rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2008-491rsp-629Research ArticleСтатьиArticlesЛефлуномид в базисной терапии ревматоидного артрита у больных пожилого возрастаLeflunomide in disease modifying treatment of rheumatoid arthritis in elderly patientsNikitinaN ANikitinaN A-MutovinaS. Y.MutovinaS. Y.-PozarovI. V.PozarovI. V.-RosanovaI. V.RosanovaI. V.-UskovaY AUskovaY A-GordeevA. I.GordeevA. I.-200815122008466№6 (2008)5663Copyright © Nikitina N.A., Mutovina S.Y., Pozarov I.V., Rosanova I.V., Uskova Y.A., Gordeev A.I., 20082008Nikitina N.A., Mutovina S.Y., Pozarov I.V., Rosanova I.V., Uskova Y.A., Gordeev A.I.Nikitina N.A., Mutovina S.Y., Pozarov I.V., Rosanova I.V., Uskova Y.A., Gordeev A.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/629

Резюме Цель. Оценить эффективность и переносимость лефлуномида в базисной терапии ревматоидного артрита (РА) у пациентов пожилого возраста. Материал и методы. Ретроспективно была сформирована группа из 46 пациентов в возрасте 65 лет и старше (35 жен. и 11 муж.), страдающих РА. Все получали лефлуномид по стандартной схеме или в комбинации с метотрексатом, инфликсимабом и ритуксимабом. Клинико-лабораторная активность заболевания оценивалась по индексу Ричи и DAS 28, СОЭ, выраженности анемии и тромбоцитоза, функциональная недостаточность — по индексу HAQ. Период наблюдения составил в среднем 11 мес. Математическая обработка данных проводилась с помощью программы Statistica 7. Результаты. За период наблюдения отмечено статистически значимое снижение показателей индекса Ричи, DAS 28 и HAQ. Уровни лабораторных маркеров воспаления, креатинина сыворотки и скорость клубочковой фильтрации (СКФ) существенно не менялись, однако на фоне лечения вдвое снизилась потребность пациентов в НПВП и глюкокортикоидах. Препарат был отменен из-за развития побочных эффектов (артериальная гипертензия, послабление стула, токсический гепатит) у 6 человек. Заключение. Проведенный анализ демонстрирует эффективность и хорошую переносимость моно- и комбинированной базисной терапии лефлуномидом и позволяет рекомендовать его как препарат выбора для лечения ревматоидного артрита у пациентов пожилого возраста.

Objective. To assess efficacy and tolerability of leflunomide in elderly pts with rheumatoid arthritis (RA). Material and methods. 46 pts with RA aged 65 years and older (35 female and 11 male) were included in a retrospective study. All pts received leflunomide according to standard scheme or in combination with methotrexate, infliximab, rituximab. Ritchie index, DAS 28, ESR, anemia intensity, platelet count and functional disability (HAQ) were used as activity measures. Mean follow up period was 11 months. Statistica 7 program was used for data processing. Results. Ritchie index, DAS 28 and HAQ significantly decreased during follow up. Level of laboratory markers of inflammation, serum creatinine and glomerular filtration rate did not significantly changed. NSAIDs and glucocorticoid requirement decreased by 50%. The drug was withdrawn due to adverse events (hypertension, diarrhea, toxic hepatitis) in 6 pts. Conclusion. These results show high efficacy and good tolerability of mono- and combined disease modifying therapy with leflunomide and allow to recommend it as drug of choice for treatment of rheumatoid arthritis in elderly pts

ревматоидный артритпожилой возрастлефлуномидбазисная терапияrheumatoid arthritiselderly ageleflunomidedisease modifying anti-rheumatic drugsReferences<div><p>Амирджанова В. Н. Ревматоидный артрит с позиций оценки качества жизни больных. Тер. архив, 2007, 79(5), 15-20.</p><p>Гордеев А.В., Мутовина З.Ю., Насанкаева Е.К. Эффективное лечение системного склероза лефлуномидом. Тер. архив, 2005, 77(5), 57-58.</p><p>Диагностика и лечение ревматоидного артрита. Клинические рекомендации. Ревматология. Гл.ред. чл.-корр. РАМН Насонов Е.Л. М., ТЭОТАР-Медиа, 2006, 35.</p><p>Каратеев Д.Е., Олюнин Ю.А. О классификации ревматоидного артрита. Научно-практич. рев- матол., 2008, 1, 5-16.</p><p>Насонов Е.Л. Метотрексат: перспективы применения в ревматологии. М., Филоматис, 2005, 24, 25, 57, 117.</p><p>Arnett F.C., Edworthy S. М., Bloch D.A. et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthr. Rheum., 1988, 31, 315-324.</p><p>Berard A., Solomon D.H., Avorn J. Patterns of drug use in rheumatoid arthritis. J. Rheumatol., 2000, 27(7), 1648-1655.</p><p>Bressolle F., Bologna C., Kinowski J.M. et al. Effects of moderate renal insufficiency on pharmacokinetics of methotrexate in rheumatoid arthritis patients. Ann. Rheum. Dis., 1998, 57, 110-113.</p><p>Bukhari М., Lunt М., Barton A. et al. Increasing age at symptom onset is associated with worse radiological damage at presentation in patients with early inflammatory polyarthritis. Ann. Rheum. Dis., 2007, 66(3), 389-393</p><p>Callahan D. Meulen R.H., Topincova E.A. World Growing Old. The Coming Health Care Challenges. Washington, DC: Georgetown University Press, 1995, 1-6, 39, 53, 62-65, 74-78, 97-106.</p><p>Cohen S., Cannon G. W, SchiffM. Two-year, blinded, randomized, controlled trial of treatment of active rheumatoid arthritis with leflunomide compared with methotrexate. Arthr. Rheum., 2001, 44, 9, 1984— 1992</p><p>Farragher T.M., Lunt М., Bunn D.K. et al. Early functional disability predicts both all-cause and cardiovascular mortality in people with inflammatory polyarthritis: results from the Norfolk Arthritis Register. Ann. Rheum. Dis., 2007, 66(4), 486-492.</p><p>Filippini М., Bazzani C., Zingarelli S. et al. Anti- TNFalpha agents in elderly patients with rheumatoid arthritis: a study of a group of 105 over sixty five years old patients. Reumatismo, 2008, 60(1), 41-49.</p><p>Genevay S., Finckh A., Ciurea A. et al. Tolerance and effectiveness of anti-tumor necrosis factor a therapies in elderly patients with rheumatoid arthritis: a population-based study. Arthr. Rheum. 2007, 15, 57(4), 679-685.</p><p>Gossec L., Dougados М., Goupille P. et al. Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study. Ann. Rheum. Dis., 2004, 63(6), 675-680</p><p>Grimble R.F. Inflammatory response in the elderly. Curr. Opin. Clin. Nutr. Metab. Care, 2003, 6(1), 21-29.</p><p>Iwamoto М., Нотта S., Asano Y. etal. Administration of leflunomide to a patient with rheumatoid arthritis on haemodialysis. Scand. J. Rheumatol., 2005, 34(5), 410-411.</p><p>Smolen J. S., Emery P., Kalden J.R. etal. The efficacy of leflunomide monotherapy in rheumatoid arthritis: towards the gaols of disease modifying antirheumatic drug therapy. J. Rheumatol., suppl., 2004, 71, 13-20.</p><p>Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp. Gerontol., 2004, 39(5), 687-699.</p><p>McDuffie F.C. Morbidity impact of rheumatoid arthritis on society. Am. J. Med., 1985, 21, 78(1A), 1-5.</p><p>Migita K., Miyashita Т., Maeda Y. et al. An active metabolite of leflunomide, A771726, inhibits the production of serum amyloid A protein in human hepato- cytes. Rheumatology, 2005, 44, 443-448.</p><p>Mikuls T.R., Saag K.G. Comorbidity in rheumatoid arthritis. Rheum. Dis. Clin. North Am., 2001, 27(2), 283-303.</p><p>Olivieri I., PalazzJC., PeruzG., PadulaA. Management issues with elderly-onset rheumatoid arthritis: an update. Drugs Aging, 2005, 22(10), 809-822.</p><p>Peltomaa R., Leirisalo-Repo М., Helve Т., Paimela L. Effect of age on 3 year outcome in early rheumatoid arthritis. J. Rheumatol., 2000, 27(3), 638-643.</p><p>Prakash A., Jarvis B. Leflunomide: a review of its use in active rheumatoid arthritis. Drugs, 1999, 58(6), 1137-1164.</p><p>Schmajuk G., Schneeweiss S., Katz J-N. et a I. Treatment of older adult patients diagnosed with rheumatoid arthritis: improved but not optimal. Arthr. Rheum., 2007, 57(6), 928-934.</p><p>Sebastiani M.,Giuggioli D., VespriniE. etal. Successful treatment with leflunomide of arthritis in systemic sclerosis patients. Rheumatology (Oxford), 2006, 45(9), 1175-1176.</p><p>Sihvonen S., Korpela М., Mustonen J. et al. Renal disease as a predictor of increased mortality among patients with rheumatoid arthritis. Nephron Clin. Pract., 2004, 96(4), 107-114.</p><p>Strand V., Cohen S., Schiff M. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Arch. Intern. Med, 1999, 159, 22, 2542-2550</p><p>Tutuncu Z., Reed G., Kremer J., Kavanaugh A. et al. Do patients with older-onset rheumatoid arthritis receive less aggressive treatment? Ann. Rheum. Dis., 2006, 65(9), 1226-1229</p><p>Van Schaardenburg D. Rheumatoid arthritis in the elderly. Prevalence and optimal management. Drugs Aging, 1995, 7(1), 30-37</p></div><br /><div><p>Амирджанова В. Н. Ревматоидный артрит с позиций оценки качества жизни больных. Тер. архив, 2007, 79(5), 15-20.</p><p>Гордеев А.В., Мутовина З.Ю., Насанкаева Е.К. Эффективное лечение системного склероза лефлуномидом. Тер. архив, 2005, 77(5), 57-58.</p><p>Диагностика и лечение ревматоидного артрита. Клинические рекомендации. Ревматология. Гл.ред. чл.-корр. РАМН Насонов Е.Л. М., ТЭОТАР-Медиа, 2006, 35.</p><p>Каратеев Д.Е., Олюнин Ю.А. О классификации ревматоидного артрита. Научно-практич. рев- матол., 2008, 1, 5-16.</p><p>Насонов Е.Л. Метотрексат: перспективы применения в ревматологии. М., Филоматис, 2005, 24, 25, 57, 117.</p><p>Arnett F.C., Edworthy S. М., Bloch D.A. et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthr. Rheum., 1988, 31, 315-324.</p><p>Berard A., Solomon D.H., Avorn J. Patterns of drug use in rheumatoid arthritis. J. Rheumatol., 2000, 27(7), 1648-1655.</p><p>Bressolle F., Bologna C., Kinowski J.M. et al. Effects of moderate renal insufficiency on pharmacokinetics of methotrexate in rheumatoid arthritis patients. Ann. Rheum. Dis., 1998, 57, 110-113.</p><p>Bukhari М., Lunt М., Barton A. et al. Increasing age at symptom onset is associated with worse radiological damage at presentation in patients with early inflammatory polyarthritis. Ann. Rheum. Dis., 2007, 66(3), 389-393</p><p>Callahan D. Meulen R.H., Topincova E.A. World Growing Old. The Coming Health Care Challenges. Washington, DC: Georgetown University Press, 1995, 1-6, 39, 53, 62-65, 74-78, 97-106.</p><p>Cohen S., Cannon G. W, SchiffM. Two-year, blinded, randomized, controlled trial of treatment of active rheumatoid arthritis with leflunomide compared with methotrexate. Arthr. Rheum., 2001, 44, 9, 1984— 1992</p><p>Farragher T.M., Lunt М., Bunn D.K. et al. Early functional disability predicts both all-cause and cardiovascular mortality in people with inflammatory polyarthritis: results from the Norfolk Arthritis Register. Ann. Rheum. Dis., 2007, 66(4), 486-492.</p><p>Filippini М., Bazzani C., Zingarelli S. et al. Anti- TNFalpha agents in elderly patients with rheumatoid arthritis: a study of a group of 105 over sixty five years old patients. Reumatismo, 2008, 60(1), 41-49.</p><p>Genevay S., Finckh A., Ciurea A. et al. Tolerance and effectiveness of anti-tumor necrosis factor a therapies in elderly patients with rheumatoid arthritis: a population-based study. Arthr. Rheum. 2007, 15, 57(4), 679-685.</p><p>Gossec L., Dougados М., Goupille P. et al. Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study. Ann. Rheum. Dis., 2004, 63(6), 675-680</p><p>Grimble R.F. Inflammatory response in the elderly. Curr. Opin. Clin. Nutr. Metab. Care, 2003, 6(1), 21-29.</p><p>Iwamoto М., Нотта S., Asano Y. etal. Administration of leflunomide to a patient with rheumatoid arthritis on haemodialysis. Scand. J. Rheumatol., 2005, 34(5), 410-411.</p><p>Smolen J. S., Emery P., Kalden J.R. etal. The efficacy of leflunomide monotherapy in rheumatoid arthritis: towards the gaols of disease modifying antirheumatic drug therapy. J. Rheumatol., suppl., 2004, 71, 13-20.</p><p>Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp. Gerontol., 2004, 39(5), 687-699.</p><p>McDuffie F.C. Morbidity impact of rheumatoid arthritis on society. Am. J. Med., 1985, 21, 78(1A), 1-5.</p><p>Migita K., Miyashita Т., Maeda Y. et al. An active metabolite of leflunomide, A771726, inhibits the production of serum amyloid A protein in human hepato- cytes. Rheumatology, 2005, 44, 443-448.</p><p>Mikuls T.R., Saag K.G. Comorbidity in rheumatoid arthritis. Rheum. Dis. Clin. North Am., 2001, 27(2), 283-303.</p><p>Olivieri I., PalazzJC., PeruzG., PadulaA. Management issues with elderly-onset rheumatoid arthritis: an update. Drugs Aging, 2005, 22(10), 809-822.</p><p>Peltomaa R., Leirisalo-Repo М., Helve Т., Paimela L. Effect of age on 3 year outcome in early rheumatoid arthritis. J. Rheumatol., 2000, 27(3), 638-643.</p><p>Prakash A., Jarvis B. Leflunomide: a review of its use in active rheumatoid arthritis. Drugs, 1999, 58(6), 1137-1164.</p><p>Schmajuk G., Schneeweiss S., Katz J-N. et a I. Treatment of older adult patients diagnosed with rheumatoid arthritis: improved but not optimal. Arthr. Rheum., 2007, 57(6), 928-934.</p><p>Sebastiani M.,Giuggioli D., VespriniE. etal. Successful treatment with leflunomide of arthritis in systemic sclerosis patients. Rheumatology (Oxford), 2006, 45(9), 1175-1176.</p><p>Sihvonen S., Korpela М., Mustonen J. et al. Renal disease as a predictor of increased mortality among patients with rheumatoid arthritis. Nephron Clin. Pract., 2004, 96(4), 107-114.</p><p>Strand V., Cohen S., Schiff M. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Arch. Intern. Med, 1999, 159, 22, 2542-2550</p><p>Tutuncu Z., Reed G., Kremer J., Kavanaugh A. et al. Do patients with older-onset rheumatoid arthritis receive less aggressive treatment? Ann. Rheum. Dis., 2006, 65(9), 1226-1229</p><p>Van Schaardenburg D. Rheumatoid arthritis in the elderly. Prevalence and optimal management. Drugs Aging, 1995, 7(1), 30-37</p></div><br />

The authors declare that there are no conflicts of interest present.