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Objective – to compare the clinical efficacy and cost-effectiveness of IL-17 inhibitors (SEC, IXE, NTK) in the treatment of adult patients with ankylosing spondylitis (AS) in the healthcare system of the Russian Federation.Material and methods. The study is a sub-analysis of a previously published systematic review and network meta-analysis of the comparative efficacy of biologics in adult patients with AS in the Russian Federation. NNT values were calculated for BASDAI 50 and ASAS 20/40 after 16 weeks of therapy for all studied drugs. CpR was estimated for each biologic after 16 weeks and one year of therapy. Additionally, we carried out an assessment of the financial burden of the most cost-effective strategies for the treatment of AS.Results. The use of NTK is characterized by an average of no more than three patients needed to treat to achieve one ASAS 20/40 or BASDAI 50 response, while on IXE and SEC – no more than 4–5 patients need to be treated, depending on the estimated effectiveness criterion. According to CpR estimate, NTK is the most cost-effective IL-17 inhibitor for the treatment of AS, both after 16 weeks and after one year of therapy.Conclusion. The obtained results make it possible to compare the effectiveness of IL-17 inhibitors from a clinical and economic points of view and can be used both in decision making process of treatment strategies for individual patients, and at the population level – when deciding on the reimbursement of drugs

The beginning of the 21st century was marked by a simultaneous changes in view on pathogenesis, diagnostics and treatment of axial spondyloarthritis (axSpA). Anti-TNFα inhibitors were the first biologics prescribed in axSpA. 20 year after the biological treatment was first prescribed we have enough data to understand their long-term efficacy.The aim of this study is to evaluate the long-term efficacy of etanercept in patients with axial spondyloarthritis based on data published in periodicals and clinical practice.Patients and methods. An analysis of publications from medical database and data from the St. Petersburg register of patients with rheumatic diseases (n=68) was performed to assess the effectiveness of etanercept in axSpA treatment in the long-term perspectives. Descriptive statistics methods were used.Results. In clinical studies and in real word practice, etanercept has shown high efficiency in reducing clinical, laboratory and visual manifestations of non-radiographic and radiographic axial spondyloarthritis at early and advanced stages of their development.Conclusions. In the long term, the use of etanercept is associated with an increasing slowdown in structural progression while maintaining a stable clinical and laboratory improvement. Discontinuation of treatment in the majority of patients leads to exacerbation of axSpA. At the same time, the low immunogenicity of etanercept allows the resumption of axSpA treatment with a high probability of re-achieving the lost effect with a low probability of secondary ineffectiveness or anaphylaxis.

Netakimab is a humanized anti-interleukin-17А monoclonal antibody approved for the treatment of psoriatic arthritis, ankylosing spondylitis, moderate to severe psoriasis. Herein, we report the accumulated efficacy data and safety findings of 54-week netakimab treatment during the PATERA study. The aim of the study was to assess the long-term efficacy and safety of netakimab in patients with active psoriatic arthritis. Materials and methods. 194 patients with active psoriatic arthritis despite the previous therapy with nonsteroidal anti-inflammatory drugs, conventional or biologic disease-modifying antirheumatic drugs were initially randomized to receive 120 mg netakimab or placebo (1:1) at weeks 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. At week 16 inadequate responders in placebo group were reassigned to netakimab in a blinded manner. From week 24 all patients receive open-label netakimab. The analyzed period includes 54 weeks. Results. Netakimab demonstrated sustained treatment response. 94.9% of patients in the netakimab group achieved ACR20 at week 54; 89.5% achieved PASI75 response. Axial disease, dactylitis, and enthesitis significantly improved with netakimab. A similar pattern was observed for placebo/netakimab treated patients. Netakimab was well tolerated. The majority of adverse events were mild and moderate. The most frequent treatment-related adverse events were lymphopenia, increased alanine aminotransferase, hypercholesterolemia. Adverse events of grade 3–4 were observed in 2%. Conclusion. Netakimab demonstrated sustained efficacy in key psoriatic arthritis domains at week 54 with a favorable longterm safety profile.

IgA anti-CD74 can be a promising marker for diagnosis, assessment of activity and prognosis for ankylosing spondylitis. The aim of the study was to determine the level of IgA anti-CD74 in patients with ankylosing spondylitis and to evaluate its relationships with ankylosing spondylitis activity and carriership of genetic alleles. Materials and methods . In 48 patients with a reliable diagnosis of ankylosing spondylitis, aged 18 to 69 years were measured the ASDAScrp, BASDAI, level of highly sensitive С-reactive protein, concentration of IgA anti-CD74. The polymorphisms of the genes interleukin (IL)-17A197 a/g, IL-17F7 histidine (His) / arginine (Arg), IL-17F11139 c/g, TNF-a-863, TNFα-308, TNFα-238, IL-1B-31, IL- 4-590, IL-6-174, IL-10-1082, IL-10-592, vascular endothelial growth factor (VEGF)-2578, VEGF-936, matrix metalloproteinase (MMP)2-1306, MMP3-5A6A, MMP9-1562, HLA-B27 were evaluated in their relationships with AS activity and IgA anti-CD74 levels. Results . The mean age of patients was 45.1±14.2 years, male - 72.9%, psoriasis - 10.4%, IBD - 2.1%, BASDAI -2.99±0.28, ASDAS - 2.29±0.16, CRP - 6.5±1.65 mg/L, IgA эпй-СВ74 - 18.6±1.73 U/mL (72.9% of the patients with >12 U/mL). The relationship between an increase in concentration of IgA anti-CD74 and ASDAScrp, BASDAI activity indices, between an increase in the level of CRP and the presence of the IL-17A genotype heterozygous for the AA allele (r=0.965) was determined. CRP did not demonstrate the relationship with the BASDAI. An association of IL-17F-11139 СС and the presence of psoriasis (r=0.870) was established. 93.8% of patients with ankylosing spondylitis were carriers of the homozygous histidine allele IL-17F7 (his/his) and the TNF238 allele (GG). Conclusions . The increase in anti-CD74 IgA level was found in 72.9% of patients with ankylosing spondylitis receiving inhibitors of TNF-a and NSAIDs and associated with clinical and laboratory indicators of ankylosing spondylitis activity and with carriage of the homozygous histidine allele IL-17F7 (his/his) detected in 93.8% of patients. Carriage of TNF-238 GG; TNF-863 CC; HLA-B27; TNF-308 GG; IL-4-590 CC; IL-6-174 CG; MMP9-1562 CC; MMP9-1562 CC; VEGF- 936 CC alleles was not associated with an increase in concentration of IgA anti-CD74. CRP demonstrated an association with IL-17A-197 AA (r=0.965) detected in 29.2% of patients with no correlation with the clinical ankylosing spondylitis activity in patients receiving treatment with iTNF-α and NSAIDs.

Netakimab (NTK) is a humanized anti-interleukin-17А (IL-17A) monoclonal antibody approved for the treatment of psoriatic arthritis, ankylosing spondylitis, moderate to severe psoriasis. Here, we present the results of the 24-weeks double blind period of the PATERA study.Objective. The objective of the study was to evaluate the efficacy and safety of NTK compared to placebo in patients with psoriatic arthritis (PsA).Patients and methods. 194 patients with active PsA with an inadequate response to previous therapy with nonsteroidal anti-inflammatory drugs, conventional or biologic disease-modifying antirheumatic drugs, were randomized in a 1:1 ratio to receive subcutaneous 120 mg NTK or placebo at weeks 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. At week 16 ACR20 (20% improvement in the American College of Rheumatology response criteria) non-responders in placebo group were reassigned to NTK in a blinded manner. The primary endpoint was the proportion of patients achieved ACR20 response at week 24.Results. 82,5% of patients in the NTK group and 9.3% of patients in the placebo group achieved ACR20 at week 24 with the 95% CI [0,63; 0,84] (p < 0,0001). Skin manifestations and axial disease significantly improved with NTK. The safety profile of NTK was comparable to placebo. The most frequent treatment-related AEs were expected and common for all other IL-17 inhibitors: increased alanine aminotransferase (ALT), infections, lymphopenia.Conclusion. NTK in the dose of 120 mg has superior efficacy over placebo in patients with active psoriatic arthritis. The safety profile is consistent with other IL-17 inhibitors.

The paper presents the results of a double-blind (BCD-085-3/AILAS) phase II clinical trial of the original interleukin 17A (IL17A) inhibitor BCD-085 prescribed at different doses to patients with active ankylosing spondylitis (AS) and those of an extended (BCD-085-3ext/AILAS-II) trial characterizing the efficacy and safety of this drug when used for a year. The objective of the AILAS study is to determine the therapeutically effective and safe dose of BCD-085 in the treatment of active AS. The efficacy, safety, and immunogenicity of BCD-085 during its annual use were additionally evaluated in the extended trial. Subjects and methods . The investigation enrolled 89 patients diagnosed as having active (BASDAI scores >4.0; mean spinal pain scores >4.0) AS that met the 1984 New York classification criteria. After the end of the screening period, the patients were randomized at a ratio of 1:1:1:1 in one of four groups that received 40; 80 or 120 mg of BCD-085 subcutaneously or placebo on day 1 of weeks 0, 1, 2 and then once every two weeks up to week 12. The primary end point was the number of patients who achieved an ASAS20 response at week 16. The investigation evaluated the safety of the drug, by calculating the total incidence of adverse events (AEs) and serious AEs (SAEs) and the number of cases of premature therapy termination because of AEs. Results and discussion . An ASAS20 response at week 16 was achieved in 72.7% of patients receiving 40 mg of BCD-085, in 81.8% of those receiving 80 mg, in 90.9% of those receiving 120 mg, and in 42.9% of cases in the placebo group (p=0.004). The superiority of BCD-085 over placebo was proven for 80- and 120-mg doses. The fastest and most pronounced effect was observed in patients treated with 120 mg of BCD-085. In the extended study, an ASAS20 response at week 52 was recorded in 86.4% of patients. One or more AEs during the first 16 weeks of therapy were reported in 11 (50.0%) patients of the 40-mg group; in 6 (27.3%) of the 80 mg group; in 4 (18.2%) of the 120 mg group and in 7 (31.8%) of the placebo group (p=0.183). The frequency and spectrum of AEs did not significantly differ in patients who received placebo and BCD-085 in different doses. No SAE was recorded. Conclusion. Phase II study yielded data demonstrating the high efficacy and good tolerance of BCD-085 in the treatment of active AS. The best effect and optimal tolerance were demonstrated for a dose of 120 mg.

The paper discusses the process for validation of the Russian-language EQ-5D-5L version to assess quality of life. According to international and national guidelines, the primary goal of treating spondyloarthritis (SpA) is to preserve the quality of life (QOL) of a patient as long as possible, by achieving control of the main symptoms of the disease and inflammation, by preventing the development and progression of structural changes in the locomotor system, and by preserving/normalizing the patient's functional activity and social adaptation. QOL is the integral characteristic of the physical, psychological, social and emotional status of the patient, which is assessed on the basis of his subjective perception. At the moment, there are no generally accepted national tools for assessing QOL in Russia, so the problem of adaptation and validation of international questionnaires is very actual.Objective: to evaluate the psychometric properties of the Russian-language EQ-5D-5L version in patients with SpA.Subjects and methods. Examinations were made in 163 patients older than 18 years with axial or peripheral SpA, who met the Assessment of Spondyloarthritis International Society (ASAS) criteria. The disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS); their functional status was estimated by the Bath Ankylosing Spondylitis Functional Index (BASFI), and spinal mobility was evaluated by the Bath Ankylosing Spondylitis Metrology Index (BASMI). The ASAS Health Index (HI) was used to comprehensively analyze the impact of SpA on the patient's health. The EQ-5D-5L version was employed for the first time in Russia to assess the quality of life of patients. Its main psychometric properties, such as reproducibility, validity, sensitivity, were evaluated.Results and discussion. The median age of the patients was 39.50 [28.00; 48.00] years. Among them, there were 64.8% of men. The median value of EQ-5D (a 5L version) was 0.53 [0.29; 0.65]. There were statistically significant relationships between the EQ-5D-5L values and BASDAI, BASFI, ASDAS, BASMI, ASAS HI, and the SF-36 questionnaire for QOL assessment. The test-retest reliability study showed that the internal consistency (Cronbach's alpha) was 0.96. The median value of the EQ-5D-5L was 0.55 [0.37; 0.63] at the first visit and 0.60 [0.40; 0.69] at the second visit after prescribing therapy (p = 0.01).Conclusion. The validation has indicated that the EQ-5D-5L version is a reliable, change-sensitive, easy-to-use, and physician-patient-friendly tool to assess QOL.