Background/Purpose: C-OPTIMISE was a phase 3b study investigating certolizumab pegol (CZP) maintenance dose continuation, reduction or withdrawal following achievement of sustained remission in patients with axial spondyloarthritis (axSpA). During the C‑OPTIMISE maintenance period, the majority of patients randomized to CZP, either the full or reduced maintenance dose, did not experience disease flares. Conversely, in those who had CZP withdrawn, only a minority of patients remained flare-free.¹ This post-hoc analysis evaluates disease activity and clinical markers of inflammation in patients who did not experience a disease flare following randomization to CZP full maintenance dose, CZP reduced maintenance dose or placebo (PBO) during the C‑OPTIMISE maintenance period (Weeks [Wks] 48–96).

Methods: C-OPTIMISE (NCT02505542) was a multicenter, double-blind, parallel-group, randomized phase 3b study with a 48-wk open-label run-in period.¹ Adult patients with early (< 5 years’ symptom duration) active axSpA received open-label CZP 200 mg every 2 wks (Q2W) for the first 48 wks; from Wk 48, patients who achieved sustained remission (Ankylosing Spondylitis Disease Activity Score [ASDAS] < 1.3 at Wk 32/36 and Wk 48) were randomized 1:1:1 to double-blind CZP 200 mg Q2W (full maintenance dose), CZP 200 mg Q4W (reduced maintenance dose) or PBO for a further 48 wks (maintenance period). A flare was defined as ASDAS ≥2.1 at two consecutive visits or ASDAS >3.5 at any visit. We report ASDAS, BASDAI, and C-reactive protein (CRP) and fecal calprotectin levels during Wks 48–96 in CZP- and PBO-randomized patients who did not experience a flare (completed Wk 96 on randomized treatment). Missing data were imputed using last observation carried forward.

Results: Of 313 patients entering the maintenance period at Wk 48 (CZP 200 mg Q2W: 104; CZP 200 mg Q4W: 105; PBO: 104), 197 (62.9%) completed Wk 96 on randomized treatment without experiencing a flare; of these, 89 (85.6%) and 84 (80.0%) patients were in the CZP 200 mg Q2W and CZP 200 mg Q4W arm, respectively, with only 24 (23.1%) patients randomized to PBO not experiencing a flare. Baseline characteristics of patients are shown in the Table. During Wk 48–96, disease activity (ASDAS, BASDAI) and CRP levels were comparable between the CZP full and reduced maintenance dose group, and lower in both CZP arms than in PBO (Figure A–C). From Wk 60 up to Wk 96, PBO patients who did not flare had consistently higher mean ASDAS, BASDAI and CRP levels compared with CZP-randomized patients (Figure A–C). Similarly, there was a greater increase in fecal calprotectin levels between Wks 48 and 96 in the PBO arm compared with both CZP arms (Figure D).

Conclusion: Despite not meeting the threshold for a flare, numerically higher disease activity and increases in serologic and inflammatory biomarkers were observed in PBO-randomized patients who did not experience a flare compared to those who remained on CZP. These findings confirm that patients with axSpA who achieve sustained remission benefit from continued CZP treatment, either with the full or reduced maintenance dose, over treatment withdrawal.

References: 1. Ritchlin CT. Lancet 2020;395:427–40; 2. McInnes IB. ARD 2020;79:1153–4.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/disease-activity-and-inflammation-in-axial-spondyloarthritis-patients-who-did-not-experience-flares-following-certolizumab-pegol-withdrawal-dose-reduction-or-dose-continuation/