Long-term safety and clinical outcomes of certolizumab pegol treatment in patients with active non-radiographic axial spondyloarthritis: 3-year results from the phase 3 C-axSpAnd study

Abstract

Background: 52-week results from C-axSpAnd demonstrated the safety and efficacy of certolizumab pegol (CZP) in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) and objective signs of inflammation (sacroiliitis on MRI and/or elevated C-reactive protein levels). Long-term safety and clinical outcomes, including MRI assessments, are evaluated up to 3 years for CZP-treated patients with nr-axSpA.

Methods: C-axSpAnd was a phase 3 study comprising a 1-year double-blind, placebo-controlled period and 2-year open-label safety follow-up extension (SFE). At baseline, 317 patients were randomised 1:1 to placebo or CZP 200 mg every 2 weeks. Patients completing the double-blind phase who enrolled into the SFE received open-label CZP for an additional 104 weeks. Long-term safety and clinical outcomes are reported to Week 156. Continuous outcomes are presented as observed case (OC) and dichotomous outcomes as OC and with non-responder imputation.

Results: 243/317 (76.7%) patients entered the SFE, during which 149 (61.3%) experienced ≥1 treatment-emergent adverse event (TEAE); 15 (3.3/100 patient-years) experienced serious TEAEs. Continuous outcome scores (including Ankylosing Spondylitis Disease Activity Score [ASDAS]: 1.8; Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]: 2.7) at Week 52 were maintained at Week 156 (ASDAS: 1.8; BASDAI: 2.6) for the initial CZP-randomised group. Mean SPARCC MRI sacroiliac joint inflammation scores for these patients decreased at Week 52 (baseline: 7.6; Week 52: 1.7), remaining low at Week 156 (2.4).

Conclusions: CZP treatment was well tolerated up to 3 years, with no new safety signals versus previous reports. Clinical outcomes achieved after 1 year were sustained to 3 years.

Trial registration number: NCT02552212.

Keywords: certolizumab pegol; spondylitis, ankylosing; tumour necrosis factor inhibitors.

Conflict of interest statement

Competing interests: DvdH: consultant of AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma. Director of Imaging Rheumatology BV. LSG: research grants from Novartis, Pfizer and UCB Pharma. Consulting fees from AbbVie, GSK, Janssen, Lilly, Novartis, Pfizer and UCB Pharma. WPM: grants from AbbVie, Novartis and Pfizer. Consulting fees from Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly and UCB Pharma. Honoraria/speakers’ bureau from AbbVie, Novartis, Pfizer and UCB Pharma. Chief Medical Officer for CARE Arthritis Limited. RL: grants from Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma and Wyeth. Consultancy fees from Abbott, Ablynx, Amgen, AstraZeneca, BMS, Centocor, GSK, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma and Wyeth. Honoraria/speakers’ bureau from Abbott, Amgen, BMS, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma and Wyeth. MR: consulting fees from UCB Pharma. Honoraria/speakers’ bureau AbbVie, Eli Lilly, Janssen, Novartis and UCB Pharma. Participation on a Data Safety Monitoring or Advisory Board for AbbVie, Eli Lilly, Janssen-Cilag, Novartis and UCB Pharma. LB, BH, TK, MK, SEA: employees and stockholders of UCB Pharma. AD: grants from Abbvie, Eli Lilly, GSK, Novartis, Pfizer and UCB Pharma. Consulting fees from AbbVie, Amgen, Aurinia, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma. Speaker for Janssen, Novartis and Pfizer.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Patient disposition and retention to week 156. Randomised set (N=317). Percentages shown are calculated using the total number of patients starting the specified study period, and within the respective treatment arm, as the denominator. CZP, certolizumab pegol; NBBM, non-biological background medication; OL, open-label; Q2W, every 2 weeks; SFE, safety follow-up extension.

Figure 2

Continuous measures of clinical outcomes reported up to Week 156 (OC). aASQoL measured on a scale of 0–1. Mean values for clinical outcomes at Week 0, 52 and 156 using OC analysis. ASDAS, Ankylosing Spondylitis Disease Activity Score; ASQoL, Ankylosing Spondylitis Quality of Life; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; CZP, certolizumab pegol; OC, observed case; PGADA, Patients Global Assessment of Disease Activity; Q2W, every 2 weeks; SI, sacroiliac; SPARCC, SpondyloArthritis Research Consortium of Canada.

Figure 3

The proportion of patients achieving ASDAS-MI, ASAS40, BASDAI50 (OC and NRI). ASAS40, Assessment of SpondyloArthritis international Society ≥40% improvement; ASDAS: Ankylosing Spondylitis Disease Activity Score; ASDAS-MI, Ankylosing Spondylitis Disease Activity Score Major Improvement (reduction of ≥2 units from baseline); BASDAI50, Bath Ankylosing Spondylitis Disease Activity Index ≥50% improvement; CZP, certolizumab pegol; NRI: non-responder imputation; OC, observed case; Q2W, every 2 weeks.

Figure 4

The proportion of patients in each ASDAS disease state (OC). ASDAS scores used to assign disease activity were as follows: vHDA: >3.5; HDA: ≥2.1–≤3.5; LDA: ≥1.3–