Relationship between disease activity status or clinical response and patient-reported outcomes in patients with non-radiographic axial spondyloarthritis: 104-week results from the randomized controlled EMBARK study

Abstract

Background: We assessed the external validity of composite indices Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Assessment in SpondyloArthritis international Society (ASAS) 40 response (ASAS40) by evaluating the correlations between the changes in some patient reported outcomes (PROs) for patients with non-radiographic axial spondyloarthritis (nr-axSpA) and the changes in the scores of the composite indices.

Methods: This was a post-hoc analysis of data from the EMBARK study in patients with nr-axSpA treated with etanercept. PROs were grouped according to ASDAS status (inactive [< 1.3], low [≥ 1.3 to < 2.1], high [≥ 2.1 to ≤3.5], and very high [> 3.5]), patient achievement of > 50% improvement in BASDAI (BASDAI50 responders), and > 40% improvement in ASAS (ASAS40 responders) at 104 weeks. Analyses were conducted on observed cases available at Week 104. Changes in PROs from Baseline to Week 104 were assessed using analysis of covariance with adjustment for baseline with linear contrast.

Results: Higher ASDAS disease activity at 104 weeks was associated with lower long-term improvement from baseline in PROs (e.g., total back pain [visual analog scale, cm (95% confidence interval): - 4.58 (- 4.95, - 4.21), - 3.86 (- 4.28, - 3.43), - 2.15 (- 2.68, - 1.61), and 1.30 (- 0.51, 3.12) for inactive, low, high, and very high ASDAS disease activity, respectively; Multidimensional Fatigue Inventory (MFI) general fatigue: - 4.77 (- 5.70, - 3.84), - 2.96 (- 4.04, - 1.87), - 1.00 (- 2.32, 0.31), and 2.14 (- 2.10, 6.38); all p < 0.001)]. BASDAI50 non-responders had less improvement in PROs from Baseline to Week 104 vs. responders (e.g., total back pain: - 1.61 (- 2.05, - 1.18) vs. -4.43 (- 4.69, - 4.18); MFI general fatigue: - 0.01 (- 1.12, 1.09) vs. -4.30 (- 4.98, - 3.62); all p < 0.001). ASAS40 non-responders also had less improvement in PROs from Baseline to Week 104 vs. responders (e.g., total back pain: - 1.91 (- 2.30, - 1.52) vs. -4.75 (- 5.05, - 4.46); MFI general fatigue: - 0.63 (- 1.56, 0.30) vs. -4.64 (- 5.37, - 3.91); all p < 0.001).

Conclusion: Composite indices are valid for monitoring treatment response and adequately reflect treatment-related changes experienced by patients with nr-axSpA.

Trial registration: ClinicalTrials.gov identifier: NCT01258738. Registered 9 December 2010.

Keywords: Axial spondyloarthritis; Non-radiographic axial spondyloarthritis; Patient-reported outcome measures.

Fig. 1

PROs by ASDAS disease activity at Week 104. The response status was defined at Week 104, and only patients with data available at that week were included. Data shown are the adjusted mean change from Baseline (95% CI) except plots for WPAI data, which show adjusted mean change from Baseline in the percentage of patients (95% CI). The number of patients with change from Baseline data are shown in or near the columns. *p < 0.001 for the trend test of adjusted mean change from Baseline. ASDAS, Ankylosing Spondylitis Disease Activity Score; ASQoL, ankylosing spondylitis quality of life; CFB, change from Baseline; CI, confidence interval; EQ-5D, EuroQol-5 Dimensions; MCS, mental component summary; MFI, Multidimensional Fatigue Inventory; NA, not available; PCS, physical component summary; PRO, patient-reported outcome; SF-36, 36-item short form health survey; VAS, visual analog scale; WPAI, Work Productivity and Activity Index

Fig. 2

PROs by BASDAI50 response at Week 104. The response status was defined at Week 104, and only patients with data available at that week were included. Data shown are the adjusted mean change from Baseline (95% CI) except plots for WPAI data, which show adjusted mean change from Baseline in the percentage of patients (95% CI). The numbers of patients with available change from Baseline data are shown in or near the columns. Significant difference in change in PRO adjusted mean from Baseline between BASDAI50 responders and non-responders is indicated (***p < 0.001). ASDAS, Ankylosing Spondylitis Disease Activity Score; ASQoL, ankylosing spondylitis quality of life; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; CFB, change from Baseline; CI, confidence interval; EQ-5D, EuroQol-5 Dimensions; MCS, mental component summary; MFI, Multidimensional Fatigue Inventory; PCS, physical component summary; PRO, patient-reported outcome; SF-36, 36-item short form health survey; VAS, visual analog scale; WPAI, Work Productivity and Activity Index

Fig. 3

PROs by ASAS40 response at Week 104. The response status was defined at Week 104, and only patients with data available at that week were included. Data shown are the adjusted mean change from Baseline (95% CI) except plots for WPAI data, which show adjusted mean change from Baseline in the percentage of patients (95% CI). The numbers of patients with available change from Baseline data are shown in or near the columns. Significant difference in change in PRO adjusted mean from Baseline between ASAS40 responders and non-responders is indicated (**p < 0.01; ***p < 0.001). ASDAS, Ankylosing Spondylitis Disease Activity Score; ASQoL, ankylosing spondylitis quality of life; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; CFB, change from Baseline; CI, confidence interval; EQ-5D, EuroQol-5 Dimensions; MCS, mental component summary; MFI, Multidimensional Fatigue Inventory; PCS, physical component summary; PRO, patient-reported outcome; SF-36, 36-item short form health survey; VAS, visual analog scale; WPAI, Work Productivity and Activity Index