rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.47360/1995-4484-2020-691-694rsp-2969Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHВозможности модификации терапии у пациентов с анкилозирующим спондилитом, достигших частичной ремиссии на фоне лечения адалимумабом: данные реальной практикиPossibility of treatment modification in patients with ankylosing spondylitis achieved of partial remission on treatment with adalimumab: Real practice datahttps://orcid.org/0000-0002-6398-2545ПетровА. В.PetrovA. V.

Петров Андрей Владимирович

295051, Симферополь, бульвар Ленина, 5/7

Andrey V. Petrov

295051, Simferopol, Lenin boulevard, 5/7

petroff14@yandex.ruhttps://orcid.org/0000-0003-0497-4630ШевнинаЯ. О.ShevninaYa. O.

295017, Симферополь, ул. Киевская, 69

Yana O. Shevnina

295017, Simferopol, Kievskaya str., 69

https://orcid.org/0000-0002-5610-4760ГаффароваА. С.GaffarovaA. S.

295051, Симферополь, бульвар Ленина, 5/7

Anife S. Gaffarova

295051, Simferopol, Lenin boulevard, 5/7

https://orcid.org/0000-0002-0119-8106МатвееваН. В.MatveevaN. V.

295051, Симферополь, бульвар Ленина, 5/7

Natalia V. Matveeva

295051, Simferopol, Lenin boulevard, 5/7

Медицинская академия им. С.И. Георгиевского, ФГАОУ ВО Крымский федеральный университет им. В.И. ВернадскогоРоссияMedical Academy named after S.I. Georgievsky of Vernadsky CFURussian FederationГБУЗ Республики Крым Республиканская клиническая больница им. Н.А. СемашкоРоссияCrimean Republican Clinical Hospital named after N.A. SemashkoRussian Federation202014012021586691694Copyright © Петров А.В., Шевнина Я.О., Гаффарова А.С., Матвеева Н.В., 20212021Петров А.В., Шевнина Я.О., Гаффарова А.С., Матвеева Н.В.Petrov A.V., Shevnina Y.O., Gaffarova A.S., Matveeva N.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/2969

Цель исследования — оценить длительность сохранения ремиссии или статуса неактивного заболевания у больных анкилозирующим спондилитом с частичной ремиссией на фоне лечения адалимумабом (АДА) после его отмены.

Материалы и методы

Материалы и методы. Наблюдались 26 больных с анкилозирующим спондилитом, у которых в результате длительного применения (в течение 24 месяцев и более) АДА в виде подкожных инъекций по 40 мг 1 раз в две недели наблюдалась частичная клиническая ремиссия заболевания. АДА отменялся после 3-4-месячного периода применения в деэскалационном режиме в виде 1 инъекции (40 мг) 1 раз в 4 недели. После отмены АДА больные продолжали принимать нестероидные противовоспалительные препараты, сульфасалазин в дозе 1,5—2 г в сутки (n =11) и метотрексат 10 мг в неделю (n=3). Оценка клинических, лабораторных и ультрасонографических параметров анкилозирующего спондилита проводилась через 3, 6 и 12 месяцев после отмены АДА.

Результаты и обсуждение

Результаты и обсуждение. Через 6 месяцев частичная ремиссия анкилозирующего спондилита сохранялась у 12 (46,2%), а через 12 месяцев - у 10 (38,5%) больных. Низкая активность заболевания (BASDAI <4) отмечена у 14 (53,8%) и 12 (46,2%) больных соответственно.

Заключение

Заключение. В течение 12 месяцев после отмены АДА обострение анкилозирующего спондилита наблюдалось у 53,8% больных с частичной клинической ремиссией.

Objective

Objective. To assess the duration of remission or inactive disease status in patients with achieved partial remission due to treatment with adalimumab (ADA) after it discontinuation.

Materials and methods

Materials and methods. A dynamic observation was conducted of 26 patients with ankylosing spondylitis with partial remission achieved due to prolonged use (for 24 months or more) of subcutaneous injections of 40 mg ADA once every two weeks. The discontinuation of ADA was carried out after a 3-4 month period of its use in de-escalation mode in the form of 1 injection (40 mg) once every 4 weeks. After discontinuation of ADA, patients continued to take non-steroidal anti-inflammatory drugs, sulfasalazine at a dose of 1.5-2 g per day (11 patients) and methotrexate 10 mg per week (3 patients). Assessment of the clinical, laboratory and ultrasonographic parameters of ankylosing spondylitis was carried out in 3, 6 and 12 months after the abolition of the ADA.

Results and discussion

Results and discussion. Among the observed patients, partial clinical remission of ankylosing spondylitis maintained after 6 months in 12 (46.2%) patients, and after 12 months - in 10 (38.5%). A low degree of ankylosing spondylitis activity (BASDAI <4) was maintained for 6 months after the abolition of ADA in 14 (53.8%) patients, and after 12 months - in 12 (46.2%).

Conclusion

Conclusion. Within 12 months after cancellation of ADA, ankylosing spondylitis exacerbation was observed in 53.8% of patients with initially achieved partial clinical remission.

ankylosing spondylitispartial clinical remissionadalimumabASDAS-CRPindexBASDAI indexReferencesРевматология: Российские клинические рекомендации. Под ред. ЕЛ Насонова. М.: ГЭОТАР-Медиа; 2017: 464.Rheumatology: Russian Clinical Guidelines. Edited by Nasonov EL. Moscow: GEOTAR-Media; 2017: 464. (In Russ.).Taurog JD, Chhabra A, Colbert RA. Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med. 2016;374(26):2563-2574. DOI: 10.1056/NEJMra1406182Taurog JD, Chhabra A, Colbert RA. Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med. 2016;374(26):2563-2574. DOI: 10.1056/NEJMra1406182Эрдес ШФ. Обновленные рекомендации ASAS-EULAR для аксиального спондилоартрита. Научно-практическая ревматология. 2016;54(5):508-509. DOI: 10.14412/1995-4484-2016-508-509Erdes SF. Updated ASAS-EULAR guidelines for axial spondyloarthritis. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(5):508-509 (In Russ.). DOI: 10.14412/1995-4484-2016-508-509van der Heijde D, Ramiro S, Landewc R, et al. 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. Ann Rheum Dis. 2017;76(6):978-991. DOI: 10.1136/ANNRHEUMDIS-2016-210770van der Heijde D, Ramiro S, Landewc R, et al. 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. Ann Rheum Dis. 2017;76(6):978-991. DOI: 10.1136/ANNRHEUMDIS-2016-210770van der Heijde D, Dijkmans B, Geusens P, et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: Results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum. 2005;52(2):582-591. DOI: 10.1002/art.20852van der Heijde D, Dijkmans B, Geusens P, et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: Results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum. 2005;52(2):582-591. DOI: 10.1002/art.20852Yates M, Hamilton LE, Elender F, et al. Is etanercept 25 mg once weekly as effective as 50 mg at maintaining response in patients with ankylosing spondylitis? A randomized control trial. J Rheumatol. 2015;42(7):1177-1185. DOI: 10.3899/jrheum.141335Yates M, Hamilton LE, Elender F, et al. Is etanercept 25 mg once weekly as effective as 50 mg at maintaining response in patients with ankylosing spondylitis? A randomized control trial. J Rheumatol. 2015;42(7):1177-1185. DOI: 10.3899/jrheum.141335Navarro-Compan V, Moreira V, Ariza-Ariza R, et al. Low doses of etanercept can be effective in ankylosing spondylitis patients who achieve remission of the disease. Clin Rheumatol. 2011;30(7):993-996. DOI: 10.1007/s10067-011-1722-5Navarro-Compan V, Moreira V, Ariza-Ariza R, et al. Low doses of etanercept can be effective in ankylosing spondylitis patients who achieve remission of the disease. Clin Rheumatol. 2011;30(7):993-996. DOI: 10.1007/s10067-011-1722-5De Stefano R, Frati E, De Quattro D, et al. Low doses of etanercept can be effective to maintain remission in ankylosing spondylitis patients. Clin Rheumatol. 2014;33(5):707-711. DOI: 10.1007/s10067-013-2372-6De Stefano R, Frati E, De Quattro D, et al. Low doses of etanercept can be effective to maintain remission in ankylosing spondylitis patients. Clin Rheumatol. 2014;33(5):707-711. DOI: 10.1007/s10067-013-2372-6Sebastian A, Wojtala P, Lubinski L, et al. Disease activity in axial spondyloarthritis after discontinuation of TNF inhibitirs therapy. Reumatologia. 2017;55(4):157-162. DOI: 10.5114/reum.2017.69775Sebastian A, Wojtala P, Lubinski L, et al. Disease activity in axial spondyloarthritis after discontinuation of TNF inhibitirs therapy. Reumatologia. 2017;55(4):157-162. DOI: 10.5114/reum.2017.69775Gonzalez-Alvaro I, Martinez-Fernandez C, Dorantes-Calderon B, et al. Spanish Rheumatology Society and Hospital Pharmacy Society Consensus on recommendations for biologics optimization in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Rheumatology (Oxford). 2015;54(7):1200-1209. DOI: 10.1093/rheumatology/keu461Gonzalez-Alvaro I, Martinez-Fernandez C, Dorantes-Calderon B, et al. Spanish Rheumatology Society and Hospital Pharmacy Society Consensus on recommendations for biologics optimization in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Rheumatology (Oxford). 2015;54(7):1200-1209. DOI: 10.1093/rheumatology/keu461Baraliakos X, Listing J, Brandt J, et al. Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab. Arthritis Res Ther. 2005;7(3):R439-R444. DOI: 10.1186/ar1693Baraliakos X, Listing J, Brandt J, et al. Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab. Arthritis Res Ther. 2005;7(3):R439-R444. DOI: 10.1186/ar1693Landewc R, Sieper J, Mease P, et al. Efficacy and safety of continuing versus withdrawing adalimumab (ADA) in maintaining remission in patients with non-radiographic axial spondyloarthritis (NR-AXSPA). Ann Rheum Dis. 2018;77:213. DOI: 10.1136/annrheumdis-2012-201766Landewc R, Sieper J, Mease P, et al. Efficacy and safety of continuing versus withdrawing adalimumab (ADA) in maintaining remission in patients with non-radiographic axial spondyloarthritis (NR-AXSPA). Ann Rheum Dis. 2018;77:213. DOI: 10.1136/annrheumdis-2012-201766Anderson JJ, Baron G, van der Heijde D et al. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum. 2001;44(8):1876-1886. DOI: 10.1002/1529-0131(200108)44:8<1876::AID-ART326>3.0.CO;2-FAnderson JJ, Baron G, van der Heijde D et al. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum. 2001;44(8):1876-1886. DOI: 10.1002/1529-0131(200108)44:8<1876::AID-ART326>3.0.CO;2-Fvan der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27(4):361-368. DOI: 10.1002/art.1780270401van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27(4):361-368. DOI: 10.1002/art.1780270401van der Heijde D, Lie E, Kvien TK, et al. ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis. 2009;68(12):1811-1818. DOI: 10.1136/ARD.2008.100826van der Heijde D, Lie E, Kvien TK, et al. ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis. 2009;68(12):1811-1818. DOI: 10.1136/ARD.2008.100826Lee H, Jung Y, Song S, et al. Dosage and duration of etanercept therapy for ankylosing spondylitis: A meta-analysis. Int J Technol Assess Health Care. 2017;33(1):69-75. DOI: 10.1017/S0266462317000150Lee H, Jung Y, Song S, et al. Dosage and duration of etanercept therapy for ankylosing spondylitis: A meta-analysis. Int J Technol Assess Health Care. 2017;33(1):69-75. DOI: 10.1017/S0266462317000150Song IH, Althoff CE, Haibel H, et al. Frequency and duration of drug-free remission after 1 year of treatment with etanercept versus sulfasalazine in early axial spondyloarthritis: 2 year data of the ESTHER trial. Ann Rheum Dis. 2012;71(7):1212-1215. DOI: 10.1136/annrheumdis-2011-201010Song IH, Althoff CE, Haibel H, et al. Frequency and duration of drug-free remission after 1 year of treatment with etanercept versus sulfasalazine in early axial spondyloarthritis: 2 year data of the ESTHER trial. Ann Rheum Dis. 2012;71(7):1212-1215. DOI: 10.1136/annrheumdis-2011-201010Sieper J, van der Heijde D, Dougados M, et al. Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloar-thritis: Results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis. 2013;72(6):815-822. DOI: 10.1136/ANNRHEUMDIS-2012-201766Sieper J, van der Heijde D, Dougados M, et al. Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloar-thritis: Results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis. 2013;72(6):815-822. DOI: 10.1136/ANNRHEUMDIS-2012-201766Haibel H, Heldmann F, Listing J, et al. Long-term efficacy of adalimumab after drug withdrawal and retreatment of flare patients in active non-radiographic, axial spondyloarthritis. Arthritis Rheum. 2013;65(8):2211-2213. DOI: 10.1002/art.38014Haibel H, Heldmann F, Listing J, et al. Long-term efficacy of adalimumab after drug withdrawal and retreatment of flare patients in active non-radiographic, axial spondyloarthritis. Arthritis Rheum. 2013;65(8):2211-2213. DOI: 10.1002/art.38014Braun J, Brandt J, Listing J, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet. 2002;359(9313):1187-1193. DOI: 10.1016/s0140-6736(02)08215-6Braun J, Brandt J, Listing J, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet. 2002;359(9313):1187-1193. DOI: 10.1016/s0140-6736(02)08215-6Breban M, Vignon E, Claudepierre P, et al. Efficacy of infliximab in refractory ankylosing spondylitis: Results of a six-month openlabel study. Rheumatology (Oxford). 2002;41(11):1280-1285. DOI: 10.1093/rheumatology/41.11.1280Breban M, Vignon E, Claudepierre P, et al. Efficacy of infliximab in refractory ankylosing spondylitis: Results of a six-month openlabel study. Rheumatology (Oxford). 2002;41(11):1280-1285. DOI: 10.1093/rheumatology/41.11.1280Brandt J, Khariouzov A, Listing J, et al. Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthritis Rheum. 2003;48(6):1667-1675. DOI: 10.1002/art.11017Brandt J, Khariouzov A, Listing J, et al. Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthritis Rheum. 2003;48(6):1667-1675. DOI: 10.1002/art.11017

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