Effect of Upadacitinib on Quality of Life and Work Productivity in Active Non-radiographic Axial Spondyloarthritis: Results From Randomized Phase 3 Trial SELECT-AXIS 2.

INTRODUCTION: To evaluate the effect of upadacitinib vs. placebo on health-related quality of life (HRQoL) and work productivity in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) enrolled in the SELECT-AXIS 2 phase 3 randomized controlled trial. METHODS: Adult patients with active nr-axSpA and an inadequate response to non-steroidal anti-inflammatory drugs were randomized 1:1 to receive upadacitinib 15 mg once daily or placebo. Mean changes from baseline in measures of HRQoL (Ankylosing Spondylitis QoL [ASQoL], Assessment of SpondyloArthritis international Society Health Index [ASAS HI], Short-Form 36 Physical Component Summary [SF-36 PCS] score) and Work Productivity and Activity Impairment (WPAI) were assessed through 14 weeks based on mixed-effects repeated measures or analysis of covariance models. The proportions of patients with improvements ≥ minimum clinically important differences (MCID) were assessed in HRQoL measures at week 14 using non-responder imputation with multiple imputation. RESULTS: At week 14, upadacitinib- vs. placebo-treated patients reported greater improvements from baseline in ASQoL and ASAS HI (ranked, P < 0.001) and in SF-36 PCS and WPAI overall work impairment (nominal P < 0.05). Improvements were observed as early as week 2 in ASAS HI. Greater proportions of upadacitinib vs. placebo-treated patients reported improvements ≥ MCID in ASQoL (62.6 vs. 40.9%), ASAS HI (44.8 vs. 28.8%), and SF-36 PCS (69.3 vs. 52.0%), with numbers needed to treat < 10 for all (nominal P ≤ 0.01). Improvements ≥ MCID were consistently observed irrespectively of prior exposure to tumor necrosis factor inhibitors. CONCLUSIONS: Upadacitinib provides clinically meaningful improvements in HRQoL and work productivity in patients with active nr-axSpA. CLINICAL REGISTRATION NUMBER: NCT04169373, SELECT-AXIS 2.

A review of JAK-STAT signalling in the pathogenesis of spondyloarthritis and the role of JAK inhibition.

Spondyloarthritis (SpA) comprises a group of chronic inflammatory diseases with overlapping clinical, genetic and pathophysiological features including back pain, peripheral arthritis, psoriasis, enthesitis and dactylitis. Several cytokines are involved in the pathogenesis of SpA, variously contributing to each clinical manifestation. Many SpA-associated cytokines, including IL-23, IL-17, IL-6, type I/II interferon and tumour necrosis factor signal directly or indirectly via the Janus kinase (JAK)-signal transducer and activator of transcription pathway. JAK signalling also regulates development and maturation of cells of the innate and adaptive immune systems. Accordingly, disruption of this signalling pathway by small molecule oral JAK inhibitors can inhibit signalling implicated in SpA pathogenesis. Herein we discuss the role of JAK signalling in the pathogenesis of SpA and summarize the safety and efficacy of JAK inhibition by reference to relevant SpA clinical trials.

Geographic Variations in Diagnosis and Treatment of Ankylosing Spondylitis in the United States: A Real-World Study.

INTRODUCTION: Diagnosis difficulties are common for ankylosing spondylitis (AS) patients, leading to inadequate and inconsistent treatment. We evaluated the national and geographic variability in disease diagnosis and treatment in the United States. METHODS: This retrospective, cross-sectional analysis utilized the IBM® MarketScan® Administrative Claims Database from 2014 to 2019. AS patients ≥ 18 years of age with continuous medical and pharmacy enrollment during the calendar year and complete geographic information during the study period were included. Patient cohorts assessed were D1 (≥ 1 AS diagnoses within each calendar year of assessment between 2014 and 2019), D2 (≥ 2 non-rheumatologist AS diagnoses), and D3 (≥ 2 rheumatologist AS diagnoses). For D2 and D3, diagnoses were ≥ 6 months apart, but within 18 months. Annual AS diagnostic prevalence and treatment rates were determined from 2014 to 2019 nationally and per state in 2019. Treatments assessed were disease-modifying antirheumatic drugs (DMARDs), opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and methotrexate. RESULTS: Nationally, AS diagnostic prevalence increased from 2014 to 2019, with 2019 rates of 9.6 (D1), 5.1 (D2), and 3.5 (D3) per 10,000 persons. Diagnostic prevalence varied between states, which was not explained by age, sex, racial distribution, or rheumatologists per capita. Nationally, a greater percentage of D3 patients vs. D1 and D2 patients received biologic/targeted synthetic DMARDs (bDMARD/tsDMARDs) and conventional synthetic DMARD. Opioid use ranged from 37 to 40% in 2019 and decreased from 2014 for all cohorts. Corticosteroid and methotrexate use decreased slightly, while NSAID and bDMARD/tsDMARD use generally increased from 2014 to 2019. CONCLUSIONS: AS diagnostic prevalence is increasing nationally, though it remains low among some states. bDMARD/tsDMARDs use was more common among patients treated by rheumatologists. Opioid and corticosteroid use is decreasing, though national rates remain high with significant state variability. Further education is needed, particularly in states with low prevalence and inadequate treatment, to improve diagnosis and treatment.