Цели леченияОсновной целью лечения остеопороза (ОП) является снижение риска переломов (в первую очередь прокси-мальных отделов бедра и позвонков), которые сопряже-ны с наибольшей инвалидизацией и летальностью. Риск переломов зависит от многих причин, не всегда связан-ных с костной прочностью. Важной составляющей рис-ка является склонность пациента к падениям. Способ-ность кости противостоять механическим воздействиям определяется не только степенью минерализации, но и качеством ее микроархитектоники и прочностью матри-кса. Классическими примерами роли микроархитекто-ники являются остеопетроз и результаты лечения боль-шими дозами флюоридов, когда частота переломов зна-чительно возрастает, несмотря на существенно увели-ченную минеральную плотность кости (МПК). Значение прочности коллагеновой и неколлагеновой составляю-щих костного матрикса хорошо иллюстрируется повы-шенным риском переломов костей у больных с различ-ными врожденными соединительнотканными дисплази-ями (включая синдромы Марфана и Элерса-Данло) не-зависимо от уровня МПК.К сожалению, сегодня из всех перечисленных фак-торов мы можем реально воздействовать лишь на МПК и частоту падений. Эти же параметры удается достаточно достоверно оценивать до и во время лечения. Хотя име-ются данные о характере воздействия на микроархитек-тонику кости некоторых препаратов, используемых в ле-чении ОП, говорить о возможности направленной ее коррекции преждевременно. Единственный доступный метод оценки качества структуры кости -гистологиче-ское исследование костных биоптатов -пока широко не используется.Отбор больных для лечения Главными клиническими проявлениями ОП явля-ются переломы и их последствия. Поскольку цель лече-ния -их предупреждение, то в идеале терапия должна быть начата до появления симптомов заболевания. Следовательно, важнейшая проблема -активное выяв-ление больных ОП, подлежащих лечению. Сегодня ос-новным критерием для назначения терапии является уровень МПК. Для его оценки используются преиму-щественно три метода: ультразвуковая, компьютерно-томографическая денситометрия и двухфотонная рент-геновская абсорбциометрия (dual energy X-ray absorbtiometry -DXA).Ультразвуковая денситометрия (УЗД), оценивающая степень поглощения и отражения ультразвука от близко-расположенных к коже костей (пяточная или лучевая) -недорогой и относительно точный метод. Благодаря мо-бильной аппаратуре его можно использовать в любом ле-

Рис. 7. Сцинтиграфия, планарные проекции (ноябрь 2007 г.)

Aim: to evaluate the possibility of clinically significant analgesic effect of tofacitinib in patients with rheumatoid arthritis (RA) under the conditions of actual clinical practice. Patients and Methods: data of patients with RA from the Moscow Unified Register of Arthritis (MERA) were analyzed. The subjective indica-tors included tender joint count (TJC), the HAQ (Health Assessment Questionnaire) Functional Capacity Index, the RAPID3 (Routine Assess-ment of Patient Index Data 3) Disease Activity Index. Swollen joint count (SJC) and the level of C-reactive protein (CRP) were analyzed as objective indicators of inflammatory activity. The estimation was conducted of the quotient obtained when subjective indicators were divided by objective indicators in all possible combinations for various targeted medications used in the studied group of patients. Given the observa-tional nature of the study, the search was carried out for confounding factors for all of these quotients. The calculated indices were compared during treatment with various targeted medications, adjusted for detected confounding factors. The process of selecting confounding factors was carried out in 2 stages — preliminary selection of indicators that have a significant one-factor association with the dependent variable, and subsequent reverse stepwise selection of variables within the framework of a generalized linear model.Results: the analysis included 944 episodes of treatment in 832 patients. The duration of episodes was 1312±1006 days. In particular, 93 epi-sodes of tofacitinib treatment were analyzed (average duration — 836±453 days). When the analysis was adjusted for the detected confound-ing factors, it was found that the indicators of TJC/(SJC+1), HAQ/(SJC+1) and RAPID3/(SJC+1) during tofacitinib therapy were significantly lower than the average values obtained with target medications. There were no significant differences between the medications in relation to the studied subjective indicators and the level of CRP.Conclusions: the severity of subjective perceptions and functional disorders in patients treated with tofacitinib may be less with the same severity of arthritis objective indicators compared to genetically engineered anti-inflammatory drugs.KEYWORDS: targeted medication, genetically engineered anti-inflammatory drug, tofacitinib, rheumatoid arthritis, real clinical practice.FOR CITATION: Zhilyaev E.V., Lukina G.V., Koltsova E.N. et al. Clinical significance of the direct analgesic effect of targeted medications in patients with rheumatoid arthritis. Russian Medical Review. 2020;4(8):483–486. DOI: 10.32364/2587-6821-2020-4-8-483-486.

Background:A personalized approach to prescribing targeted drugs implies the availability of data that can be used to suggest that a particular drug is better suited for a given patient than others. Retention on the treatment can be considered as an integral indicator of the acceptability of the drug in real practice. For the purposes of treatment personalization, the indicators that are associated with better retention on some drugs and with worse retention, or that do not have a clear association with retention on others, are of particular interest.Objectives:to identify predictors those are differently associated with retention on different targeted drugs for the treatment of rheumatoid arthritis.Methods:Data of the patients with rheumatoid arthritis (RA) from the Moscow Unified Register of Arthritis (MUAR) were used. The analysis includes episodes of treatment with biological or synthetic targeted drugs (tDMARDs) that continue or end during the patient’s follow-up in the registry. Within the framework of the Cox proportional risk regression model, significant independent predictors of tDMARDs cancellation were identified. These indicators were later considered as confounders. Further, in the generated linear regression risk model, all available indicators were tested for the presence of a statistically significant interaction with the factor of used tDMARD.Results:The study included 944 episodes of tDMARDs treatment (Table 1.) in 832 patients. The average age is 55.3 + 12.4 years. There were 131 males (16.1%). The average duration of the disease is 13.1 + 9.4 years. Smoking, family history of RA, and the nature of RA onset (acute or gradual) were identified as reliable mutually independent predictors of retention on tDMARDs treatment. As a result of the search for indicators that reliably interact with used tDMARD, patient’s reports of the association of the onset of arthritis 1) with symptoms of intestinal dyspepsia (p < 0.001), 2) with genital inflammatory disease (p = 0.002) were revealed. Most strongly associated with factor 1) was retention on abatacept (ABA), rituximab (RIT), and tofacitinib (TOFA). The second indicator was most strongly associated with retention on ABA, adalimumab (ADA) and TOFA (Picture 1).Table 1.Description of treatment episodes included in the analysisABAADACERETAтGOLINFRITTOCTOFATotalNumber of episodes1751503418685513011393944Completed (%)39 (22,3%)51 (34,0%)13 (38,2%)55 (29,6%)2 (25,0%)39 (70,9%)31 (23,8%)14 (12,4%)9 (9,7%)253 (26,8%)Line of treatment 183 (47,4%)24 (70,6%)113 (60,8%)120 (80,0%)3 (37,5%)50 (90,9%)70 (61,9%)66 (50,8%)35 (37,6%)564 (59,7%) 262 (35,4%)6 (17,6%)52 (28,0%)24 (16,0%)2 (25,0%)4 (7,3%)22 (19,5%)39 (30,0%)30 (32,3%)241 (25,5%) 322 (12,6%)1 (2,9%)13 (7,0%)6 (4,0%)1 (12,5%)1 (1,8%)15 (13,3%)21 (16,2%)14 (15,1%)94 (10,0%)>  38 (4,6%)3 (8,8%)8 (4,3%)0 (0,0%)2 (25,0%)0 (0,0%)6 (5,3%)4 (3,1%)14 (15,1%)45 (4,8%)ABA – abatacept, ADA – adalimumab, CER – certolizumab paegol, ETA- etanercept, GOL – golimumab, INF – infliximab, TOC- tocilizumab, TOFA – tofacitinib.Conclusion:Anamnestic indications of the association of the onset of rheumatoid arthritis with symptoms of intestinal dyspepsia and with preceding genital inflammation are differently associated with retention on different targeted drugs in patients with RA. These indicators can be used to personalize the treatment.Picture 1.Retention on the abatacept depending on the features of the onset of rheumatoid arthritisDisclosure of Interests:None declared

Background: the list expansion of genetically engineered biological drugs (GEBD) used for the treatment of ankylosing spondylitis (AS) determines the relevance of studies aimed at comparing them and determining their place in this disease treatment. Real clinical practice studies are the preferred source of this data type. Aim: to evaluate the efficacy of various GEBD in patients with AS according to the Moscow Unified Arthritis Registry (MUAR). Material and methods: the analysis of the MUAR data was carried out. These included clinical cases with GEBD, for which there were data of a completed visit after 6 months or more after the treatment initiation. Parameters values achieved during treatment with various drugs were analyzed. The comparison was conducted during a multivariate analysis with adjustments for the identified confounders. Non-clinical parameters that were reliably and independently associated with the achieved BASDAI index (CRP) values were considered as confounders. Results: the study included 363 treatment episodes with GEBP in 361 patients. As mutually independent significant predictors of the achieved ASDAS (confounders) values, GEBD treatment duration were established until the evaluation of indicators (p<0.001) and the age of the patient (p=0.006). Significant association between the established values of the studied parameters and the used GEBD were found for the achieved ASDAS (p=0.033) and ESR (p=0.007) values. In a pairwise drug comparison using the conservative Šidák correction, the achieved values of ASDAS and ESR during infliximab and adalimumab administration were significantly less than during certolizumab pegol administration. Conclusion: infliximab, adalimumab, etanercept, certolizumab pegol, golimumab, secukinumab in real clinical practice demonstrate generally similar clinical efficacy in the treatment of AS. The effect of golimumab and secukinumab, recently introduced into clinical practice, does not significantly differ from the effect produced by long-term TNF-α inhibitors. Certain disease activity preservation in a significant part of patients gives grounds to continue the search for new treatment methods. KEYWORDS: ankylosing spondylitis, genetically engineered biological drugs, tumor necrosis factor inhibitors, C-reactive protein, confounders, registry. FOR CITATION: Rosochkina E.A., Lukina G.V., Koltsova E.N. et al. Comparative efficacy of genetically engineered biological drugs in real clinical practice according to the Moscow Unified Arthritis Registry (MUAR) data. Russian Medical Inquiry. 2021;5(2):58–63. DOI: 10.32364/2587-6821-2021-5-2-58-63.