Thu0191 upadacitinib as Monotherapy in Patients With Rheumatoid Arthritis: Results at 48 Weeks From the Select-Monotherapy Study

Smolen, Josef S.; Emery, Paul; Rigby, William F.C.; Tanaka, Yoshiya; Vargas, Juan Ignacio; Damjanov, Nemanja; Jain, Manish; Sui, Yunxia; Enejosa, Jeffrey; Pangan, Aileen L.; Camp, Heidi S.; Cohen, Stanley

doi:10.1136/annrheumdis-2019-eular.491

Cited by 4 publications

(4 citation statements)

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“…Upadacitinib 15 mg, as monotherapy or in combination with csDMARDs/methotrexate, met all primary and ranked secondary efficacy endpoints and achieved significantly higher remission and LDA rates than placebo, methotrexate, and adalimumab across all five pivotal phase III trials in the SELECT clinical program [25,29,48,49,54].…”

Section: Summary Of Benefit-risk Assessmentmentioning

confidence: 95%

Upadacitinib in Rheumatoid Arthritis: A Benefit–Risk Assessment Across a Phase III Program

Conaghan

Mysler²,

Tanaka

et al. 2021

Drug Saf

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Treating to a target of clinical remission or low disease activity is an important principle for managing rheumatoid arthritis (RA). Despite the availability of biologic disease-modifying antirheumatic drugs (bDMARDs), a substantial proportion of patients with RA do not achieve these treatment targets. Upadacitinib is a once-daily, oral Janus kinase (JAK) inhibitor with increased selectivity for JAK1 over JAK2, JAK3, and tyrosine kinase 2. The SELECT phase III upadacitinib clinical program comprised five pivotal trials of approximately 4400 patients with RA, including inadequate responders (IR) to conventional synthetic (cs)DMARDs or bDMARDs. This review aims to provide insights into the benefit–risk profile of upadacitinib in patients with RA. Upadacitinib 15 mg once daily, in combination with csDMARDs or as monotherapy, achieved all primary and ranked secondary endpoints in the five pivotal trials across csDMARD-naïve, csDMARD-IR, and bDMARD-IR populations. Upadacitinib 15 mg also demonstrated significantly higher rates of remission and low disease activity in all five pivotal trials, compared with placebo, methotrexate, or adalimumab. Labeled warnings of JAK inhibitors include serious infections, herpes zoster, malignancies, major cardiovascular events, and venous thromboembolic events. Short- and long-term integrated analyses showed that upadacitinib 15 mg was associated with increased risk of herpes zoster and creatine phosphokinase elevations compared with methotrexate and adalimumab but otherwise had comparable safety with these active comparators. This review suggests that upadacitinib 15 mg had a favorable benefit–risk profile. The safety of upadacitinib will continue to be monitored in long-term extensions and post-marketing studies. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-020-01036-w.

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Section: Summary Of Benefit-risk Assessmentmentioning

confidence: 95%

Upadacitinib in Rheumatoid Arthritis: A Benefit–Risk Assessment Across a Phase III Program

Conaghan

Mysler²,

Tanaka

et al. 2021

Drug Saf

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“…From 1,565 unique records, we identified 14 trials that met our inclusion criteria, involving 13,524 patients (Kremer et al, 2013;Fleischmann et al, 2015;Taylor et al, 2017;Burmester et al, 2018;Genovese et al, 2018;Fleischmann et al, 2019;Smolen et al, 2019;Rubbert-Roth et al, 2020;van Vollenhoven et al, 2020;Ozdede and Yazıcı, 2022). See Figure 1 for the PRISMA flow diagram summarizing search results.…”

Section: Search Results and Description Of Included Studiesmentioning

confidence: 99%

Cardiovascular safety of Janus kinase inhibitors in patients with rheumatoid arthritis: systematic review and network meta-analysis

et al. 2023

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Background: Janus kinase (JAK) inhibitors have emerged as a progressively utilized therapeutic approach for the management of rheumatoid arthritis (RA). However, the complete determination of their cardiovascular safety remains inconclusive. Hence, the primary objective of this network meta-analysis is to meticulously assess and juxtapose the cardiovascular risks linked to distinct JAK inhibitors employed in RA patients.Methods: A systematic review and network meta-analysis were meticulously conducted, encompassing a collection of randomized controlled trials (RCTs) that focused on investigating the incidence of major adverse cardiovascular events (MACE) and all-cause mortality associated with Janus kinase (JAK) inhibitors administered to patients with rheumatoid arthritis (RA). Extensive exploration was performed across multiple electronic databases, incorporating studies published until March 2023. To be included in this analysis, the RCTs were required to involve adult participants diagnosed with RA who received treatment with JAK inhibitors. To ensure accuracy, two authors independently undertook the selection of eligible RCTs and meticulously extracted aggregate data. In order to examine the outcomes of MACE and all-cause mortality, a frequentist graph theoretical approach within network meta-analyses was employed, utilizing random-effects models. Third study has been registered on PROSPERO under the reference CRD42022384611.Findings: A specific selection encompassing a total of 14 meticulously chosen randomized controlled trials was undertaken, wherein 13,524 patients were assigned randomly to distinct treatment interventions. The analysis revealed no notable disparity in the occurrence of major adverse cardiovascular events (MACE) between the interventions and the placebo group. However, in comparison to adalimumab, the employment of JAK inhibitors exhibited an association with higher rates of all-cause mortality [odds ratio (OR): 1.7, 95% confidence interval (CI): 1.02–2.81]. This observed increase in risk primarily stemmed from the usage of tofacitinib (OR: 1.9, 95% CI: 1.12–3.23). None of the other JAK inhibitors exhibited a statistically significant variance in all-cause mortality when compared to adalimumab.Interpretation: Our study suggests that JAK inhibitors may not increase the risk of MACE in RA patients but may be associated with a higher risk of all-cause mortality compared to adalimumab, primarily due to tofacitinib use. Rheumatologists should carefully consider the cardiovascular risks when prescribing JAK inhibitors, particularly tofacitinib, for RA patients.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=384611, CRD42022384611.

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“…The flowchart of the literature selection is shown in Figure 1. Of 3,428 studies initially identified, a total of 44 citations including 47 distinct RCTs (Fleischmann et al, 2012;van Vollenhoven et al, 2012;Kremer et al, 2013;van der Heijde et al, 2013;Lee et al, 2014;Bachelez et al, 2015;Fleischmann et al, 2015;Keystone et al, 2015;Papp et al, 2015;Tanaka et al, 2015;Genovese et al, 2016a;Genovese et al, 2016b;Takeuchi et al, 2016;Abe et al, 2017;Dougados et al, 2017;Fleischmann et al, 2017;Gladman et al, 2017;Kavanaugh et al, 2017;Kivitz et al, 2017;Mease et al, 2017;Panés et al, 2017;Sandborn et al, 2017;Taylor et al, 2017;van der Heijde et al, 2017;Vermeire et al, 2017;Westhovens et al, 2017;Zhang et al, 2017;Burmester et al, 2018;Genovese et al, 2018;Mease et al, 2018;Genovese et al, 2019;Smolen et al, 2019;Takeuchi et al, 2019;van der Heijde et al, 2019;Deodhar et al, 2021;Feagan et al, 2021;McInnes et al, 2021;Mease et al, 2021;Chen et al, 2022;Danese et al, 2022;Deodhar et al, 2022;…”

Section: Search Strategy and Study Characteristicsmentioning

confidence: 99%

Risk of herpes zoster associated with JAK inhibitors in immune-mediated inflammatory diseases: a systematic review and network meta-analysis

Xu,

He,

Yin

2023

Front. Pharmacol.

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Objective: Janus kinase (JAK) inhibitors are a novel class of drugs that have shown efficacy in treating immune-mediated inflammatory diseases (IMIDs). However, their safety profile in terms of herpes zoster infection remains unclear. We aimed to evaluate the risk of herpes zoster associated with JAK inhibitors in patients with IMIDs.Methods: A systematic search of electronic databases was conducted to identify randomized controlled trials (RCTs) that evaluated the safety of JAK inhibitors in patients with IMIDs including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriasis (PsO), and psoriatic arthritis (PsA). The primary outcome of interest was the incidence of herpes zoster infection. Network meta-analysis was performed to compare the risk of herpes zoster among different JAK inhibitors and placebo.Results: A network meta-analysis was conducted using data from 47 RCTs including 24,142 patients. In patients with IMIDs, peficitinib 100 mg QD was associated with the highest risk of herpes zoster infection in patients with IMIDs, followed by baricitinib 4 mg QD and upadacitinib 30 mg QD. No difference in herpes zoster risk was found for other JAK inhibitors compared with placebo. Subgroup analysis indicated that higher incidence of herpes zoster was found in patients treated by baricitinib 4 mg QD, peficitinib 100 mg QD, and upadacitinib 30 mg QD only in patients with RA.Conclusion: Our study suggests that some JAK inhibitors, particularly peficitinib, baricitinib, and tofacitinib, are associated with a higher risk of herpes zoster infection in patients with IMIDs.

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Thu0191 upadacitinib as Monotherapy in Patients With Rheumatoid Arthritis: Results at 48 Weeks From the Select-Monotherapy Study

Cited by 4 publications

References 0 publications

Upadacitinib in Rheumatoid Arthritis: A Benefit–Risk Assessment Across a Phase III Program

Upadacitinib in Rheumatoid Arthritis: A Benefit–Risk Assessment Across a Phase III Program

Cardiovascular safety of Janus kinase inhibitors in patients with rheumatoid arthritis: systematic review and network meta-analysis

Risk of herpes zoster associated with JAK inhibitors in immune-mediated inflammatory diseases: a systematic review and network meta-analysis

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