<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">clinvest</journal-id><journal-title-group><journal-title xml:lang="ru">Качественная клиническая практика</journal-title><trans-title-group xml:lang="en"><trans-title>Kachestvennaya Klinicheskaya Praktika = Good Clinical Practice</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2588-0519</issn><issn pub-type="epub">2618-8473</issn><publisher><publisher-name>ООО «Издательство ОКИ</publisher-name></publisher></journal-meta><article-meta><article-id custom-type="elpub" pub-id-type="custom">clinvest-54</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ФАРМАКОЭКОНОМИКА</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PHARMACOECONOMICS</subject></subj-group></article-categories><title-group><article-title>Фармакоэкономический анализ применения препарата Актемра® в первой линии лечения ревматоидного артрита в режимах комбинированной и монотерапии</article-title><trans-title-group xml:lang="en"><trans-title>Pharmacoeconomic analysis of Actemra® in first-line treatment of rheumatoid arthritis in the modes of combination and monotherapy</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Зырянов</surname><given-names>С. К.</given-names></name><name name-style="western" xml:lang="en"><surname>Zyryanov</surname><given-names>S. K.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чеберда</surname><given-names>А. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Cheberda</surname><given-names>A. E.</given-names></name></name-alternatives><email xlink:type="simple">aecheberda@healtheconomics.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Белоусов</surname><given-names>Д. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Belousov</surname><given-names>D. Yu.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГАОУ ВО «Российский университет дружбы народов», г. Москва</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Peoples' Friendship University of Russia, Moscow, Russia</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ООО "Центр фармакоэкономических исследований", г. Москва</institution><country>Россия</country></aff><aff xml:lang="en"><institution>LLC "Center for pharmacoeconomics research", Moscow</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ООО "Центр фармакоэкономических исследований", г. Москва</institution><country>Россия</country></aff><aff xml:lang="en"><institution>LLC "Center for Pharmacoeconomics Research", Moscow</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2016</year></pub-date><pub-date pub-type="epub"><day>16</day><month>05</month><year>2018</year></pub-date><volume>0</volume><issue>3</issue><fpage>22</fpage><lpage>34</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Зырянов С.К., Чеберда А.Е., Белоусов Д.Ю., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Зырянов С.К., Чеберда А.Е., Белоусов Д.Ю.</copyright-holder><copyright-holder xml:lang="en">Zyryanov S.K., Cheberda A.E., Belousov D.Y.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.clinvest.ru/jour/article/view/54">https://www.clinvest.ru/jour/article/view/54</self-uri><abstract/><trans-abstract xml:lang="en"><p>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.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>ревматоидный артрит</kwd><kwd>тоцилизумаб</kwd><kwd>адалимумаб</kwd><kwd>фармакоэкономика</kwd><kwd>анализ эффективности затрат</kwd><kwd>анализ влияния на бюджет</kwd><kwd>rheumatoid arthritis</kwd><kwd>tocilizumab</kwd><kwd>adalimumab</kwd><kwd>pharmacoeconomics</kwd><kwd>cost-effectiveness analysis</kwd><kwd>budget impact analysis</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Данное фармакоэкономическое исследование было профинансировано фармацевтической компанией ЗАО «Рош-Москва», однако это не оказало влияния на полученные результаты.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Alivernini S., Laria A., Gremese E., Zoli A., Ferraccioli G. ACR70-disease activity score remission achievement from switches between all the available biological agents in rheumatoid arthritis: a systematic review of the literature. Arthritis Research &amp; Therapy. 2009; 11 (6): R163. doi:10.1186/ar2848.</mixed-citation><mixed-citation xml:lang="en">Alivernini S., Laria A., Gremese E., Zoli A., Ferraccioli G. ACR70-disease activity score remission achievement from switches between all the available biological agents in rheumatoid arthritis: a systematic review of the literature. Arthritis Research &amp; Therapy. 2009; 11 (6): R163. doi:10.1186/ar2848.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Bansback N., Brennan A., Ghatnekar O. Cost effectiveness of adalimumab in the treatment of patients with moderate to severe rheumatoid arthritis in Sweden. Annals of the Rheumatic Diseases. 2005; 64 (7): 995-1002. doi:10.1136/ard.2004.027565.</mixed-citation><mixed-citation xml:lang="en">Bansback N., Brennan A., Ghatnekar O. Cost effectiveness of adalimumab in the treatment of patients with moderate to severe rheumatoid arthritis in Sweden. Annals of the Rheumatic Diseases. 2005; 64 (7): 995-1002. doi:10.1136/ard.2004.027565.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Buch M.H., Conaghan P.G., Quinn M.A., Bingham S.J., Veale D., Emery P. True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin alpha? Ann Rheum Dis. 2004; 63: 1344-1346. doi: 10.1136/ard.2003.014878.</mixed-citation><mixed-citation xml:lang="en">Buch M.H., Conaghan P.G., Quinn M.A., Bingham S.J., Veale D., Emery P. True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin alpha? Ann Rheum Dis. 2004; 63: 1344-1346. doi: 10.1136/ard.2003.014878.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Dougados M., Kissel K., Sheeran T. et al. Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis. 2013; 72 (1): 43-50.</mixed-citation><mixed-citation xml:lang="en">Dougados M., Kissel K., Sheeran T. et al. Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis. 2013; 72 (1): 43-50.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Emery P. et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008; 67: 1516-1523.</mixed-citation><mixed-citation xml:lang="en">Emery P. et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008; 67: 1516-1523.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Gabay C., Emery P., van Vollenhoven R. et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. 2013; 381 (9877): 1541-50.</mixed-citation><mixed-citation xml:lang="en">Gabay C., Emery P., van Vollenhoven R. et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. 2013; 381 (9877): 1541-50.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Keystone E.C., Kavanaugh A.F., Sharp J.T. et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab a human anti-tumor necrosis factor monoclonal antibody in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004; 50 (5): 1400-11.</mixed-citation><mixed-citation xml:lang="en">Keystone E.C., Kavanaugh A.F., Sharp J.T. et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab a human anti-tumor necrosis factor monoclonal antibody in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004; 50 (5): 1400-11.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Shetty A., Hanson R., Korsten P., Shawagfeh M., Arami S., Volkov S. et al. Tocilizumab in the treatment of rheumatoid arthritis and beyond. Drug Des Devel Ther. 2014; 8: 349-64.</mixed-citation><mixed-citation xml:lang="en">Shetty A., Hanson R., Korsten P., Shawagfeh M., Arami S., Volkov S. et al. Tocilizumab in the treatment of rheumatoid arthritis and beyond. Drug Des Devel Ther. 2014; 8: 349-64.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Blanco R., Brzosko M., et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum. 2011; 63 (3): 609-21.</mixed-citation><mixed-citation xml:lang="en">Blanco R., Brzosko M., et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum. 2011; 63 (3): 609-21.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">MacKinnon G.E. (ed). Understanding Health Outcomes and Pharmacoeconomics. Burlington MA: Jones &amp; Barrtlett Learning, 2013; 183-185.</mixed-citation><mixed-citation xml:lang="en">MacKinnon G.E. (ed). Understanding Health Outcomes and Pharmacoeconomics. Burlington MA: Jones &amp; Barrtlett Learning, 2013; 183-185.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Moreland L.W., Schiff M.H., Baumgartner S.W. et al. Etanercept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med. 1999; 130 (6): 478-86.</mixed-citation><mixed-citation xml:lang="en">Moreland L.W., Schiff M.H., Baumgartner S.W. et al. Etanercept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med. 1999; 130 (6): 478-86.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Munro R., Capell H. Prevalence of low body mass in rheumatoid arthritis: association with the acute phase response. Ann Rheum Dis. 1997; 56: 326-29</mixed-citation><mixed-citation xml:lang="en">Munro R., Capell H. Prevalence of low body mass in rheumatoid arthritis: association with the acute phase response. Ann Rheum Dis. 1997; 56: 326-29</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">NICE technology appraisal guidance TA375: Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed [Электронный ресурс]. URL: https://www.nice.org.uk/guidance/ta375.</mixed-citation><mixed-citation xml:lang="en">NICE technology appraisal guidance TA375: Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed [Электронный ресурс]. URL: https://www.nice.org.uk/guidance/ta375.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Ramiro S., Landew? R., van der Heijde D., Harrison D., Collier D., Michaud K. Discontinuation rates of biologics in patients with rheumatoid arthritis: are TNF inhibitors different from non-TNF inhibitors? RMD Open. 2015; 1 (1): e000155. doi:10.1136/rmdopen-2015-000155.</mixed-citation><mixed-citation xml:lang="en">Ramiro S., Landew? R., van der Heijde D., Harrison D., Collier D., Michaud K. Discontinuation rates of biologics in patients with rheumatoid arthritis: are TNF inhibitors different from non-TNF inhibitors? RMD Open. 2015; 1 (1): e000155. doi:10.1136/rmdopen-2015-000155.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Saag K.G., Teng G.G., Patkar N.M., et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008; 59: 762-84.</mixed-citation><mixed-citation xml:lang="en">Saag K.G., Teng G.G., Patkar N.M., et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008; 59: 762-84.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Schulman E., Andersen K., Zhang M., Goodman S.M., Lin D., Boire G., Haraoui B., Hitchon C., Jamal S., Keystone E.C., Pope J.E., Tin D., Thorne C., Bykerk V. High Body Mass Index Negatively Impacts Time to Achieving Sustained Remission in Early Rheumatoid Arthritis: Results from a Multicenter Early Arthritis Cohort Study. Arthritis Rheumatol. 2015; 67: Suppl 10.</mixed-citation><mixed-citation xml:lang="en">Schulman E., Andersen K., Zhang M., Goodman S.M., Lin D., Boire G., Haraoui B., Hitchon C., Jamal S., Keystone E.C., Pope J.E., Tin D., Thorne C., Bykerk V. High Body Mass Index Negatively Impacts Time to Achieving Sustained Remission in Early Rheumatoid Arthritis: Results from a Multicenter Early Arthritis Cohort Study. Arthritis Rheumatol. 2015; 67: Suppl 10.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Schwartz R. Biological Modeling and Simulation: A Survey of Practical Models, Algorithms and Numerical Methods. 2008. The MIT Press.</mixed-citation><mixed-citation xml:lang="en">Schwartz R. Biological Modeling and Simulation: A Survey of Practical Models, Algorithms and Numerical Methods. 2008. The MIT Press.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Smolen J.S., Aletaha D., Bijlsma J. W., Breedveld F.C., Boumpas D., Burmester G. et al; T2T Expert Committee. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010; 69: 631-7.</mixed-citation><mixed-citation xml:lang="en">Smolen J.S., Aletaha D., Bijlsma J. W., Breedveld F.C., Boumpas D., Burmester G. et al; T2T Expert Committee. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010; 69: 631-7.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Smolen J.S., Beaulieu A., Rubbert-Roth A. et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008; 371 (9617): 987-97.</mixed-citation><mixed-citation xml:lang="en">Smolen J.S., Beaulieu A., Rubbert-Roth A. et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008; 371 (9617): 987-97.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Smolen J.S., Landewe R., Breedveld F.C., et al. EULAR Smolen J.S., Landew? R., Breedveld F.C. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014; 73: 492-509.</mixed-citation><mixed-citation xml:lang="en">Smolen J.S., Landewe R., Breedveld F.C., et al. EULAR Smolen J.S., Landew? R., Breedveld F.C. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014; 73: 492-509.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">van de Putte L.B., Atkins C, Malaise M., et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis. 2004; 63 (5): 508-16.</mixed-citation><mixed-citation xml:lang="en">van de Putte L.B., Atkins C, Malaise M., et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis. 2004; 63 (5): 508-16.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">van der Heijde D., Klareskog L., Boers M., et al. Comparison of different definitions to classify remission and sustained remission: 1 year TEMPO results. Ann Rheum Dis. 2005; 64: 1582-7.</mixed-citation><mixed-citation xml:lang="en">van der Heijde D., Klareskog L., Boers M., et al. Comparison of different definitions to classify remission and sustained remission: 1 year TEMPO results. Ann Rheum Dis. 2005; 64: 1582-7.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Van Vilsteren M., Boot C.R., Knol D.L., et al. Productivity at work and quality of life in patients with rheumatoid arthritis. BMC Musculoskeletal Disorders. 2015; 16: 107. doi:10.1186/s12891-015-0562-x.</mixed-citation><mixed-citation xml:lang="en">Van Vilsteren M., Boot C.R., Knol D.L., et al. Productivity at work and quality of life in patients with rheumatoid arthritis. BMC Musculoskeletal Disorders. 2015; 16: 107. doi:10.1186/s12891-015-0562-x.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">van Vollenhoven R.F., Kinnman N., Vincent E., Wax S., Bathon J. Atacicept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase II, randomized, placebo-controlled trial. Arthritis Rheum. 2011; 63 (7): 1782-92.</mixed-citation><mixed-citation xml:lang="en">van Vollenhoven R.F., Kinnman N., Vincent E., Wax S., Bathon J. Atacicept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase II, randomized, placebo-controlled trial. Arthritis Rheum. 2011; 63 (7): 1782-92.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">van Vollenhoven R.F., Fleischmann R., Cohen S., Lee E.B., Garc?a Meijide J.A., Wagner S. et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012; 367 (6): 508-19.</mixed-citation><mixed-citation xml:lang="en">van Vollenhoven R.F., Fleischmann R., Cohen S., Lee E.B., Garc?a Meijide J.A., Wagner S. et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012; 367 (6): 508-19.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Villeneuve E., Haraoui B. To switch or to change class-the biologic dilemma in rheumatoid arthritis. Nat Rev Rheumatol. 2010; 6: 301-305. doi: 10.1038/ nrrheum.2010.45.</mixed-citation><mixed-citation xml:lang="en">Villeneuve E., Haraoui B. To switch or to change class-the biologic dilemma in rheumatoid arthritis. Nat Rev Rheumatol. 2010; 6: 301-305. doi: 10.1038/ nrrheum.2010.45.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Weinblatt M.E., Keystone E.C., Furst D.E. et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003; 48 (1): 35-45.</mixed-citation><mixed-citation xml:lang="en">Weinblatt M.E., Keystone E.C., Furst D.E. et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003; 48 (1): 35-45.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Weinblatt M.E., Schiff M., Valente R. et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum. 2013; 65 (1): 28-38.</mixed-citation><mixed-citation xml:lang="en">Weinblatt M.E., Schiff M., Valente R. et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum. 2013; 65 (1): 28-38.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Аналитическая информация, IMS Россия, 2015 г. [Электронный ресурс]. URL:http://www.ims.ru/.</mixed-citation><mixed-citation xml:lang="en">Аналитическая информация, IMS Россия, 2015 г. [Электронный ресурс]. URL:http://www.ims.ru/.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Ашихмин Я.И. Вопрос к авторам статьи: Панасюк Е.Ю., Амирджанова В.Н., Авдеева А.С. и др. «Опыт применения тоцилизумаба у больных ревматоидным артритом (по данным многоцентрового исследования ЛОРНЕТ). Научно-практическая ревматология. 2016; 54 (2): 238.</mixed-citation><mixed-citation xml:lang="en">Ашихмин Я.И. Вопрос к авторам статьи: Панасюк Е.Ю., Амирджанова В.Н., Авдеева А.С. и др. «Опыт применения тоцилизумаба у больных ревматоидным артритом (по данным многоцентрового исследования ЛОРНЕТ). Научно-практическая ревматология. 2016; 54 (2): 238.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Балабанова Р.М., Эрдес Ш.Ф. Распространенность ревматических заболеваний в России в 2012-2013 гг. Научно-практическая ревматология. 2015; 53 (2): 120-124. DOI:10.14412/1995-4484-2015-120-124. http://rsp.ima-press.net/rsp/article/view/2064/1295.</mixed-citation><mixed-citation xml:lang="en">Балабанова Р.М., Эрдес Ш.Ф. Распространенность ревматических заболеваний в России в 2012-2013 гг. Научно-практическая ревматология. 2015; 53 (2): 120-124. DOI:10.14412/1995-4484-2015-120-124. http://rsp.ima-press.net/rsp/article/view/2064/1295.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Белоусов Ю.Б., Белоусов Д.Ю. Учебное пособие «Основы фармакоэкономических исследований», М. 2000 г. Национальный фонд содействия научным и клиническим исследованиям при РГМУ</mixed-citation><mixed-citation xml:lang="en">Белоусов Ю.Б., Белоусов Д.Ю. Учебное пособие «Основы фармакоэкономических исследований», М. 2000 г. Национальный фонд содействия научным и клиническим исследованиям при РГМУ</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Государственный реестр предельных отпускных цен. [Электронный ресурс] http://grls.rosminzdrav.ru/pricelims.aspx.</mixed-citation><mixed-citation xml:lang="en">Государственный реестр предельных отпускных цен. [Электронный ресурс] http://grls.rosminzdrav.ru/pricelims.aspx.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Заболеваемость всего населения России в 2012 году. Москва 2013.</mixed-citation><mixed-citation xml:lang="en">Заболеваемость всего населения России в 2012 году. Москва 2013.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Информационный сервис «aptekamos.ru» [Электронный ресурс]. URL: http://aptekamos.ru/ (дата обращения: 08.04.2016).</mixed-citation><mixed-citation xml:lang="en">Информационный сервис «aptekamos.ru» [Электронный ресурс]. URL: http://aptekamos.ru/ (дата обращения: 08.04.2016).</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Каратеев Д.Е. Современная медикаментозная терапия ревматоидного артрита. Леч врач. 2007; 2: 40-6.</mixed-citation><mixed-citation xml:lang="en">Каратеев Д.Е. Современная медикаментозная терапия ревматоидного артрита. Леч врач. 2007; 2: 40-6.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Каратеев Д.Е., Лучихина Е.Л. Современное состояние проблемы раннего артрита. // Научно-практическая ревматология. 2010; 4: прил.2: 27-31.</mixed-citation><mixed-citation xml:lang="en">Каратеев Д.Е., Лучихина Е.Л. Современное состояние проблемы раннего артрита. // Научно-практическая ревматология. 2010; 4: прил.2: 27-31.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов Е.Л., Каратеев Д.Е., Балабанова Р.М. Ревматоидный артрит. В кн.: Ревматология. Национальное руководство. Под ред. Е.Л. Насонова, В.А. Насоновой. Москва: ГЭОТАР-Медиа; 2008; 290-331.</mixed-citation><mixed-citation xml:lang="en">Насонов Е.Л., Каратеев Д.Е., Балабанова Р.М. Ревматоидный артрит. В кн.: Ревматология. Национальное руководство. Под ред. Е.Л. Насонова, В.А. Насоновой. Москва: ГЭОТАР-Медиа; 2008; 290-331.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов Е.Л., Каратеев Д.Е., Чичасова Н.В. Рекомендации EULAR по лечению ревматоидного артрита-2013: общая характеристика и дискуссионные проблемы. Научно-практическая ревматология. 2013; 51 (6): 609-22.</mixed-citation><mixed-citation xml:lang="en">Насонов Е.Л., Каратеев Д.Е., Чичасова Н.В. Рекомендации EULAR по лечению ревматоидного артрита-2013: общая характеристика и дискуссионные проблемы. Научно-практическая ревматология. 2013; 51 (6): 609-22.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов Е.Л., Мазуров В.И., Каратеев Д.Е. и др. Проект рекомендаций по лечению ревматоидного артрита Общероссийской общественной организции «Ассоциация ревматологов России» - 2014 (часть 1). Научно-практическая ревматология. 2014; 52 (5): 477-94.</mixed-citation><mixed-citation xml:lang="en">Насонов Е.Л., Мазуров В.И., Каратеев Д.Е. и др. Проект рекомендаций по лечению ревматоидного артрита Общероссийской общественной организции «Ассоциация ревматологов России» - 2014 (часть 1). Научно-практическая ревматология. 2014; 52 (5): 477-94.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Отраслевой стандарт «Клинико-экономические исследования. Общие положения» Приказ Минздрава РФ от 27.05.2002 №163 вместе с ост 91500.14.0001-2002 [Электронный ресурс]. http://www.healtheconomics.ru/index.php?option=com_content&amp;view=artide&amp;id=300:-q-q&amp;catid=55:2009-05-29-19-56-44&amp;Itemid=104.</mixed-citation><mixed-citation xml:lang="en">Отраслевой стандарт «Клинико-экономические исследования. Общие положения» Приказ Минздрава РФ от 27.05.2002 №163 вместе с ост 91500.14.0001-2002 [Электронный ресурс]. http://www.healtheconomics.ru/index.php?option=com_content&amp;view=artide&amp;id=300:-q-q&amp;catid=55:2009-05-29-19-56-44&amp;Itemid=104.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Приказ Министерства труда и социальной защиты РФ от 29 сентября 2014 г. N 664н «О классификациях и критериях, используемых при осуществлении медико-социальной экспертизы граждан федеральными государственными учреждениями медико-социальной экспертизы»</mixed-citation><mixed-citation xml:lang="en">Приказ Министерства труда и социальной защиты РФ от 29 сентября 2014 г. N 664н «О классификациях и критериях, используемых при осуществлении медико-социальной экспертизы граждан федеральными государственными учреждениями медико-социальной экспертизы»</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Ревматология: клинические рекомендации. Под ред. акад. РАМН Е.Л. Насонова. 2-е изд., испр. и доп. М.: ГЭТОТАР-медиа, 2010; 752.</mixed-citation><mixed-citation xml:lang="en">Ревматология: клинические рекомендации. Под ред. акад. РАМН Е.Л. Насонова. 2-е изд., испр. и доп. М.: ГЭТОТАР-медиа, 2010; 752.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Российский мониторинг экономического положения и здоровья населения НИУ ВШЭ: Национальный исследовательский университет «Высшая школа экономики» [Электронный ресурс]. http://www.hse.ru/rlms/reg.</mixed-citation><mixed-citation xml:lang="en">Российский мониторинг экономического положения и здоровья населения НИУ ВШЭ: Национальный исследовательский университет «Высшая школа экономики» [Электронный ресурс]. http://www.hse.ru/rlms/reg.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Стандарт первичной медико-санитарной помощи при первичном коксартрозе, ревматоидном артрите, подагре с поражением тазобедренных суставов, остеонекрозе и кистах головки бедренной кости. Утверждён приказом МЗ РФ №1132н от 1 февраля 2013 г.</mixed-citation><mixed-citation xml:lang="en">Стандарт первичной медико-санитарной помощи при первичном коксартрозе, ревматоидном артрите, подагре с поражением тазобедренных суставов, остеонекрозе и кистах головки бедренной кости. Утверждён приказом МЗ РФ №1132н от 1 февраля 2013 г.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Тарифы на медицинские услуги Московского городского фонда ОМС, введённые в действие в 2015 г. [Электронный ресурс]. http://www.mgfoms.ru.</mixed-citation><mixed-citation xml:lang="en">Тарифы на медицинские услуги Московского городского фонда ОМС, введённые в действие в 2015 г. [Электронный ресурс]. http://www.mgfoms.ru.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Федеральная служба государственной статистики, 2015 г. [Электронный ресурс]. http://www.gks.ru/wps/wcm/connect/rosstat_main/rosstat/ru/statistics/ accounts/#(дата обращения: 02.04.2016)</mixed-citation><mixed-citation xml:lang="en">Федеральная служба государственной статистики, 2015 г. [Электронный ресурс]. http://www.gks.ru/wps/wcm/connect/rosstat_main/rosstat/ru/statistics/ accounts/#(дата обращения: 02.04.2016)</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Федеральная служба государственной статистики, 2015 г. [Электронный ресурс]. http://www.gks.ru/wps/wcm/connect/rosstat_main/rosstat/ru/statistics/ population/demography/# (дата обращения: 10.04.2016). Численность и состав населения в 2015 г.</mixed-citation><mixed-citation xml:lang="en">Федеральная служба государственной статистики, 2015 г. [Электронный ресурс]. http://www.gks.ru/wps/wcm/connect/rosstat_main/rosstat/ru/statistics/ population/demography/# (дата обращения: 10.04.2016). Численность и состав населения в 2015 г.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Федеральный закон от 24.11.1995 N 181-ФЗ (ред. от 29.06.2015) «О социальной защите инвалидов в Российской Федерации».</mixed-citation><mixed-citation xml:lang="en">Федеральный закон от 24.11.1995 N 181-ФЗ (ред. от 29.06.2015) «О социальной защите инвалидов в Российской Федерации».</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Ягудина Р.И., Куликов А.Ю., Метелкин И.А. Методология анализа «Затраты-эффективность» при проведении фармакоэкономических исследований. Фармакоэкономика. Современная фармакоэкономика и фармакоэпидемиология. 2012; 4: 3-8.</mixed-citation><mixed-citation xml:lang="en">Ягудина Р.И., Куликов А.Ю., Метелкин И.А. Методология анализа «Затраты-эффективность» при проведении фармакоэкономических исследований. Фармакоэкономика. Современная фармакоэкономика и фармакоэпидемиология. 2012; 4: 3-8.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Ягудина Р.И., Куликов А.Ю., Серпик В.Г. Дисконтирование при проведении фармакоэкономических исследований. Фармакоэкономика. 2009; 4: 10-13.</mixed-citation><mixed-citation xml:lang="en">Ягудина Р.И., Куликов А.Ю., Серпик В.Г. Дисконтирование при проведении фармакоэкономических исследований. Фармакоэкономика. 2009; 4: 10-13.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
