rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2013-649rsp-787Research ArticleСтатьиArticlesКак же назначать фолиевую кислоту при ревматоидном артрите в период лечения метотрексатом?How is folic acid to be used in rheumatoid arthritis during methotrexate treatment?МуравьевЮ. В.MuravyevYuri Vladimirovichmuravyu@mail.ru201315042013512№2 (2013)201204Copyright © Муравьев Ю.В., 20132013Муравьев Ю.В.Muravyev Y.V.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/787References<div><p>Combe B., Landewe R., Lukas C. et al. EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2007;66:34-45.</p><p>Tugwell P., Bennett K., Gent M. Methotrexate in rheumatoid arthritis. Indications, contraindications, efficacy, and safety. Ann Intern Med 1987;107:358-66.</p><p>Felson D., Anderson J.J., Meenan R.F. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two meta-analyses. Arthr Rheum 1990;33:1449-61.</p><p>Felson D.T., Anderson J.J., Meenan R.F. Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid arthritis. A meta-analysis of published clinical trials. Arthr Rheum 1992;35:1117-25.</p><p>Cronstein B.N. Molecular therapeutics. Methotrexate and its mechanism of action. Arthr Rheum 1996;39:1951-60.</p><p>Morgan S.L., Baggott J.E., Vaughn W.H. et al. The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with rheumatoid arthritis. Arthr Rheum 1990;33:9-18.</p><p>Alarcon G.S., Tracy I.C., Blackburn W.D. Methotrexate in rheumatoid arthritis. Toxic effects as the major factor in limiting long-term treatment. Arthr Rheum 1989;32:671-6.</p><p>Ortiz Z., Shea B., Suarez-Almazor M.E. et al. The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis. A metaanalysis of randomized controlled trials. J Rheumatol 1998;25:36-43.</p><p>Guidelines for monitoring drug therapy in rheumatoid arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthr Rheum 1996;39:723-31.</p><p>National Guidelines for the Monitoring of Second Line Drugs. London: British Society for Rheumatology, 2000.</p><p>Canhao H., Santos M.J., Costa L. et al. Portuguese recommendations for the use of methotrexate in the treatment of rheumatoid arthritis. Acta Reumatol Port 2009;34:78-95.</p><p>Diaz-Borpn A. Guidelines for the use of conventional and newer disease-modifying antirheumatic drugs in elderly patients with rheumatoid arthritis. Drugs Aging 2009;26:273-93.</p><p>Pavy S., Constantin A., Pham T. et al. Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion. Joint Bone Spine 2006;73:388-95.</p><p>Endresen G.K., Husby G. Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis. An update and proposals for guidelines. Scand J Rheumatol 2001;30:129-34.</p><p>Morgan S.L., Baggott J.E., Vaughn W.H. et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 1994;121:833-41.</p><p>Morgan S.L., Baggott J.E., Vaughn W.H. et al. 5 mg or 50 mg/week of folic acid supplementation does not alter the efficacy of methotrexate treated rheumatoid arthritis patients [abstract]. Arthr Rheum 1992;35(Suppl 5):18.</p><p>Van Ede A.E., Laan R.F., Rood M.J. et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthr Rheum 2001;44:1515-24.</p><p>Whittle S.L., Hughes R.A. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology (Oxford) 2004;43:267-71.</p><p>Strand V., Cohen C., Schiff M. et al. Treatment of active rheumatoid arthritis with leflunomidecompared with placebo and methotrexate. Arch Intern Med 1999;159:2542-50.</p><p>Emery P., Breedveld F.C., Lemmel E.M. et al. A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology 2000;39:655-65.</p><p>Schiff M.H. Leflunomide versus methotrexate: a comparison of the European and American experience. Scand J Rheumatol 1999;112(Suppl):31-5.</p><p>Strand V., Alto P., Morgan S.L. et al. Folic acid supplementation and methotrexate efficacy: comment on articles by Schiff, Emery et al, and others. Arthr Rheum 2000;43:2615-6.</p><p>Griffith S.M., Fisher J., Clarke S. et al. Do patients with rheumatoid arthritis established on methotrexate and folic acid 5 mg daily need to continue folic acid supplements long term? Rheumatology 2000;39:1102-9.</p><p>Регистр лекарственных средств России. Энциклопедия лекарств. М.: ООО «РЛС», 2004; 544 с.</p><p>Инструкция по медицинскому применению препарата Метотрексат-ЭБЕВЕ (methotrexate-ebewe). Регистрационный номер: П № 015225/01, П № 015225/02, П № 015225/03.EBEWE Pharma Ges.m.b.H.Nfg.KG A-4866 Unterach, Austria.</p><p>Инструкция по медицинскому применению препарата Метотрексат(Methotrexate), регистрационный номер Р № 000970/01, ОАО «Валента Фармацевтика».</p><p>Ревматические болезни: Руководство для врачей. Под ред. В.А. Насоновой, Н.В. Бунчука. М.: Медицина, 1997; 520 с.</p><p>Клиническая ревматология: Руководство для врачей. Под ред. чл.-корр. РАМН проф. В.И. Мазурова. 2-е изд., перераб. и доп. СПб.: ФОЛИАНТ, 2005; 520 с.</p><p>Вест С.Дж. Секреты ревматологии: Пер с англ. М.-СПб.: Изд-во БИНОМ Невский Диалект, 1999; 768 с.</p><p>Cush J.J. Rheumatoid arthritis. Clin Simp 1999;51:2-40.</p><p>Ревматология: Национальное руководство. Под ред. Е.Л. Насонова, В.А. Насоновой. М.: ГЭОТАР-Медиа, 2008; 209 с.</p><p>Haagsma C.J., Blom H.J., van Riel P.L. et al. Influence of sul-phasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Ann Rheum Dis 1999;58:79-84.</p><p>Andersen L.S., Hansen E.L., Knudsen J.B. et al. Prospectively measured red cell folate levels in mеthotrexate treated patients with rheumatoid arthritis: relation to withdrawal and side effects. J Rheumatol 1997;24:830-7.</p><p>Van Ede A.E., Laan R.F., Blom H.J. et al. Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. Rheumatology (Oxford) 2002;41:658-65.</p><p>Rubenoff R., Dellapria P., Nadeau M.R. et al. Abnormal homocystein metabolism in rheumatoid arthritis. Arthr Rheum 1997;40:718-22.</p><p>Welch G.N., Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med 1998;338:1042-50.</p><p>Frosst P., Blom H.J., Milos R. et al. A candidate genetic risk for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genet 1995;10:111-3.</p><p>Engbersen A.M.T., Franken D.G., Boers G.H.J. et al. Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia. Am J Hum Genet 1995;56:142-50.</p><p>Rosen R. Genetic predisposition to hyperhomocysteinemia: deficiency of methylentetrahyddrofolate reductase (MTHFR). Thromb Haemost 1997;78:523-6.</p><p>Butz L.W., Du Vigneaud V. The formation of a homologue of cys tine by the decomposition of methionine with sulfuric acid. J Biol Chem 1932;99:135-42.</p><p>Mudd S.H., Finkelstein J.D., Refsum H. et al. Homocysteine and its disulfide derivatives: a suggested consensus terminology. Arterioscler Thromb Vasc Biol 2000;20:1704-6.</p><p>Rubenoff R., Dellapria P., Nadeau M. R. et al. Abnormal homocystein metabolism in rheumatoid arthritis. Arthr Rheum 1997;40:718-22.</p><p>McCully K.S. Vascular pathology of homocysteinemia; implications for the the patogenesis of arteriosclerosis. Am J Pathol 1969;56:111-28.</p><p>Nygard O., Nordrehaug J.E., Refsum H. et al. Plasma homocysteine levels and mortaliry in patients with coronary artery disease. N Engl J Med 1997;337:230-7.</p><p>Shiroky J.B., Neville C., Esdaile J.M. et al. Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis: results of a multicenter randomised, double-blind, placebo-controlled trial. Arthr Rheum 1993;36:795-803.</p><p>Шершава В.С., Шершава Н.В. Современные научные представления о факторах риска развития сердечнососудистых заболеваний (по материалам 15-го Всемирного Конгресса по кардиологии, состоявшегося 5-9 мая 2002 г. в г. Сиднее, Австралия). Кардиоваск тер профилакт 2003;2:111-7.</p><p>Graham I., Daly L., Refsum H. et al. Plasma homocysteine as a risk factor for vascular disease. JAMA 1997;277:1775-81.</p><p>Mangioni A.A., Jackson S.H.D. Homocysteine and cardiovascular disease: current evidence and future prospects. Am J Med 2002;112:556-65.</p><p>Landewe R.B., van den Borne B.E., Beedveld F.C., Dijkmans B.A. Methotrexate effects in patients with rheumatoid arthritis with cardiovascular comorbidity. Lancet 2000;355:1616-7.</p><p>Erb N., Kitas G.D. Homocysteine modulation as a reason for continuous folic acid supplementation in methotrexate-treated rheumatoid arthritis patients. Rheumatology (Oxford) 2001;40:715-6.</p><p>Clarke R., Daly L., Robinson K. et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 1991;324:1149-55.</p><p>Morgan S.L., Baggott J.E., Lee J.Y., Alarcon G.S. Folic acid supplementation prevent deficient blood folate levels and hyperhomo-cysteinemia duruing longterm, low dose methoterxate therapy for rheumatoid arthritis:implications for cardiovascular disease prevention. J Rheumatol 1998;25:441-6.</p><p>Slot O. Changes in plasma homocysteine in arthritis patients starting treatment with low-dose methotrexate subsequently supplemented with folic acid. Scand J Rheumatol 2001;30:305-7.</p><p>Hoekstra M., Haagsma C.J., Doelman C.J.A., van de Laar M.A.FJ. Intermittent rises in plasma homocysteine in patients with rheumatoid arthritis treated with higher dose methotrexate. Ann Rheum Dis 2005;64:141-3.</p><p>Whittle S.L., Hughes R.A. Folate supplementation and methotrexate treatment rheumatoid arthritis:a review. Rheumatology 2004;43:267-71.</p><p>Baggott J.E., Oster R.A., Tamura T. Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiol 2012;36:78-81.</p></div><br /><div><p>Combe B., Landewe R., Lukas C. et al. EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2007;66:34-45.</p><p>Tugwell P., Bennett K., Gent M. Methotrexate in rheumatoid arthritis. Indications, contraindications, efficacy, and safety. Ann Intern Med 1987;107:358-66.</p><p>Felson D., Anderson J.J., Meenan R.F. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two meta-analyses. Arthr Rheum 1990;33:1449-61.</p><p>Felson D.T., Anderson J.J., Meenan R.F. Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid arthritis. A meta-analysis of published clinical trials. Arthr Rheum 1992;35:1117-25.</p><p>Cronstein B.N. Molecular therapeutics. Methotrexate and its mechanism of action. Arthr Rheum 1996;39:1951-60.</p><p>Morgan S.L., Baggott J.E., Vaughn W.H. et al. The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with rheumatoid arthritis. Arthr Rheum 1990;33:9-18.</p><p>Alarcon G.S., Tracy I.C., Blackburn W.D. Methotrexate in rheumatoid arthritis. Toxic effects as the major factor in limiting long-term treatment. Arthr Rheum 1989;32:671-6.</p><p>Ortiz Z., Shea B., Suarez-Almazor M.E. et al. The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis. A metaanalysis of randomized controlled trials. J Rheumatol 1998;25:36-43.</p><p>Guidelines for monitoring drug therapy in rheumatoid arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthr Rheum 1996;39:723-31.</p><p>National Guidelines for the Monitoring of Second Line Drugs. London: British Society for Rheumatology, 2000.</p><p>Canhao H., Santos M.J., Costa L. et al. Portuguese recommendations for the use of methotrexate in the treatment of rheumatoid arthritis. Acta Reumatol Port 2009;34:78-95.</p><p>Diaz-Borpn A. Guidelines for the use of conventional and newer disease-modifying antirheumatic drugs in elderly patients with rheumatoid arthritis. Drugs Aging 2009;26:273-93.</p><p>Pavy S., Constantin A., Pham T. et al. Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion. Joint Bone Spine 2006;73:388-95.</p><p>Endresen G.K., Husby G. Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis. An update and proposals for guidelines. Scand J Rheumatol 2001;30:129-34.</p><p>Morgan S.L., Baggott J.E., Vaughn W.H. et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 1994;121:833-41.</p><p>Morgan S.L., Baggott J.E., Vaughn W.H. et al. 5 mg or 50 mg/week of folic acid supplementation does not alter the efficacy of methotrexate treated rheumatoid arthritis patients [abstract]. Arthr Rheum 1992;35(Suppl 5):18.</p><p>Van Ede A.E., Laan R.F., Rood M.J. et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthr Rheum 2001;44:1515-24.</p><p>Whittle S.L., Hughes R.A. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology (Oxford) 2004;43:267-71.</p><p>Strand V., Cohen C., Schiff M. et al. Treatment of active rheumatoid arthritis with leflunomidecompared with placebo and methotrexate. Arch Intern Med 1999;159:2542-50.</p><p>Emery P., Breedveld F.C., Lemmel E.M. et al. A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology 2000;39:655-65.</p><p>Schiff M.H. Leflunomide versus methotrexate: a comparison of the European and American experience. Scand J Rheumatol 1999;112(Suppl):31-5.</p><p>Strand V., Alto P., Morgan S.L. et al. Folic acid supplementation and methotrexate efficacy: comment on articles by Schiff, Emery et al, and others. Arthr Rheum 2000;43:2615-6.</p><p>Griffith S.M., Fisher J., Clarke S. et al. Do patients with rheumatoid arthritis established on methotrexate and folic acid 5 mg daily need to continue folic acid supplements long term? Rheumatology 2000;39:1102-9.</p><p>Регистр лекарственных средств России. Энциклопедия лекарств. М.: ООО «РЛС», 2004; 544 с.</p><p>Инструкция по медицинскому применению препарата Метотрексат-ЭБЕВЕ (methotrexate-ebewe). Регистрационный номер: П № 015225/01, П № 015225/02, П № 015225/03.EBEWE Pharma Ges.m.b.H.Nfg.KG A-4866 Unterach, Austria.</p><p>Инструкция по медицинскому применению препарата Метотрексат(Methotrexate), регистрационный номер Р № 000970/01, ОАО «Валента Фармацевтика».</p><p>Ревматические болезни: Руководство для врачей. Под ред. В.А. Насоновой, Н.В. Бунчука. М.: Медицина, 1997; 520 с.</p><p>Клиническая ревматология: Руководство для врачей. Под ред. чл.-корр. РАМН проф. В.И. Мазурова. 2-е изд., перераб. и доп. СПб.: ФОЛИАНТ, 2005; 520 с.</p><p>Вест С.Дж. Секреты ревматологии: Пер с англ. М.-СПб.: Изд-во БИНОМ Невский Диалект, 1999; 768 с.</p><p>Cush J.J. Rheumatoid arthritis. Clin Simp 1999;51:2-40.</p><p>Ревматология: Национальное руководство. Под ред. Е.Л. Насонова, В.А. Насоновой. М.: ГЭОТАР-Медиа, 2008; 209 с.</p><p>Haagsma C.J., Blom H.J., van Riel P.L. et al. Influence of sul-phasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Ann Rheum Dis 1999;58:79-84.</p><p>Andersen L.S., Hansen E.L., Knudsen J.B. et al. Prospectively measured red cell folate levels in mеthotrexate treated patients with rheumatoid arthritis: relation to withdrawal and side effects. J Rheumatol 1997;24:830-7.</p><p>Van Ede A.E., Laan R.F., Blom H.J. et al. Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. Rheumatology (Oxford) 2002;41:658-65.</p><p>Rubenoff R., Dellapria P., Nadeau M.R. et al. Abnormal homocystein metabolism in rheumatoid arthritis. Arthr Rheum 1997;40:718-22.</p><p>Welch G.N., Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med 1998;338:1042-50.</p><p>Frosst P., Blom H.J., Milos R. et al. A candidate genetic risk for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genet 1995;10:111-3.</p><p>Engbersen A.M.T., Franken D.G., Boers G.H.J. et al. Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia. Am J Hum Genet 1995;56:142-50.</p><p>Rosen R. Genetic predisposition to hyperhomocysteinemia: deficiency of methylentetrahyddrofolate reductase (MTHFR). Thromb Haemost 1997;78:523-6.</p><p>Butz L.W., Du Vigneaud V. The formation of a homologue of cys tine by the decomposition of methionine with sulfuric acid. J Biol Chem 1932;99:135-42.</p><p>Mudd S.H., Finkelstein J.D., Refsum H. et al. Homocysteine and its disulfide derivatives: a suggested consensus terminology. Arterioscler Thromb Vasc Biol 2000;20:1704-6.</p><p>Rubenoff R., Dellapria P., Nadeau M. R. et al. Abnormal homocystein metabolism in rheumatoid arthritis. Arthr Rheum 1997;40:718-22.</p><p>McCully K.S. Vascular pathology of homocysteinemia; implications for the the patogenesis of arteriosclerosis. Am J Pathol 1969;56:111-28.</p><p>Nygard O., Nordrehaug J.E., Refsum H. et al. Plasma homocysteine levels and mortaliry in patients with coronary artery disease. N Engl J Med 1997;337:230-7.</p><p>Shiroky J.B., Neville C., Esdaile J.M. et al. Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis: results of a multicenter randomised, double-blind, placebo-controlled trial. Arthr Rheum 1993;36:795-803.</p><p>Шершава В.С., Шершава Н.В. Современные научные представления о факторах риска развития сердечнососудистых заболеваний (по материалам 15-го Всемирного Конгресса по кардиологии, состоявшегося 5-9 мая 2002 г. в г. Сиднее, Австралия). Кардиоваск тер профилакт 2003;2:111-7.</p><p>Graham I., Daly L., Refsum H. et al. Plasma homocysteine as a risk factor for vascular disease. JAMA 1997;277:1775-81.</p><p>Mangioni A.A., Jackson S.H.D. Homocysteine and cardiovascular disease: current evidence and future prospects. Am J Med 2002;112:556-65.</p><p>Landewe R.B., van den Borne B.E., Beedveld F.C., Dijkmans B.A. Methotrexate effects in patients with rheumatoid arthritis with cardiovascular comorbidity. Lancet 2000;355:1616-7.</p><p>Erb N., Kitas G.D. Homocysteine modulation as a reason for continuous folic acid supplementation in methotrexate-treated rheumatoid arthritis patients. Rheumatology (Oxford) 2001;40:715-6.</p><p>Clarke R., Daly L., Robinson K. et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 1991;324:1149-55.</p><p>Morgan S.L., Baggott J.E., Lee J.Y., Alarcon G.S. Folic acid supplementation prevent deficient blood folate levels and hyperhomo-cysteinemia duruing longterm, low dose methoterxate therapy for rheumatoid arthritis:implications for cardiovascular disease prevention. J Rheumatol 1998;25:441-6.</p><p>Slot O. Changes in plasma homocysteine in arthritis patients starting treatment with low-dose methotrexate subsequently supplemented with folic acid. Scand J Rheumatol 2001;30:305-7.</p><p>Hoekstra M., Haagsma C.J., Doelman C.J.A., van de Laar M.A.FJ. Intermittent rises in plasma homocysteine in patients with rheumatoid arthritis treated with higher dose methotrexate. Ann Rheum Dis 2005;64:141-3.</p><p>Whittle S.L., Hughes R.A. Folate supplementation and methotrexate treatment rheumatoid arthritis:a review. Rheumatology 2004;43:267-71.</p><p>Baggott J.E., Oster R.A., Tamura T. Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiol 2012;36:78-81.</p></div><br />
The authors declare that there are no conflicts of interest present.