Search

Adalimumab is a biological drug effectively used in the treatment of several immune-mediated inflammatory diseases, including ankylosing spondylitis, juvenile idiopathic arthritis, and psoriasis. This study analyzed the therapeutic and economic benefits of adalimumab. Patients with ankylosing spondylitis showed significant improvements in quality of life and work productivity after treatment with adalimumab, confirming its clinical and economic efficacy. In the case of juvenile idiopathic arthritis and psoriasis, adalimumab demonstrated high efficacy and safety, significantly improving patients' conditions, establishing it as the gold standard of therapy. The use of adalimumab biosimilars offers accessible alternatives to the original drugs, expanding treatment options and reducing the economic burden on patients.

Objective: to compare the clinical efficacy of seniprutug (BCD-180) and adalimumab (ADA) in the treatment of adults with active radiographic axial spondyloarthritis (r-axSpA).Materials and methods. Based on the results of a previously conducted systematic review, an unanchored matching-adjusted indirect comparison (MAIC) was performed, adjusting for confounding factors. The analysis was based on the results of randomized placebo-controlled clinical trials of seniprutug (BCD-180-2/ELEFTA, NCT05445076) and ADA (ATLAS, NCT00085644) that met the selection criteria. We chose ASAS40 and ASAS20 measurements at week 24 as efficacy outcomes. Initial BASDAI and BASFI indices, proportion of women in the study population, time from disease onset, and baseline C-reactive protein (CRP) levels were considered as confounders.Results and discussion. The MAIC showed a statistically significant advantage in the clinical efficacy of seniprutug (BCD-180) over ADA. When adjusted, the odds ratios (OR) with 95% confidence intervals (CI) for seniprutug (BCD-180)/ADA were 1.86 (1.15; 3.02) and 2.21 (1.34; 3.72) for ASAS40 and ASAS20, respectively, at week 24.Conclusion. The MAIC demonstrated statistically significant superiority of seniprutug (BCD-180) over ADA on the key efficacy endpoints ASAS40 and ASAS20 at week 24 in adults with active r-axSpA. The inclusion of the innovative domestic drug seniprutug into treatment paradigm of active r-axSpA will potentially reduce the socio-economic burden of this disease by providing an affordable, effective and safe therapy while optimizing healthcare costs

Introduction. Adalimumab, a fully humanized monoclonal antibody, is a tumor necrosis factor (TNFα) inactivator that is used against a number of autoimmune diseases such as rheumatoid arthritis and other most common inflammatory arthropathies (ankylosing spondylitis, psoriatic arthritis). Despite the proven efficacy of adalimumab treatment, there is a risk of adverse events, tied up with the formation of anti-drug antibodies, including neutralizing antibodies. Currently, the evaluation and characterization of neutralizing antibodies has become an important part of clinical trials in the development of new drugs and biosimilars.Aim. The aim of this study is to develop and validate the cell-based functional method for neutralizing anti-adalimumab antibodies determination in human serum.Materials and methods. For determination of neutralizing anti-adalimumab antibodies, the cell line L-929 has been employed. L-929 is a cell line sensitive to the TNFα-mediated apoptosis; the neutralizing antibodies interact with adalimumab that leads to TNFα-mediated cytotoxicity. Cytotoxicity was measured using resazurin, an aromatic compound that is a redox indicator.Results and discussion. The developed method was validated for cut point, selectivity, sensitivity, precision, specificity and stability (short- and long-term). An important part of a method development for determining neutralizing antibodies is the selection of concentrations of TNFα (4 ng/ml) and adalimumab (250 ng/ml), as well as determining the minimum required dilution – this parameter is established as 1 : 20. Cut point was chosen as a «floating» cut point, and a correction factor (normalization factor) was determined equal to 0,86. The sensitivity of the developed method was estimated at 108,9 ng/ml of neutralizing anti-adalimumab antibodies.Conclusion. The obtained results can be applied for determining anti-adalimumab neutralizing antibodies in the assessment of the adalimumab immunogenicity, including clinical trials.

The article provides information on the pathogenesis, classification and frequency of ophthalmic extra-intestinal manifestations in patients with inflammatory bowel diseases (IBD). A clinical observation of a patient with autoimmune uveitis and IBD is described, demonstrating the importance of early diagnosis of immuno-inflammatory diseases in the implementation of multidisciplinary management of patients with IBD and extraintestinal manidestations. The use of genetically engineered biological drugs helps to control the course of IBD, ophthalmic manifestations and prevents the development of complications.

Aim: to highlight current trends in the diagnosis and treatment of inflammatory bowel diseases in children.Key points. The incidence of inflammatory bowel disease among children has increased significantly over the past three decades. Moreover, these diseases are often characterized by a severe course. At the same time, strategies for diagnosing and treating these patients are being improved: doctors began using high-definition endoscopy and video capsule endoscopy, the determination of fecal calprotectin, biological therapy (infliximab, adalimumab, vedolizumab, and ustekinumab) and drug monitoring. Particular attention is paid to the role of dietary recommendations.Conclusion. Currently, there has been significant progress in the diagnosis and treatment of inflammatory bowel diseases in children.

Background. Psoriasis is an independent risk factor for cardiovascular diseases (CVD). One of the markers associated with the CVD course is epicardial fatty tissue (EFT) that is thicker in psoriasis patients. EFT assessment can be used as a useful indicator of CVD in psoriasis patients. The data about the effect of genetically engineered biological therapy (GEBT), used for psoriasis management, on the EFT thickness is limited. Examination of GEBT effects on EFT may improve our understanding of CVD prevention in psoriasis patients.Objective. The aim of the study is to study the changes in EFT thickness on GEBT.Methods. A prospective cohort study included 56 children with severe and moderate psoriasis. Patients underwent transthoracic two-dimensional echocardiography (M-mode) with EFT thickness assessment and PASI (Psoriasis Area and Severity Index) scoring before the GEBT initiation. All the parameters were re-evaluated after 16 weeks. All patients were divided into three groups according to the initiated therapy: adalimumab, secukinumab and ustekinumab. When dividing the therapy received into groups, the age of the patients was taken into account: inclusion in the adalimumab group was carried out from 4 years, in the secukinumab and ustekinumab groups — from 6 years. Otherwise, the process of group assignment was random. The study results were processed using descriptive statistics methods: the changes in EFT thickness in individual groups were compared via the Wilcoxon test, and results were considered statistically significant at p 0.05.Results. Before the start of therapy, in 56 patients the mean of EFT thickness was 2.11 mm, the mean PASI — 18.32. The adalimumab group had the following indicators: the mean EFT thickness before the therapy was 2.1 mm, and it has decreased to 1.77 mm after 16 weeks of therapy. The mean change in EFT thickness was 0.33 mm, and the median — 0.17 mm [CI 0.33 ± 0.25]. The ustekinumab group: the mean EFT thickness before the therapy was 2.13 mm, 16 weeks after — 1.69 mm. The mean change in EFT thickness was 0.44 mm, and the median — 0.38 [CI 0.44 ± 0.13]. The secukinumab group: the mean EFT thickness before the therapy was 2.08 mm, 16 weeks after — 1.82 mm. The mean change in EFT thickness was 0.27 mm, and the median — 0.27 [CI 0.27 ± 0.07]. Evaluation of indicators via Wilcoxon test has shown statistically significant decrease in the EFT after therapy in all groups (p 0.05). 73% of patients achieved PASI 50, and 6% — PASI 75 in the adalimumab group. 21% of patients did not achieve PASI 50. The mean PASI score before therapy was 16.73 points, and after 16 ± 4 weeks — 6.4 points, the mean dynamics was 10.33 points, the median dynamics was 7 points [CI 10.33 ± 4]. All patients achieved PASI 50, 75.3% — PASI 75, 8% — PASI 90, and 16.7% — PASI 100 in the ustekinumab group. The mean PASI score before therapy was 22.17 points, and after 16 weeks — 3.67 points, the mean dynamics was 19.28 points, the median dynamics was 17 points [CI 18.5 ± 3.03]. All patients achieved PASI 50, 47% — PASI 75, and 11% — PASI 90 in the secukinumab group. The median PASI before therapy was 14.29 points, and after 16 ± 4 weeks — 3.71 points, the mean PASI score before therapy was 14.29 points, and after 16 weeks — 3.7 points, the mean dynamics was 10.59 points, the median dynamics was 10 points [CI 10.59 ± 2.27]. Evaluation of indicators via Wilcoxon test has shown statistically significant decrease in the PASI after therapy in all groups (p 0.05). There were no adverse events leading to cessation of therapy during the follow-up period.Conclusion. All groups have shown decrease in the in EFT thickness and in the PASI score. The most significant dynamics was observed in the ustekinumab group. Research limitations were the small patients sample and the absence of a control group (participants without psoriasis).

Granuloma annulare (GA) is a chronic inflammatory necrobiotic granulomatous skin disease, which is based on a delayed hypersensitivity reaction caused by the production of interferon- (IFN-) by tissue macrophages and th1-limocytes, tumor necrosis factor- (TNF-) and matrix metalloproteinases (MMP), which leads to the degradation of connective tissue. The most frequent form of GA if localized which is characterized clinically by grouped papules and plaques of red or pink color on the extremities. although disseminated variants of disease occur in 15% of all cases of ag. in contrast to the practically asymptomatic course of the localized form, typical signs of disseminated form are intensive sense of itching, the presence of at least ten foci of skin lesions, recurrent and resistance to treatment course. A 53-year-old female patient with a long-term recurrent course of annular granuloma after a weak clinical response to therapy with pentoxifilin, methotrexate and azathioprine turned to the dermatology department of the university hospital. In light of the lack of satisfactory treatment options anti-cytokine therapy with adalimumab was recommended at a daily dosage of 80 mg, once a week, for 2 weeks, then 1 time every two weeks for 1.5 months. Already on the 5th day after receiving the first injection, the patient reported that the feeling of itching disappeared. By the end of the second week of the induction phase of biotherapy, it became obvious that new rashes did not appear, and the old elements of the skin rash had significantly flattened, turned pale and decreased in volume. After the second week of consolidated therapy, the dermatologist confirmed the convalescence.

The article discusses the common pathogenetic pathways of autoimmune skin diseases – psoriasis and vitiligo. Currently proposed treatments for vitiligo do not significantly reduce or completely restore skin pigmentation. The use of adalimumab for 6 years in a patient suffering from psoriasis, psoriatic arthritis (PsA), vitiligo and autoimmune thyroiditis made it possible to control the activity of psoriasis and PsA, and also contributed to the regression of depigmentation foci. The use of biologic disease-modifying antirheumatic drug therapy in this group of patients in order to achieve repigmentation may be promising.

Background. There is a need to study genetically engineered biological therapy (GEBT) survivability and identify any significant risk factors for its ineffectiveness due to the increasing prevalence of psoriasis among children and the spreading GEBT administration. Such information has practical importance, it can be used to predict treatment outcomes and to develop individual therapeutic approaches. Objective. Our aim was to study biological therapy survivability and to identify risk factors for its ineffectiveness in children with moderate and severe forms of psoriasis. Methods. The study included data from 4-17 years old patients with moderate and severe forms of psoriasis vulgaris. Groups were formed according to the biological medication used. Statistical analyses were performed via SPSS Statistics. Biologic therapy survivability was determined via Kaplan-Meier method with the assessment of differences significance using log-rank test. Significant factors affecting cumulative risk growth were determined by Cox multiple regression method. Results. The study analysed data from the medical records of 105 patients. The average survivability of ustekinumab was 28.7 months, etanercept — 23.1, and adalimumab — 18.4. In the group of bio-naive patients, the survivability was higher: 30.8 months for ustekinumab and 24.4 months for ethanercept, while in the group of patients administrated previously with biological medication the survivability was 24.2 and 8.3 months, respectively. No statistically significant difference was revealed for adalimumab therapy. Significant risk factors for therapy ineffectiveness were the following: high body mass index (BMI) at the time of GEBT onset, aggravated family history, and prior use of one or several subsequent GEBT lines. Conclusion. The therapy survivability is inevitably declining over time. The best results were noted in bio-naive patients treated with ustekinumab that allows us to recommend it as the first-line drug in children with severe and moderate forms of psoriasis.

This article considers the relevance of treating psoriatic arthritis with genetically engineered drugs such as adalimumab and secukinumab. Also, it conducts retrospective analysis of the medical history of the patient, who had this therapy.

TNF-α has been known since 1985. It is a multifunctional proinflammatory cytokine, synthesized mainly by monocytes and macrophages. Since its discovery, many studies have been conducted that have proven that it provides homeostatic function and regulates many biological processes in the body. Violation of its regulation in humans is associated with the development of many autoimmune diseases. The intensive studies that led to the understanding of its polyfunctionality and its role in the immunopathogenesis of a number of diseases served as the basis for the development of anti-cytokine therapy with monoclonal antibodies. In 1975, a technique for producing such antibodies was developed. The first antibodies against TNF-α obtained were chimeric, consisting of 30% mouse protein. Because of this feature, drugs based on chimeric antibodies had immunogenicity, which was manifested in the formation of antibodies to the drug, which led to a decrease in their effectiveness. To reduce immunogenicity, scientists in 1990 created the first fully human monoclonal antibody based on a technology called phage display. This is how adalimumab was born, the first fully human multi-clonal antibody to TNF-α. Humira® (adalimumab) is currently considered a widely studied drug from the group of TNF-α inhibitors, with a good safety and efficacy profile. The article presents current data that demonstrate that the drug significantly improves the course of diseases such as rheumatoid and psoriatic arthritis, and will allow for long-term remission in Crohn’s disease.

The review highlights the problem of finding new effective treatment strategies for COVID-19. Tumor necrosis factor α (TNF-α) is considered as a therapeutic target. The theoretical basis for the successful use of TNF-α inhibitors (ITNFα) for the treatment of COVID-19 is presented, as well as data on existing practical developments, including ongoing clinical trials. Two drugs from the group of ITNFα – infliximab and adalimumab – are currently being considered as possible options. The safety issues of ITNFα treatment in patients with immunophaling rheumatic diseases and COVID-19 are discussed. The review also provides current data on vaccination against COVID-19, in particular on the vaccines currently available in Russia, which are at different stages of clinical trials. We conclude that randomized clinical trials of the effectiveness and safety of ITNF-α in patients with the new coronavirus infection are needed. Such trials will promote transition from theoretical speculations to real clinical practice.

Objective: to conduct a cost-effectiveness study of major biologic disease-modifying antirheumatic drugs (bDMARDs) used for the treatment of ankylosing spondylitis (AS) in Russian health care system with the focus on the new effective drug netakimab (NTK).Patients and methods. Based on the available meta-analysis, a Markov model for therapy was constructed using reference drugs. Then, based on the simulation results, a Cost-Effectiveness Analysis (CEA) and a Budget Impact Analysis (BIA) were carried out. The robustness of the result has been confirmed by several sensitivity analyzes.Results and discussion. NTK showed an advantage in CEA, including the cases when the direct costs of therapy were lower for the reference drug (which shows the greater efficacy of NTK). According to the BIA, the extension of NTK administration in naive patients was consistently associated with a decrease in the budgetary burden. Sensitivity analyzes confirmed the robustness of the result.Conclusion. NTK has clinical and economic advantage in the treatment of AS, it is attractive in terms of both patient's and health care benefit in general. More extensive use of NTK can save more than 5 billion RUB.

Objective. To assess the duration of remission or inactive disease status in patients with achieved partial remission due to treatment with adalimumab (ADA) after it discontinuation.Materials and methods. A dynamic observation was conducted of 26 patients with ankylosing spondylitis with partial remission achieved due to prolonged use (for 24 months or more) of subcutaneous injections of 40 mg ADA once every two weeks. The discontinuation of ADA was carried out after a 3-4 month period of its use in de-escalation mode in the form of 1 injection (40 mg) once every 4 weeks. After discontinuation of ADA, patients continued to take non-steroidal anti-inflammatory drugs, sulfasalazine at a dose of 1.5-2 g per day (11 patients) and methotrexate 10 mg per week (3 patients). Assessment of the clinical, laboratory and ultrasonographic parameters of ankylosing spondylitis was carried out in 3, 6 and 12 months after the abolition of the ADA.Results and discussion. Among the observed patients, partial clinical remission of ankylosing spondylitis maintained after 6 months in 12 (46.2%) patients, and after 12 months - in 10 (38.5%). A low degree of ankylosing spondylitis activity (BASDAI

Introduction. Despite improvements in earlier diagnosis and the development of conservative therapy for Crohn’s disease (CD), approximately 70%–80% of patients undergo surgical treatment for complications. Surgical treatment is not a cure for this disease. The question of choosing therapy as a prevention of postoperative relapse of CD is still open. AIM. To compare the effectiveness of immunosuppressive and biological therapy as a postoperative preventive therapy.Materials and methods. The retrospective study included 125 patients with CD who underwent surgery in terms from 2010 to 2017. After the operation, patients were divided into 3 groups. Patients from the first group received azathioprine, from the second - adalimumab, and patients from the third group were prescribed combined therapy with azathioprine and adalimumab. Clinical, endoscopic, and laboratory data for analysis of disease activity was collected 3, 6, and 12 months after surgery.Results. During the year of therapy in all three groups relapses occurred in only 22 patients (22/125 17.6%). There were no statistically significant differences between the groups at any of the assessment stages. There was also no statistically significant correlation between the presence of risk factors and relapses.Conclusion. Our research has shown that the choice of anti-relapse therapy depending on risk factors is controversial. However, active endoscopic monitoring is important regardless of the treatment strategy. Also, our data allow us to conclude that the frequency of relapses of CD during the postoperative preventive therapy does not depend on the specific drug chosen, as well as on demographic and anamnestic parameters.

Objective: to analyze the data available in the literature on the efficacy and safety of ixekizumab (IXE) and adalimumab (ADA) via their direct comparisons in the treatment of psoriatic arthritis (PsA).Patients and methods. The results of the SPIRIT H2H study were analyzed, the aim of which was to investigate the potential superiority of IXE to ADA for arthritis and skin manifestations in a group of patients with active PsA, stable plaque psoriasis with an inadequate response to synthetic disease-modifying antirheumatic drugs (sDMARDs) who had not previously received biological agents (BAs).Design: a 52-week multicenter, randomized, parallel-group study. The patients were randomized 1:1 to open IXE or ADA administration groups for 52 weeks. This review presents the data obtained at 24-week follow-up.Of the 684 screened patients, 566 (82.7%) were included in the study; moreover, the distribution of the patients was equal between the ADA (n=283) and IXE (n=283) groups. At 6 months, 269 (95%) patients in the ADA group and 262 (93%) in the IXE one continued to participate in the study. Efficacy analysis was made based on the achievement of the primary endpoint that was considered to be related to the relative number of patients, who had simultaneously achieved improvements in the joints and skin according to the ACR50 and PASI100 criteria.Results and discussion. At 24 weeks, the proportion of patients who had simultaneously achieved ACR50 and PASI100 responses was significantly higher in the IXE group (36%) than in the ADA one (28%) (p=0.036). It was found that the IXE group was not inferior to the ADA one in terms of ACR50 response rates (in 51% (IXE) and 47% (ADA) patients) and was superior in achieving PASI100 response rates (in 60% (IXE) and 47% (ADA) patients) (p=0.001). The IXE group was recorded to have a higher response than the ADA group and in terms of other manifestations of the disease: the severity of skin and nail psoriasis, enthesitis, remission achievement, minimal and very low disease activity, and improved quality of life. Comparable effectiveness was noted for the effect of the drugs on dactylitis, as well as for the simultaneous achievement of remission and low disease activity in psoriatic arthritis according DAPSA. Serious adverse events (SAEs) were recorded in 8.5% (ADA) and 3.5% (IXE) patients.The safety and tolerability of both BAs corresponded to their previously presented safety profile. The findings were also confirmed at 52-week follow-up, presented at the Meetings of the American College of Rheumatology in November 2019 and the European League Against Rheumatism in June 2020, and published in the leading journals of rheumatology.Conclusion. The first randomized placebo-controlled study (SPIRIT H2H) directly comparing the two BAs with different mechanisms of action demonstrated the advantage of IXE over ADA in simultaneously reducing the activity of arthritis and psoriasis and showed their comparable efficacy comparable efficacy regarding joint symptoms. The use of IXE versus ADA was accompanied by the more frequent achievement of a combined endpoint related to the signs of joint and skin damages in patients with PSA, as well as by the quantitatively lower frequency of SAEs in patients with active PSA who had failed previous sDMARD therapy. The findings are of great importance for clinical practice from the point of view of the reasonable choice of a treatment strategy in these patients.

Objective: to compare the clinical efficacy in real clinical practice of the targeted synthetic disease-modifying antirheumatic drug (sDMARD) tofacitinib (TOFA) and the biologic DMARD (bDMARD), an inhibitor of tumor necrosis factor alpha (TNFα), adalimumab (ADA) in patients with psoriatic arthritis (PsA), included in the Russian nationwide register of patients with PsA.Patients and methods. The study included 77 patients with PsA (43 men and 34 women) who met the CASPAR criteria and were observed in the Russian nationwide register. Patients were divided into two groups depending on the treatment. Group 1, in which oral TOFA was prescribed, 5 mg 2 times a day, included 41 patients: 24 (58.5%) men and 17 (41.5%) women, the median age was 41 [34; 50] years, the median duration of PsA was 72 [35; 120] months. Group 2, in which subcutaneous ADA was used, 40 mg every 2 weeks, included 36 patients: 19 (52.8%) men and 17 (47.2%) women, the median age was 44 [34; 51] years, the median duration of PsA was 59 [22; 102] months. Combination therapy, including methotrexate (MT), received 80.5% of patients in the TOFA group and 52.8% of patients in the ADA group. At the beginning of the study and every 6 months further, the activity and efficacy of PsA therapy were assessed in all patients according to DAPSA and criteria for minimal disease activity – MDA (number of painful joints ≤1, number of swollen joints ≤1, PASI ≤1 or BSA ≤3 , pain score ≤15, patient's general assessment of disease activity ≤20 mm on a visual analogue scale, HAQ ≤0.5, enthesitis ≤1), dynamics of BASDAI and BSA were also assessed. The number of patients who achieved remission (DAPSA ≤4) or MDA (5 criteria out of 7) during therapy with TOFA and ADA was determined.Results and discussion. Before the start of the therapy in the 1st group, the median DAPSA was 44.2 [37.8; 55.3]: moderate PsA activity was in 5 (12.2%) patients, high in 36 (87.8%) patients. In group 2, the median DAPSA was 35.8 [21.1; 52]: low activity was detected in 3 (8.6%), moderate – in 11 (31.4%), high – in 21 (60%) patients (data from 35 patients was available). 6 months after the start of treatment in patients of the 1st and the 2nd group, there was a significant decrease in all indicators of PsA activity compared to the baseline. The median DAPSA was 11 [4.3; 17.3] and 9.1 [6; 19.6]; remissions according to DAPSA reached 11 (26.8%) and 6 (20.8%) patients, respectively, low activity – 15 (36.6%) and 13 (44.8%), MDA – 16 (40%) and 9 (30%). The number of patients with dactylitis in the 1st and in the 2nd group significantly decreased: from 22 (53.7%) to 5 (13.2%) and from 13 (36.1%) to 6 (20%), respectively. Median HAQ decreased from 1 [0.625; 1.5] to 0.5 [0; 0.875] and from 0.875 [0.5; 1.38] to 0.5 [0; 0.875]; median BASDAI – from 6 [4.2; 7] to 1.4 [0.6; 3.2] and from 4.4 [1.9; 5.8] to 3 [0.8; 4.5], respectively. In group 1, the number of patients with BSA> 3% decreased from 16 (39%) to 8 (26.7%; p

Patients with psoriatic arthritis (PsA) have a higher risk of cardiovascular disease (CVD) compared with the general population. Inflammation and traditional CVD risk factors (RFs), including dyslipidemia, make a significant contribution to the development of CVD and their complications in patients with PsA.Objective: to assess the time course of changes in lipid profile measures in patients with early PsA (ePsA) during adalimumab (ADA) treatment for 3-months.Subjects and methods. The investigation enrolled 16 patients (11 women, 5 men; median (Me) age, 45.5 years) with early PsA (ePsA) (disease duration, 7.7 months). ADA was administered subcutaneously at doses of 40 mg once every 2 weeks for 3 months. Before and 3 months after the start of ADA therapy, DAS, C-reactive protein levels, and traditional CVD RFs, including lipid profile measures (total cholesterol, TC, low-density lipoprotein cholesterol, LDL-C, triglycerides, TG, high-density lipoprotein cholesterol, HDL-C, and atherogenic coefficient, AC) were estimated. Ten-year risk for fatal CVD was assessed using the SCORE scale.Results and discussion. Lipid profile disorders mainly associated with elevated LDL-C levels were revealed in 11 (69%) patients; according to the SCORE scale, the total 10-year risk for fatal CVD was low and moderate in 10 (62.5%) and 6 (37.5%) patients, respectively. A correlation was found between the baseline DAS and TG (r=0.53; p0.05). Conclusion. Lipid profile changes were found in 69% of patients with ePSA and correlated with disease activity. The lower inflammatory activity during ADA therapy was accompanied by elevated TC and TG levels.

Hip joint (HJ) inflammation in ankylosing spondylitis (AS) is a frequent manifestation and an unfavorable prognostic feature of the disease and it requires total hip arthroplasty in 7–8% of patients. Nonsteroidal anti-inflammatory drugs (NSAIDs), sulfasalazine (SSZ), and tumor necrosis factor-α inhibitors are used to treat AS-associated coxitis. However, the influence of these treatments on the time course of HJ structural changes has not been currently studied.Objective: to estimate the time course of HJ changes clinical, X-ray, and ultrasonographic examination was performed in AS patients receiving various drugs: NSAIDs, SSZ, and adalimumab (ADA) during 12 months.Subjects and methods. Seventy-eight AS patients who had clinical, ultrasonographic, and radiological signs of HJ inflammation were followed up. The patients were divided into three groups: 1) 25 patients who took NSAIDs daily; 2) 26 patients who received NSAIDs and SSZ in a daily dose of 2–3 g; 3) 27 patients who were treated with NSAIDs and subcutaneous injections of ADA 40 mg once every 2 weeks. In addition to conventional clinical and laboratory investigations, all the patients underwent radiography with Bath Ankylosing Spondylitis Radiology HIP Index (BASRI-Hip) estimation and HJ ultrasonography.Results and discussion. In Group 2, 12-month SSZ use led to a reduction in median pain intensity during HJ movements on a visual analog scale (VAS) from 26.1 [13.9; 42.7] to 69.3 [56.8; 79.3] mm (p

Is necessary to ensure thorough purification of the target proteins, since the presence of host cell proteins (HCP) from CHO cells in the final product is fraught with a number of negative consequences. Thus, it is has to reduce the contamination of HCP to minimum levels. A comparison of the immunoenzymatic assays of the second and third generations of Cygnus technologies for the quantification of host cell proteins (CHO) in a monoclonal antibody adalimumab was done. It was found that a kit of the 2nd generation does not show the true level of the host cell proteins, underestimating the result. In this connection, it becomes necessary to confirm the validity of the method for determining the total quantity of host cell proteins (CHO) by a set of 3rd generation in adalimumab substance according to the following analytical characteristics: system suitability test, specificity, limit of detection, limit of quantitation, hook capacity, precision.

The paper gives the results of the phase III clinical trial of adalimumab (ADA) biosimilar, (BCD-057) (BIOCAD, Russia), which demonstrate the clinical equivalence of the biosimilar to the ADA innovator Humira® in patients with moderate and severe psoriasis.Objective. The BCD-057-2/CALYPSO phase III international, multicenter, randomized double-blind clinical trial of the efficacy and safety of BCD-057 (International Nonproprietary Name (INN): adalimumab, ZAO «BIOCARD», Russia) versus Himura® (INN: adalimumab (OOO «Abbvie») in patients with plaque psoriasis aims to prove the equivalent pharmacokinetics, efficacy, safety, and immunogenicity of these medicines in both direct parallel comparison and subsequent switching from innovator to biosimilar.Patients and methods. The investigation enrolled 346 adult patients diagnosed with moderate to severe plaque psoriasis lasting at least 6 months. After screening, the patients were randomized in a 1:1 ratio into BCD-057 or Humira® groups. At week 24, the patients taking Humira® were re-randomized 1:1 into a group to continue treatment with the ADA innovator or into that to switch to BCD-057. The primary efficacy endpoint was to estimate the proportion of patients who had achieved a 75% improvement in Psoriasis Area and Severity Index (PASI75) at week 16. The secondary endpoints included the assessment of the time course of changes in the skin, nails, degree of itching, and quality of life at weeks 16 and 24. Safety was evaluated from the incidence of treatment-associated adverse events (AEs), cases of severe toxicity (grades 3–4 AEs according to the Common Terminology Criteria Adverse Event (CTCAE) 4.03), cases of early patient withdrawal due to AEs, as well as cases of toxicity potentially associated with the use of tumor necrosis factor-α inhibitors. Immunogenicity was determined using the validated test of patient serum samples for binding antibodies (BAb) and neutralizing antibodies.Results and discussion. The per-protocol population for efficacy evaluation included 342 patients. At week 16, the primary endpoint of PASI75 was shown to be achieved by 62.5% (105/168) and 66.46% (109/164) of the patients in the BCD-057 and Himura® groups, respectively; p=0.45). The difference between the groups in PASI75 responses was 3.22% with 95% confidence interval [-14.25%; 6.32%]. The analysis of additional endpoints revealed no significant differences in the efficacy of the biosimilar and innovator. During 24 weeks of the investigation, treatment-associated AEs were recorded in 31.03 and 25.58% of the patients in the BCD-057 and Humira® groups, respectively (p=0.31). The proportion of patients with BAb detected at 16 weeks of the investigation was 25.44 and 24.07% in the BCD-057 and Humira® groups, respectively (p=0.87).Conclusion. The investigation provided convincing clinical evidence for of the equivalent efficacy, safety, and immunogenicity of BCD-057 and Humira®.

Background. Tumour necrosis factor alpha inhibitors are widely used in the treatment of juvenile idiopathic arthritis (JIA). To achieve maximum efficiency of genetically engineered biologic drugs, it is necessary to study predictors of the response to therapy. Objective. Our aim was to identify early predictors of the response to adalimumab therapy in patients with JIA without systemic manifestations. Methods. A prospective cohort study analysed treatment results of patients with JIA without systemic manifestations, who were prescribed adalimumab for the period from August 2008 to August 2014. We studied the relationship between baseline demographic indicators as well as baseline and registered after one month of treatment clinical and laboratory parameters and the best (remission according to the Wallace criteria) response to therapy after one year. Results. In the first year of therapy, 94 (43.9%) of 214 patients achieved remission according to the Wallace criteria. In a multivariate analysis, predictors of achieving remission after one year of adalimumab therapy were the improvement according to the ACR70 criterion after one month of therapy [odds ratio (OR) 3.3; 95% confidence interval (CI) 1.7–6.7], a history of uveitis (OR 1.86; 95% CI 1.03–3.33), a decrease in the number of joints with active arthritis after one month of therapy (OR 1.09; 95% CI 1.02–1.16). During therapy, injection reactions in the form of pain were observed in 36 (16.8%) of 214 patients, infectious diseases of ENT organs — in 85 (39.7%), of the respiratory tract — in 17 (7.9%), and tubinfection — in 13 (6.1%) children. Conclusion. The presence of uveitis, rapid reduction in the number of joints with active arthritis and a high level of response to treatment after one month of adalimumab therapy are predictors for achieving remission during the first year of treatment.

Tumor necrosis factor alpha (generally known as cachectin) was noted as a hallmark since the time of its discovery and still retains its position as one of the most intensely studied molecules in the field of biomedicine. TNFα is considered a prototype molecule of the family which, on the one hand, plays an important role in regulating normal differentiation, growth and metabolism of various cells, and on the other hand, acts as mediator of inflammatory processes in various human diseases. Intensive interdisciplinary studies of TNFα biological role and therapeutic use have led to understanding of its polyfunctional effects and establishment of its leading role in immune pathogenesis of diseases, which was the basis for the development of “anticytokine” therapy with highly specific monoclonal antibodies. We aimed for a search of literature in the field of studying TNFα structure and properties, its role under normal conditions, in different diseases and therapy. The literature studies were performed using scientific searching systems and databases. The results are as follows: the role of tumor necrosis factor-α (TNFα) in human body in normal and pathological state was considered. Possible TNF-inducible signaling pathways, as well as existing inhibitors based on monoclonal antibodies for the treatment of rheumatoid arthritis and other autoimmune diseases are described. In conclusion, intensive interdisciplinary studies of TNFα biological functions in normal state and diseases are still relevant today, despite huge knowledge gained on this subject.Undisputable progress in understanding the functional multiplicity of TNFα as a participant in regulation of various physiological and pathological processes in the human body has promoted development of biological agents, i.e., the tumor necrosis factor inhibitors based on monoclonal antibodies, which proved to be highly effective drugs for treatment of rheumatoid arthritis and other diseases, thus being effective and safe biopharmaceuticals.

Objective: to assess whether adalimumab (AD) can be gradually discontinued during continuous methotrexate (MTX) use in patients with early rheumatoid arthritis (ERA).Subjects and methods. Within the REMARCA (the Russian study of methotrexate and biological agents in early active arthritis) study, the investigators examined 20 patients (17 women and 3 men; median age, 51 [41.5; 56] years) with ERA (disease duration, 10 [5.5; 20] months; DAS28, 5.17 [4.37; 6.51]; 85% of the patients were seropositive for rheumatoid factor and 85% for anti-cyclic citrullinated peptide antibodies.Results and discussion. All the patients received subcutaneous MTX 25 mg/week. Twelve weeks after beginning therapy with MTX, due to its inefficiency, ADA was added according to the standard scheme. At week 24, the median DAS28 was 3.0 [1.65; 3.73]; 85% of the patients achieved remission or low disease activity. After 3 months of ADA therapy, high or moderate disease activity remained in 3 (15%) patients; median DAS28 was 4.4 [4.3; 6.1]; the drug was discontinued in them due to ineffective therapy. After 12-month follow-up, low DAS28 scores were observed in 5 (29.4%), DAS28 remission was in 12 (70.6%) of the 17 patients who continued ADA treatment; after 24 months, all the 17 patients were noted to have remission. After achieving sustained remission (≥ 6-month duration during ADA therapy), there was a carefully controlled reduction (titration) in the dose of ADA with its complete discontinuation, by maintaining remission at 36-month follow-up; the median DAS28 was 1.6 [1.4; 2.2]. During ADA treatment, one female patient developed pustular psoriasis and therefore the drug was discontinued at 24-month follow-up during the period of sustained remission. Other serious adverse events and tuberculosis cases were not recorded.Conclusion. Thus, the results of the study are indicative of the high clinical efficiency of the therapy. After ADA discontinuation, sustained remission can be maintained in patients with ERA and if they took biological agents early.

Purpose. To evaluate the cost effectiveness of use of ustekinumab (Stelara®), infliximab (Remicade®) and adalimumab (Humira®) for treatment of moderate and severe psoriasis. Methods. A cost-effectiveness analysis and budget impact analysis have been conducted. Clinical efficacy was evaluated by reduction in PASI scores by 50, 75 and 90%. The efficacy and safety of compared anti-psoriasis agents were derived from a meta-analysis of efficacy of biologic agents in treatment of moderate and severe plague psoriasis containing all compared drugs. The expenses counted includes costs of anti-psoriasis therapy, cost of drug administration and associated medical services. Results. Ustekinumab (Stelara®) was shown to be the most cost-effective biologic agent with respect to the cost per patient achieving PASI50, PASI75 and PASI90 scores. Total direct medical costs associated with use of ustekinumab for treatment of psoriasis turned to be 2 824 rub. (0.2%) per patient per year less than total cost of treatment associated with adalimumab and 444 315 rub. (27.3%) per patient per year less than total costs associated with infliximab. Thus, treatment of patient with moderate and severe psoriasis with ustekinumab results in optimal health care resource utilization. Conclusion. Prescribing of ustekinumab (Stelara®) was demonstrated to be dominating strategy of treatment of moderate and severe psoriasis being the most effective and less costly strategy among those based on other biologic agents.

Rheumatoid arthritis (RA) is a severe, autoimmune disorder characterized by relatively high prevalence among working-age adult population, significant quality of life and work performance impact, as well as high risk of complete disability in case of inadequate or ineffective treatment. The creation of Biologic Disease-modifying anti-rheumatic drugs (bDMARDs) has allowed to significantly improving prognosis for many RA patients, however, the issue of choosing therapy for patients with RA, especially in case of resistance to methotrexate treatment remains problematic, especially in terms of pharmacoeconomic justification of bDMARD choice. Ongoing improvement of clinical understanding of bDMARDs also ensures the significance of further investigating the pharmacoeconomic qualities of these drugs. Aim. To perform the pharmacoeconomic analysis (PHe) of therapy using tocilizumab, adalimumab, as first-line bDMARD therapy in patients with RA receiving standard combination therapy with methotrexate, as well as in patients who require bDMARD monotherapy due to methotrexate resistance, methotrexate nonresponse, or other issues within context of Russian healthcare Methodology. This PHe is conducted from societal perspective which includes interests of Russian healthcare system within context of Obligatory Medical Insurance system and interests of Russian economic system as a whole, including impact on. The time horizon for this research was 2 years. Randomized controlled clinical trials investigating safety and efficacy of these drugs when used in combination with methotrexate and as monotherapy were used as data source on safety and efficacy. A complex PHe model consisting of a «decision tree» (used to form simulated cohorts of patients for each investigated drug, 1 000 simulated patients per cohort) and a Markov model for evaluating treatment outcomes was constructed. Cycle length for the Markov component of the model was 1 week. Clinical improvement of ACR70 was chosen as efficacy end-point because of its high clinical and social relevance. Patients achieving ACR70 can return to workforce. The results of this modelling were used to perform cost-effectiveness analysis (CEA) and budget impact analysis (BIA). Result stability was confirmed by performing sensitivity analyses (SA). Result. During CEA, tocilizumab dominated in terms of cost-effectiveness ratio (CER). CER was 28 525 007 rub. for tocilizumab, 30 898 104 rub. for adalimumab per 1 000 simulated per year in patients receiving standard combination therapy and 21 564 612 rub. for tocilizumab, 30 970 348 rub. for adalimumab per 1 000 simulated per year in patients receiving monotherapy), as well as in terms of clinical effectiveness (as expressed with number of patients achieving ACR70) and with highest healthcare resource utilization effectiveness. BIA indicates that tocilizumab is associated with 4,8% reduction in budget burden compared to adalimumab (estimated per 100 000 per 2 years of Russian population (246 patients), accounted for RA prevalence) in case of standard combination therapy and a 3,98% reduction of budget burden in patients receiving monotherapy. That amounts to 35 575 400 rub. and 28 835 840 rub. respectively (taking into consideration 3,5% discounting factor). SA confirms result robustness to price fluctuations up to 20%.for patients receiving combination therapy and more than 25% for patients receiving monotherapy. Additional sensitivity analysis investigating possible effects of assuming strict safety and efficacy equivalence between the investigated drugs confirms tocilizumab advantage even under such assumption. Conclusion. Modelling results indicate that tocilizumab is pharmacoeconomically rational which is associated with higher effectiveness of healthcare resource utilization. Tocilizumab treatment is also attractive in terms of budget impact as it is associated with up to 4,8% budget burden reduction within scope of 2 years, which is a significant result in context of treating an expensive, potentially debilitating pathology such as RA. Aforementioned results demonstrate that tocilizumab is attractive, pharmacoeconomically effective option for treating patients with in the RF. Prioritization of tocilizumab within context of relevant purchasing channels is thus highly recommended.

This review article was designed to systematize the literature data concerning the role of targeted therapy in the treatment of patients with inflammatory bowel diseases. It presents the data of the latest randomized clinical trials and meta-analyses evaluating the efficacy and safety of targeted drugs for the treatment of Crohn’s disease and ulcerative colitis.

The authors present an overview of the present day knowledge of methods of biological therapy used for treatment of severe psoriasis at an early age. Data is presented on efficiency, safety, required monitoring of clinical and laboratory performance, specifics of vaccination during the treatment of children with genetically engineered biological drugs. Data is presented on the authors’ own clinical observations of 10 adolescents who were administered the preparation of ustekinumab. The objective of the observational study was assessment of efficiency and safety of application of ustekinumab for treatment of severe psoriasis with children over 12 years of age. Materials and Methods. The observation covered 10 children, their average age being 15±2.8 years old, the PASI index 39.3±9.5, who were administered ustekinumab at a dose of 45 mg under a standard administration regimen. Results. The therapeutic effect was assessed based on the PASI index, which was found to decrease by 75% with 6 adolescents, and by 90% with 4 adolescents as soon as by week 14 of the therapy. As is shown by the follow-up observation, the skin pathological process was completely resolved with 80% of adolescents after 3 injections of ustekinumab, and with 100% after 4 injections. Conclusion. The preparation of ustekinumab is efficient and safe for treatment of psoriasis at an early age. As based on the PASI index as the main criterion of assessment of treatment efficiency, ustekinumab (Stelara) is the medicine of choice for treatment of severe forms of the disease from the age of 12 years old.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that mainly affects the sites of the apocrine glands; HS is characterised by relapsing painful knots and abscesses, leading to the formation of fistulas and scarring. Modern ideas about the pathogenesis of HS allow us to consider it as a kind of inverse acne, since the mechanism of development of HS and inverse acne does not differ. Detailed studies of patients with HS in recent years have provided the basis for several authors to suggest that HS is a systemic, chronic, immune-mediated progressive disease. The key role of the proinflammatory cytokine tumor necrosis factor Į (TNF-Į) in the development of the inflammatory process during HS was determined. Elevated TNF-Į levels are found in the blood and HS lesions, having a positive correlation of the TNF-Į level with the severity of the disease. At the present time, the treatment with a TNF-Į blocker, adalimumab (the only one genetically engineered biological preparation approved for treatment of HS/inverse acne in the world and in Russia), is recommended as a first-line therapy in the absence of an adequate response to standard systemic therapy in the case of active HS of moderate or utmost severity. The presented clinical case confirms the fact that for HS patients it is very important to determine the correct diagnosis as quickly as possible and to prescribe the appropriate treatment according to the developed recommendations. Erroneous diagnoses, inadequate therapy (surgical treatment, short courses of antibiotics, etc.) contribute to the progression of the disease, to the appearance of common symptoms due to the attachment of secondary infection and increase in general intoxication, to limited working capacity, to the emergence of persistent and gross scars, as well as to the deformations of affected skin. Our clinical case of adalimumab (Humira) treatment of a patient with an extremely severe HS form demonstrated that the application of this medication can be effective and well tolerated.

Copyright of Pocki is the property of Zaslavsky O.Yu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article presents a case of a severe progressive course of polyarticular juvenile idiopathic arthritis, debuting at an early age, refractory to the therapy with methotrexate, cyclosporine, and glucocorticosteroids. A clinical example demonstrates that switching to the second TNF inhibitor in the case of developing secondary resistance to the first drug from this group provides restoration of the therapeutic effect and is not accompanied by serious adverse events. Six months after switching to adalimumab, due to the «escape» of the effect of etanercept, the inflammatory changes in the patient were reversed; the volume of movements in the joints increased, and the laboratory parameters of the disease activity were normalized. After 1 year, there was a remission of the disease. The child managed to completely eliminate glucocorticosteroids for oral ingestion. The duration of the joint syndrome remission was 3 years. Adverse events were not serious and did not become a basis for drug withdrawal.

Aims of the study: to assess health care costs of the use of biological agents (vedolizumab and various TNF-α inhibitors) in adult patients with moderate to severe active ulcerative colitis (UC) and moderate or severe active Crohn’s disease (CT) with an unsatisfactory response, loss of response, or intolerance to one or more chemotherapeutic agents, and TNF-α inhibitors.Materials and Methods. Statistical analysis, published reports on inflammatory bowel disease (IBD) treatment, the highest quoted prices of drugs from the list of vital and essential drugs (VED), the size of the maximal wholesale mark-ups, and the regulations of financial expenses in the Russian Federation Health system in 2016, were used in this analysis. Since Vedolizumab has been just recently registered in theRussian Federation and it is yet to be included in the VED, for now the drug has no quoted price. Therefore, we used the price suggested by the manufacturer added with the wholesale markup and VAT.Results. As compared with the biological agents-TNF-α inhibitors currently used in the treatment of adult patients with moderate to severe active UC and moderate to severe active CD who showed an unsatisfactory response, loss of response or intolerance of one or more components of standard therapy, or TNF-α inhibitors, the introduction of Vedolizumab with shares of 3%, 4% and 7% for the first, second and third year is expected to result in cost savings of 26.4 million rubles (0.62%) for UC and 21.5 million rubles (0.63%) for CD.

Objective: clinical and economic analysis of including of secukinumab (SEC) in the essential drug list (EDL) and Federal Reimbursement (ONLS) to ensure the availability of the drug to patients with ankylosing spondylitis (AS) at the expense of health. Material and methods. A budget impact analysis was used. Only cost of drugs was taken into account. Adalimumab (ADA) and infliximab (INF) were used for comparison. Basing on the calculated number of patients treated with these drugs in 2016 from the budget of health care system impact on 3-years budgets of State Guarantee Program (SGP) and ONLS was analyzed. The analysis scenario was based on the replacement of ADA and INF with SEC. Results. Expenditure of a 3-year therapy cycle with SEC amounted to 1.703 million rubles, which was 41.6% less than that with ADA (2.917 million rubles) and 57.7% less than that with INF (4.022 million rubles) in the same period. The budget impact analysis to estimate the cost of SGP demonstrated that the use of SEC during a 3-year period would result in a reduction in expenses by 51.2% (saving of 3.8 billion rubles). When SEC is used within the ONLS, its cost during 3 years will be reduced by 51.9% (savings of 1.9 billion rubles). Conclusion. The inclusion of SEC in EDL and ONLS is appropriately and economically justified, as it enables a substantial reduction in the expenditure of health care budgets to treat patients with AS and to maintain the clinical effectiveness of therapy.

Aim. To evaluate the efficacy and safety of adalimumab (ADA) in patients with Crohn’s disease (CD) treated at the Department of Inflammatory Bowel Diseases, Moscow Clinical Research and Practical Center, and to determine the predictors of a therapy response. Subjects and methods. All the patients with CD treated with ADA were followed up for at least 6 months or until the drug was discontinued. Therapeutic effectiveness was evaluated at 4 weeks and 6 months after the initiation of treatment and at the end of a follow-up. Complete intestinal mucosal healing was assessed at 3 and 12 months following treatment initiation. Univariate and multivariate analyses were used to determine the predictors of treatment response. Results. A clinical analysis covered 70 patients (57.1% male); the follow-up period averaged 112 weeks. Perianal fistulas were at baseline established in 22 (31.4%) patients with CD. 12 (17.4%) patients had been previously treated with infliximab (INF), 7 of them discontinued the drug for secondary loss of response and 5 for adverse reactions. 68 (97.1%) patients responded to an induction course of ADA. At 4 weeks, 6 months, and at the end of the follow-up, clinical remission occurred in 66.7, 80.4 and 67.4 % of patients with luminal CD and in 45.4, 36.5, and 36.4% of those with perianal CD, respectively. At 3 and 12 months and at the end of the follow-up, there was complete healing of the intestinal mucosa in 23.5, and 41.2 and 29.5% of cases, respectively. Six (8.8%) patients responding to the induction course needed to be optimized with ADA to 40 mg weekly. The time interval between treatment initiation and dose optimization averaged 30 weeks (range 12-120 months). There were 15 (21,4%) adverse events that were responsible for ADA discontinuation in 3 (4,2%) patients. Conclusion. The findings demonstrate the efficacy and safety of ADA used in clinical practice.

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.

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.

Objective. To perform health economic evaluation of several antirheumatic drugs in patients with rheumatoid arthritis (RA) progressed after DMARDs.Materials and methods. Three consequent line of rheumatoid arthritis therapy in patients progressed after methotrexate were modeled in Russian economic conditions. Markov modelling and CEA accounting for direct medical costs were used. The effectiveness criteria of RA treatment were: patient-years in remission and patient-years in low disease activity. We compared 12 different treatment regimens of second, third and fourth therapy line in patients progressed after methotrexate.Results. The health economic analysis of different RA treatment regimen after progression on methotrexate showed that evaluated regimens do not differs in terms of effectiveness and safety. At the mean time the model account for the patients compliance and showed that the maximum number of patient-years in remission can be reached with etanercept and tofacitinib treatment. Moreover, above mentioned combination in comparison to adalimumab and infliximab showed the positive budget impact.Conclusion. The choice of etanercept and tofacitinib in case of similar economics should be done accounting for individual patient features.

Background: Juvenile idiopathic arthritis (JIA) associated uveitis may be the cause of not only visual acuity decrement, but also blindness. At the same time, in some patients therapy with methotrexate can not prevent the development of these complications.Objective: Our aim was to investigate the efficiency and safety of using a tumor necrosis factor inhibitor (adalimumab) in patients with JIA-associated uveitis.Methods: We conducted a retrospective single-arm study of a series of cases. The results of using adalimumab were evaluated in patients with JIA-associated chronic anterior uveitis, who have been under observation for no less than 1 year before and after starting using adalimumab. The latter was prescribed due to progressing and/or recidivous methotrexate-resistant uveitis.Results: We have analyzed clinical case records of 36 children with JIA-associated uveitis. At the start of therapy with adalimumab, actual uveitis was diagnosed in 30 (83%) patients. Remission was achieved in 29 of 30 cases in 2 (2; 12) weeks in patients with actual uveitis. 11 (31%) patients had a uveitis exacerbation 28 (13; 69) weeks after adalimumab therapy started. Adalimumab reduced the exacerbation frequency from 4 (1; 9) to 0 (0; 1) exacerbations per year for one patient (p < 0,001), and reduced the proportion of patients who were treated with topical glucocorticosteroids (from 83 to 8%). There were no differences (in achieving remission and reducing exacerbation frequency) with regard to patients’ sex, involvement of one or both eyes in the disease onset, antinuclear factor seropositiveness, uveitis type and character of joints affection.Conclusion: Adalimumab promotes fast and long-lasting remission of JIA-associated methotrexate-resistant uveitis.

The paper considers the very urgent problem of optimization of the management of rheumatoid arthritis (RA) patients who have achieved remission (or persistent low disease activity) during therapy using biologicals. It analyzes the results of BeSt, OPTIMA, HIT HARD, ACT-RAY, AVERT, PRESERVE, RETRO, PRIZE, DRESS, HOPEFUL-2, and HONOR studies, the data of NinJa and CORRONA registries, and the experience gained in treating psoriasis concerning practically important issues, such as whether tumor necrosis factor-α inhibitors and biologicals with other mechanisms of action can be discontinued; whether the whole anti-inflammatory therapy can be stopped; whether the dose of biologicals can be reduced as an alternative to complete discontinuation or as a step to discontinue biologicals; whether repeated or intermittent therapy with biologicals can be used; what value of the depth of suppression of inflammatory activity is in solving the problem of whether biologicals can be discontinued. The current results may lead to the conclusion that in RA the dose of biologicals may be successfully reduced and, in some cases, the latter may be completely discontinued. This possibility seems to be associated with the depth of remission. Repeated use of biologicals generally gives rise to prompt improvement in patients with a recurrent disease-activity rebound. The results of a trial of etanercept are most optimistic. Re-treatment with biologicals generally provides fast improvement in patients with a relapse of disease activity. The results of the trials of etanercept are most optimistic.

The article presents a clinical case of successful use of adalimumab (monoclonal antibodies to TNF ) as a drug of choice for treating continuously recurrent chronic bilateral uveitis complicated with a cataract that developed in the onset of juvenile idiopathic arthritis long before articular syndrome in the absence of humoral activity in a child who developed the disease at the age of 12 years. Adalimumab therapy launch induced uveitis remission 12 weeks after initiation.

Background: Methotrexate is the first-line drug for treating patients with juvenile idiopathic arthritis (JIA). If it is ineffective or intolerable, prescription of genetically engineered biopharmaceuticals is indicated. Objective: The study was aimed at assessing effectiveness and safety of genetically engineered biopharmaceutical adalimumab for treating children with JIA. Methods: A retrospective cohort study was conducted to analyze results of treating patients with JIA aged 2–17 years. Adalimumab would be prescribed biweekly in the dose of 24 mg/m2 (body surface) subcutaneously (if body weight is under 30 kg) or in the dose of 40 mg/m2 (if body weight is > 30 kg). Effectiveness and safety would be assessed after 4–12–24–48–96 weeks. Results: We analyzed treatment results of 17 patients (15 children with active joint syndrome, 2 — with active uveitis). All patients with active joint syndrome had been receiving adalimumab for 12 weeks, 12 patients — for 24 weeks, 8 — for 48 weeks, 5 — for 96 weeks. 30/50/70% improvement in terms of the ACRpedi criteria was observed in 15/11/4 children after 4 weeks, after 12 weeks — in 15/13/11 patients, after 48 weeks — in 7/6/6 patients. The status of inactive disease was established in 5 patients (33%) after 12 weeks, after 24 weeks — in 9 children (75%), after 48 weeks — in 7 children (70%), after 96 weeks — in 4 (80%) children. Active uveitis was terminated in all 5 patients with signs of eye damage in the treatment onset. 1 patient suffered from exacerbation of the disease after 48 weeks of therapy; the drug was withdrawn. Tubercular infection without local manifestations was established in 1 patient after 96 weeks (positive Mantoux test, papule — 10 mm). Adalimumab injection was terminated for the period of chemotherapy. Conclusion: Adalimumab has a sufficiently high effectiveness and safety for long-term (up to 2 years) treatment of children with JIA.

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).

Background: The use of genetically engineered biological agents in patients with juvenile idiopathic arthritis (JIA) allows to achieve good results in treatment. However, their efficacy in patients refractory to basic antirheumatic drugs, requires further analysis.Objective: To study the efficacy and safety of the combination therapy by adalimumab with methotrexate and of the monotherapy by methotrexate in children with JIA.Methods: It was conducted a perspective (annual) comparative research with the analysis of the results of treating children with polyarticular seronegative JIA refractory to basic immunosuppressive therapy. The efficacy was assessed by ACRpedi criteria and by dynamics of values of cellular and humoral immunity indicators. Safety was determined by the number of adverse effects.Results: The combination therapy by methotrexate with adalimumab for children with JIA (n = 14) in a shorter time than the monotherapy by methotrexate (n = 17) induced arthritis remission. After 46 weeks of treatment, the remission of arthritis and the normalization of laboratory findings were reported in 6 (43%) patients treated by adalimumab with methotrexate, and in 3 (18%) children — methotrexate (p = 0.233); adverse effects — in 4 (29%) and 14 (82%) cases (p = 0.004), respectively. No serious adverse effects have been registered.Conclusion: The prescription of adalimumab in combination with methotrexate in children with JIA, refractory to basic immunosuppressive therapy, allows to achieve rapid remission of the disease while preserving the effect in a significant number of patients within 46 weeks of therapy.

Analysis of the literature on anti-cytokine therapy demonstrates the effectiveness of this therapy, compared with conventional glucocorticosteroid and immunosuppressive therapy. Drugs with anti-cytokine mechanism of action can be used in Ophthalmology, as inhibitors of angiogenesis in neovascularization and anti-inflammatory therapy in uveitis. Route of administration of TNF inhibitors are intravenous and subcutaneous. They can be used as monotherapy or with the glucocorticosteroid and immunosuppressive therapy. From the literature it is obvious, that the effect of the use of this group of drugs are dose-dependent and they can be positive (anti-angiogenic and anti-inflammatory) and negative – toxic. In a comparative aspects, studies show, that Infliximab has more pronounced anti-inflammatory effect, but at the same time, use of Infliximab is more often with side effects and complications. According to different authors, doses that cause side effects, are not comparable. It seems that, localization of inflammatory process plays a role in the vascular tract of the eye (front, rear), etiologic factor, causing the inflammation and, of course, the intensity of cytokine responses. Therefore, the question, the efficacy and tolerability of anti-cytokine drugs are dose-dependent, and whether, there are other factors that influence on the success of treatment -remains open. To answer these questions is required a detailed study, investigating the influence of this group of drugs on the eye tissues, pathological angiogenesis processes depending on the drug, the dose and the conditions of its application, and testing of optimal dosage of drugs to avoid side effects

The rheumatoid arthritis (RA) session was held in Sochi on April 25, 2015, within the framework of the National Rheumatology Summit. Leading Russian and foreign experts discussed the general provisions of the 2013 European League Against Rheumatism (EILAR) guidelines and the Association of Rheumatologists of Russia (ARR) ones for the management of RA, considered optimal usage periods for biological agents to achieve the goals of treatment for early and long-term RA, by using adalimumab (ADA) as an example, and analyzed the results of trials of the efficiency and safety of combined therapy with ADA and methotrexate. Particular emphasis was placed on the results of introducing the treatto-target concept into Russian clinical practice and on those of monitoring RA patients.

Background: Treatment of patients with juvenile idiopathic arthritis (JIA) is one of the most complex and urgent problems of rheumatology.Objective: Our aim was to evaluate the efficacy and safety of adalimumab therapy combined with immunosuppressants in patients with JIA without systemic manifestations.Methods: A monocentre observational comparative study was held. We studied the results of treatment of patients with JIA being treated with adalimumab combined with immunosuppressants (n = 215) and methotrexate (n = 200). The efficacy of the therapy was evaluated using the paediatric criteria of the American College of Rheumatology (ACRpedi) and remission criteria by C. Wallace during 5 years.Results: After 6 and 12 months the remission of articular syndrome was registered in 72 and 81% of patients treated with adalimumab combined with immunosuppressants, and in 53 and 65% treated with methotrexate. Laboratory indicators of the disease activity corresponded to the reference values after 6 months in 73 and 48%, after 12 months — in 94 and 68% of patients in the comparison groups, respectively. After 6 and 12 months of supervision the activity according to the CHAQ questionnaire was fully recovered in 63 and 79%; 47 and 62% of children. After 1 month the improvement according to the ACRpedi30/50/70 criteria was registered in 87/54/25% of the observed treated with adalimumab. After 6 months the ACRpedi30/50/70 index was 93/89/76% and 63/57/47% for adalimumab therapy with immunosuppressants and methotrexate, respectively. Adalimumab combined with immunosuppressants more quickly than methotrexate induced the stage of inactive disease/remission — after 5 (3; 8) and 12 (6; 18) months, respectively (p < 0.001). After 6 and 12 months of supervision the stage of inactive disease/remission was reported in 43 and 47% of patients treated with adalimumab combined with immunosuppressants, and in 9 and 38% of patients receiving the methotrexate therapy. Adalimumab and methotrexate were well tolerated by 58 and 73% of patients with JIA without systemic manifestations. The adverse events were reported in 42 and 27% of patients, but became the reason for drug dechallenge only in 6 and 10% of patients.Conclusion: Adalimumab combination therapy combined with immunosuppressants has faster and more evident anti-inflammatory effect than the treatment with classical immunosuppressant methotrexate.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and it is characterized by a primary lesion of the joints, organs and tissues with the formation of multiple organ failure of varying severity. The article describes the results of studying the efficacy and safety of adalimumab in combination with methotrexate (n = 26) and methotrexate monotherapy (n = 17) when treating the patients with polyarticular JIA and uveitis refractory to the basic immunosuppressive therapy. It was shown that the combination therapy induced the remission of arthritis in children with JIA in a shorter period of time. After 1 year, the disease remission was recorded in 42% of children in the treatment group and in 18% of children in the comparison group, the uveitis remission — in 26 (54%) of 48 eyes and 2 (7%) of 28 eyes with signs of lesions, respectively. It should be noted that adalimumab in combination with methotrexate was well tolerated and no serious adverse effects were recorded. Thus, the introduction of adalimumab in the treatment regimen of children with JIA and uveitis refractory to the basic immunosuppressive therapy allowed for the rapid disease remission while preserving the effect in a significant number of patients during the following year.

Objective: to assess the relationship of the efficiency of adalimumab (ADA) therapy in early rheumatoid arthritis (RA) with the serum level of the drug and with the presence of antibody (Ab) to it.Subjects and methods. Serum concentration of ADA and Ab against it (μg/ml) were measured using an enzyme immunoassay in 25 patients with early RA before, 12 and 24 weeks after beginning of the therapy. All patients received the disease-modifying antirheumatic drug methotrexate and ADA 40 mg subcutaneously every other week. ADA was the first biological agent for all patients.Results. The patients were divided into the following groups: those with a serum ADA level of

The article presents a case of severe juvenile idiopathic arthritis associated uveitis in a patient who contracted the disease at the age of 10 year. Uveitis developed 9 months after manifestation of the articular syndrome in the event of etanercept therapy. Switch to adalimumab induced remission of the articular syndrome and uveitis. By the 8th week of treatment, an inactive disease stage (6 months) was diagnosed in a child.

The case of early debut and heavy course of juvenile idiopathic arthritis in the patient at the age of 1 year and 8 months, associated with uveitis refractory to the therapy by methotrexate and nonsteroid antiinflammatory preparations is presented. The given clinical example shows high therapeutic efficiency of the adalimumab. To the 8th week of treatment inflammatory changes in conjunctiva were stopped, to the 12th week the stage of inactive illness was registered, i.e. the patient had no inflammatory changes in joints, uveitis activity signs, increase of laboratory indicators of illness activity. Duration of remission of articulate syndrome and uveitis made 9 months.