Ixekizumab Improves Patient-Reported Outcomes in Non-Radiographic Axial Spondyloarthritis: Results from the Coast-X Trial

Abstract

Introduction Ixekizumab, an interleukin-17A antibody, has shown efficacy in non-radiographic axial spondyloarthritis (nr-axSpA). The objectives of this analysis were (a) to measure improvement in ixekizumab-treated patients in Assessment of Spondyloarthritis International Society (ASAS) response domains and other patient-reported outcomes (PROs) and (b) to determine how ASAS responses were associated with changes in patient global disease activity (PtGA), spinal pain, function, stiffness, fatigue, and spinal pain at night. Methods COAST-X was a phase 3, 52-week multicenter, randomized, controlled trial investigating the efficacy and safety of 80-mg ixekizumab every 2 weeks (Q2W) and every 4 weeks (Q4W) in patients with active nr-axSpA. Changes from baseline in PROs were analyzed via mixed-effects models for repeated measures. Association analyses for ASAS responses used analysis of covariance with Scheffé’s method. Results Patients treated with ixekizumab Q2W and Q4W reported significantly greater improvements in PtGA, spinal pain, function, and stiffness at week 1, when these measures were first assessed, compared with placebo ( p < 0.05). ASAS40 responders, in comparison to ASAS20 non-responders, had the highest correlations with improvements in all response domains (PtGA, spinal pain, function, and stiffness) as well as fatigue and spinal pain at night ( p < 0.001). ASAS40 responses were associated with 3.5- to 48.0-fold greater improvements in these PROs, with the highest values for PtGA and function, compared to ASAS20 non-achievement. Conclusions As early as week 1, patients with nr-axSpA treated with ixekizumab reported significant improvements in PtGA, spinal pain, function, and stiffness compared with those taking placebo. ASAS40 responders reported significantly greater improvements in all ASAS response domains (PtGA, spinal pain, function, and stiffness) as well as fatigue and spinal pain at night than ASAS20 non-responders. Improvements in PtGA and function appear to be major drivers in achieving ASAS40 response in patients with nr-axSpA. Trial Registration NCT02757352. Electronic supplementary material The online version of this article (10.1007/s40744-020-00254-z) contains supplementary material, which is available to authorized users.

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

“…Furthermore, positive improvements in pain, as well as physical function and general HRQoL as measured by SF-36 PCS and ASAS HI, were consistent with previous studies with IL-17 inhibitors [ 28 , 29 ]. Results were also consistent with studies with TNFi treatments in nr-axSpA [ 30 – 32 ].…”

“…Several studies have demonstrated that improvements in PROs are associated with improved clinical measures of disease activity and symptoms, which is critical in axSpA given the high disease burden [ 28 , 30 , 33 – 35 ]. A significantly greater proportion of patients with active nr-axSpA treated with upadacitinib vs. placebo achieved the primary endpoint of ASAS40 at week 14 as well as the threshold of ASDAS inactive disease [ 17 ].…”

Inhibiting IL-17A and IL-17F in Rheumatic Disease: Therapeutics Help to Elucidate Disease Mechanisms

“…The results after 52 weeks showed that the initial improvements noted above were maintained. Post hoc analysis of the COAST-X, COAST-W, and COAST-V trials shows that patient-reported outcomes relating to quality of life, fatigue, function, health status, and work productivity improved with ixekizumab [100][101][102][103]. Interestingly, these improvements in patient-reported outcomes were correlated with the patients' ASAS20/40 response [100,102].…”

“…Post hoc analysis of the COAST-X, COAST-W, and COAST-V trials shows that patient-reported outcomes relating to quality of life, fatigue, function, health status, and work productivity improved with ixekizumab [100][101][102][103]. Interestingly, these improvements in patient-reported outcomes were correlated with the patients' ASAS20/40 response [100,102]. Further analysis of the clinical trial data showed that 75% of patient had no radiographic progression over 2 years [104].…”

Papel del eje intestino-piel-articulaci�n en enfermedades inmunomediadas. Papel de nuevas terapias con JAKinibs selectivos e inhibidores IL23p19

“…Además de la inhibición de la IL-23, se han evaluado diferentes tratamientos dirigidos a moléculas efectoras de la inmunidad tipo 3 como la IL-17 y la IL-22. La inhibición de la IL-17 ha sido revisada ampliamente y los ensayos clínicos, tanto de secukinumab como de ixekizumab (los dos agentes que bloquean la IL-17) han demostrado efectividad y han resultado muy valiosos en el entendimiento de las enfermedades inmunomediadas relacionadas con PsO [116][117][118][119][120] y SpA 117,[121][122][123][124] . De forma interesante, se ha reportado que la inhibición de IL-17 en pacientes con EII resulta en un agravamiento del daño intestinal, probablemente relacionado con una disminución de la función de barrera 125,126 .…”