Female spine

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

Scroll or click the links to jump to any section below:
Off

Study design

Targeting Icon
paragraph-section-content-block

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; 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

""
Zoom Icon

Figure 1.

C-OPTIMISE study design. axSpA, axial spondyloarthritis; CZP, certolizumab pegol; LD, loading dose; Q2W, every 2 weeks; Q2W, every 2 weeks; Q4W, every 4 weeks.

Adapted from: Landewé et al., 2020.

Off

Efficacy

Efficacy icon
paragraph-section-content-block

Cimzia in axSpA: Key Efficacy Trial Data

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

""
Zoom Icon

Figure 2.
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.

Maintenance period
""
Zoom Icon

Figure 3.
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.

Adapted from: Landewé et al., 2020.

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 dose).1

""
Zoom Icon

Figure 4.
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, certolizumab pegol; Q2W, every 2 weeks; Q4W, every 4 weeks.

Adapted from: Landewé et al., 2020.

Main secondary outcome

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

Other secondary outcomes
  • 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 or
    • BASDAI501,2
  • Between weeks 48 and 96, in patients randomised to the Cimzia full or reduced maintenance dose, ASDAS, BASDAI, BASFI and BASMI 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
On

Safety profile

Safety icon
paragraph-section-content-block

Cimzia in axSpA: Key safety 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 and 68.7% of patients with nr-axSpA.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
Off

Conclusion

paragraph-section-content-block

Sustained remission was achieved in over 40% of patients during 48 weeks of open-label treatment with Cimzia, demonstrating the benefits of early treatment in patients with axSpA.1,2

Patients with early axSpA who achieve sustained remission at 48 weeks can reduce their Cimzia maintenance dose; however, treatment should not be completely discontinued due to the high risk of flare following Cimzia withdrawal.1,2

Off

References

paragraph-section-content-block
  1. Landewé, R. et al., 2020. Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction. Annals of the Rheumatic Diseases, 79(7), pp.920-928.
  2. Landewé, R. et al., 2020. Induction of Sustained Clinical Remission in Early Axial Spondyloarthritis Following Certolizumab Pegol Treatment: 48-Week Outcomes from C-OPTIMISE. Rheumatology and Therapy, 7(3), pp.581-599.
On
Because we're in this together...

Report adverse events

Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.mhra.gov.uk and hpra.ie/homepage/about-us/report-an-issue.

Adverse events should also be reported to UCB Pharma Ltd Email: UCBCares.UK@ucb.com and UCBCares.IE@ucb.com.

Feature requests

Help us to grow our resource the way you want it to grow.

Get in touch now

Date of preparation: May 2021
IE-P-CZ-AS-2100010