rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2015-200-204rsp-2076Research ArticleОБЗОРREVIEWБЕЗОПАСНОСТЬ ГОЛИМУМАБА ПО ДАННЫМ КЛИНИЧЕСКИХ ИССЛЕДОВАНИЙGOLIMUMAB SAFETY ACCORDING TO CLINICAL FINDINGSЛукинаГ. В.LukinaG. V.

Contact: Galina Lukina; gvl3@yandex.ru

gvl3@yandex.ruСигидинЯ. А.SigidinYa. A.

Contact: Galina Lukina; gvl3@yandex.ru

gvl3@yandex.ruНаучноисследовательский институт ревматологии им. В.А. Насоновой, МоскваРоссияV.A. Nasonova Research Institute of Rheumatology, MoscowRussian Federation201529042015532200204Copyright © Лукина Г.В., Сигидин Я.А., 20152015Лукина Г.В., Сигидин Я.А.Lukina G.V., Sigidin Y.A.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/2076

В обзоре представлен  анализ исследований, посвященных безопасности применения голимумаба (ГЛМ) в ревматологии. Этот препарат был последним  внедренным в практику ингибитором ФНОα, и поэтому оценка его переносимости особенно  актуальна. Полученные в ходе крупных клинических исследований данные свидетельствуют о благоприятном профиле  безопасности ГЛМ. Наиболее  частыми нежелательными реакциями (НР) были инфекции, в большинстве случаев нетяжелые.  Частота инфекций при назначении ГЛМ в дозе 100 мг была выше, чем при его применении в дозе 50 мг. Общая частота злокачественных опухолей за период наблюдения до 160 нед не повысилась. Однако частота лимфом среди получавших ГЛМ в дозе 100 мг оказалась  выше по сравнению с ГЛМ в дозе 50 мг, общей популяцией и особенно  с группой плацебо. НР были равномерно распределены  среди пациентов с ревматоидным артритом,  псориатическим артритом и анкилозирующим спондилитом. В целом полученные данные соответствуют материалам  о безопасности ранее применявшихся ингибиторов ФНОα. Каких-либо принципиально новых НР не встретилось.  Необходимо накапливать данные по применению ГЛМ в условиях реальной клинической практики, что позволит более объективно  определить его место в современной терапии ревматических заболеваний.

                                                     The review analyzes trials dealing with the safety of golimumab (GLM)  used in rheumatology.  This drug was the latest

 

 

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Поступила 12

Поступила 12.05.14

tumor necrosis factor α (TNF-α) inhibitor introduced  into clinical practice and therefore the estimation of its tolerability is particularly relevant. The data obtained in large-scale clinical trials suggest that GLM has a good safety profile. The most common  adverse events (AE) were infections, more often mild. The rate of infections was higher with the use of GLM 100 mg than with that of 50 mg. The overall cancer rate did not increase during a follow-up of less than 160 weeks. However, the rate of lymphomas in patients receiving GLM 100 mg proved to be higher than in those taking GLM 50 mg, in the general population, and in the placebo group in particular. AE were evenly distributed among patients with rheumatoid  arthritis, psoriatic arthritis, or ankylosing spondylitis. Overall, the findings are in agreement with the data on the safety of previously used TNF-α inhibitors. No fundamentally new AE have been encountered. It is necessary to accumulate  data on the use of GLM in real clinical practice, which will be able to more objectively define its place in the current therapy of rheumatic diseases.

голимумаббезопасностьнежелательные реакцииревматические заболеванияsafetyadverse eventsrheumatic diseasesReferencesSmolen JS, Aletaha D, Koeller M, et al. New therapies for treatment of rheumatoid arthritis. Lancet. 2007;370:1861–74. doi: 10.1016/S0140-6736(07)60784-3Smolen JS, Aletaha D, Koeller M, et al. New therapies for treatment of rheumatoid arthritis. Lancet. 2007;370:1861–74. doi: 10.1016/S0140-6736(07)60784-3Насонов ЕЛ. Перспективы лечения ревматических заболеваний в начале 21 века. Терапевтический архив. 2011;(5):5–9. [Nasonov EL. Prospects for treatment of rheumatic diseases in the early 21st century. Terapevticheskii arkhiv. 2011;(5):5–9. (In Russ.)].Насонов ЕЛ. Перспективы лечения ревматических заболеваний в начале 21 века. Терапевтический архив. 2011;(5):5–9. [Nasonov EL. Prospects for treatment of rheumatic diseases in the early 21st century. Terapevticheskii arkhiv. 2011;(5):5–9. (In Russ.)].Feldman M, Maini RN. Role of cytokines in rheumatoid arthritis: an education in pathophysiology ant therapeutics. Immunol Rev. 2008;223:7–19. doi: 10.1111/j.1600-065X.2008.00626.xFeldman M, Maini RN. Role of cytokines in rheumatoid arthritis: an education in pathophysiology ant therapeutics. Immunol Rev. 2008;223:7–19. doi: 10.1111/j.1600-065X.2008.00626.xTaylor PC. Pharmacology of TNF blockade in rheumatoid arthritis and other chronic inflammatory diseases. Curr Opin Pharmacol. 2010;10:308–15. doi: 10.1016/j.coph.2010.01.005Taylor PC. Pharmacology of TNF blockade in rheumatoid arthritis and other chronic inflammatory diseases. Curr Opin Pharmacol. 2010;10:308–15. doi: 10.1016/j.coph.2010.01.005Насонов ЕЛ. Место голимумаба при ревматоидном артрите. Научно-практическая ревматология. 2012;51(Прил. 3):2–10. [Nasonov EL. Place of golimumab in rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2012;51(Прил. 3):2–10. (In Russ.)].Насонов ЕЛ. Место голимумаба при ревматоидном артрите. Научно-практическая ревматология. 2012;51(Прил. 3):2–10. [Nasonov EL. Place of golimumab in rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2012;51(Прил. 3):2–10. (In Russ.)].Эрдес ШФ. Применение голимумаба при анкилозирующем спондилите. Научно-практическая ревматология. 2012;51(Прил. 3):11–6. [Erdes ShF. The use of golimumab in ankylosing spondylitis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2012;51(Прил. 3):11–6. (In Russ.)].Эрдес ШФ. Применение голимумаба при анкилозирующем спондилите. Научно-практическая ревматология. 2012;51(Прил. 3):11–6. [Erdes ShF. The use of golimumab in ankylosing spondylitis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2012;51(Прил. 3):11–6. (In Russ.)].Коротаева ТВ. Результаты оценки эффективности и безопасности голимумаба — нового ингибитора фактора некроза опухоли альфа в лечении псориатического артрита. Научно-практическая ревматология. 2012;51(Прил. 3):17–22. [Korotaeva TV. The results of evaluation of the effectiveness and safety of golimumab – new inhibitor of tumor necrosis factor Alfa treatment of psoriatic arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2012;51(Прил. 3):17–22. (In Russ.)].Коротаева ТВ. Результаты оценки эффективности и безопасности голимумаба — нового ингибитора фактора некроза опухоли альфа в лечении псориатического артрита. Научно-практическая ревматология. 2012;51(Прил. 3):17–22. [Korotaeva TV. The results of evaluation of the effectiveness and safety of golimumab – new inhibitor of tumor necrosis factor Alfa treatment of psoriatic arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2012;51(Прил. 3):17–22. (In Russ.)].Beevor CP, Hull R, Thomas A, et al. Anti TNFa therapy reduce emergency health services usage. Ann Rheum Dis. 2006;65 Suppl II:176.Beevor CP, Hull R, Thomas A, et al. Anti TNFa therapy reduce emergency health services usage. Ann Rheum Dis. 2006;65 Suppl II:176.Gomez-Reino JJ, Dasgupta B, Haugeberg G, et al. Mortality rate is reduced in RA patients treated with TNF antagonists. Data from Biobadaser. Ann Rheum Dis. 2006;65 Suppl II:318.Gomez-Reino JJ, Dasgupta B, Haugeberg G, et al. Mortality rate is reduced in RA patients treated with TNF antagonists. Data from Biobadaser. Ann Rheum Dis. 2006;65 Suppl II:318.Abbott Laboratories. Humira (adalimumab) [highlights of prescribing information]. Last revised September 2012. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/12505 7s232lbl.pdf (accessed 17 Apr 2013).Abbott Laboratories. Humira (adalimumab) [highlights of prescribing information]. Last revised September 2012. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/12505 7s232lbl.pdf (accessed 17 Apr 2013).UCB Inc. Cimzia (certolizumab) [highlights of prescribing information]. Last revised November 2012. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/12516 0s189lbl.pdf (accessed 17 Apr 2013).UCB Inc. Cimzia (certolizumab) [highlights of prescribing information]. Last revised November 2012. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/12516 0s189lbl.pdf (accessed 17 Apr 2013).Amgen Wyeth, manufactured by Immunex. Enbrel (etanercept) [highlights of prescribing information]. Last revised December 2012. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103795s5507lbl.pdf (accessed 17 Apr 2013).Amgen Wyeth, manufactured by Immunex. Enbrel (etanercept) [highlights of prescribing information]. Last revised December 2012. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103795s5507lbl.pdf (accessed 17 Apr 2013).Janssen Biotech, Inc. Remicade (infliximab) [highlights of prescribing information]. Last revised March 2013. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/103772s5345lbl.pdf (accessed 17 Apr 2013).Janssen Biotech, Inc. Remicade (infliximab) [highlights of prescribing information]. Last revised March 2013. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/103772s5345lbl.pdf (accessed 17 Apr 2013).Zhou H, Xu Z, Rahman MU, et al. Exposure-efficacy assessment of golimumab in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2006;65:514.Zhou H, Xu Z, Rahman MU, et al. Exposure-efficacy assessment of golimumab in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2006;65:514.Smolen J, Kay J, Doyle MK, et al. Golimumab, a new human anti-TNF-alpha monoclonal antibody. Ann Rheum Dis. 2008;67 Suppl II:50–1.Smolen J, Kay J, Doyle MK, et al. Golimumab, a new human anti-TNF-alpha monoclonal antibody. Ann Rheum Dis. 2008;67 Suppl II:50–1.Keystone E, Genovese MC, Klareskog L, et al. Golimumab, a new human anti-TNF-alpha monoclonal antibody. Ann Rheum Dis. 2009;68:789–96. doi: 10.1136/ard.2008.099010Keystone E, Genovese MC, Klareskog L, et al. Golimumab, a new human anti-TNF-alpha monoclonal antibody. Ann Rheum Dis. 2009;68:789–96. doi: 10.1136/ard.2008.099010Kay J, Fleischmann R, Keystone E, et al. Golimumab 3-year safety update: an analysis of pooled data from the long-term extensions of randomised, double-blind, placebo-controlled trials conducted in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. Ann Rheum Dis. Published Online First: doi: 10.1136/ annrheumdis-2013-204195Kay J, Fleischmann R, Keystone E, et al. Golimumab 3-year safety update: an analysis of pooled data from the long-term extensions of randomised, double-blind, placebo-controlled trials conducted in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. Ann Rheum Dis. Published Online First: doi: 10.1136/ annrheumdis-2013-204195Gomez-Reino JJ, Carmona L, Valverde VR, et al. Treatment of rheumatoid arthritis wth tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum. 2003;48:2122–7. doi: 10.1002/art.11137Gomez-Reino JJ, Carmona L, Valverde VR, et al. Treatment of rheumatoid arthritis wth tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum. 2003;48:2122–7. doi: 10.1002/art.11137Насонов ЕЛ, Козлов РС, Якушин СБ. Инфекционные осложнения терапии блокаторами фактора некроза опухоли: предупрежден – значит вооружен. Клиническая микробиология и антимикробная химиотерапия.Насонов ЕЛ, Козлов РС, Якушин СБ. Инфекционные осложнения терапии блокаторами фактора некроза опухоли: предупрежден – значит вооружен. Клиническая микробиология и антимикробная химиотерапия.;(4):1–11. [Nasonov EL, Kozlov RS, Yakushin SB. Infectious complications of therapy of tumor necrosis factor blockers: forewarned – is forearmed. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya. 2006;(4):1–11. (In Russ.)].;(4):1–11. [Nasonov EL, Kozlov RS, Yakushin SB. Infectious complications of therapy of tumor necrosis factor blockers: forewarned – is forearmed. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya. 2006;(4):1–11. (In Russ.)].Furst DE, Keystone EC, Fleischmann R, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2009. Ann Rheum Dis. 2010;69 Suppl:i2–29. doi: 10.1136/ard.2009.123885Furst DE, Keystone EC, Fleischmann R, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2009. Ann Rheum Dis. 2010;69 Suppl:i2–29. doi: 10.1136/ard.2009.123885Cellestis. QuantiFERON-TB Gold clinicians guide and QuantiFERON-TB Gold In-Tube method package insert. Available from: www.cellestis.comCellestis. QuantiFERON-TB Gold clinicians guide and QuantiFERON-TB Gold In-Tube method package insert. Available from: www.cellestis.comOxford Immunotec. T-SPOT.TB. Available from: http://www.oxford immunotec.com/T-SPOT_InternationalOxford Immunotec. T-SPOT.TB. Available from: http://www.oxford immunotec.com/T-SPOT_InternationalHsia E, Cush J, Eric L, et al. Comprehensive tuberculosis screening program in patients with inflammatory arthritides treated with golimumab, a human anti-tumor necrosis factor antibody, in phase III clinical trials. Arthritis Care Res. 2013 Feb;65(2):309–13. doi: 10.1002/acr.21788Hsia E, Cush J, Eric L, et al. Comprehensive tuberculosis screening program in patients with inflammatory arthritides treated with golimumab, a human anti-tumor necrosis factor antibody, in phase III clinical trials. Arthritis Care Res. 2013 Feb;65(2):309–13. doi: 10.1002/acr.21788Carmona L, Gomez-Reino JJ, Rodriguez-Valverde V, et al.; on behalf of the BIOBADASER Group. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum. 2005;52:1766–72. doi: 10.1002/art.21043Carmona L, Gomez-Reino JJ, Rodriguez-Valverde V, et al.; on behalf of the BIOBADASER Group. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum. 2005;52:1766–72. doi: 10.1002/art.21043Available from: www.who.int/tb/country/data/download/en/index.htmlAvailable from: www.who.int/tb/country/data/download/en/index.htmlJanssen Biotech, Inc. Simponi (golimumab) [highlights of prescribing information]. Last revised November 2012. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125289s070lbl.pdf (accessed 17 Apr 2013).Janssen Biotech, Inc. Simponi (golimumab) [highlights of prescribing information]. Last revised November 2012. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125289s070lbl.pdf (accessed 17 Apr 2013).Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev 2011;2:CD008794. doi: 10.1002/14651858.CD008794.pub2Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev 2011;2:CD008794. doi: 10.1002/14651858.CD008794.pub2Kay J, Rahman MU. Golimumab: A novel human anti-TNFalpha monoclonal antibody for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Core Evid. 2010;4:159–70.Kay J, Rahman MU. Golimumab: A novel human anti-TNFalpha monoclonal antibody for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Core Evid. 2010;4:159–70.

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