Выживаемость при генно-инженерной биологической терапии у бионаивных больных ревматоидным артритом: данные ретроспективного 12-месячного наблюдения
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Aronova E.S., Lukina G.V., Glukhova S.I., et al. Survival of bDMARDs in bionaive patients with rheumatoid arthritis: data from a retrospective 12-month follow-up. Therapeutic Archive. 2020; 92 (5): 39–45. DOI: 10.26442/00403660.2020.05.000630
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Материалы и методы. В ретроспективное исследование включены 204 взрослых пациента с достоверным диагнозом РА.
В условиях стационара больным впервые назначена терапия различными генно-инженерными биологическими препаратами (ГИБП): инфликсимабом, адалимумабом, этанерцептом, цертолизумабом пеголом, тоцилизумабом, абатацептом (АБА), ритуксимабом (РТМ). Пациенты разделены по возрасту в соответствии с классификацией, принятой Всемирной организацией здравоохранения. Клинические формы РА представлены: РА, серопозитивным по ревматоидному фактору, РА, серонегативным по ревматоидному фактору, РА с внесуставными проявлениями, болезнью Стилла, РА с ювенильным началом. Причины отмены ГИБП в течение первого года лечения: недостаточная эффективность (в том числе первичная неэффективность), нежелательные реакции, административные причины, клинико-лабораторная ремиссия, смерть.
Результаты. Через год с момента включения в исследование 92 (45%) больных продолжали ГИБТ и у 112 лечение прекращено. Среднее время терапии составило 0,75±0,33 года. Наибольшая продолжительность лечения – в группах РТМ и АБА (0,92±0,22 и 0,83±0,29 года соответственно). У 56 (50%) больных ГИБП отменен в связи с недостаточной эффективностью (включая первичную неэффективность), 28 (25%) – вследствие развития нежелательных реакций, 19 (17%) – по административным причинам, 7 (6,25%) – в связи с медикаментозной ремиссией. В течение первого года терапии зарегистрировано 2 (1,75%) случая смерти в связи с тяжелыми коморбидными состояниями у больных, один из которых получал РТМ, другой – тоцилизумаб.
Заключение. Данное исследование показало, что 45% больных РА продолжают лечение впервые назначенным ГИБП более 12 мес. Наиболее частой причиной прекращения терапии являлась ее недостаточная эффективность. Наилучшая выживаемость ГИБТ отмечалась на фоне РТМ и АБА. При подборе ГИБП в каждом случае необходимо учитывать преемственность на всех этапах лечения.
Ключевые слова: биологическая терапия, выживаемость, генно-инженерные биологические препараты, абатацепт, тоцилизумаб, ритуксимаб, инфликсимаб, ингибиторы фактора некроза опухоли a, нежелательные реакции, недостаточная эффективность, ревматоидный артрит.
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Aim. Analysis of survival on biological therapy in previously bionaive patients with rheumatoid arthritis (RA) during the first year of therapy in real clinical practice.
Materials and methods. The retrospective study included 204 adult patients with RA. In the hospital, patients were first prescribed therapy with various biological disease-modifying antirheumatic drugs (bDMARDs): infliximab, adalimumab, etanercept, certolizumab pegol, tocilizumab, abatacept (ABA), rituximab (RTM). Patients were divided by age in accordance with the classification adopted by WHO. Clinical forms of RA were presented: RA, seropositive for rheumatoid factor, RA, seronegative for rheumatoid factor, RA with extra-articular manifestations, adult-oneset Still's disease, juvenile RA. The reasons for the cancellation of bDMARD during the first year of treatment were: insufficient effectiveness (including primary inefficiency), adverse events, administrative reasons, clinical and laboratory remission, death.
Results. A year after being included in the study, treatment was continued in 92 (45%) patients and was discontinued in 112 patients. The average time of treatment amounted to 0.75±0.33 years. The longest duration of treatment was in the RTM and ABA groups (0.92±0.22 and 0.83±0.29 years, respectively). In 56 (50%) patients, bDMARD was canceled due to insufficient effectiveness (including primary inefficiency), 28 patients (25%) – due to the development of adverse reactions, 19 (17%) patients – for administrative reasons, 7 (6.25%) patients – due to drug remission. During the first year of therapy, there were 2 (1.75%) deaths due to severe comorbid conditions in patients, one of whom received RTM, the other – tocilizumab.
Conclusion. Study showed that 45% of patients with RA continue treatment with first-time bDMARD for more than 12 months. The most common reason for discontinuation of therapy was its lack of effectiveness. The best survival rate of bDMARDs was observed in RTM and ABA. When selecting bDMARD in each case, it is necessary to take into account the continuity at all stages of treatment.
Keywords: biological therapy, drug survival, gene-engineering biological drugs, bDMARDs, abatacept, tocilizumab, rituximab, infliximab, tumor necrosis factor-a blockers, adverse events, inefficacy, rheumatoid arthritis.
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5. Oldroyd AGS, Symmons DPM, Sergeant JC, et al. Long-term persistence with rituximab in patients with rheumatoid arthritis. Rheumatology (Oxford). 2018;57(6):1089-96. doi: 10.1093/rheumatology/key036
6. Narongroeknawin P, Chevaisrakul P, Kasitanon N, Kitumnuaypong T. Drug survival and reasons for discontinuation of the first biological disease modifying antirheumatic drugs in Thai patients with rheumatoid arthritis: Analysis from the Thai Rheumatic Disease Prior Authorization registry. Int J Rheum Dis. 2018;21(1):170-8. doi: 10.1111/1756-185X.12937
7. Лукина Г.В., Сигидин Я.А., Кузикянц К.Х. и др. Опыт применения ритуксимаба у больных ревматоидным артритом в реальной клинической практике по данным Российского регистра АРБИТР. Русский медицинский журнал. 2011;25:1518-23 [Lukina GV, Sigidin YA, Kuzikyants KH, et al. Opyt primenenia rituximaba u bolhyh revmatoidnym artritom v real`noy klinicheskoi praktike po dannym Rossiyskogo registra ARBITR. Russian Medical Journal. 2011;25:1518-23 (In Russ.)].
8. Лукина Г.В., Сигидин Я.А., Мазуров В.И., Насонов Е.Л. Ритуксимаб в реальной клинической практике: регистры Арбитр и CERERRA. В кн. под ред. Е.Л. Насонова: Генно-инженерные биологические препараты в лечении ревматоидного артрита. М.: ИМА-ПРЕСС, 2013; с. 362-9 [Lukina GV, Sigidin YA, Mazurov VI, Nasonov EL. Rituximab in real clinical practice: Arbiter and CERERRA registers. In the book under the editorship of E.L. Nasonova: Genetically engineered biologicals in the treatment of rheumatoid arthritis. Moscow: IMA-PRESS, 2013; p. 362-9 (In Russ.)].
9. Brodszky V, Bíró A, Szekanecz Z, et al. Determinants of biological drug survival in rheumatoid arthritis: evidence from a Hungarian rheumatology center over 8 years of retrospective data. ClinicoEconomics Outcomes Res. 2017;9:139-47. doi: 10.2147/ceor.s124381
10. Ebina K, Hashimoto M, Yamamoto W, et al. Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis. The ANSWER cohort study. Arthritis Res Ther. 2019;21:91. doi: 10.1186/s13075-019-1880-4
11. Papadopoulos CG, et al. Eight-year survival study of first-line tumour necrosis factor α inhibitors in rheumatoid arthritis: real-world data from a university center registry. Rheumatol Advanc Pract. 2019;3:1-11. doi: 10.1093/rap/rkz007
12. Ebina K, Hashimoto M, Yamamoto W, et al. Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis. The ANSWER cohort study. PLoS One. 2018;13(3):e0194130. doi: 10.1371/journal.pone.0194130
13. Bolge SC, Goren A, Tandon N. Reasons for discontinuation of subcutaneous biologic therapy in the treatment of rheumatoid arthritis: a patient perspective. Patient Prefer Adherence. 2015;9:121-31. doi: 10.2147/ppa.s70834
14. Strand V, Miller P, Williams SA, et al. Discontinuation of Biologic Therapy in Rheumatoid Arthritis: Analysis from the Corrona RA Registry. Rheumatol Ther. 2017;4:489. doi: 10.1007/s40744-017-0078-y
15. Kondo M, Yamada H. Drug survival rates of biological disease-modifying antirheumatic drugs and Janus kinase-inhibitor therapy in 801 rheumatoid arthritis patients: a 14 year-retrospective study from a rheumatology clinic in Japan. Modern Rheumatol. 2019;29(Issue 6). doi: 10.1080/14397595.2018.1537556
16. Souto A, Maneiro JR, Gómez-Reino JJ. Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and metaanalysis of drug registries and health care databases. Rheumatology (Oxford). 2016;55(3):523-34. doi: 10.1093/rheumatology/kev374
17. Wiens A, Borba HHL, Leonart LP, et al. Treatment interruption of biological drugs and tofacitinib in rheumatoid arthritis: a systematic review of case reports. Braz J Pharm Sci. 2018;54(4):e17437. doi: 10.1590/s2175-97902018000417437
18. Martínez-Santana V, González-Sarmiento E, Calleja-Hernández MA, Sánchez-Sánchez T. Comparison of drug survival rates for tumor necrosis factor antagonists in rheumatoid arthritis. Patient Prefer Adherence. 2013;7:719-27. doi: 10.2147/ppa.s47453
19. Murata K, Ito H, Hashimoto M, et al. Elderly onset of early rheumatoid arthritis is a risk factor for bone erosions, refractory to treatment: KURAMA cohort. Int J Rheum Dis. 2019;22(6):1084-93. doi: 10.1111/1756-185x.13428
20. Ishchenko A, Lories RJ. Safety and Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance. Drugs Aging. 2016;33(6):387-98. doi: 10.1007/s40266-016-0374-1
21. Ebina K, Hashimoto M, Yamamoto W, et al. Drug tolerability and reasons for discontinuation of seven biologics in elderly patients with rheumatoid arthritis. The ANSWER cohort study. PLoS One. 2019;14(5):e0216624. doi: 10.1371/journal.pone.0216624
22. Leon L, Gomez A, Vadillo C, et al. Severe adverse drug reactions to biological disease-modifying anti-rheumatic drugs in elderly patients with rheumatoid arthritis in clinical practice. Clin Exp Rheumatol. 2018 Jan-Feb;36(1):29-35.
23. Chatzidionysiou K, Lie E, Lukina G, et al. Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist yas failed: pooled data from 10 European register. Ann Rheum Dis. 2011;70(Issue 9):1575-80. doi: 10.1136/ard.2010.148759
24. Ogawa Y, Takahashi N, Kaneko A, et al. Association between seropositivity and discontinuation of tumor necrosis factor inhibitors due to ineffectiveness in rheumatoid arthritis. Clin Rheumatol. 2019 Oct;38(10):2757-63. doi: 10.1007/s10067-019-04626-x
25. Gottenberg JE, Courvoisier DS, Hernandez MV, et al. Brief report: association of rheumatoid factor and anti-citrullinated protein antibody positivity with better effectiveness of abatacept: results from the pan-european registry analysis. Arthritis Rheumatol. 2016 Jun;68(6):1346-52. doi: 10.1002/art.39595
26. Аронова Е.С., Лукина Г.В., Сигидин Я.А. Эффективность инфликсимаба при ревматоидном артрите – зависимость от суммарной дозы препарата. Научно-практическая ревматология. 2015;53(5):506-11 [Aronova ES, Lukina GV, Sigidin YA. Efficacy of infliximab in rheumatoid arthritis: a relationship to the total dose of the drug. Rheumatology Science and Practice. 2015;53(5):506-11 (In Russ.)]. doi: 10.14412/1995-4484-2015-506-511
27. Emery P, Vlahos B, Szczypa P, et al. Long-term drug survival of tumor necrosis factor inhibitors in patients with rheumatoid arthritis. J Rheumatol. 2019 June;46(Issue 12). doi: 10.3899/jrheum.181398
28. Silvagni E, Bortoluzzi A, Carrara G, et al. Comparative effectiveness of first-line biological monotherapy use in rheumatoid arthritis: a retrospective analysis of the RECord-linkage On Rheumatic Diseases study on health care administrative databases. BMJ Open. 2018;8:e021447. doi: 10.1136/bmjopen-2017-021447
29. Gabay C, Riek M, Scherer A, Finckh A. Effectiveness of biologic DMARDs in monotherapy versus in combination with synthetic DMARDs in rheumatoid arthritis: data from the Swiss Clinical Quality Management Registry. Rheumatology (Oxford). 2015;54(9):1664-72. doi: 10.1093/rheumatology/kev019
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1. Nasonov EL, Karateev DE, Balabanova RM. Rheumatoid arthritis. In: Rheumatology. National Guide. Nasonov EL, Nasonova VA, editors. Moscow: GEOTAR-Media, 2008; p. 290-331 (In Russ.)
2. Erdes SF, Goryachev DV. Kliniko-ekonomicheskyi analiz lekarstvennoy terapii revmatoidnogo artrita: vazhnost` problemy, nereshennye zadachi. Rheumatology Science and Practice. 2010;48(1):75-80 (In Russ.) doi: 10.14412/1995-4484-2010-1409
3. Nasonov EL. Genetically engineered biologicals in the treatment of rheumatoid arthritis. Moscow: IMA-PRESS, 2013 (In Russ.)
4. Kudryavtseva AV, Lukina GV, Smirnov AV, Glukhova SI. Evaluation of the clinical and anti-destructive effect of an anti-B cell preparation depending on concomitant therapy with basic anti-inflammatory drugs and glucocorticoids in patients with rheumatoid arthritis. Meditsinskiy sovet = Medical Council. 2019;18:110-7 (In Russ.) doi: 10.21518/2079-701X-2019-18-110-117
5. Oldroyd AGS, Symmons DPM, Sergeant JC, et al. Long-term persistence with rituximab in patients with rheumatoid arthritis. Rheumatology (Oxford). 2018;57(6):1089-96. doi: 10.1093/rheumatology/key036
6. Narongroeknawin P, Chevaisrakul P, Kasitanon N, Kitumnuaypong T. Drug survival and reasons for discontinuation of the first biological disease modifying antirheumatic drugs in Thai patients with rheumatoid arthritis: Analysis from the Thai Rheumatic Disease Prior Authorization registry. Int J Rheum Dis. 2018;21(1):170-8. doi: 10.1111/1756-185X.12937
7. Lukina GV, Sigidin YA, Kuzikyants KH, et al. Opyt primenenia rituximaba u bolhyh revmatoidnym artritom v real`noy klinicheskoi praktike po dannym Rossiyskogo registra ARBITR. Russian Medical Journal. 2011;25:1518-23 (In Russ.)
8. Lukina GV, Sigidin YA, Mazurov VI, Nasonov EL. Rituximab in real clinical practice: Arbiter and CERERRA registers. In the book under the editorship of E.L. Nasonova: Genetically engineered biologicals in the treatment of rheumatoid arthritis. Moscow: IMA-PRESS, 2013; p. 362-9 (In Russ.)
9. Brodszky V, Bíró A, Szekanecz Z, et al. Determinants of biological drug survival in rheumatoid arthritis: evidence from a Hungarian rheumatology center over 8 years of retrospective data. ClinicoEconomics Outcomes Res. 2017;9:139-47. doi: 10.2147/ceor.s124381
10. Ebina K, Hashimoto M, Yamamoto W, et al. Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis. The ANSWER cohort study. Arthritis Res Ther. 2019;21:91. doi: 10.1186/s13075-019-1880-4
11. Papadopoulos CG, et al. Eight-year survival study of first-line tumour necrosis factor α inhibitors in rheumatoid arthritis: real-world data from a university center registry. Rheumatol Advanc Pract. 2019;3:1-11. doi: 10.1093/rap/rkz007
12. Ebina K, Hashimoto M, Yamamoto W, et al. Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis. The ANSWER cohort study. PLoS One. 2018;13(3):e0194130. doi: 10.1371/journal.pone.0194130
13. Bolge SC, Goren A, Tandon N. Reasons for discontinuation of subcutaneous biologic therapy in the treatment of rheumatoid arthritis: a patient perspective. Patient Prefer Adherence. 2015;9:121-31. doi: 10.2147/ppa.s70834
14. Strand V, Miller P, Williams SA, et al. Discontinuation of Biologic Therapy in Rheumatoid Arthritis: Analysis from the Corrona RA Registry. Rheumatol Ther. 2017;4:489. doi: 10.1007/s40744-017-0078-y
15. Kondo M, Yamada H. Drug survival rates of biological disease-modifying antirheumatic drugs and Janus kinase-inhibitor therapy in 801 rheumatoid arthritis patients: a 14 year-retrospective study from a rheumatology clinic in Japan. Modern Rheumatol. 2019;29(Issue 6). doi: 10.1080/14397595.2018.1537556
16. Souto A, Maneiro JR, Gómez-Reino JJ. Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and metaanalysis of drug registries and health care databases. Rheumatology (Oxford). 2016;55(3):523-34. doi: 10.1093/rheumatology/kev374
17. Wiens A, Borba HHL, Leonart LP, et al. Treatment interruption of biological drugs and tofacitinib in rheumatoid arthritis: a systematic review of case reports. Braz J Pharm Sci. 2018;54(4):e17437. doi: 10.1590/s2175-97902018000417437
18. Martínez-Santana V, González-Sarmiento E, Calleja-Hernández MA, Sánchez-Sánchez T. Comparison of drug survival rates for tumor necrosis factor antagonists in rheumatoid arthritis. Patient Prefer Adherence. 2013;7:719-27. doi: 10.2147/ppa.s47453
19. Murata K, Ito H, Hashimoto M, et al. Elderly onset of early rheumatoid arthritis is a risk factor for bone erosions, refractory to treatment: KURAMA cohort. Int J Rheum Dis. 2019;22(6):1084-93. doi: 10.1111/1756-185x.13428
20. Ishchenko A, Lories RJ. Safety and Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance. Drugs Aging. 2016;33(6):387-98. doi: 10.1007/s40266-016-0374-1
21. Ebina K, Hashimoto M, Yamamoto W, et al. Drug tolerability and reasons for discontinuation of seven biologics in elderly patients with rheumatoid arthritis. The ANSWER cohort study. PLoS One. 2019;14(5):e0216624. doi: 10.1371/journal.pone.0216624
22. Leon L, Gomez A, Vadillo C, et al. Severe adverse drug reactions to biological disease-modifying anti-rheumatic drugs in elderly patients with rheumatoid arthritis in clinical practice. Clin Exp Rheumatol. 2018 Jan-Feb;36(1):29-35.
23. Chatzidionysiou K, Lie E, Lukina G, et al. Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist yas failed: pooled data from 10 European register. Ann Rheum Dis. 2011;70(Issue 9):1575-80. doi: 10.1136/ard.2010.148759
24. Ogawa Y, Takahashi N, Kaneko A, et al. Association between seropositivity and discontinuation of tumor necrosis factor inhibitors due to ineffectiveness in rheumatoid arthritis. Clin Rheumatol. 2019 Oct;38(10):2757-63. doi: 10.1007/s10067-019-04626-x
25. Gottenberg JE, Courvoisier DS, Hernandez MV, et al. Brief report: association of rheumatoid factor and anti-citrullinated protein antibody positivity with better effectiveness of abatacept: results from the pan-european registry analysis. Arthritis Rheumatol. 2016 Jun;68(6):1346-52. doi: 10.1002/art.39595
26. Aronova ES, Lukina GV, Sigidin YA. Efficacy of infliximab in rheumatoid arthritis: a relationship to the total dose of the drug. Rheumatology Science and Practice. 2015;53(5):506-11 (In Russ.) doi: 10.14412/1995-4484-2015-506-511
27. Emery P, Vlahos B, Szczypa P, et al. Long-term drug survival of tumor necrosis factor inhibitors in patients with rheumatoid arthritis. J Rheumatol. 2019 June;46(Issue 12). doi: 10.3899/jrheum.181398
28. Silvagni E, Bortoluzzi A, Carrara G, et al. Comparative effectiveness of first-line biological monotherapy use in rheumatoid arthritis: a retrospective analysis of the RECord-linkage On Rheumatic Diseases study on health care administrative databases. BMJ Open. 2018;8:e021447. doi: 10.1136/bmjopen-2017-021447
29. Gabay C, Riek M, Scherer A, Finckh A. Effectiveness of biologic DMARDs in monotherapy versus in combination with synthetic DMARDs in rheumatoid arthritis: data from the Swiss Clinical Quality Management Registry. Rheumatology (Oxford). 2015;54(9):1664-72. doi: 10.1093/rheumatology/kev019
1 ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия;
2 ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Россия
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E.S. Aronova1, G.V. Lukina1,2, S.I. Glukhova1, G.I. Gridneva1, A.V. Kudryavtseva1
1 Nasonova Research Institute of Rheumatology, Moscow, Russia;
2 Loginov Moscow Clinical Scientific Center, Moscow, Russia