Predictors of long-term clinical response in patients with non-radiographic axial spondyloarthritis receiving certolizumab pegol

Abstract

Background: Identification of predictive clinical factors of long-term treatment response may contribute to improved management of non-radiographic axSpA (nr-axSpA) patients. This analysis aims to identify whether any baseline characteristics or Week 12 clinical outcomes in nr-axSpA patients with elevated C-reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI) enrolled in the C-axSpAnd study are predictive of achieving clinical response after 1 year of certolizumab pegol (CZP).

Methods: C-axSpAnd (NCT02552212) was a phase 3, multicentre study, including a 52-Week double-blind, placebo-controlled period. Enrolled patients were randomised to CZP 200 mg Q2W or placebo. Predictors of Week 12 (CZP group only) and Week 52 clinical response were identified using a multivariate stepwise logistic regression analysis. Response variables included Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI), Assessment of SpondyloArthritis International Society 40% response (ASAS40), Bath Ankylosing Spondylitis Disease Activity Index 50% response (BASDAI50) and ASDAS inactive disease (ASDAS-ID). Predictive factors assessed included demographic and baseline characteristics and clinical outcomes at Week 12. A p-value <0.05 was required for forward selection into the model and p ≥0.1 for backward elimination. Missing data or values collected after switching to open-label treatment were accounted for using non-responder imputation. Sensitivity analyses accounted for patients with changes in non-biologic background medication.

Results: Of 317 enrolled patients, 159 and 158 were randomised to CZP and placebo, respectively. Younger age and male sex were identified as predictors of Week 12 response across all assessed efficacy outcomes in CZP-treated patients. Consistent predictors of Week 52 response, measured by ASDAS-MI, ASAS40 and BASDAI50, included human leukocyte antigen (HLA)-B27 positivity and sacroiliitis on MRI at baseline. MRI positivity was also predictive of achieving ASDAS-ID at Week 52. Sensitivity analyses were generally consistent with the primary analysis. In placebo-treated patients, no meaningful predictors of Week 52 response were identified.

Conclusions: In this 52-Week, placebo-controlled study in nr-axSpA patients with elevated CRP and/or active sacroiliitis on MRI at baseline, MRI sacroiliitis and HLA-B27 positivity, but not elevated CRP or responses at Week 12, were predictive of long-term clinical response to CZP. Findings may support rheumatologists to identify patients suitable for TNFi treatment.

Trial registration: ClinicalTrials.gov, NCT02552212 . Registered on 15 September 2015.

Keywords: Axial spondyloarthritis; Certolizumab pegol; Predictors; TNF inhibitor.

Conflict of interest statement

WPM: honoraria/consulting fees from AbbVie, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; research grants from AbbVie and Pfizer; educational grants from AbbVie, Janssen, Novartis and Pfizer; Chief Medical Officer for CARE Arthritis Limited. TK, SEA, BH and LB: employees of UCB Pharma; own stock awards in UCB Pharma. MR: speakers bureau for AbbVie, Eli Lilly, Novartis and UCB Pharma; consultant of AbbVie, Celgene, Eli Lilly, Janssen, Novartis and UCB Pharma.

© 2021. The Author(s).

Figures

Fig. 1

Predictive factors of Week 12 response in CZP-treated patients. Randomised set (NRI). Patients received CZP 200 mg Q2W (400 mg loading dose at Weeks 0, 2 and 4) plus non-biologic background medication. aIncluded in the predictive model as continuous variables; for these factors, an odds ratio >1 indicates a higher probability of larger values being predictive of a response. ASAS40 Assessment of SpondyloArthritis International Society 40%, ASDAS Ankylosing Spondylitis Disease Activity Score, ASDAS-ID ASDAS inactive disease (ASDAS <1.3), ASDAS-MI ASDAS major improvement (reduction in ASDAS ≥2.0), BASDAI50 Bath Ankylosing Spondylitis Disease Activity Index 50%, CI confidence interval, CRP C-reactive protein, CZP certolizumab pegol, NRI non-responder imputation, PtGADA Patient’s Global Assessment of Disease Activity, Q2W every 2 Weeks, ULN upper limit of normal (9.99 mg/L), vs versus

Fig. 2

Predictive factors of Week 52 response in CZP-treated patients. Randomised set (NRI). Patients received CZP 200 mg Q2W (400 mg loading dose at Weeks 0, 2 and 4) plus non-biologic background medication. aIncluded in the predictive model as continuous variables; for these factors, an odds ratio >1 indicates a higher probability of larger values being predictive of a response. For Week 12 change from baseline measures, a lower (negative) value is indicative of improvement, while larger (positive) values indicate worsening. ASAS40 Assessment of SpondyloArthritis International Society 40%, ASDAS Ankylosing Spondylitis Disease Activity Score, ASDAS-ID ASDAS inactive disease (ASDAS<1.3), ASDAS-MI ASDAS major improvement (reduction in ASDAS≥2.0), ASQoL ankylosing spondylitis quality of life, BASDAI50 Bath Ankylosing Spondylitis Disease Activity Index 50%, BASFI Bath Ankylosing Spondyloarthritis Functional Index, BASMI Bath Ankylosing Spondylitis Metrology Index, CI confidence interval, CZP certolizumab pegol, HLA-B27 human leukocyte antigen-B27, MRI+/− presence/absence of sacroiliitis on magnetic resonance imaging, MASES Maastricht Ankylosing Spondylitis Enthesitis Score (range 0−13), NRI non-responder imputation, NSAID non-steroidal anti-inflammatory drug, PtGADA Patient Global Assessment of Disease Activity, Q2W every 2 Weeks, vs versus