Результаты применения стратегии «Лечение до достижения цели» у больных ранним псориатическим артритом через 1 год после начала терапии: данные исследования РЕМАРКА
Результаты применения стратегии «Лечение до достижения цели» у больных ранним псориатическим артритом через 1 год после начала терапии: данные исследования РЕМАРКА
Результаты применения стратегии «Лечение до достижения цели» у больных ранним псориатическим артритом через 1 год после начала терапии: данные исследования РЕМАРКА
Цель исследования – оценить эффективность применения стратегии «Лечение до достижения цели» – «treat-to-target» (Т2Т) при раннем периферическом псориатическом артрите (рПсА) спустя 1 год после начала лечения. Материалы и методы. Наблюдали 44 больных (18 мужчин и 26 женщин) c рПсА, соответствующих критериям CASPAR, средний возраст 37,5±11,3 года, в течение 12 мес терапии по принципам T2T. Исходно всем пациентам назначали монотерапию метотрексатом (МТ) подкожно по 10 мг в неделю с повышением дозы на 5 мг каждые 2 нед до 20–25 мг/нед. Оценивали количество больных, достигших минимальной активности болезни (МАБ). Ответ на терапию оценивали по критериям ACR, при отсутствии ответа через 3 мес пациентам назначали комбинированную терапию МТ по 20–25 мг/нед и адалимумабом (АДА) по 40 мг 1 раз в 2 нед. Общая длительность терапии составила 12 мес. Результаты. После окончания лечения наблюдали значимое улучшение всех клинико-лабораторных параметров активности рПсА и функционального состояния больных. Ответ ACR 20/50/70 наблюдался в 88, 77 и 59% случаев соответственно. Ответ PASI 75 отмечен у 81% больных с общей площадью поражения кожных покровов псориазом (BSA) ≥3%. Установлено, что ведение больных рПсА по принципам Т2Т, которое подразумевает строгий контроль за активностью болезни и результатами лечения, является эффективной стратегией, позволяющей через 1 год достичь МАБ у 2/3 (65,9%) и ремиссии по DAS у 61,4% больных. Показано, что лечение в соответствии с данной стратегией обеспечивает эффективное подавление всех основных клинических проявлений рПсА: артрита, энтезита, дактилита. У 55% больных рПсА монотерапия МТ в подкожной форме является эффективной. Заключение. Предложенная стратегия лечения способствует улучшению функционального состояния больных рПсА и обеспечивает сопоставимые результаты как у чувствительных, так и у резистентных к монотерапии МТ пациентов.
Ключевые слова: ранний псориатический артрит, метотрексат, стратегия «лечение до достижения цели», минимальная активность заболевания, энтезит, дактилит.
________________________________________________
Objectives: to study efficacy of treat-to-target (T2T) strategy in early peripheral psoriatic arthritis (EPsA) after one year of treatment. Methods: 44 (M/F – 18/26) DMARD-naїve patients (pts) with active EPsA, according to the CASPAR criteria, mean age 37.5±11.3 years, PsA duration 7 [4; 24] months, psoriasis duration 36 [12; 84] months, disease activity index (DAS) 3.78 [3.18; 4.67], DAS28 4.33 [3.67; 4.8] study were included. At the baseline and every other 3 months for total 12 months of therapy all pts underwent standard clinical examination, tender joint count (TJC), swollen joint count (SJC), patient pain VAS, patient/physician´s global disease activity VAS, enthesitis by Leeds Enthesial Index (LEI)+Plantar Fascia (PF), dactylitis, Psoriasis Area Severity Index (PASI), body surface area (BSA), Health Assessment Questionnaire (HAQ), DAS, DAS28-C-RP, C-RP (mg/l). The dose of MTX s/c was escalated by 5 mg every 2 weeks from 10 mg/wk to appropriate dose 20-25 mg/wk according to the drug intolerance. If pts does not achieve the lower disease activity (LDA), MDA or remission after 3 months of MTX subcutaneous (s/c) mono-therapy, then combination therapy of MTX+Adalimumab (ADA) by standard regime was continued up to one year. At 12 months of therapy the proportion of pts who attained LDA by DAS/DAS28 or remission by DAS<1.6/DAS28-C-RP<2.6 or MDA, ACR20/50/70, PASI75 and dynamics of HAQ, LEI+PF, dactylitis were calculated. Mean±SD, Me [Q25; Q75], %, Friedman (Fr.) ANOVA, U-test, Wilcoxon test were performed. All p<0.05 were considered to indicate statistical significance. Results: At one year of treatment according to T2T strategy significant improvements disease activity and physical health function related to quality of life was seen. By 12 months of therapy remission by DAS and MDA was reached 61.4%/65.9% of pts accordingly. By 12 months of therapy ACR20/50/70 was seen in 88%/77%/59% of pts. In pts with BSA≥3% (n=16) at baseline psoriasis improvements by PASI75 was seen in 88% of pts. In 55% of active EPsA pts MTX (s/c) mono-therapy was an effective treatment. Conclusions: One-year treatment according to T2T strategy significantly improves all PsA clinical domains - arthritis, dactylitis, enthesitis, skin psoriasis and quality of life despite of type of treatment. It seems that T2T is a useful strategy in EPsA but additional research concerning its implementation in real practice are needed.
1. Helliwell PS, Ruderman E. Natural history, prognosis, and Socioeconomic aspects of psoriatic arthritis. Rheum Dis Clin N Am. 2015; 4: 581-591. doi: 10.1016/j.rdc.2015.07.004
2. Egeberg A, Kristensen LE, Thyssen JP, Gislason GH, Gottlieb AB, Coates LC, Jullien D, Gisondi P, Gladman DD, Skov L, Mallbris L. Incedence and prevalence of psoriatic arthritis in Denmark: a nationwide register linkage study. Ann Rheum Dis. 2017;0:1-7. doi:10.1136/annrheumdis-2016-210579
3. Kristensen LE, Jorgensen TD, Christensen R., Gudbergsen H, Dreyer L, Ballegaard C, Jacobsson LTH, Strand V, Mease PJ, Kjellberg J. Societal costs and patients‘ experience of health inequities before and after diagnosis of psoriatic arthritis: a Danish cohort study. Ann Rheum Dis. 2017;0:1-7. doi:10.1136/annrheumdis-2016-210579
4. Coates LC, Mease P, Kirhman B, McLeod LD, Mpofu S, Karyekar C, Gandhi K. Secukinumab improves minimal disease activity response rates in patients with active psoriatic arthritis: data from the randomized phase 3 study, Future 2. Ann Rheum Dis. 2016;75(Suppl 2): 605. doi: 10.1136/annrheumdis-2016-EULAR.3949
5. Theander E, Husmark T, Alenius GM, Larsson PT, Teleman A, Geijer M, Lindqvist UR. Early psoriatic arthritis: short symptom duration, male gender and preserved physical functioning at presentation predict favourable outcome at 5-year follow-up. Results from the Swedish Early Psoriatic Arthritis Register (SwePsA). Ann Rheum Dis. 2013; 73(2): 407-13
6. Mease P, Deodhar A, Fleischmann R, Wollenhaupt J, Gladman D, Leszczyński P, Vitek P, Turkiewicz A, Khraishi M, FitzGerald O, Landewé R, de Longueville M, Hoepken B, Peterson L, van der Heijde D. Effect of certolizumab pegol over 96 weeks in patients with psoriatic arthritis with and without prior anti tumor necrosis factor exposure. RMD Open. 2015 Jun 25;1(1): e000119. doi:10.1136/rmdopen-2015-000119
7. Lubrano E, Parsons WJ, Perrotta FM. Assessment of response to treatment, remission, and minimal disease activity in axial psoriatic arthritis treated with tumor necrosis factor inhibitors. J Rheumatol. 2016;43:918-23. doi:10.3899/jrheum.151404
8. Kavanaugh A. Psoriatic arthritis: treat-to-target. Clin Exp Rheumatol. 2012; 30 (Suppl 73):123-125.
9. Gossec L, Smolen JS, Ramiro S, de Wit M, Cutolo M, Dougados M, Emery P, Landewé R, Oliver S, Aletaha D, Betteridge N, Braun J, Burmester G, Cañete JD, Damjanov N, FitzGerald O, Haglund E, Helliwell P, Kvien TK, Lories R, Luger T, Maccarone M, Marzo-Ortega H, McGonagle D, McInnes IB, Olivieri I, Pavelka K, Schett G, Sieper J, van den Bosch F, Veale DJ, Wollenhaupt J, Zink A, van der Heijde D. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016; 75:499-5. doi: 10.1136/annrheumdis-2015-208337
10. Smolen JS, Schöls M, Braun J, Dougados M, FitzGerald O, Gladman DD, Kavanaugh A, Landewé R, Mease P, Sieper J, Stamm T, Wit M, Aletaha D, Baraliakos X, Betteridge N, Bosch FVD, Coates LC, Emery P, Gensler LS, Gossec L, Helliwell P, Jongkees M, Kvien TK, Inman RD, McInnes IB, Maccarone M, Machado PM, Molto A, Ogdie A, Poddubnyy D, Ritchlin C, Rudwaleit M, Tanew A, Thio B, Veale D, Vlam K, Heijde DV. Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. Ann Rheum Dis. 2017; 0:1-15. doi: 10.1136/Ann Rheum Dis-2017-211734
11. Coates LC, Moverley AR, McParland L, Brown S, Navarro-Coy N, O'Dwyer JL, Meads DM, Emery P, Conaghan PG, Helliwell PS. Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial. Lancet. 2015 Dec 19;386(10012):2489-98. doi: 10.1016/S0140-6736(15)00347-5
12. Coates LC, Helliwell PS. Treating to target in psoriatic arthritis: How to implement in clinical practice. Ann Rheum Dis. 2015;4:640-643. doi: 10.1097/bor.0000000000000140
13. Коротаева Т.В., Логинова Е.Ю., Каратеев Д.Е., Глазков А.А., Насонов Е.Л. Стратегия «Лечение до достижения цели» при раннем псориатическом артрите (предварительные результаты исследования РЕМАРКА). Науч-практич ревматол. 2016;54 (Прил. 2): 71-75.[ Korotaeva TV, Loginova EYu, Karateev DE, Glazkov AA, Nasonov EL.Treat-to-target strategy for early psoriatic arthritis (preliminary results of the REMARCА study). Nauch-praktich Revmatol. 2016;54 (Pril. 2): 71-75. (In Russ.)]. doi.org/10.14412/1995-4484-2014-376-380
14. Coates LC, Helliwell PS. Disease measurement – enthesitis, skin, nails, spine and dactylitis. Best Pract Res Clin Rheumatol. 2010; 24(5):659-70. doi: 10.1016/j.berh.2010.05.004
15. Coates LC, Helliwell PS. Methotrexate efficacy in the Tight Control in Psoriatic Arthritis (TICOPA) study. J Rheumatol. 2016; 43(2):356-361. doi:10.3899/jrheum.150614
16. Bianchi G, Caporali R, Mattana P. Methotrexate and rheumatoid arthritis: current evidence regarding subcutaneous versus oral routes of administration. Adv Ther. 2016; 33:369-378. doi: 10/1007/s12325-016-0295-8
17. Hazlewood GS, Thorne JC, Pope JE, Lin D, Tin D, Boire G, Haraoui B, Hitchon CA, Keystone EC, Jamal S, Bykerk VP. The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment of early rheumatoid arthritis. Ann Rheum Dis. 2016; 75: 1003-1008. doi: 10.1136/annrheumdis-2014-206504
18. Sheane BJ, Thavaneswaran A, Gladman DD, Chandran V. Attainment of Minimal Disease Activity Using Methotrexate in Psoriatic Arthritis. J Rheumatol. 2016; 43 (9): 1718-1723. doi:10.3899/jrheum.160111
________________________________________________
1. Helliwell PS, Ruderman E. Natural history, prognosis, and Socioeconomic aspects of psoriatic arthritis. Rheum Dis Clin N Am. 2015; 4: 581-591. doi: 10.1016/j.rdc.2015.07.004
2. Egeberg A, Kristensen LE, Thyssen JP, Gislason GH, Gottlieb AB, Coates LC, Jullien D, Gisondi P, Gladman DD, Skov L, Mallbris L. Incedence and prevalence of psoriatic arthritis in Denmark: a nationwide register linkage study. Ann Rheum Dis. 2017;0:1-7. doi:10.1136/annrheumdis-2016-210579
3. Kristensen LE, Jorgensen TD, Christensen R., Gudbergsen H, Dreyer L, Ballegaard C, Jacobsson LTH, Strand V, Mease PJ, Kjellberg J. Societal costs and patients‘ experience of health inequities before and after diagnosis of psoriatic arthritis: a Danish cohort study. Ann Rheum Dis. 2017;0:1-7. doi:10.1136/annrheumdis-2016-210579
4. Coates LC, Mease P, Kirhman B, McLeod LD, Mpofu S, Karyekar C, Gandhi K. Secukinumab improves minimal disease activity response rates in patients with active psoriatic arthritis: data from the randomized phase 3 study, Future 2. Ann Rheum Dis. 2016;75(Suppl 2): 605. doi: 10.1136/annrheumdis-2016-EULAR.3949
5. Theander E, Husmark T, Alenius GM, Larsson PT, Teleman A, Geijer M, Lindqvist UR. Early psoriatic arthritis: short symptom duration, male gender and preserved physical functioning at presentation predict favourable outcome at 5-year follow-up. Results from the Swedish Early Psoriatic Arthritis Register (SwePsA). Ann Rheum Dis. 2013; 73(2): 407-13
6. Mease P, Deodhar A, Fleischmann R, Wollenhaupt J, Gladman D, Leszczyński P, Vitek P, Turkiewicz A, Khraishi M, FitzGerald O, Landewé R, de Longueville M, Hoepken B, Peterson L, van der Heijde D. Effect of certolizumab pegol over 96 weeks in patients with psoriatic arthritis with and without prior anti tumor necrosis factor exposure. RMD Open. 2015 Jun 25;1(1): e000119. doi:10.1136/rmdopen-2015-000119
7. Lubrano E, Parsons WJ, Perrotta FM. Assessment of response to treatment, remission, and minimal disease activity in axial psoriatic arthritis treated with tumor necrosis factor inhibitors. J Rheumatol. 2016;43:918-23. doi:10.3899/jrheum.151404
8. Kavanaugh A. Psoriatic arthritis: treat-to-target. Clin Exp Rheumatol. 2012; 30 (Suppl 73):123-125.
9. Gossec L, Smolen JS, Ramiro S, de Wit M, Cutolo M, Dougados M, Emery P, Landewé R, Oliver S, Aletaha D, Betteridge N, Braun J, Burmester G, Cañete JD, Damjanov N, FitzGerald O, Haglund E, Helliwell P, Kvien TK, Lories R, Luger T, Maccarone M, Marzo-Ortega H, McGonagle D, McInnes IB, Olivieri I, Pavelka K, Schett G, Sieper J, van den Bosch F, Veale DJ, Wollenhaupt J, Zink A, van der Heijde D. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016; 75:499-5. doi: 10.1136/annrheumdis-2015-208337
10. Smolen JS, Schöls M, Braun J, Dougados M, FitzGerald O, Gladman DD, Kavanaugh A, Landewé R, Mease P, Sieper J, Stamm T, Wit M, Aletaha D, Baraliakos X, Betteridge N, Bosch FVD, Coates LC, Emery P, Gensler LS, Gossec L, Helliwell P, Jongkees M, Kvien TK, Inman RD, McInnes IB, Maccarone M, Machado PM, Molto A, Ogdie A, Poddubnyy D, Ritchlin C, Rudwaleit M, Tanew A, Thio B, Veale D, Vlam K, Heijde DV. Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. Ann Rheum Dis. 2017; 0:1-15. doi: 10.1136/Ann Rheum Dis-2017-211734
11. Coates LC, Moverley AR, McParland L, Brown S, Navarro-Coy N, O'Dwyer JL, Meads DM, Emery P, Conaghan PG, Helliwell PS. Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial. Lancet. 2015 Dec 19;386(10012):2489-98. doi: 10.1016/S0140-6736(15)00347-5
12. Coates LC, Helliwell PS. Treating to target in psoriatic arthritis: How to implement in clinical practice. Ann Rheum Dis. 2015;4:640-643. doi: 10.1097/bor.0000000000000140
13. [ Korotaeva TV, Loginova EYu, Karateev DE, Glazkov AA, Nasonov EL.Treat-to-target strategy for early psoriatic arthritis (preliminary results of the REMARCА study). Nauch-praktich Revmatol. 2016;54 (Pril. 2): 71-75. (In Russ.)]. doi.org/10.14412/1995-4484-2014-376-380
14. Coates LC, Helliwell PS. Disease measurement – enthesitis, skin, nails, spine and dactylitis. Best Pract Res Clin Rheumatol. 2010; 24(5):659-70. doi: 10.1016/j.berh.2010.05.004
15. Coates LC, Helliwell PS. Methotrexate efficacy in the Tight Control in Psoriatic Arthritis (TICOPA) study. J Rheumatol. 2016; 43(2):356-361. doi:10.3899/jrheum.150614
16. Bianchi G, Caporali R, Mattana P. Methotrexate and rheumatoid arthritis: current evidence regarding subcutaneous versus oral routes of administration. Adv Ther. 2016; 33:369-378. doi: 10/1007/s12325-016-0295-8
17. Hazlewood GS, Thorne JC, Pope JE, Lin D, Tin D, Boire G, Haraoui B, Hitchon CA, Keystone EC, Jamal S, Bykerk VP. The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment of early rheumatoid arthritis. Ann Rheum Dis. 2016; 75: 1003-1008. doi: 10.1136/annrheumdis-2014-206504
18. Sheane BJ, Thavaneswaran A, Gladman DD, Chandran V. Attainment of Minimal Disease Activity Using Methotrexate in Psoriatic Arthritis. J Rheumatol. 2016; 43 (9): 1718-1723. doi:10.3899/jrheum.160111
1 ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», лаборатория диагностики и инновационных методов лечения псориатического артрита, Москва, Россия;
2 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России, кафедра ревматологии института профессионального образования, Москва, Россия
1 V.A. Nasonova Scientific and Research Institute of Rheumatology, Department of Psoriatic
arthritis, Moscow, Russia;
2 I.M. Sechenov First Moscow State Medical University, Department of Rheumatology, Moscow, Russia