 patients were a subgroup of advanced-stage RA (disease duration >6 months (mean 30.8±32.7 months)). In all the patients, therapy was initiated by using subcutaneous MT with its rapid dose escalation up to 20–30 mg/week and the achievement of the treatment goal (low disease activity or remission) was checked every 3 months and depending on the result a decision had been taken to add or not to add a biological agent (BA) (a tumor necrosis factor inhibitor or abatacept). If the former was insufficiently effective, it was substituted for a BA from another class. Results . Subcutaneous MT monotherapy provided remission or low disease activity in 49 (37.7%) patients; a BA was given to 81 (62.3%) patients. Following 6 and 12 months, low activity or remission according to SDAI was observed significantly more frequently in the patients who continued subcutaneous MT monotherapy than in those who received combined therapy with MT and BA. The similar results were obtained by using DAS28 and CDAI to assess a trend in disease activity. After 6and 12-month follow-up, there was a significantly more marked decline of tender joint count, SDAI and CDAI in early RA than in advanced-stage RA; at 12 months, SDAI remission rate was 45.7% and 28.3%, respectively (p=0.047). Conclusion . The treat-to-target strategy should be used in real clinical practice and can yield spectacular results. Active therapy with subcutaneous MT with its rapid dose escalation to the maximally tolerable dose allows identification of a considerable group of patients (38%) with a good response to MT monotherapy.

The paper presents a classification of adverse drug reactions and their characteristics. Bisphophonates (BP) that are have been prescribed for more than 30 years to prevent and treat all forms of osteoporosis (OP) and recognized as first-line drugs for its treatment are used as an example to see the history of investigating rare and unexpected adverse reactions. The direct correlation between the rare adverse reactions of Ps and their use remains to be proven today. The proposal to reduce the prescriptions of BPs is unfounded. The evidence for the efficacy and safety of BPs in OP has been obtained and confirmed by multiple trials and many years X real practice. Alendronate (fosavance) is the most studied BP now.