EN PL
PRACA ORYGINALNA
 
SŁOWA KLUCZOWE
DZIEDZINY
STRESZCZENIE
Introduction:
This study compared treatment with biologic agents and Janus kinase inhibitors (JAKi) in combination with methotrexate (MTX) for rheumatoid arthritis (RA) in a real-world setting at a large center in Poland. There is a persistent shortage of such studies, and illustrating the switching of medications in search of a suitable way of treatment for a given patient is a crucial step towards future personalized therapy.

Aim of the study:
This study is an extension of the initial work published in 2022 in Reumatologia, with the addition of an analysis of patients treated with upadacitinib. The study compared the effectiveness and side effects after treatment of biological disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in combination with MTX.

Materials and methods:
A total of 130 patients with active severe RA (Disease Activity Score for 28 joints based on the erythrocyte sedimentation rate [DAS28(ESR)] value > 5.1) were treated at the Rheumatologic Outpatients Department of the Central Clinical Hospital of the Ministry of the Interior and Administration, Warsaw, Poland between January 2010 and September 2021. All patients were treated with MTX 25 mg per week. They were divided into two groups: group I (80 patients) treated with biologic agents, and group II (50 patients) treated with JAKi. Assessment of DAS28(ESR) and Simplified Disease Activity Index (SDAI) and analy­sis of Boolean criteria for remission were performed. Remission or low disease activity, switching between drugs and adverse events were assessed and compared between studied groups.

Results:
Patients treated with tsDMARDs had previously used a higher number of conventional synthetic DMARDs (csDMARDs) and bDMARDs compared to those treated with bDMARDs. However, they achieved lower SDAI and assessment of disease activity using Visual Analogue Scale (VAS) values, and a higher proportion of patients achieved Boolean criteria for remission after treatment.

Conclusions:
The results of treatment with JAKi were successful, but the potential side effects indicate that this treatment may not be equally suitable for all RA patients.

 
REFERENCJE (40)
1.
O’Shea JJ, Schwartz DM, Villarino AV, et al. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med 2015; 66: 311–328, DOI: 10.1146/annurev-med-051113-024537.
 
2.
Charles-Schoeman C, Bush MH, Dougados M, et al. Risk of major adverse cardiovascular events with tofacitinib versus tumour necrosis factor inhibitors in patients with rheumatoid arthritis with or without a history of atherosclerotic cardiovascular disease: a post hoc analysis from ORAL Surveillance. Ann Rheum Dis 2023; 82: 119–129, DOI: 10.1136/ard-2022-222259.
 
3.
Wisłowska M. Comparison of treatment of severe rheumatoid arthritis patients with biological agents and JAK-STAT inhibitors. An observational study. Reumatologia 2022; 60: 81–91, DOI: 10.5114/reum.2022.115987.
 
4.
Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–324, DOI: 10.1002/art.1780310302.
 
5.
Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid Arthritis Classification Criteria. An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arthritis Rheum 2010; 62: 2569–2581, DOI: 10.1002/art.27584.
 
6.
Larsen A, Dale K, Eek M. Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films. Acta Radiolog Diagn 1977; 18: 481–490, DOI: 10.1177/028418517701800415.
 
7.
Fries JF, Spitz PW, Young DY. The dimensions for health outcomes: the health assessment questionnaire, disability and pain scale. J Rheumatol 1982; 9: 189–196.
 
8.
Prevoo ML, van’t Hof MA, Kupern HH, et al. Modified disease activity scores that include twenty-eight-joints counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38: 44–48, DOI: 10.1002/art.1780380107.
 
9.
Smolen JS, Breedveld FC, Schiff MH, et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology 2003; 42: 244–257, DOI: 10.1093/rheumatology/keg072.
 
10.
Aletaha D, Wang X, Zhong S, et al. Differences in disease acti­vity measures in patients with rheumatoid arthritis who achieved DAS, SDAI, or CDAI remission but not Boolean remission. Semin Arthritis Rheum 2020; 50: 276–284, DOI: 10.1016/j.semarthrit.2019.09.005.
 
11.
Smolen JS, Landewé RB, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. 2022 update. Ann Rheum Dis 2023; 83: 3–18, DOI: 10.1136/ard-2022-223356.
 
12.
Smolen JS, Han C, Bala M, et al. ATTRACT Study Group: Evi­dence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical response. Arthritis Rheum 2005; 52: 1020–1030, DOI: 10.1002/art.20982.
 
13.
Smolen JS, van der Heijde D, St Clair EW, et al. Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) Study Group. Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab. Results from the Aspire trial. Arthritis Rheum 2006; 54: 702–710, DOI: 10.1002/art.21678.
 
14.
Klarenbeek NB, Guler-Yuksel M, van der Kooij SM, et al. The impact of four dynamic, good-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study. Ann Rheum Dis 2011; 70: 1039–1046, DOI: 10.1136/ard.2010.141234.
 
15.
Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomized, double-blind, parallel trial. Lancet 2008; 372: 375–382, DOI: 10.1016/S0140-6736(08)61000-4.
 
16.
Van der Heijde D, Klareskog L, Singh A, et al. Patient reported outcomes in a trial of combination therapy with etanercept and methotrexate for rheumatoid arthritis: the TEMPO trial. Ann Rheum Dis 2005; 63: 328–334, DOI: 10.1136/ard.2005.035709.
 
17.
Weinblatt ME, Keystone EC, Furst DE, et al. Long term efficacy and safety of adalimumab plus methotrexate in patients with rheumatoid arthritis: ARMADA 4-year extended study. Ann Rheum Dis 2006; 65: 753–759, DOI: 10.1136/ard.2005.044404.
 
18.
Smolen J, Landewé RB, Mease P, et al. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomized controlled trial. Ann Rheum Dis 2009; 69: 797–804, DOI: 10.1136/ard.2008.101659.
 
19.
Emery P, Fleischmann RM, Strusberg I, et al. Efficacy and safety of subcutaneous golimumab in methotrexate -naïve patients with rheumatoid arthritis: five-year results of a randomized clinical GO-BEFORE trial. Arthritis Care Res (Hoboken) 2016; 68: 744–752, DOI: 10.1002/acr.22759.
 
20.
Schiff M, Keiserman M, Codding C, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomized, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis 2008; 67: 1–8, DOI: 10.1136/ard.2007.080002.
 
21.
Gabay C, Emery P, van Vollenhoven R, et al. on behalf of the ADACTA Study Investigators. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomized, double-blind, controlled phase 4 trial. Lancet 2013; 381: 1541–1550, DOI: 10.1016/S0140-6736(13)60250-0.
 
22.
Emery P, Fleischmann RM, Filipowicz-Sosnowska A, et al. DANCER study group. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase II B, randomizeds, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 2006; 54: 1390–1400, DOI: 10.1002/art.21778.
 
23.
Tanaka Y, Suzuki M, Nakamura H, et al. Tofacitinib Study Investigators. Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Care Res (Hoboken) 2011; 63: 1150–1158, DOI: 10.1002/acr.20494.
 
24.
Keystone EC, Taylor PC, Drescher E, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Ann Rheum Dis 2015; 74: 333–340, DOI: 10.1136/annrheumdis-2014-206478.
 
25.
Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med 2017; 376: 652–662.
 
26.
Mohamed MEF, Camp HS, Jiang P, et al. Pharmacokinetics, safety and tolerability of ABT-494, a novel selective JAK1 inhibitor, in healthy volunteers and subjects with rheumatoid arthritis. Clin Pharmacokinet 2016; 55: 1547–1558, DOI: 10.1007/s40262-016-0419-y.
 
27.
Burmester GR, Blanco R, Schoeman CC, et al. on behalf of the ORAL Step investigators. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumor necrosis factor inhibitors, a randomized phase 3 trial. Lancet 2013; 381: 451–460, DOI: 10.1016/S0140-6736(12)61424-X.
 
28.
Strand V, Kremer J, Wallenstein G, et al. Effect of tofacitinib monotherapy on patients- reported outomes in a randomized phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs. Arthritis Res Ther 2015; 17: 307–314, DOI: 10.1186/s13075-015-0825-9.
 
29.
Fleischmann R, Pangan AL, Ho Song I, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, doube-blind, randomized controlled trial. Arthritis Rheumatol 2019; 71: 1788–1800, DOI: 10.1002/art.41032.
 
30.
Fleischmann RM, Genovese MC, Enejosa JV, et al. Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis 2019; 78: 1454–1462, DOI: 10.1136/annrheumdis-2019-215764.
 
31.
Fleischmann R, Pangan AL, Mysier E, et al. A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. ACR 2018, Abstract 890.
 
32.
Fleischmann R, Song IH, Enejosa J, et al. Long-term safety and effectiveness of upadacitinib or adalimumab in patients with rheumatoid arthritis: results at 72 weeks from the select-compare study. EULAR 2020: THU0201.
 
33.
Combe B, Kivitz A, Tanaka Y, et al. Efficacy and safety of Filgotinib for patients with rheumatoid arthritis with inadequate response to methotrexate: FINCH1 primary outcome results. ACR2019: Abstract 506.
 
34.
Van der Heijde D, Tanaka Y, Fleischmann R, et al. and the ORAL Scan Investigators. Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis Rheum 2013; 65: 559–570, DOI: 10.1002/art.37816.
 
35.
Van Vollenhoven RF, Fleischmann R, Cohen S, et al. for the ORAL Standard Investigators. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med 2012; 367: 508–519, DOI: 10.1056/NEJMoa1112072.
 
36.
Smolen JS, Aletaha D, Gruber D, et al. Brief Report: Remission rates with tofacitinib treatment in rheumatoid arthritis: a comparison of various remission criteria. Arthritis Rheumatol 2017: 69: 728–734, DOI: 10.1002/art.39996.
 
37.
Dougados M, van der Heijde D, Chen Y-C, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis. 2017; 76: 88–95, DOI: 10.1136/annrheumdis-2016-210094.
 
38.
Scott IC, Hider S, Scott DL. Thromboembolism with Janus Kinase (JAK) inhibitors for rheumatoid arthritis: how real is the risk. Drug Saf 2018; 41: 645–653, DOI: 10.1007/s40264-018-0651-5.
 
39.
Pawar A, Desai RJ, Gautm N, Kim SC. Risk of admission to hospital for serious infection after initiating tofacitinib versus biologic DMARDs in patients with rheumatoid arthritis: a multi database cohort study. Lancet Rheumatol 2020; 2: E84E98, DOI: 10.1016/S2665-9913(19)30137-7.
 
40.
Fleischmann R, Blanco R, Hall S, et al. Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis. Ann Rheum Dis 2021; 80: 432–439, DOI: 10.1136/annrheumdis-2020-218412.
 
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