rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2005-617rsp-755Research ArticleСтатьиArticlesЭффективность и переносимость сульфасалазина при ревматических заболеванияхSulfasalazine efficacy and tolerability in rheumatic diseasesБадокинВ. В.BadokinV. V.-200515082005434№4 (2005)4752Copyright © Бадокин В.В., 20052005Бадокин В.В.Badokin V.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/755

Резюме Сульфасалазин является одним из основных болезнь-модифицирующих препаратов в лечении хронических воспалительных заболеваний суставов и позвоночника. В статье представлен механизм действия сульфасалазина и его активных метаблитов. Детально рассматриваются пути реализации антивоспали- тельного и иммуносупрессивного действия препарата. Приводятся результаты многочисленных исследований по эффективности сульфасалазина при ревматоидном артрите, анкилозируюшем спондилоа- ртрите, псориатическом артрите и реактивных артритах с позиций доказательной медицины. Приводятся данные по переносимости и безопасности сульфасалазина с выделением гиперчувствитсльных и дозозависимых побочных реакций, а также конкретные мероприятия по их устранению и профилактике.

Sulfasalazine is one of the main disease modifying drugs for the treatment of chronic inflammatory joint and spine diseases. The article describes mechanism of action of sulfasalazine and its main metabolites. Detailed information about anti-inflammatory and immunosuppressive action of the drug is presented. Results of many studies of sulfasalazine efficacy in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and reactive arthritis are discussed from the evidence based medicine point of view. Data on sulfasalazine tolerability and safety are presented with separate discussion of hypersensitivity and dose-dependent adverse reactions so as their treatment and prophylaxis.

сульфасалазинболезнь-модифицирующая терапияревматоидный артритсеронегативные спондилоартритыsulfasalazinedisease modifying drugsrheumatoid arthritisseronegative spondyloarthritidesReferences<div><p>Насонова ВА., Насонов ЕЛ. Рациональная фармакотерапия ревматических заболеваний. М., Литтерра, 2003.</p><p>Сигидин Я.А., Г.ВЛукина. Ревматоидный артрит. М., 2001.</p><p>American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis. 2002 Update. Arthr. Rheum., 2002, 46, 328-346.</p><p>Azulfidine, EN-Tabs. In: Physicians Desk Reference, Medical Economics Company, 52nd ed. Montvale, NJ, 1998, 2239.</p><p>Boers М., 4’rhoeven A.C., Marcusse H.M. et al. Randomised comparison of combinet step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet, 1997,350, 1568-1573.</p><p>Box S.A., Pullar T. Sulphasalazine in the treatment of rheumatoid arthritis. Br. J. Rheumatol., 1997, 36, 382.</p><p>Brandt J., Buss B., SieperJ., Braun J. Efficacy of treatment with sulphasalazine versus azathioprine in ankylosing spondylitis. J. Rheumatol., 2000, 27, suppl. 59, I82-1S4.</p><p>Calin A., Taurog J.D. Spondylarthritides. Oxford University Press, 1998.</p><p>Clegg D.O., Reda D.J., Mejias E. et al. Comparison of sulfasalazine and placebo for the treatment of psoriatic arthritis and cutaneous psoriasis. Arthr. Rheum., 1996, 39, 2013-2020.</p><p>Clegg D.O., Reda D.J., Wfeisman M.N. et al. Comparison of sulphasalazine and placebo in the treatment of reactive arthritis (Reiter s syndrome). A Department of feterans Affairs Cooperative study. Arthr. Rheum., 1996, 39, 2021-2027.</p><p>Clegg L.J, Reda D.J, Abdellatif M. Comparison of sulphasalazine for the treatment and placebo of axial and peripher- ial articular manifestations of the seronegative spondyloarthropathies. Arthr. Rheum., 1999, 42, 2325-2329.</p><p>Combe B., Goupill P., Kunntz J.L. et al. Sulphasalazine in psoriatic arthritis: a rondomized, multicentre, placebo-controlled study. BrJ.Rheumatol., 1996, 35, 664-668.</p><p>Conell W, Miller A. Treating inflammatory bowel disease during pregnance. Risks and safety of drug therapy. Drug Safety, 1999,4, 311-323.</p><p>Dougados М., Dijrmans B., Khan M. et al. Conventional treatments for ankylosing spondylitis. Ann. Rheum. Dis. 2002, 61,suppl. 111,40-50.</p><p>Dougados M. Sulfasalazine. In: Therapy of Systemic Rheumatic Disorders, van de Putte, LBA, Furst, DE, Williams, HJ, van Riel, PLCM, (Eds), Marcel Dekker, New York, 1998.</p><p>Dougados M, van der Linden S., Leirisalo-Repo M. et al. Sulfasalazine in the treatment of spondyloarthropathy. A randomized, multicenter, double-blind, placebo-controlled study. Arthr. Rheum., 1995, 38,618-627.</p><p>Egsmose C., Hansen Т., Andersen L.S. et al. Limited effect of sulphasalazine treatment in reactive arthritis. A randomised double blind placebo controlled trial. Ann. Rheum. Dis., 1997, 56, 32-36.</p><p>Ferraz MB, Tugwell P, Goldsmith CH, Atra E. Meta-analysis of sulfasalazine in ankylosing spondylitis. J. Rheumatol., 1990,17,1482-1486.</p><p>Fraser S.M., Hopkins R., Hunter J.A. Sulphazalazine in the management of psoriatic arthritis. Br. J. Rheumatol., 1993, 32, 923-925.</p><p>Fuchs, H.A. Use of sulfasalazine in rheumatic diseases. Bull. Rheum. Dis., 1997, 46, 3.</p><p>Gladman D.D. Effictiveness of psoriatic arthritis. Sem. Arthr. Rheum., 2003, 33. 29-31.</p><p>Gupta A.K., Grober J.S., Hamilton T.A. et al. Sulphasalazine therapy for psoriatic arthritis: a double blind placebo controlled trial. J.Rheumatol., 1995, 22, 894-898.</p><p>Haagsma C.J., van Riel P.L., De Jong A.J., van de Putte L.B. Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, double-blind, 52 week clinical trial. Br. J. Rheumatol., 1997,36,1082.</p><p>Hannoncn P., Mottinen Т., Hakola М., Oka M. Sulfasalazine in early rheumatoid arthritis: A 48 week double-blind prospective, placebo-controlled study. Arthr. Rheum. 1993,36,1501.</p><p>Jones G, Crotty M, Brooks P. Interventions for treating psoriatic arthritis. Cochrane Database Syst. Rev., 2000,3, CD000212.</p><p>Mottonen Т., Hannonen P. Leirisalo-Repo M. et al. Comparison of combination therapy with single in early rheumatoid arthritis. Lancet. 1999, 353, 1568-1573.</p><p>Nash P., Clegg D.O. Psoriatic arthritis therapy: NSAlDs and traditional DMARDs. Ann. Rheum. Dis., 2005,64, suppl. II, 7477.</p><p>О Dell J., Yaire S., Erikson N. et al. Triple DMARD therapy for rheumatoid arthritis is well tolerated. Arthr. Rheum., 1994, suppl. 10, 37.</p><p>Peppercorn M.A. Sulphasalazine: pharmacology, clinical use, toxicity and related new drug development. Ann. Intern. Med., 1984, 101,377-386.</p><p>Rahman P., Gladman D.D., Thome J.C. et al. The use sulphasalazine in psoriatic arthritis: a clinical experience. J. Rheumatol., 1998.25, 1957-1961.</p><p>Rains C.P., Noble S., Faulds D. Sulphasalazine. A review of its pharmacological properties and theraupetic efficacy in the treatment of rheumatoid arthritis. Drugs, 1995, 50, 137-156.</p><p>Rodenburg R.J., Ganga A., van Lent PL. et al. The antiinflammatory drug sulfasalazine inhibits tumor necrosis factor alpha expression in macrophages by inducing apoptosis. Arthr, Rheum., 2000, 43. 1941.</p><p>SieperJ., Braun J., Rudwaleit M. et al. Ankylosing spondylitis: an overview. Ann. Rheum. Dis. 2002, 61, suppl. 111,8-18.</p><p>Salvarani C., Macchioni P., Olivieri I. et al. A comparison of cyclosporine, sulphasala-zine and symptomatic therapy in the treatment of psoriatic arthritis. J. Rheumatol., 2001, 28, 22742282.</p><p>SmolenJ.S., Kalden J.R., Scott D.L. etal. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group. Lancet, 1999, 353. 259.</p><p>Taggard A.J., Gardiner P.V., Me Ewoy F.M. et al. Which is active moiety of sulphasalazine in ankylosing spondylitis? Arthr. Rheum., 1996, 39, 1400-1405.</p><p>Tanaka Е., Taniguchi A., Urano W. et al. Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene. J. Rheumatol., 2002, 29, 2492.</p><p>&amp;n der Heijde D.M., van Riel., P.L., Nuver-Zvart H.H., van de Putte L.B. Sulphasalazine versus hydroxychloroquine in rheumatoid arthritis: 3-year follow-up. Lancet, 1990, 335, 539.</p><p>Wahl C., Lipty S., Adler G., Schmid R.M. Sulfasalazine, a potent and specific inhibitor of nuclear factor kappa Br. J. Clin. Invest., 1998, 101, 1163.</p><p>Wteinblatt M.E., Reda D., Henderson W. et al. Sulphasalazine treatment for rheumatoid arthritis: a metaanalysis of 15 randomized trials. J. Rheumatol., 1999, 26, 2123.</p></div><br /><div><p>Насонова ВА., Насонов ЕЛ. Рациональная фармакотерапия ревматических заболеваний. М., Литтерра, 2003.</p><p>Сигидин Я.А., Г.ВЛукина. Ревматоидный артрит. М., 2001.</p><p>American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis. 2002 Update. Arthr. Rheum., 2002, 46, 328-346.</p><p>Azulfidine, EN-Tabs. In: Physicians Desk Reference, Medical Economics Company, 52nd ed. Montvale, NJ, 1998, 2239.</p><p>Boers М., 4’rhoeven A.C., Marcusse H.M. et al. Randomised comparison of combinet step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet, 1997,350, 1568-1573.</p><p>Box S.A., Pullar T. Sulphasalazine in the treatment of rheumatoid arthritis. Br. J. Rheumatol., 1997, 36, 382.</p><p>Brandt J., Buss B., SieperJ., Braun J. Efficacy of treatment with sulphasalazine versus azathioprine in ankylosing spondylitis. J. Rheumatol., 2000, 27, suppl. 59, I82-1S4.</p><p>Calin A., Taurog J.D. Spondylarthritides. Oxford University Press, 1998.</p><p>Clegg D.O., Reda D.J., Mejias E. et al. Comparison of sulfasalazine and placebo for the treatment of psoriatic arthritis and cutaneous psoriasis. Arthr. Rheum., 1996, 39, 2013-2020.</p><p>Clegg D.O., Reda D.J., Wfeisman M.N. et al. Comparison of sulphasalazine and placebo in the treatment of reactive arthritis (Reiter s syndrome). A Department of feterans Affairs Cooperative study. Arthr. Rheum., 1996, 39, 2021-2027.</p><p>Clegg L.J, Reda D.J, Abdellatif M. Comparison of sulphasalazine for the treatment and placebo of axial and peripher- ial articular manifestations of the seronegative spondyloarthropathies. Arthr. Rheum., 1999, 42, 2325-2329.</p><p>Combe B., Goupill P., Kunntz J.L. et al. Sulphasalazine in psoriatic arthritis: a rondomized, multicentre, placebo-controlled study. BrJ.Rheumatol., 1996, 35, 664-668.</p><p>Conell W, Miller A. Treating inflammatory bowel disease during pregnance. Risks and safety of drug therapy. Drug Safety, 1999,4, 311-323.</p><p>Dougados М., Dijrmans B., Khan M. et al. Conventional treatments for ankylosing spondylitis. Ann. Rheum. Dis. 2002, 61,suppl. 111,40-50.</p><p>Dougados M. Sulfasalazine. In: Therapy of Systemic Rheumatic Disorders, van de Putte, LBA, Furst, DE, Williams, HJ, van Riel, PLCM, (Eds), Marcel Dekker, New York, 1998.</p><p>Dougados M, van der Linden S., Leirisalo-Repo M. et al. Sulfasalazine in the treatment of spondyloarthropathy. A randomized, multicenter, double-blind, placebo-controlled study. Arthr. Rheum., 1995, 38,618-627.</p><p>Egsmose C., Hansen Т., Andersen L.S. et al. Limited effect of sulphasalazine treatment in reactive arthritis. A randomised double blind placebo controlled trial. Ann. Rheum. Dis., 1997, 56, 32-36.</p><p>Ferraz MB, Tugwell P, Goldsmith CH, Atra E. Meta-analysis of sulfasalazine in ankylosing spondylitis. J. Rheumatol., 1990,17,1482-1486.</p><p>Fraser S.M., Hopkins R., Hunter J.A. Sulphazalazine in the management of psoriatic arthritis. Br. J. Rheumatol., 1993, 32, 923-925.</p><p>Fuchs, H.A. Use of sulfasalazine in rheumatic diseases. Bull. Rheum. Dis., 1997, 46, 3.</p><p>Gladman D.D. Effictiveness of psoriatic arthritis. Sem. Arthr. Rheum., 2003, 33. 29-31.</p><p>Gupta A.K., Grober J.S., Hamilton T.A. et al. Sulphasalazine therapy for psoriatic arthritis: a double blind placebo controlled trial. J.Rheumatol., 1995, 22, 894-898.</p><p>Haagsma C.J., van Riel P.L., De Jong A.J., van de Putte L.B. Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, double-blind, 52 week clinical trial. Br. J. Rheumatol., 1997,36,1082.</p><p>Hannoncn P., Mottinen Т., Hakola М., Oka M. Sulfasalazine in early rheumatoid arthritis: A 48 week double-blind prospective, placebo-controlled study. Arthr. Rheum. 1993,36,1501.</p><p>Jones G, Crotty M, Brooks P. Interventions for treating psoriatic arthritis. Cochrane Database Syst. Rev., 2000,3, CD000212.</p><p>Mottonen Т., Hannonen P. Leirisalo-Repo M. et al. Comparison of combination therapy with single in early rheumatoid arthritis. Lancet. 1999, 353, 1568-1573.</p><p>Nash P., Clegg D.O. Psoriatic arthritis therapy: NSAlDs and traditional DMARDs. Ann. Rheum. Dis., 2005,64, suppl. II, 7477.</p><p>О Dell J., Yaire S., Erikson N. et al. Triple DMARD therapy for rheumatoid arthritis is well tolerated. Arthr. Rheum., 1994, suppl. 10, 37.</p><p>Peppercorn M.A. Sulphasalazine: pharmacology, clinical use, toxicity and related new drug development. Ann. Intern. Med., 1984, 101,377-386.</p><p>Rahman P., Gladman D.D., Thome J.C. et al. The use sulphasalazine in psoriatic arthritis: a clinical experience. J. Rheumatol., 1998.25, 1957-1961.</p><p>Rains C.P., Noble S., Faulds D. Sulphasalazine. A review of its pharmacological properties and theraupetic efficacy in the treatment of rheumatoid arthritis. Drugs, 1995, 50, 137-156.</p><p>Rodenburg R.J., Ganga A., van Lent PL. et al. The antiinflammatory drug sulfasalazine inhibits tumor necrosis factor alpha expression in macrophages by inducing apoptosis. Arthr, Rheum., 2000, 43. 1941.</p><p>SieperJ., Braun J., Rudwaleit M. et al. Ankylosing spondylitis: an overview. Ann. Rheum. Dis. 2002, 61, suppl. 111,8-18.</p><p>Salvarani C., Macchioni P., Olivieri I. et al. A comparison of cyclosporine, sulphasala-zine and symptomatic therapy in the treatment of psoriatic arthritis. J. Rheumatol., 2001, 28, 22742282.</p><p>SmolenJ.S., Kalden J.R., Scott D.L. etal. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group. Lancet, 1999, 353. 259.</p><p>Taggard A.J., Gardiner P.V., Me Ewoy F.M. et al. Which is active moiety of sulphasalazine in ankylosing spondylitis? Arthr. Rheum., 1996, 39, 1400-1405.</p><p>Tanaka Е., Taniguchi A., Urano W. et al. Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene. J. Rheumatol., 2002, 29, 2492.</p><p>&amp;n der Heijde D.M., van Riel., P.L., Nuver-Zvart H.H., van de Putte L.B. Sulphasalazine versus hydroxychloroquine in rheumatoid arthritis: 3-year follow-up. Lancet, 1990, 335, 539.</p><p>Wahl C., Lipty S., Adler G., Schmid R.M. Sulfasalazine, a potent and specific inhibitor of nuclear factor kappa Br. J. Clin. Invest., 1998, 101, 1163.</p><p>Wteinblatt M.E., Reda D., Henderson W. et al. Sulphasalazine treatment for rheumatoid arthritis: a metaanalysis of 15 randomized trials. J. Rheumatol., 1999, 26, 2123.</p></div><br />

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