Upadacitinib in active ankylosing spondylitis: results of the 2-year, double-blind, placebo-controlled SELECT-AXIS 1 study and open-label extension

Heijde, Desirée van der; Deodhar, Atul; Maksymowych, Walter P.; Sieper, Joachim; Bosch, Filip Van den; Kim, So Yeon; Kishimoto, Mitsumasa; Östör, A.; Combe, Bernard; Sui, Yunxia; Duan, Yupeng; Wung, P.; Song, In‐Ho

doi:10.1136/rmdopen-2022-002280

Cited by 24 publications

(18 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Using the appropriate search terms, we identified 543 records and, finally, 19 studies met the inclusion criteria [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. The excluded studies [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ], together with the reasons for their exclusion, are presented in Supplementary Table S2 .…”

Section: Resultsmentioning

confidence: 99%

The Effect of Upadacitinib on Lipid Profile and Cardiovascular Events: A Meta-Analysis of Randomized Controlled Trials

Makris

Barkas

Sfikakis

et al. 2022

JCM

View full text Add to dashboard Cite

Background: Our aim was to systematically investigate the effect of upadacitinib, an oral JAK-1 selective inhibitor, on lipid profile and cardiovascular disease risk. Methods: PubMed, PubMed Central and ClinicalTrials.gov databases were searched for relevant randomized controlled trials (RCTs) up to 31 July 2022. We performed a qualitative synthesis of published RCTs to investigate the associations of upadacitinib with lipoprotein changes, along with a quantitative synthesis of MACE and mean lipoprotein changes where there were available data. Results: Nineteen RCTs were eligible for the present systematic review, which included 10,656 patients with a mean age of 51 years and a follow-up period of 12–52 weeks. Increases in low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were noted upon upadacitinib administration (3–48 mg/day) in 15 studies, while the LDL-C:HDL-C ratio remained unchanged. The pooled analyses of three placebo-controlled RCTs (n = 2577) demonstrated that upadacitinib at 15 mg increased the LDL-C by 15.18 mg/dL (95% CI: 7.77–22.59) and HDL-C by 7.89 mg/dL (95% CI: 7.08–8.69). According to the pooled analysis of 15 placebo-controlled RCTs (n = 7695), upadacitinib had no effect on MACE (risk ratio, RR: 0.62; 95% CI: 0.24–1.60). A sub-analysis focusing on upadacitinib at 15 mg (12 studies, n = 5395) demonstrated similar results (RR: 0.67; 95% CI: 0.19–2.36). Conclusions: Treatment with upadacitinib increases both LDL-C and HDL-C levels. Nevertheless, upadacitinib had no significant effect on the cardiovascular disease risk during a ≤52-week follow-up.

show abstract

Section: Resultsmentioning

confidence: 99%

The Effect of Upadacitinib on Lipid Profile and Cardiovascular Events: A Meta-Analysis of Randomized Controlled Trials

Makris

Barkas

Sfikakis

et al. 2022

JCM

View full text Add to dashboard Cite

show abstract

“…This safety analysis of 6991 patients receiving upadacitinib with a maximum of 5.45 years of follow-up appears largely consistent across RA, PsA, AS and AD for key AESIs such as MACE, VTE and malignancy excluding NMSC, and no new or unexpected safety risks were identified compared with previous reports. [24][25][26][27] Differences in AE types and rates across disease states reflect expected distinctions between disease-specific patient populations and background risks. [28][29][30][31] Long-term exposures with adalimumab (RA and PsA) and MTX (RA only), although with lower numbers of patients evaluated, within the upadacitinib clinical trial programme further enabled the contextualisation of the described upadacitinib safety profile alongside active comparators.…”

Section: Discussionmentioning

confidence: 99%

Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis

et al. 2023

Self Cite

View full text Add to dashboard Cite

ObjectiveTo evaluate the long-term safety profile for upadacitinib across rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and atopic dermatitis (AD).MethodsSafety data from clinical trials of upadacitinib 15 mg and upadacitinib 30 mg (AD only) for treating RA, PsA, AS and AD as of 30 June 2021 were analysed; some RA and PsA studies included adalimumab and methotrexate as active comparators. Treatment-emergent adverse events (TEAEs) were presented by disease as exposure-adjusted event rates per 100 patient years (E/100 PY).ResultsThe analysis included 6991 patients (RA, n=3209; PsA, n=907; AS, n=182; AD, n=2693) who received at least one dose of upadacitinib, representing 15 425 PY of exposure (maximum duration 2.75–5.45 years) across diseases. Rates (E/100 PY) of any TEAE (205.5–278.1) and TEAE leading to discontinuation (4.5–5.4) were similar across diseases; serious TEAEs were numerically higher in patients with RA and PsA. Rates of herpes zoster (1.6–3.6), non-melanoma skin cancer (0–0.8) and elevations in creatine phosphokinase levels (4.4–7.9) were higher with upadacitinib than with active comparators in the RA and PsA populations. Deaths (0–0.8), serious infections (0–3.9), major adverse cardiovascular events (0–0.4), venous thromboembolism (<0.1–0.4) and malignancies (0.3–1.4) were observed, with rates generally lowest in AS and AD. Increased rates of acne were observed in patients with AD only.ConclusionsFindings from this analysis demonstrate that upadacitinib is generally well tolerated with observed differences in safety profiles likely reflective of varying patient characteristics across RA, PsA, AS and AD populations.Trial registration numbersNCT02675426,NCT02706951,NCT02706847,NCT02629159,NCT02706873,NCT03086343,NCT03104374,NCT03104400,NCT03178487,NCT03569293,NCT03568318andNCT03607422.

show abstract

“…In the third paper, the 2-year data of UPA in AS with 187 randomised patients are presented. 18 Most patients (n = 144) completed week 104 (77%). The ASAS 40 response rate in patients receiving continuous UPA at week 104 was 85.9% (as observed) and 65.6% (non-responder imputation).…”

Section: Studies In R-axspa With Upadacitinibmentioning

confidence: 99%

“… 16 SELECT-AXIS is a two-period, parallel-group study that enrolled patients in 20 countries in 62 sites, registered at ClinicalTrials.gov as NCT03178487. Eligible patients who had to fulfil the modified New York criteria for AS 18 also had to have an inadequate response to at least two or intolerance or contraindication to non-steroidal anti-inflammatory drugs (NSAIDs). Previous treatment with bDMARDs was not allowed.…”

Section: Studies In R-axspa With Upadacitinibmentioning

confidence: 99%

Management of Axial Spondyloarthritis – Insights into Upadacitinib

Braun¹,

Kiltz²,

Baraliakos³

2022

DDDT

View full text Add to dashboard Cite

Although the pathogenesis of spondyloarthritis (SpA) has still not been elucidated our options to treat SpA have definitely improved in the last decades. There are two main types of SpA: (i) axial spondyloarthritis (axSpA), also covering the classical ankylosing spondylitis (AS) which is largely equivalent to radiographic (r)-axSpA but different from non-radiographic (nr)-axSpA, and (ii) peripheral SpA (pSpA) also covering psoriatic arthritis (PsA) as the main subtype. The subtype nr-axSpA has historically developed because the approval of drugs for AS did not cover forms without structural changes in the sacroiliac joints which is mandatory in the 1984 New York criteria. The definitions for axSpA are based on the 2009 Assessments in AxSpA International Society (ASAS) classification criteria. Several biologic disease modifying anti-rheumatic drugs (bDMARDs) such as the tumor necrosis factor alpha inhibitors (TNFi) and the interleukin-17-inhibitors (IL-17i) are approved mostly for the whole spectrum of SpA including axSpA and PsA but L-17i does not work in inflammatory bowel disease (IBD). Targeted synthetic (ts) DMARDs cover mainly the janus kinase (JAK)-inhibitors which have recently been developed to inhibit inflammation in several rheumatic and other immune mediated diseases such as IBD. Indeed, the physiologic mechanism of JAK-mediated signal transduction has been recognized as an important target because the inhibition of its actions was shown to successfully work as a therapeutic mechanism. There are now 4 small molecule JAK inhibitors (JAKi) that currently play a role in rheumatology with variable selectivity for the four different JAK isoforms: tofacitinib, baricitinib, upadacitinib and filgotinib. In this review, we summarize current clinical trial data and evaluate the use of the JAK1 selective inhibitor upadacitinib in the treatment of axSpA, including nr-axSpA and r-axSpA. Even though the efficacy and safety of upadacitinib over shorter periods of time has been convincing to date, long-term trials are needed to fully establish its performance and also evaluate the safety at higher doses, and its use in PsA.

show abstract

Upadacitinib in active ankylosing spondylitis: results of the 2-year, double-blind, placebo-controlled SELECT-AXIS 1 study and open-label extension

Cited by 24 publications

References 38 publications

The Effect of Upadacitinib on Lipid Profile and Cardiovascular Events: A Meta-Analysis of Randomized Controlled Trials

The Effect of Upadacitinib on Lipid Profile and Cardiovascular Events: A Meta-Analysis of Randomized Controlled Trials

Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis

Management of Axial Spondyloarthritis – Insights into Upadacitinib

Contact Info

Product

Resources

About