rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2017-112-114rsp-2347Research ArticleДИСКУССИИDISCUSSIONПочему для лечения ревматоидного артрита не применяются рекомендуемые дозы метотрексата: кто виноват и что делать?WHY ARE THE RECOMMENDED METHOTREXATE DOSES NOT USED FOR THE TREATMENT OF RHEUMATOID ARTHRITIS: WHO IS GUILTY AND WHAT TO DO?МуравьевЮ. В.MuravyevYu. V.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

murawyu@mail.ruНасоновЕ. Л.NasonovE. L.

115522 Москва, Каширское шоссе, 34А

119991 Москва, ул. Трубецкая, 8, стр. 2

кафедра ревматологии Института профессионального образования

 

34A, Kashirskoe Shosse, Moscow 115522

8, Trubetskaya St., Build. 2, Moscow 119991

Department of Rheumatology

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой» ФГБОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава РоссииРоссияV.A. Nasonova Research Institute of Rheumatology Institute of Professional Education, I.M. Sechenov First Moscow State Medical University, Ministry of Health of RussiaRussian Federation201709032017551112114Copyright © Муравьев Ю.В., Насонов Е.Л., 20172017Муравьев Ю.В., Насонов Е.Л.Muravyev Y.V., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2347

Дискуссия посвящена проблеме применения рекомендуемых для лечения ревматоидного артрита доз метотрексата в рандомизированных клинических сравнительных с генно-инженерными биологическими препаратами исследованиях.

The paper discusses the use of the recommended methotrexate doses for the treatment of rheumatoid arthritis in the randomized clinical comparative trials with biological agents.

ревматоидный артритметотрексатрандомизированные клинические исследованиягенно-инженерные биологические препаратыrheumatoid arthritismethotrexaterandomized clinical trialsbiological agentsReferencesDuran J, Bockorny M, Dalal D, et al. Methotrexate dosage as a source of bias in biologic trials in rheumatoid arthritis:a systematic review. Ann Rheum Dis. 2016;75:1595-8. doi: 10.1136/annrheumdis-2016-209383Duran J, Bockorny M, Dalal D, et al. Methotrexate dosage as a source of bias in biologic trials in rheumatoid arthritis:a systematic review. Ann Rheum Dis. 2016;75:1595-8. doi: 10.1136/annrheumdis-2016-209383Kremer JM. Bias? Not so fast. Ann Rheum Dis. 2016;75(9):1581-2. doi: 10.1136/annrheumdis-2016-209505Kremer JM. Bias? Not so fast. Ann Rheum Dis. 2016;75(9):1581-2. doi: 10.1136/annrheumdis-2016-209505Visser K, Katchamart W, Loza E, et al. Multinational evidencebased recommendations for the use of methotrexate in rheumatic disorders with a focus onrheumatoid arthritis: integrating systematic literature research and expert opinion of a broad internationalpanel of rheumatologists in the 3E Initiative. Ann Rheum Dis. 2009;68:1086-93. doi: 10.1136/ard.2008.094474Visser K, Katchamart W, Loza E, et al. Multinational evidencebased recommendations for the use of methotrexate in rheumatic disorders with a focus onrheumatoid arthritis: integrating systematic literature research and expert opinion of a broad internationalpanel of rheumatologists in the 3E Initiative. Ann Rheum Dis. 2009;68:1086-93. doi: 10.1136/ard.2008.094474Dervieux T, Greenstein N, Kremer J. Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis Rheum. 2006;54:3095-103. doi: 10.1002/art.22129Dervieux T, Greenstein N, Kremer J. Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis Rheum. 2006;54:3095-103. doi: 10.1002/art.22129Wessels JA, de Vries-Bouwstra JK, Heijmans BT, et al. EfficacyWessels JA, de Vries-Bouwstra JK, Heijmans BT, et al. Efficacyand toxicity of methotrexate in early rheumatoid arthritis are associated with single nucleotide polymorphisms in genes coding for folate pathway enzymes. Arthritis Rheum. 2006;54:1087-95. doi: 10.1002/art.21726and toxicity of methotrexate in early rheumatoid arthritis are associated with single nucleotide polymorphisms in genes coding for folate pathway enzymes. Arthritis Rheum. 2006;54:1087-95. doi: 10.1002/art.21726Schiff MH, Jaffe JS, Freundlich B. Head-to-head, randomised, crossover study of oralversus subcutaneous methotrexate in patients with rheumatoid arthritis:drug-exposure limitations of oral methotrexate at doses ≥15 mg may be overcome with subcutaneous administration. Ann Rheum Dis. 2014;73:1549-51. doi: 10.1136/annrheumdis-2014-205228Schiff MH, Jaffe JS, Freundlich B. Head-to-head, randomised, crossover study of oralversus subcutaneous methotrexate in patients with rheumatoid arthritis:drug-exposure limitations of oral methotrexate at doses ≥15 mg may be overcome with subcutaneous administration. Ann Rheum Dis. 2014;73:1549-51. doi: 10.1136/annrheumdis-2014-205228Hazlewood GS, Thorne JC, Pope JE, et al. The comparative effectiveness of oralversus subcutaneous methotrexate for the treatment of early rheumatoid arthritis. Ann Rheum Dis. 2016;75:1003-8. doi: 10.1136/annrheumdis-2014-206504Hazlewood GS, Thorne JC, Pope JE, et al. The comparative effectiveness of oralversus subcutaneous methotrexate for the treatment of early rheumatoid arthritis. Ann Rheum Dis. 2016;75:1003-8. doi: 10.1136/annrheumdis-2014-206504Braun J, Kä stner P, Flaxenberg P, et al. Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum. 2008;58:73-81. doi: 10.1002/art.23144Braun J, Kä stner P, Flaxenberg P, et al. Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum. 2008;58:73-81. doi: 10.1002/art.23144Islam MS, Haq SA, Islam MN, et al. Comparative efficacy of subcutaneous versus oralmethotrexate in active rheumatoid arthritis. Mymensingh Med J. 2013;22:483-8.Islam MS, Haq SA, Islam MN, et al. Comparative efficacy of subcutaneous versus oralmethotrexate in active rheumatoid arthritis. Mymensingh Med J. 2013;22:483-8.Mü ller RB, von Kempis J, Haile SR, et al. Effectiveness, tolerability, and safety of subcutaneous methotrexate in early rheumatoid arthritis: a retrospective analysis of real- world data from the St. Gallen cohort. Semin Arthritis Rheum. 2015;45:28-34. doi: 10.1016/j.semarthrit.2015.02.009Mü ller RB, von Kempis J, Haile SR, et al. Effectiveness, tolerability, and safety of subcutaneous methotrexate in early rheumatoid arthritis: a retrospective analysis of real- world data from the St. Gallen cohort. Semin Arthritis Rheum. 2015;45:28-34. doi: 10.1016/j.semarthrit.2015.02.009Gunn J, Panopolou A, Steuer A. Efficacy and tolerability of subcutaneous methotrexate for inflammatory arthritis: a retrospective observational cohort study [abstract]. Arthritis Rheum. 2014;66:S1079.Gunn J, Panopolou A, Steuer A. Efficacy and tolerability of subcutaneous methotrexate for inflammatory arthritis: a retrospective observational cohort study [abstract]. Arthritis Rheum. 2014;66:S1079.Kremer JM. Let's re-examine these MTX points once again. Ann Rheum Dis. 2016;75(8):e54. doi: 10.1136/annrheumdis-2016-209834Kremer JM. Let's re-examine these MTX points once again. Ann Rheum Dis. 2016;75(8):e54. doi: 10.1136/annrheumdis-2016-209834Duran J, Felson DT. Why methotrexate suboptimal dosing is a potential source of bias in biologic drugs clinical trials. Ann Rheum Dis. 2016;75(8):e53. doi: 10.1136/annrheumdis- 2016-209791Duran J, Felson DT. Why methotrexate suboptimal dosing is a potential source of bias in biologic drugs clinical trials. Ann Rheum Dis. 2016;75(8):e53. doi: 10.1136/annrheumdis- 2016-209791Nair SC, Jacobs JW, Bakker MF, et al; Utrecht Arthritis Cohort Study Group. Determining the lowest optimally effective methotrexate dose for individual ra patients using their doseNair SC, Jacobs JW, Bakker MF, et al; Utrecht Arthritis Cohort Study Group. Determining the lowest optimally effective methotrexate dose for individual ra patients using their doseresponse relation in a tight control treatment approach. PLoS One. 2016 Mar 17;11(3):e0148791. doi: 10.1371/journal.pone.0148791response relation in a tight control treatment approach. PLoS One. 2016 Mar 17;11(3):e0148791. doi: 10.1371/journal.pone.0148791Smolen JS, Landewe R, Breedveld FC, 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. doi: 10.1136/annrheumdis-2013-204573Smolen JS, Landewe R, Breedveld FC, 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. doi: 10.1136/annrheumdis-2013-204573Breedveld FC, Weisman MH, Kavanaugh AF, et al. The PREMIER study – A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54:26-37. doi: 10.1002/art.21519Breedveld FC, Weisman MH, Kavanaugh AF, et al. The PREMIER study – A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54:26-37. doi: 10.1002/art.21519St Clair EW, van der Heijde DM, Smolen JS, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004;50:3432-43. doi: 10.1002/art.20568St Clair EW, van der Heijde DM, Smolen JS, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004;50:3432-43. doi: 10.1002/art.20568Klareskog L, van der Heijde D, de Jager JP, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363:675-81. doi: 10.1016/S0140-6736(04)15640-7Klareskog L, van der Heijde D, de Jager JP, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363:675-81. doi: 10.1016/S0140-6736(04)15640-7Tak PP, Rigby WF, Rubbert-Roth A, et al. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011;70:39-46. doi: 10.1136/ard.2010.137703Tak PP, Rigby WF, Rubbert-Roth A, et al. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011;70:39-46. doi: 10.1136/ard.2010.137703Westhovens R, Robles M, Ximenes AC, et al. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. Ann Rheum Dis. 2009;68:1870-7. doi: 10.1136/ard.2008.101121Westhovens R, Robles M, Ximenes AC, et al. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. 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The authors declare that there are no conflicts of interest present.