Induction of Sustained Clinical Remission in Early Axial Spondyloarthritis Following Certolizumab Pegol Treatment: 48-Week Outcomes from C-OPTIMISE

Robert Landewé, Désirée van der Heijde, Maxime Dougados, Xenofon Baraliakos, Filip Van den Bosch, Karl Gaffney, Lars Bauer, Bengt Hoepken, Natasha de Peyrecave, Karen Thomas, Lianne S Gensler, Robert Landewé, Désirée van der Heijde, Maxime Dougados, Xenofon Baraliakos, Filip Van den Bosch, Karl Gaffney, Lars Bauer, Bengt Hoepken, Natasha de Peyrecave, Karen Thomas, Lianne S Gensler

Abstract

Introduction: Achievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP.

Methods: C-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA, < 5 years' symptom duration, and fulfilling Assessment of SpondyloArthritis international Society classification criteria, were included. During the induction period, patients received a loading dose of CZP 400 mg at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) up to week 48. The main outcome of the 48-week induction period was the achievement of sustained clinical remission (defined as an Ankylosing Spondylitis Disease Activity Score [ASDAS] < 1.3 at week 32 and < 2.1 at week 36 [or vice versa], and < 1.3 at week 48).

Results: In total, 736 patients (407 with r-axSpA, 329 with nr-axSpA) were enrolled into the study. At week 48, 43.9% (323/736) of patients achieved sustained remission, including 42.8% (174/407) of patients with r-axSpA and 45.3% (149/329) with nr-axSpA. Patients also demonstrated substantial improvements in axSpA symptoms, MRI outcomes and quality of life measures. Adverse events occurred in 67.9% (500/736) of patients, of which 6.0% (44/736) were serious.

Conclusions: Over 40% of patients with early axSpA achieved sustained remission during 48 weeks of open-label CZP treatment. Additionally, patients across the axSpA spectrum demonstrated substantial improvements in imaging outcomes and quality of life following treatment. No new safety signals were identified.

Trial registration: NCT02505542.

Keywords: Axial spondyloarthritis; Clinical remission; Early disease; TNF inhibitor.

Figures

Fig. 1
Fig. 1
C-OPTIMISE study design (a) and patient disposition (b). aThe LD consisted of CZP 400 mg at weeks 0, 2 and 4. LD loading dose, r-axSpA radiographic axial spondyloarthritis, nr-axSpA non-radiographic axial spondyloarthritis, CZP certolizumab pegol, Q2W every 2 weeks, Q4W every 4 weeks, AE adverse event, LoE lack of efficacy, LtF-u lost to follow-up
Fig. 2
Fig. 2
a Proportion of patients achieving sustained remission following 48 weeks’ open-label CZP. b Kinetics of ASDAS-ID and ASDAS < 2.1 achievement to week 48 in the 323 patients who achieved sustained remission. Non-responder imputation. ASDAS-ID Ankylosing Spondylitis Disease Activity Score inactive disease, axSpA axial spondyloarthritis, r-axSpA radiographic axial spondyloarthritis, nr-axSpA non-radiographic spondyloarthritis
Fig. 3
Fig. 3
a ASDAS disease states and b ASAS responses during the 48-week induction period for the overall axSpA population (N = 736). ASDAS disease states: last observation carried forward; ASAS response: non-responder imputation, ASDAS-ID/LD/HD/vHD Ankylosing Spondylitis Disease Activity Score inactive disease/low disease/high disease/very high disease, ASAS Assessment of Spondyloarthritis international Society, axSpA axial spondyloarthritis

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