Efficacy and safety of filgotinib in patients with active radiographic and nonradiographic axial spondyloarthritis: results from OLINGUITO, a phase 3 trial consisting of 2 randomised, placebo-controlled, double-blind, parallel-group studies.
Filgotinib showed significant improvements in symptoms for patients with axial spondyloarthritis compared to placebo, but further research is needed to assess long-term safety and efficacy.
Where it sits
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This study investigated the efficacy and safety of filgotinib in patients with axial spondyloarthritis (axSpA). Patients were randomized to receive filgotinib 200 mg or placebo once daily for 16 weeks. The primary endpoint was met with significant response rates in both radiographic and nonradiographic axSpA groups.
Abstract
<h4>Objectives</h4>This study aimed to investigate the efficacy and safety of filgotinib, a JAK1 preferential inhibitor, in patients with axial spondyloarthritis (axSpA).<h4>Methods</h4>The phase 3 OLINGUITO trial comprises 2 international, randomised, double-blind, placebo (PBO)-controlled studies. Patients with an established diagnosis of radiographic (r) or nonradiographic (nr) axSpA and an inadequate response/intolerance to ≥2 nonsteroidal anti-inflammatory drugs were randomised 1:1 to filgotinib 200 mg or PBO once daily through week (W) 16 (double-blind period; stratified by high-sensitivity C-reactive protein [hs-CRP] level and prior biologic disease-modifying antirheumatic drug [bDMARD] use). After W16, patients received open-label filgotinib 200 mg through W52; patients ≥65 years and/or with prespecified risk factors received response-based dosing (100 or 200 mg). The primary (Assessment of SpondyloArthritis international Society ≥40% response [ASAS40 response]) and secondary efficacy endpoints were assessed at W16. Efficacy and safety were assessed through W52.<h4>Results</h4>At W16, the primary endpoint was met in both studies (ASAS40 response rates: r = axSpA [n = 258], 39.5% filgotinib vs 20.9% PBO [P = .001]; nr-axSpA [n = 237], 34.5% vs 17.8% [P = .003], respectively). ASAS40 improvements, irrespective of hs-CRP level/prior bDMARD use, were observed as early as W1. For secondary endpoints, significant improvements were seen in Axial Spondyloarthritis Disease Activity Score and Spondyloarthritis Research Consortium of Canada magnetic resonance imaging sacroiliac joint inflammation in both studies, and in Bath Ankylosing Spondylitis Functional Index and Ankylosing Spondylitis Quality of Life Questionnaire in patients with r-axSpA. Improvements with filgotinib were maintained/increased further through W52. Overall, 2 cases of myocardial infarction (PBO: n = 1; PBO-filgotinib: n = 1), 3 of herpes zoster (PBO-filgotinib), and 4 of malignancies (excluding nonmelanoma skin cancer; filgotinib: n = 3; PBO-filgotinib: n = 1) occurred.<h4>Conclusions</h4>Across the whole spectrum of axSpA, filgotinib provided rapid and significant patient-relevant improvements in axSpA signs and symptoms and was well tolerated.
Background
This paper addresses the efficacy and safety of filgotinib, a JAK1 preferential inhibitor, in treating axial spondyloarthritis (axSpA). Prior studies have shown varying responses to treatments in axSpA, but there is limited data on the specific effects of filgotinib. Understanding the impact of filgotinib in this patient population is critical for informing treatment strategies.
Methods
The OLINGUITO trial was a phase 3, international, randomized, double-blind, placebo-controlled study. Patients with established radiographic or nonradiographic axSpA and inadequate response to ≥2 NSAIDs were randomized 1:1 to receive filgotinib 200 mg or placebo daily for 16 weeks. The primary outcome was the ASAS40 response at week 16, with secondary outcomes assessed through week 52.
Results
At week 16, the primary endpoint was met with a 39.5% ASAS40 response rate in the radiographic axSpA group receiving filgotinib compared to 20.9% in the placebo group (P=0.001, n=258). In the nonradiographic group, the response rate was 34.5% for filgotinib versus 17.8% for placebo (P=0.003, n=237). Improvements were also noted in secondary endpoints, including disease activity scores and quality of life measures.
Interpretation
The findings indicate that filgotinib may provide significant improvements in axSpA symptoms compared to placebo, with early responses observed. However, while the statistical significance is clear, the clinical significance of the observed effect sizes should be evaluated in the context of patient-relevant outcomes. Limitations such as the short follow-up period and potential confounding factors may affect the robustness of these conclusions.
Key findings
- 39.5% ASAS40 response in r-axSpA filgotinib vs 20.9% PBO, P=0.001, n=258 at W16.
- 34.5% ASAS40 response in nr-axSpA filgotinib vs 17.8% PBO, P=0.003, n=237 at W16.
- Improvements in Axial Spondyloarthritis Disease Activity Score observed at W16.
- 2 cases of myocardial infarction reported, 1 in each treatment group.
- 3 cases of herpes zoster in the filgotinib group and 1 in the placebo group.
- 4 cases of malignancies reported, 3 in the filgotinib group and 1 in the placebo group.
Limitations
- short follow-up of 52 weeks
- industry-funded study
- open-label extension phase may introduce bias
- potential confounding factors not fully addressed