Ab0947 effect of Upadacitinib on Reducing Pain in Patients With Active Ankylosing Spondylitis and Inadequate Response to Biologic Therapy

Abstract

BackgroundPain is a debilitating symptom of ankylosing spondylitis (AS) that negatively affects patients’ lives. Upadacitinib (UPA), a Janus kinase inhibitor approved for the treatment of AS and other inflammatory diseases, showed significant efficacy vs placebo (PBO) in the phase 2/3 SELECT-AXIS 1 study in patients with AS who were biologic-naive and in the phase 3 SELECT-AXIS 2 study in patients with active AS who had an inadequate response (IR) to biological therapy[1,2]. Improvement in pain outcomes with UPA was also previously demonstrated in the SELECT-AXIS 1 study[3].ObjectivesThe objective of this post-hoc analysis of SELECT-AXIS 2 was to evaluate the efficacy of UPA vs PBO on multiple pain assessments through 14 weeks in patients with IR to a biologic disease-modifying antirheumatic drug (bDMARD-IR).MethodsSELECT-AXIS 2 (NCT04169373) enrolled adults with active AS with IR to biological therapy, including patients who discontinued biologics due to lack of efficacy or intolerance[1]. Patients were randomized 1:1 to UPA 15 mg once daily (QD) or PBO for 14 weeks. Pain endpoints evaluated here included the proportion of patients achieving ≥30%, ≥50%, and ≥70% reduction from baseline, minimal clinically important difference (MCID, defined as ≥1 point reduction or ≥15% reduction from baseline), and much better improvement (MBI, defined as ≥2 point reduction and ≥33% reduction from baseline) in Patient’s Global Assessment (PGA) of pain, total back pain, and nocturnal back pain on a 0–10 numeric rating scale[3,4]. Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.ResultsA total of 211 patients received UPA 15 mg QD and 209 patients received PBO. Higher proportions of patients receiving UPA vs PBO achieved ≥30% and ≥50% reductions in PGA of pain, total back pain, and nocturnal back pain as early as week 2 that were sustained at all time points through 14 weeks (nominalP<0.05;Figure 1a-c). Achievement of ≥70% reductions in PGA of pain and nocturnal back pain were higher at week 4 and sustained thereafter (Figures 1aand1c), and achievement of ≥70% reduction in total back pain was higher at week 2 and week 8, but not week 4, and sustained thereafter (Figure 1b). Results were similar for the proportion of patients achieving MCID and MBI, with improvements in PGA of pain, total back pain, and nocturnal back pain for UPA vs PBO as early as week 1 (MCID) or week 2 (MBI) that were sustained through week 14 (all nominalP<0.001;Table 1).Table 1.Achievement of MCID and MBI in Pain Outcomes at Week 14 (NRI-MI)Responder Rate (95% CI), %Pain OutcomesUPA 15 mgPBONominalPValuePGA of painMCID81.0(75.8–86.3)62.7(56.1–69.2)<0.0001MBI60.7(54.1–67.3)24.9(19.0–30.7)<0.0001Total back painMCID80.1(74.7–85.5)65.1(58.6–71.5)0.0005MBI58.3(51.6–64.9)25.4(19.5–31.3)<0.0001Nocturnal back painMCID82.9(77.9–88.0)61.3(54.7–67.9)<0.0001MBI61.6(55.0–68.2)32.1(25.7–38.4)<0.0001MBI, much better improvement; MCID, minimal clinically important difference; NRI-MI, non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19; PBO, placebo; PGA, Patient’s Global Assessment; UPA, upadacitinib.ConclusionIn patients with active AS who were bDMARD-IR, greater proportions of patients treated with UPA achieved rapid and clinically meaningful reductions in pain vs PBO as early as week 2 that were sustained through 14 weeks across multiple pain assessments.References[1]van der Heijde D, et al.Ann Rheum Dis. 2022;81(11):1515-1523.[2]van der Heijde D, et al.Lancet. 2019;394(10214):2108-2117.[3]McInnes IB, et al.RMD Open. 2022;8(1):doi:10.1136/rmdopen-2021-002049.[4]Salaffi F, et al.Eur J Pain. 2004;8(4):283-291.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by M. Hovenden and J. Matsuura of ICON plc (Blue Bell, PA, USA) and was funded by AbbVie.Disclosure of InterestsXenofon Baraliakos Consultant of: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, Galapagos, Janssen, Celgene, and Amgen, Grant/research support from: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, Galapagos, Janssen, Celgene, and Amgen, Marina Magrey Consultant of: UCB, Novartis, Eli Lilly, Pfizer, and Janssen, Grant/research support from: Amgen, AbbVie, BMS, and UCB Pharma, Louis Bessette Speakers bureau: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Organon, and Sanofi, Grant/research support from: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Sanofi, and Gilead, Kurt de Vlam Speakers bureau: Amgen, Celgene, Eli Lilly, Galapagos, Novartis, and UCB, Consultant of: Amgen, AbbVie, Celgene, Eli Lilly, Galapagos, Novartis, and UCB, Grant/research support from: Amgen, UCB, and MSD, Tianming Gao Shareholder of: AbbVie, Employee of: AbbVie, Anna Shmagel Shareholder of: AbbVie, Employee of: AbbVie, Ralph Lippe Shareholder of: AbbVie, Employee of: AbbVie, Ana Biljan Shareholder of: AbbVie, Employee of: AbbVie, Victoria Jasion Shareholder of: AbbVie, Employee of: AbbVie, Peter C. Taylor Speakers bureau: AbbVie, Consultant of: Lilly, AbbVie, Pfizer, Galapagos, Gilead, Janssen, GlaxoSmithKline, Sanofi, Fresenius, Nordic Pharma, UCB, and Biogen, Grant/research support from: Galapagos.

Pain in axial spondyloarthritis: role of the JAK/STAT pathway

“…In both studies, the average change from baseline to Week 14 in total back pain and nocturnal back pain was significantly greater in patients treated with upadacitinib compared to the placebo group (p < 0.001 for both comparisons). Furthermore, a post-hoc analysis of the SELECT-AXIS 2 Study 1 was conducted by Baraliakos and colleagues to further assess the efficacy of upadacitinib on several pain assessments in r-axSpA patients with bDMARDs-IR (120). Higher proportions of upadacitinib-treated patients achieved rapid and clinically relevant improvement in pain compared to placebo-treated patients by Week 2 that were maintained through Week 14 across a range of pain assessments, including ≥30%, ≥50%, and ≥70% reductions in patient global assessment of pain, total back pain, and nocturnal back pain.…”