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

Factors associated with the retention of secukinumab in patients with axial spondyloarthritis in real-world practice: results from a retrospective study (FORSYA)

“…This result was unexpected as it was observed that patients with active inflammatory disease were more likely to benefit from anti-TNF. 25 Although >20% of the data for OSI were missing, the variable was forced into the multivariate model irrespective of its significance level or rate of missing data. In this study, the majority (>85%) of patients presented with OSI at treatment initiation, which might also impact the analysis.…”

“…In various RCTs and RWE studies of axSpA patients, the factors reported to influence anti-TNF therapy efficacy and retention rate are smoking status, young age, gender, HLA-B27 positivity, radiographic status, OSI and rank of drug administration 24 25. This study aimed to evaluate whether OSI is associated with secukinumab retention and to determine if other predictive factors could be identified.…”

“…The retention of secukinumab has been evaluated in retrospective observational series and registries [17][18][19][20][21][22] including axSpA. 20 23 24 Although the factors influencing anti-TNF efficacy and retention in axSpAsuch as smoking status, young age, gender, human leucocyte antigen (HLA)-B27 positivity, radiographic status, objective signs of inflammation (OSI) and rank of drug administration-have been identified in various RCTs and RWE studies, [25][26][27] data on anti-IL17 agents are sparse. 20 22 23 The impact that patient characteristics, diagnosis or drug use (line of treatment or dosage) might have on secukinumab retention under real-life conditions in patients with axSpA is only partially understood.…”

Etanercept Withdrawal and Retreatment in Nonradiographic Axial Spondyloarthritis: Results of RE-EMBARK, an Open-Label Phase IV Trial

“…The following baseline factors that were considered potential response predictors for TNFi [12][13][14][15][16][17][18][19][20][21] were included in the univariate and multivariable analyses for P2 and P3: age (< 40 yrs vs ≥ 40 yrs), BMI (calculated as weight in kilograms divided by height in meters squared; < 25 vs ≥ 25), symptom duration (< 2 yrs vs ≥ 2 yrs), enthesitis (no enthesitis vs enthesitis), HLA-B27 status (negative vs positive), high-sensitivity CRP (hs-CRP; ≤ 3 mg/L vs > 3 mg/L), sacroiliitis on MRI at screening (negative vs positive), MRI SIJ SPARCC score (≤ 2 vs > 2), positive MRI plus hs-CRP > 3 mg/L (yes vs no), race (non-White vs White), sex, and weight (< 70 kg vs ≥ 70 kg).…”

Comparative Efficacy of Biologic Disease-Modifying Anti-Rheumatic Drugs for Non-Radiographic Axial Spondyloarthritis: A Systematic Literature Review and Bucher Indirect Comparisons

“…Treatment recommendations from the ASAS/EULAR suggest that patients start with bDMARDs early in the disease process when they have active disease, despite the use (or intolerance/contraindication) of at least two NSAIDs, and have OSI, evidenced by elevated C-reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI) [23]. In the context of OSI, it has been shown that positive MRI is the strongest independent predictor of better response to CZP in patients with nr-axSpA [24]. Furthermore, licensed indications of all bDMARDs are restricted to patients with OSI whose presence is also required by most reimbursement policies.…”