POS0923 INFLUENCE OF BASELINE DEMOGRAPHICS ON IMPROVEMENTS IN DISEASE ACTIVITY MEASURES IN PATIENTS WITH ANKYLOSING SPONDYLITIS RECEIVING UPADACITINIB: A POST HOC SUBGROUP ANALYSIS OF SELECT-AXIS 1
Authors: Van den Bosch F. , Poddubnyy D. , Stigler J. , Ostor A. , D’angelo S. , Navarro-Compán V. , Song I. H. , Gao T. , Ganz F. , Gensler L. S. 
Published: May 2021

Background:

Upadacitinib (UPA), an oral Janus kinase inhibitor, has demonstrated efficacy and safety through 14 weeks in the SELECT-AXIS 1 study in biologic disease-modifying antirheumatic drug-naïve patients with active ankylosing spondylitis (AS).1

Objectives:

To evaluate the efficacy of UPA 15 mg once daily (QD) in selected subgroups of patients with AS based on different baseline characteristics.

Methods:

In SELECT-AXIS 1, patients were randomized to 14 weeks of blinded treatment with UPA 15 mg QD or placebo (PBO). This post hoc analysis evaluated the proportions of patients achieving ≥40% improvement in Assessment of SpondyloArthritis International Society criteria (ASAS40), ≥50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), and change from baseline in Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS[CRP]) at Week 14 across subgroups based on the following baseline patient characteristics: gender, age, body mass index, AS symptom duration, C-reactive protein (CRP) levels, Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging index, and human leukocyte antigen B27 status. For missing data, non-responder imputation analysis was used for ASAS40 and BASDAI50, and mixed model repeated measures analysis was used for ASDAS(CRP).

Results:

Baseline disease characteristics were balanced between the treatment groups at randomization, as previously reported.1 ASAS40 and BASDAI50 response rates at Week 14 were numerically higher with UPA 15 mg versus PBO across the demographic and disease characteristic subgroups evaluated (Figure 1), including some subgroups with small sample sizes, such as patients with disease duration <5 years and female patients. Improvements from baseline in ASDAS(CRP) were also consistently greater with UPA 15 mg versus PBO across the subgroups evaluated (Table 1).

Conclusion:

Within subgroups evaluated, most patients with active AS receiving UPA 15 mg demonstrated greater improvements versus PBO in disease activity measures assessed by ASAS40, BASDAI50, and change from baseline in ASDAS(CRP). There was some evidence that gender, AS symptom duration, and baseline CRP levels seemed to influence outcomes, though results should be interpreted with caution due to small sample sizes for some subgroups.

References:

[1]van der Heijde D, et al. Lancet 2019;394:2108–17.

Table 1.

PBO-corrected mean change from baseline (95% CI) in ASDAS(CRP) at Week 14 in patients receiving UPA 15 mg by baseline subgroups (MMRM)

nASDAS(CRP)SubgroupUPA
15 mgPBOPBO-corrected mean change from baseline (95% CI)GenderMale5862–1.11 (–1.37, –0.84)Female2622–0.44 (–0.92, 0.03)Age<40 years2436–1.00 (–1.42, –0.58)40–<65 years5146–0.88 (–1.17, –0.59)Body mass index<25 kg/m23237–0.92 (–1.30, –0.55)≥25 kg/m25247–0.89 (–1.20, –0.59)AS symptom duration<5 years1617–0.90 (–1.46, –0.34)≥5 years6867–0.92 (–1.18, –0.66)Baseline hsCRP≤2.8 mg/L2319–0.59 (–1.02, –0.15)>2.8–<10 mg/L3934–0.59 (–0.95, –0.23)≥10 mg/L2231–1.64 (–2.01, –1.27)Inflammation based on SPARCC MRI scoresPositivea5657–0.98 (–1.27, –0.69)Negativeb2116–0.60 (–1.08, –0.12)HLA-B27 statusPositive6266–0.97 (–1.24, –0.71)Negative2017–0.73 (–1.28, –0.17)

aSpine SPARCC score ≥2 or sacroiliac joint SPARCC score ≥2. bSpine SPARCC score <2 and sacroiliac joint SPARCC score <2

ASDAS(CRP), Ankylosing Spondylitis Disease Activity Score with C-reactive protein; CI, confidence interval; HLA-B27, human leukocyte antigen B27; hsCRP, high-sensitivity C-reactive protein; MMRM, mixed model repeated measures; MRI, magnetic resonance imaging; PBO, placebo; SPARCC, Spondyloarthritis Research Consortium of Canada; UPA, upadacitinib

Acknowledgements:

AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Laura Chalmers, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.

Disclosure of Interests:

Filip van den Bosch Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Janssen, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Jayne Stigler Employee of: AbbVie employee and may own stock or options, Andrew Ostor Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Salvatore D’Angelo Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Victoria Navarro-Compán Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, In-Ho Song Employee of: AbbVie employee and may own stock or options, Tianming Gao Employee of: AbbVie employee and may own stock or options, Fabiana Ganz Employee of: AbbVie employee and may own stock or options, Lianne S. Gensler Consultant of: AbbVie, Eli Lilly, Gilead, GSK, Novartis, Pfizer, and UCB, Grant/research support from: Pfizer and UCB