Patient-related factors influencing the effectiveness and safety of Janus Kinase inhibitors in rheumatoid arthritis: a real-world study.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 Jan 2024
02 Jan 2024
Historique:
received:
13
10
2023
accepted:
19
12
2023
medline:
4
1
2024
pubmed:
4
1
2024
entrez:
3
1
2024
Statut:
epublish
Résumé
In real-world scenarios, Janus Kinase (JAK) inhibitors are often offered to "difficult-to-treat" rheumatoid arthritis patients, quite different from those included in randomized controlled trials. Our study aimed to evaluate the influence of patient-related factors on the effectiveness and safety of JAK inhibitors in real-world clinical practice. This observational retrospective study involved rheumatoid arthritis patients who received treatment with either tofacitinib, baricitinib, upadacitinib, or filgotinib. At 12 months of treatment, reasons for and rates of JAK inhibitor treatment discontinuation were examined. Treatment retentions were analyzed through Cox proportional hazard regression models and Kaplan-Meier estimates. Patient-related factors that could influence treatment retention were evaluated for the discontinuation reasons of lack of effectiveness and adverse events. At 12 months of treatment, discontinuation rates for 189 JAK inhibitor treatments were: lack of effectiveness (24.3%), adverse events (20.6%), and other reasons (3.7%). The remaining 51.4% represents the treatment continuation rate. No patient-related factors evaluated had an influence on treatment discontinuation due to lack of effectiveness. Ae significantly increased the risk of treatment discontinuation due to adverse events (p = 0.030). In terms of age, at 12 month of treatment, discontinuation rates due to adverse events were: < 65 years, 14.4% vs. 65 years or older, 26.3% (p = 0.019). Rheumatoid arthritis patients aged 65 years or older showed an increased risk of JAK inhibitor treatment discontinuation due to adverse events. Factors not related to treatment discontinuation were: sex, rheumatoid arthritis disease duration, rheumatoid arthritis disease activity, seropositivity for rheumatoid factor, seropositivity for anti-cyclic citrullinated peptides, number of prior biologic treatments, number of prior JAK inhibitor treatments, concomitant use of glucocorticoids, and concomitant use of conventional synthetic disease-modifying antirheumatic drugs.
Identifiants
pubmed: 38168532
doi: 10.1038/s41598-023-50379-8
pii: 10.1038/s41598-023-50379-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
172Informations de copyright
© 2024. The Author(s).
Références
Aletaha, D. & Smolen, J. S. Diagnosis and management of rheumatoid arthritis: A review. JAMA. 320(13), 1360–1372. https://doi.org/10.1001/jama.2018.13103 (2018).
McInnes, IB. & Schett, G. The pathogenesis of rheumatoid arthritis. N. Engl. J. Med. 365(23), 2205–2219. https://doi.org/10.1056/NEJMra1004965 (2011).
Smolen, J. S. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann. Rheum. Dis. 82(1), 3–18. https://doi.org/10.1136/ard-2022-223356 (2023).
Fraenkel, L. et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 73(7), 924–939. https://doi.org/10.1002/acr.24596 (2021).
doi: 10.1002/acr.24596
Fleischmann, R. et al. ORAL-Solo Investigators. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N. Engl. J. Med. 367(6), 495–507. https://doi.org/10.1056/NEJMoa1109071 (2012).
Kremer, J. et al. ORAL-Sync Investigators. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann. Intern. Med. 159(4), 253–261. https://doi.org/10.7326/0003-4819-159-4-201308200-00006 (2013).
Van Vollenhoven, R. F. et al. ORAL-Standard Investigators. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N. Engl. J. Med. 367(6), 508–519. https://doi.org/10.1056/NEJMoa1112072 (2012).
Van der Heijde, D. et al. 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. 65(3), 559–570. https://doi.org/10.1002/art.37816 (2013).
Burmester, G. R. et al. ORAL-Step Investigators. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: A randomised phase 3 trial. Lancet. 381(9865), 451–460. https://doi.org/10.1016/S0140-6736(12)61424-X (2013).
Lee, EB. et al. ORAL-Start Investigators. Tofacitinib versus methotrexate in rheumatoid arthritis. N. Engl. J. Med. 370(25), 2377–2386. https://doi.org/10.1056/NEJMoa1310476 (2014).
Fleischmann, R. et al. ORAL-Strategy Investigators. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): A phase 3b/4, double-blind, head-to-head, randomised controlled trial. Lancet. 390(10093), 457–468. https://doi.org/10.1016/S0140-6736(17)31618-5 (2017).
Fleischmann, R. et al. RA-BEGIN Investigators. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol. 69(3), 506–517. https://doi.org/10.1002/art.39953 (2017).
Taylor, P. C. et al. RA-BEAM Investigators. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N. Engl. J. Med. 376(7), 652–662. https://doi.org/10.1056/NEJMoa1608345 (2017).
Dougados, M. et al. RA-BUILD Investigators. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: Results from the RA-BUILD study. Ann. Rheum. Dis. 76(1), 88–95. https://doi.org/10.1136/annrheumdis-2016-210094 (2017).
Genovese, M. C. et al; RA-BEACON Investigators. Baricitinib in patients with refractory rheumatoid arthritis. N. Engl. J. Med. 374(13), 1243–1252. https://doi.org/10.1056/NEJMoa1507247 (2016).
Van Vollenhoven, R. et al. SELECT-EARLY Investigators. Efficacy and safety of upadacitinib monotherapy in methotrexate-naive patients with moderately-to-severely active rheumatoid arthritis (SELECT-EARLY): A multicenter, multi-country, randomized, double-blind, active comparator-controlled trial. Arthritis Rheumatol. 72(10), 1607–1620. https://doi.org/10.1002/art.41384 (2020).
Smolen, J. S. et al. SELECT-MONOTHERAPY Investigators. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): A randomised, placebo-controlled, double-blind phase 3 study. Lancet. 393(10188), 2303–2311. https://doi.org/10.1016/S0140-6736(19)30419-2 (2019).
Burmester, G. R. et al. SELECT-NEXT Investigators. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 391(10139), 2503–2512. https://doi.org/10.1016/S0140-6736(18)31115-2 (2018).
Fleischmann, R. et al. SELECT-COMPARE Investigators. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: Results of a phase III, double-blind, randomized controlled trial. Arthritis Rheumatol. 71(11), 1788–1800. https://doi.org/10.1002/art.41032 (2019).
Genovese, M. C. et al. SELECT-BEYOND Investigators. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): A double-blind, randomised controlled phase 3 trial. Lancet. 391(10139), 2513–2524. https://doi.org/10.1016/S0140-6736(18)31116-4 (2018).
Rubbert-Roth, A. et al. SELECT-CHOICE Investigators. Trial of upadacitinib or abatacept in rheumatoid arthritis. N. Engl. J. Med. 383(16), 1511–1521. https://doi.org/10.1056/NEJMoa2008250 (2020).
Combe, B. et al. FINCH-1 Investigators. Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: A phase III randomised clinical trial. Ann. Rheum Dis. 80(7), 848–858. https://doi.org/10.1136/annrheumdis-2020-219214 (2021).
Genovese, M. C. et al; FINCH-2 Investigators. Effect of filgotinib vs placebo on clinical response in patients with moderate to severe rheumatoid arthritis refractory to disease-modifying antirheumatic drug therapy: The FINCH 2 randomized clinical trial. JAMA. 322(4), 315–325. https://doi.org/10.1001/jama.2019.9055 (2019).
Westhovens, R. et al. FINCH-3 Investigators. Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: The phase 3, randomised controlled FINCH 3 trial. Ann. Rheum. Dis. 80(6), 727–738. https://doi.org/10.1136/annrheumdis-2020-219213 (2021).
Mahajan, R. Real world data: Additional source for making clinical decisions. Int. J. Appl. Basic Med. Res. 5(2), 82. https://doi.org/10.4103/2229-516X.157148 (2015).
doi: 10.4103/2229-516X.157148
pubmed: 26097811
pmcid: 4456898
Sherman, RE. et al. Real-world evidence - What is it and what can it tell us? N Engl J Med. 375(23), 2293–2297. https://doi.org/10.1056/NEJMsb1609216 (2016).
Nagy, G. et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 80(1), 31–35. https://doi.org/10.1136/annrheumdis-2020-217344 (2021).
Aletaha, D. et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League against rheumatism collaborative initiative. Ann. Rheum Dis. 69, 1580–1588. https://doi.org/10.1136/ard.2010.138461 (2010).
doi: 10.1136/ard.2010.138461
pubmed: 20699241
Ebina, K. et al. Factors affecting drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis: The ANSWER cohort study. Sci. Rep. 12(1), 134. https://doi.org/10.1038/s41598-021-04075-0 (2022).
doi: 10.1038/s41598-021-04075-0
pubmed: 34997059
pmcid: 8742057
Curtis, J. R. et al. Efficacy and safety of tofacitinib in older and younger patients with rheumatoid arthritis. Clin. Exp. Rheumatol. 35(3), 390–400 (2017).
Fleischmann, R. et al. Safety and efficacy of baricitinib in elderly patients with rheumatoid arthritis. RMD Open. 3(2), e000546. https://doi.org/10.1136/rmdopen-2017-000546 (2017).
doi: 10.1136/rmdopen-2017-000546
pubmed: 29071120
pmcid: 5640108
Kristensen, L. E. et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: An analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 82(7), 901–910. https://doi.org/10.1136/ard-2022-223715 (2023).
European Medicines Agency – EMA (2023). EMA confirms measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders. EMA/142279/2023. https://www.ema.europa.eu/en/medicines/human/referrals/janus-kinase-inhibitors-jaki . Accessed 22 May 2023.
Pombo-Suarez, M. et al. After JAK inhibitor failure: To cycle or to switch, that is the question—data from the JAK-pot collaboration of registries. Ann. Rheum. Dis. 82(2), 175–181. https://doi.org/10.1136/ard-2022-222835 (2023).
doi: 10.1136/ard-2022-222835
pubmed: 36100351
Bird, P. et al. Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib. RMD Open. 5(1), e000742. https://doi.org/10.1136/rmdopen-2018-000742 (2019).
doi: 10.1136/rmdopen-2018-000742
pubmed: 30886732
pmcid: 6397430
Retuerto, M. et al. Efficacy and safety of switching Jak inhibitors in rheumatoid arthritis: An observational study. Clin. Exp. Rheumatol. 39(3), 453–455. https://doi.org/10.55563/clinexprheumatol/cbanza (2021).
Cohen, S. et al. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 66(11), 2924–2937. https://doi.org/10.1002/art.38779 (2014).
doi: 10.1002/art.38779
pubmed: 25047021
Sanmartí, R. & Corominas, H. Upadacitinib for patients with rheumatoid arthritis: A comprehensive review. J. Clin. Med. 12(5), 1734. https://doi.org/10.3390/jcm12051734 (2023).
doi: 10.3390/jcm12051734
pubmed: 36902522
pmcid: 10002765