Ixekizumab improves spinal pain, function, fatigue, stiffness, and sleep in radiographic axial Spondyloarthritis: COAST-V/W 52-week results

Abstract

Background: This analysis assessed improvements in patients with radiographic axial spondyloarthritis (r-axSpA) treated with ixekizumab in the Assessment of Spondyloarthritis International Society (ASAS) treatment response domains and additional patient-reported outcomes at 1 year of treatment.

Methods: COAST-V and COAST-W were 52-week, phase 3, randomized controlled trials evaluating the efficacy and safety of ixekizumab in biologic disease-modifying antirheumatic drug (bDMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced patients with radiographic spondyloarthritis, respectively. Patients were treated with 80-mg ixekizumab either every 2 weeks or every 4 weeks. Patient-reported outcomes included Patient Global Disease Activity, Spinal Pain, stiffness as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Questions 5 and 6, function as measured by the Bath Ankylosing Spondylitis Functional Index, fatigue as measured by the Fatigue Numeric Rating Scale and BASDAI question 1, Spinal Pain at Night, and sleep quality as measured by the Jenkins Sleep Evaluation Questionnaire. Mixed-effects models for repeated measures were used to analyze changes from baseline in patient-reported outcomes from weeks 1 to 16, and descriptive statistics were reported from weeks 20 to 52. Analysis of covariance with Scheffé's method was used for the ASAS response association analyses.

Results: This study assessed 341 bDMARD-naïve and 316 TNFi-experienced patients in the placebo-controlled blinded treatment dosing period (weeks 1-16) as well as 329 bDMARD-naïve and 281 TNFi-experienced patients in the dose double-blind extended treatment period (weeks 20-52). bDMARD-naïve or TNFi-experienced patients treated with ixekizumab every 2 weeks and every 4 weeks reported improvements in patient global disease activity, spinal pain, function, stiffness, fatigue, spinal pain at night, and sleep quality through week 52. Greater correlations with improvements in all response domains were seen when comparing ASAS40 responders to ASAS20 non-responders (p < 0.001), with up to 10.5-fold greater improvements observed in ASAS40 responses compared with ASAS20 non-responders. Function and fatigue demonstrated the highest values.

Conclusions: Ixekizumab-treated bDMARD-naïve and TNFi-experienced patients with radiographic axial spondyloarthritis achieving ASAS40 reported sustained and consistent improvement in all ASAS response domains and other patient-reported outcomes though week 52, with spinal pain, function, and stiffness as major drivers of the response.

Trial registration: NCT02696785 and NCT02696798 , March 2, 2016.

Keywords: ASAS; Fatigue; Ixekizumab; PROs; Radiographic axial spondyloarthritis; Spinal pain; Stiffness.

Conflict of interest statement

AD reports consulting and advisory board from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, and UCB; research grants from AbbVie, Boehringer Ingelheim, Eli Lilly, Glaxo Smith & Kline, Novartis, Pfizer, and UCB. PM reports research grants, consulting, and/or speaker for Abbvie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB; PR reports consultant and speaker to Abbott, AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis and Pfizer; research grants from Janssen and Novartis. VNC reports consulting, speaker, and research grants from Abbvie, BMS, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, and UCB. V. Strand reports consultant to Abbvie, Amgen, Arena, Bayer, BMS, Boehringer Ingelheim, Celltrion, Galapagos, Genentech/Rooche, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Servier, and UCB. TH, RB, LL, and SL are current employees and shareholders of Eli Lilly and Company. HMO reports research grants from Janssen, Novartis; speaker honoraria and consultant from Abbvie, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Takeda, and UCB.

© 2021. The Author(s).

Figures

Fig. 1

Changes from baseline in the ASAS treatment response domains through 52 weeks of treatment. LSM (weeks 1–16) and mean (weeks 20–52) changes from baseline in the ASAS treatments response domains (PtGA, spinal pain, function, and stiffness) for bDMARD-naïve (COAST-V) and TNFi-experienced (COAST-W) patients. The 16-week data have been published previously (10). At week 16, patients who originally received ADA or PBO were rerandomised 1:1 to ixekizumab Q2W or Q4W, while patients originally randomised to receive ixekizumab Q2W or Q4W continued treatment. ADA = adalimumab; ASAS = Assessment of Spondyloarthritis International Society; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; BASFI = Bath Ankylosing Spondylitis Functional Index; bDMARD = biologic disease-modifying antirheumatic drugs; IXE = ixekizumab; LSM = least squares mean; PBO = placebo; PtGA = patient global disease activity; Q = question; Q2W = every 2 weeks; Q4W = every 4 weeks; TNFi = tumor necrosis factor inhibitor

Fig. 2

Changes from baseline in other PROs through 52 weeks of treatment. LSM (weeks 1–16) and mean (weeks 20–52) changes from baseline in other PROs for bDMARD-naïve (COAST-V) and TNFi-experienced (COAST-W) patients. The 16-week data have been published previously (10). At week 16, patients who originally received ADA or PBO were rerandomised 1:1 to ixekizumab Q2W or Q4W, while patients originally randomised to receive ixekizumab Q2W or Q4W continued those treatments. ADA = adalimumab; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; bDMARD = biologic disease-modifying antirheumatic drugs; IXE = ixekizumab; JSEQ = Jenkins Sleep Evaluation Questionnaire; LSM = least squares mean; NRS = numeric rating scale; PBO = placebo; PRO = patient-reported outcome; Q = question; Q2W = every 2 weeks; Q4W = every 4 weeks; TNFi = tumor necrosis factor inhibitor

Fig. 3

Association between ASAS response and improvements in ASAS PROs for ixekizumab-treated patients after 52 weeks. Q2W and Q4W ixekizumab-treated patients. § p < 0.001, achieved ASAS20 but not ASAS40 vs. ASAS20 not achieved; * p < 0.0001, ASAS40 achieved vs. ASAS20 not achieved; † p < 0.0001, ASAS40 achieved vs. achieved ASAS20 but not ASAS40. Results were compared using ANCOVA. Values are LSM improvements from baseline (SE). mBOCF was used for imputation of missing data. Fold difference = (ASAS40 responder/ASAS20 non-responder) -1, or (ASAS40 responder/ASAS20 but not ASAS40 responder) -1. ANCOVA = analysis of covariance; ASAS = Assessment of Spondyloarthritis International Society; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; BASFI = Bath Ankylosing Spondylitis Functional Index; bDMARD = biologic disease-modifying antirheumatic drugs; LSM = least squares mean; mBOCF = modified baseline observation carried forward; Nx = number of observations; PROs = patient-reported outcomes; PtGA = patient global disease activity; Q = question; Q2W = every 2 weeks; Q4W = every 4 weeks; SE = standard error; TNFi = tumor necrosis factor inhibitor

Fig. 4

Association between ASAS response and improvements in other PROs for ixekizumab-treated patients after 52 weeks. Q2W and Q4W ixekizumab-treated patients. § p < 0.001, achieved ASAS20 but not ASAS40 vs. ASAS20 not achieved; Φ p < 0.001, * p < 0.0001, ASAS40 achieved vs. ASAS20 not achieved; # p < 0.001, † p < 0.0001, ASAS40 achieved vs. achieved ASAS20 but not ASAS40. Results were compared using ANCOVA. Values are LSM improvements from baseline (SE). mBOCF was used for imputation of missing data. Fold difference = (ASAS40 responder/ASAS20 non-responder) -1, or (ASAS40 responder/ASAS20 but not ASAS40 responder) -1. ANCOVA = analysis of covariance; ASAS = Assessment of Spondyloarthritis International Society; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; bDMARD = biologic disease-modifying antirheumatic drugs; JSEQ = Jenkins Sleep Evaluation Questionnaire; LSM = least squares mean; mBOCF = modified baseline observation carried forward; NRS = numeric rating scale; Nx = number of observations; PROs = patients reported outcomes; Q = question; Q2W = every 2 weeks; Q4W = every 4 weeks; SE = standard error; TNFi = tumor necrosis factor inhibitor