Study to Evaluate Maintenance of Sustained Remission of axSpA With Cimzia Compared to Placebo (C-OPTIMISE)

C-OPTIMISE was a two-part, phase 3 multicentre study evaluating maintenance of remission in adult patients with early active axSpA (radiographic or non-radiographic axSpA).^1,2

During the first open label part of the study 736 patients were induced with Cimzia (CZP) 400mg per month (200mg Q2W, (every 2 weeks); after a loading dose of CZP 400mg at weeks 0, 2 and 4), with remission assessed at 48 weeks (n=659).^1,2

In the second double blind part of the study, the patients who achieved sustained remission (n=323) at 48 weeks (defined as Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 at weeks 32/36 and 48) were randomised to Cimzia 200mg every 4 weeks (maintenance dose n=104), Cimzia 200mg every 4 weeks (reduced maintenance dose n=105) or placebo (withdrawal n=104) for a further 48 weeks to week 96.^1,2

Figure 1.

C-OPTIMISE study design. axSpA, axial spondyloarthritis; CZP, certolizumab pegol; LD, loading dose; Q2W; Q4W, every 4 weeks.

Patients received reduced maintenance dose after 48 weeks of treatment. After the starting dose, the recommended maintenance dose of Cimzia for adult patients with axial spondyloarthritis is 200 mg Q2W or 400 Q4W. After at least 1 year of treatment with Cimzia, in patients with sustained remission, a reduced maintenance dose of 200 mg Q4W may be considered.

Adapted from: Landewé et al., 2020.

Cimzia in axSpA: Key Efficacy Trial Data

Primary outcome

The primary outcome of the study was the percentage of patients remaining flare-free during the maintenance period.

83.7% (87/104) and 79.0% (83/105) of patients who were randomised to the Cimzia full maintenance dose or Cimzia reduced maintenance dose, respectively, remained flare-free. Only 20.2% of patients (21/104) randomised to placebo remained flare-free (p<0.001 vs placebo for both Cimzia maintenance doses).¹

Figure 2.
Patients free of flares during the maintenance period of C-OPTIMISE. Kaplan-Meier plot of time to flare. Missing values were imputed using non-responder imputation. Flare was defined as ASDAS ≥2.1 at two consecutive visits, or ASDAS >3.5 at any visit. CZP, Q2W, Q4W.

Adapted from: Landewé et al., 2020.

Induction period

• 43.9% of patients (323/736) achieved sustained remission.^1.2
• 75.2% of all patients achieved low or inactive disease activity.^1,2
  • Defined as ASDAS < 2.1.
  • Compared to just 1.5% at study baseline.

Results were similar for the 2 sub-groups; radiographic and non-radiographic axSpA.^1,2

Figure 3.
Proportion of patients achieving sustained remission following 48-weeks’ open-label. 43.9% (323/736) of patients had achieved sustained remission according to the study definition. 
Adapted from: Landewé et al., 2020.

Figure 4.
Patients free of flares during the maintenance period of C-OPTIMISE. The proportion of patients who did not experience flares following randomisation to CZP full maintenance dose (200mg Q2W), CZP reduced maintenance dose (200mg Q4W) or placebo.

OR, observed response.

CI, confidence interval.

Adapted from: Landewé et al., 2020.

The main secondary outcome was time to flare during the maintenance part of the study. The time to flare was significantly different for each Cimzia dose versus placebo (p<0.001 vs placebo for both Cimzia treatment groups).¹

In the placebo arm, the median time to flare following randomisation was 113 days (95% CI: 1010 to 141), with the majority of flare occurring between 8 and 20-weeks post-randomisation.¹

For Cimzia patients, no median time to flare could be determined within the 48-week timeframe.¹

• At week 96 a higher percentage of patients randomised to the Cimzia full or reduced maintenance dose achieved a clinical improvement/response compared with placebo measured by:
  • ASDAS
  • ASAS20/40, (Assessment of SpondyloArthritis international Society criteria for either 20% or 40% improvement) or
  • BASDAI50, (Bath Ankylosing Spondylitis Disease Activity Index 50% improvement)^1,2

• Between weeks 48 and 96, in patients randomised to the Cimzia full or reduced maintenance dose, ASDAS, BASDAI, BASFI (Bath Ankylosing Spondylitis Functional Index) and BASMI (Bath Ankylosing Spondylitis Metrology Index) remained stable.^1,2
• In patients randomised to placebo, disease activity (ASDAS and BASDAI) and function (BASFI) worsened between weeks 48 and 96.^1,2

Cimzia in axSpA: Key Safety Profile Trial Data

Induction period

• Treatment Emergent Adverse Events (TEAEs) were reported for 67.9% of axSpA patients.²
  • 67.3% of patients with r-axSpA, (radiographic axial spondyloarthiritis) and 68.7% of patients with nr-axSpA, (non-radiographic axial spondyloarthiritis).²
• Serious TEAEs were reported for 6.0% of axSpA patients (ER = 6.74/100 PY).²
  • r-axSpA (6.1%, ER = 7.02/100 PY) and nr-axSpA patients (5.8%, ER = 6.40/100 PY).²

Maintenance period

• TEAEs were reported in 57.7%, 61.0% and 54.4% of patients randomised to Cimzia 200mg Q2W, Cimzia 200mg Q4W or placebo, respectively.^1,2
• Serious TEAEs were reported in five patients randomised to Cimzia 200mg Q2W.
  • No serious TEAEs led to patient withdrawal from the study, and
  • Complete recovery was reported for all five cases.^1,2