{"id":390630,"date":"2024-11-26T11:42:49","date_gmt":"2024-11-26T10:42:49","guid":{"rendered":"https:\/\/medizinonline.com\/switching-to-upadacitinib-as-an-advantageous-alternative-to-tnfi-cycling-1\/"},"modified":"2024-11-26T11:49:28","modified_gmt":"2024-11-26T10:49:28","slug":"switching-to-upadacitinib-as-an-advantageous-alternative-to-tnfi-cycling-1","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/switching-to-upadacitinib-as-an-advantageous-alternative-to-tnfi-cycling-1\/","title":{"rendered":"Switching to upadacitinib as an advantageous alternative to TNFi cycling [1]"},"content":{"rendered":"\n

The treatment of rheumatoid arthritis (RA) has made significant progress in recent years, but therapy remains a challenge for many patients: up to 60 % of those affected either do not respond to initial treatment or lose their response to therapy over time [2]. TNF inhibitors (TNFi) are still often routinely used as first-line therapies after conventional synthetic (cs)DMARDs and, if there is an insufficient response <\/strong> switched to a second TNFi, which is referred to as TNFi cycling [3]. Current data now suggest that this practice should be reconsidered: instead of another TNFi cycle, switching to substances with a different mechanism of action, such as Janus kinase inhibitors (JAKi), could be beneficial for patients [1]. <\/strong><\/p>\n\n\n\n

In the current treat-to-target (T2T) recommendations for RA, clinical remission is the primary treatment goal [4]. Remission is of central importance for patients, as it not only slows down the progression of joint damage, but also significantly improves the psychological well-being and physical functioning of those affected [5-7]. Early remission in particular is crucial for the long-term effects of the disease [8-10]. Study data andpatient-reported outcomes (<\/em>PRO) show that early remission is associated with long-term remission [8, 9]. Nevertheless, around 30 to 40 % of RA patients who initiate first-line therapy with TNFi discontinue treatment due to primary failure, secondary lack of response or intolerance [1]. In these cases, it is particularly important to quickly switch to an alternative therapy together in order to maintain the chance of a lasting remission and not lose disease control. <\/p>\n\n

Cycling vs. switching<\/strong><\/p>\n\n

The American College of Rheumatology<\/em> (ACR) recommends switching to a bDMARD or tsDMARD of a different drug class in RA after failure of an initial biologic or target-specific<\/em> therapeutic agent (bDMARD or tsDMARD), while the European Alliance of Associations for Rheumatology<\/em> (EULAR) recommends switching to a different mechanism of action and cycling [4, 11]. Both TNFi cycling and switching to an alternative mechanism of action are frequently used when TNFi therapy fails [12]. However, study data show that patients who undergo multiple TNFi cycles are more likely to fail therapy and switch again [13]. However, switching to a different mechanism of action would be associated with an increased chance of clinical improvement and a lower dropout rate [14,15]. <\/p>\n\n

Upadacitinib advantageous for switching<\/strong><\/p>\n\n

A multinational study that analyzed registry data of 503 RA patients after failure of first-line TNFi therapy investigated the success of different follow-up therapies [1]. Patients were compared with a switch to the JAKi upadacitinib (RINVOQ\u00ae, UPA, n=261), a second TNFi (n=128) or a DMARD with a different mechanism of action (n=114) [1, 16]. Patients who switched from a TNFi to UPA achieved significantly better clinical outcomes than those who received a second TNFi. For example, 67.7% of UPA patients achieved remission compared to 40.3% of those who received a second TNFi (p=0.002). Freedom from pain was higher with UPA (55.7 % vs. 25.4 %, p=0.001) and adherence was 60 % compared to 34.2 % among TNFi patients (p=0.005) (Fig. 1) [1]. UPA was also superior to a DMARD with a different mechanism of action in all three respects. In addition, the recently published 5-year data from the SELECT-COMPARE study underline that a change of mechanism of action appears to be beneficial for RA patients who did not reach their treatment goal and that this benefit can be maintained in the long term [17]. The study showed numerical differences mainly in favor of patients who switched from ADA to UPA [17]. However, not only in RA, but also in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), study data indicate that patients respond less well to a second or third TNFi than to the first [12, 18, 19]. <\/p>\n\n

Upadacitinib also beneficial as first-line therapy after csDMARDs<\/strong><\/p>\n\n

The efficacy of UPA versus TNFi as first-line therapy was compared in the head-to-head studies of the SELECT-COMPARE program [20, 21]. UPA + methotrexate (MTX) showed significantly higher efficacy than adalimumab (ADA) + MTX in various parameters such as DAS28\u22642.6, ACR50, change in HAQ-DI and pain relief from as early as 12 weeks [20, 21]. It was also possible to demonstrate a sustained higher remission with UPA + MTX compared to ADA + MTX over 5 years [21]. Several real-world studies have now also demonstrated the good efficacy and long treatment duration of upadacitinib in daily practice [22, 23]. In addition, the up to 7.5-year data published at EULAR 2024 confirm the known safety profile of UPA in over 4700 patients [24]. <\/p>\n\n

<\/p>\n\n

\"\"<\/figure>\n\n

Fig. 1: Significantly better clinical results when switching to UPA (TNFi-UPA) compared to a second TNFi (TNFi-TNFi). TNFi = TNF inhibitor, UPA = upadacitinib. Adapted from [1].<\/p>\n\n

Conclusion<\/strong><\/p>\n\n

The available data suggest that switching from TNFi to UPA may be a beneficial treatment option for RA patients who have not responded adequately to or are intolerant of initial TNFi therapy [1]. Compared to TNFi cycling, switching to UPA with an alternative mechanism of action offers better chances of remission, freedom from pain and treatment adherence [1]. These findings support the recommendation to switch to an alternative mechanism of action at an early stage in order to improve long-term treatment outcomes for RA patients and increase the chance of a lasting remission. <\/p>\n\n

Abbreviations: ACR = American College of Rheumatology; ACR50 = ACR response<\/em> with \u226550% improvement; ADA = adalimumab; axSpA = axial spondyloarthritis; csDMARD = conventional synthetic DMARD; DAS28 = Disease Activity Score 28<\/em>; DMARD = disease-modifying antirheumatic drugs<\/em>; EULAR = European Alliance of Associations for Rheumatology<\/em>; HAQ-DI = Health Assessment Questionnaire Disability Index<\/em>; JAK = Janus kinase; JAKi = JAK inhibitor; MTX = methotrexate; PRO = patient-reported outcome<\/em>; PsA = psoriatic arthritis; RA = rheumatoid arthritis; T2T = treat-to-target<\/em>; TNF = tumor necrosis factor; TNFi = TNF inhibitor; UPA = upadacitinib.<\/p>\n\n

Brief technical information RINVOQ\u00ae<\/a><\/p>\n\n

<\/p>\n\n

\"\"<\/figure>\n\n
\n\n

This article was produced with the financial support of AbbVie AG, Alte Steinhauserstrasse 14, 6330 Cham.<\/p>\n\n

This article has been released in German.Text: Dr. sc. nat. Stefanie JovanovicCH-RNQ-240019 11\/2024<\/p>\n\n

Literature<\/strong><\/p>\n\n

1 Caporali, R., et al, A Real-World Comparison of Clinical Effectiveness in Patients with Rheumatoid Arthritis Treated with Upadacitinib, Tumor Necrosis Factor Inhibitors, and Other Advanced Therapies After Switching from an Initial Tumor Necrosis Factor Inhibitor<\/em>. Adv Ther, 2024. 41<\/strong>(9): p. 3706-3721. 2 Vallejo-Yague, E., et al, Comparative effectiveness of biologics in patients with rheumatoid arthritis stratified by body mass index: a cohort study in a Swiss registry.<\/em> BMJ Open, 2024. 14<\/strong>(2): p. e074864. 3 Edgerton, C., et al, Real-World Treatment and Care Patterns in Patients With Rheumatoid Arthritis Initiating First-Line Tumor Necrosis Factor Inhibitor Therapy in the United States.<\/em> ACR Open Rheumatol, 2024. 6<\/strong>(4): p. 179-188. 4 Smolen, J.S., et al, EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update<\/em>. Ann Rheum Dis, 2023. 82<\/strong>(1): p. 3-18. 5 Lillegraven, S., et al, Remission and radiographic outcome in rheumatoid arthritis: application of the 2011 ACR\/EULAR remission criteria in an observational cohort<\/em>. Ann Rheum Dis, 2012. 71<\/strong>(5): p. 681-6. 6 McInnes, I.B. and G. Schett, The pathogenesis of rheumatoid arthritis.<\/em> N Engl J Med, 2011. 365<\/strong>(23): p. 2205-19.7 Einarsson, J.T., et al, Sustained Remission Improves Physical Function in Patients with Established Rheumatoid Arthritis, and Should Be a Treatment Goal: A Prospective Observational Cohort Study from Southern Sweden.<\/em> J Rheumatol, 2016. 43<\/strong>(6): p. 1017-23. 8. Ten Klooster, P.M., et al, Long-term clinical, functional, and cost outcomes for early rheumatoid arthritis patients who did or did not achieve early remission in a real-world treat-to-target strategy.<\/em> Clin Rheumatol, 2019. 38<\/strong>(10): p. 2727-2736. 9 Xie, W., J. Li, and Z. Zhang, The impact of different criteria sets on early remission and identifying its predictors in rheumatoid arthritis: results from an observational cohort (2009-2018).<\/em> Clin Rheumatol, 2020. 39<\/strong>(2): p. 381-389. 10 Snoeck Henkemans, S.V.J., et al, Patient-reported outcomes and radiographic progression in patients with rheumatoid arthritis in sustained remission versus low disease activity.<\/em> RMD Open, 2024. 10<\/strong>(1). 11 Fraenkel, L., et al, 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.<\/em> Arthritis Care Res (Hoboken), 2021. 73<\/strong>(7): p. 924-939.12 Bogas, P., et al, Comparison of long-term efficacy between biological agents following tumor necrosis factor inhibitor failure in patients with rheumatoid arthritis: a prospective cohort study.<\/em> Ther Adv Musculoskelet Dis, 2021. 13<\/strong>: p. 1759720×211060910. 13 Wei, W., et al, Treatment Persistence and Clinical Outcomes of Tumor Necrosis Factor Inhibitor Cycling or Switching to a New Mechanism of Action Therapy: Real-world Observational Study of Rheumatoid Arthritis Patients in the United States with Prior Tumor Necrosis Factor Inhibitor Therapy<\/em>. Adv Ther, 2017. 34<\/strong>(8): p. 1936-1952. 14 Migliore, A., et al, Cycling of tumor necrosis factor inhibitors versus switching to different mechanism of action therapy in rheumatoid arthritis patients with inadequate response to tumor necrosis factor inhibitors: a Bayesian network meta-analysis<\/em>. Ther Adv Musculoskelet Dis, 2021. 13<\/strong>: p. 1759720×211002682. 15 Mann, H., et al, Switching to a Targeted Drug with a Different Mode of Action After Discontinuation of the First TNF Inhibitor Is Associated with Better Drug Survival Compared to a Second TNF Inhibitor in Rheumatoid Arthritis: A Propensity Score-matched Analysis from the Czech ATTRA Registry. <\/em>Abstract 2277, presented at the ACR Convergence, November 14-19, 2024, Washington DC, USA.16. current technical information for RINVOQ\u00ae <\/sup>(upadacitinib) at www.swissmedicinfo.ch.<\/a>17 Fleischmann, R., et al, Long-term Efficacy and Safety Following Switch Between Upadacitinib and Adalimumab in Patients with Rheumatoid Arthritis: 5-Year Data from SELECT-COMPARE<\/em>. Rheumatol Ther, 2024. 11<\/strong>(3): p. 599-615. 18 Linde, L., et al, Second and third TNF inhibitors in European patients with axial spondyloarthritis: effectiveness and impact of the reason for switching.<\/em> Rheumatology (Oxford), 2024. 63<\/strong>(7): p. 1882-1892. 19 \u00d8rnbjerg, L.M., et al, Drug effectiveness of 2nd and 3rd TNF inhibitors in psoriatic arthritis – relationship with the reason for withdrawal from the previous treatment.<\/em> Joint Bone Spine, 2024. 91<\/strong>(4): p. 105729. 20 Fleischmann, R., et al, 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.<\/em> Arthritis Rheumatol, 2019. 71<\/strong>(11): p. 1788-1800.21 Fleischmann, R., et al, Long-term safety and efficacy of upadacitinib versus adalimumab in patients with rheumatoid arthritis: 5-year data from the phase 3, randomized SELECT-COMPARE study.<\/em> RMD Open, 2024. 10<\/strong>(2). 22 Witte, T., et al, The impact of C-reactive protein levels on the effectiveness of upadacitinib in patients with rheumatoid arthritis: a 12-month prospective, non-interventional German study.<\/em> Clin Exp Rheumatol, 2024. 42<\/strong>(3): p. 726-735. 23 Bessette, L., et al, Real-World Effectiveness of Upadacitinib for Treatment of Rheumatoid Arthritis in Canadian Patients: Interim Results from the Prospective Observational CLOSE-UP Study.<\/em> Rheumatol Ther, 2024. 11<\/strong>(3): p. 563-582. 24 Burmester GR, et al, Safety of Upadacitinib Across Rheumatoid Arthritis, Psoriatic Arthritis, and Axial Spondyloarthritis Encompassing 15,000 Patient-Years of Clinical Trial Data. <\/em>Presented at the European Congress of Rheumatology (EULAR), June 12-15, 2024, Vienna, Austria. POS0894. <\/p>\n\n

The references can be requested by professionals at medinfo.ch@abbvie.com.<\/p>\n\n

<\/p>\n\n

<\/a><\/p>\n\n

\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"

The treatment of rheumatoid arthritis (RA) has made significant progress in recent years, but therapy remains a challenge for many patients: up to 60 % of those affected either do…<\/p>\n","protected":false},"author":14,"featured_media":390632,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"pmpro_default_level":"","cat_1_feature_home_top":false,"cat_2_editor_pick":false,"csco_eyebrow_text":"Sponsored Content: Rheumatoid arthritis","footnotes":""},"category":[11340,11323,11480,11548],"tags":[],"powerkit_post_featured":[],"class_list":["post-390630","post","type-post","status-publish","format-standard","has-post-thumbnail","category-dermatology-and-venereology","category-partner-content-en","category-rheumatology","category-rx-en","pmpro-has-access"],"acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-05-02 23:17:59","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"wpml_current_locale":"en_US","wpml_translations":{"fr_FR":{"locale":"fr_FR","id":390639,"slug":"switching-to-upadacitinib-as-a-beneficial-alternative-to-tnfi-cycling-1","post_title":"Switching to upadacitinib as a beneficial alternative to TNFi-cycling [1]","href":"https:\/\/medizinonline.com\/fr\/switching-to-upadacitinib-as-a-beneficial-alternative-to-tnfi-cycling-1\/"},"it_IT":{"locale":"it_IT","id":390633,"slug":"passare-a-upadacitinib-come-alternativa-vantaggiosa-al-ciclo-del-tnfi-1","post_title":"Passare a upadacitinib come alternativa vantaggiosa al ciclo del TNFi [1]","href":"https:\/\/medizinonline.com\/it\/passare-a-upadacitinib-come-alternativa-vantaggiosa-al-ciclo-del-tnfi-1\/"},"pt_PT":{"locale":"pt_PT","id":390642,"slug":"mudanca-para-upadacitinib-como-uma-alternativa-vantajosa-ao-ciclo-tnfi-1","post_title":"Mudan\u00e7a para upadacitinib como uma alternativa vantajosa ao ciclo TNFi [1]","href":"https:\/\/medizinonline.com\/pt-pt\/mudanca-para-upadacitinib-como-uma-alternativa-vantajosa-ao-ciclo-tnfi-1\/"},"es_ES":{"locale":"es_ES","id":390631,"slug":"el-cambio-a-upadacitinib-como-alternativa-ventajosa-a-los-ciclos-con-tnfi-1","post_title":"El cambio a upadacitinib como alternativa ventajosa a los ciclos con TNFi [1].","href":"https:\/\/medizinonline.com\/es\/el-cambio-a-upadacitinib-como-alternativa-ventajosa-a-los-ciclos-con-tnfi-1\/"}},"_links":{"self":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/390630","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/users\/14"}],"replies":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/comments?post=390630"}],"version-history":[{"count":1,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/390630\/revisions"}],"predecessor-version":[{"id":390634,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/390630\/revisions\/390634"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media\/390632"}],"wp:attachment":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media?parent=390630"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/category?post=390630"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/tags?post=390630"},{"taxonomy":"powerkit_post_featured","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/powerkit_post_featured?post=390630"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}