Study to Investigate the Impact of Cimzia in Patients with nr-axSpA with Signs of Inflammation

C-axSpAnd was a double-blind placebo-controlled trial to investigate the impact of Cimzia in patients with non-radiographic axSpA with objective signs of inflammation.^1,2

Figure 1.
Disposition of patients.

axSpA = axial spondyloarthritis; PBO = placebo; NBBM = nonbiologic background medication; CZP = certolizumab pegol 200mg.

Adapted from: Deodhar et al., 2019

Patients were randomised 1:1 to receive placebo (n=158) or Cimzia (n=159) (400mg at weeks 0, 2, and 4, followed by 200mg every 2 weeks) in addition to nonbiologic background medication (NBBM) [Figure 1].^1,2

Switching to open-label Cimzia (or other biologic) or making background medication changes was permitted at any point during the trial, although changes before week 12 were discouraged.^1,2

Cimzia in nr-axSpA: Key Efficacy Trial Data

Primary efficacy endpoint

The primary efficacy endpoint was defined as a composite outcome measure that was achieved if all of the following 3 criteria were fulfilled:

• the patient remained in the study until week 52
• the patient continued taking double-blind study treatment throughout
• the patient achieved major improvement (MI) in the Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 52. ASDAS-MI is defined as a ≥2.0-point decrease from the baseline score in the ASDAS or achievement of the lowest possible ASDAS value³

ASDAS-MI at week 52, was reached by 47.2% (75 of 159) of Cimzia plus NBBM patients and 7.0% (11 of 158) of placebo plus NBBM patients (P < 0.0001) (OR for Cimzia plus NBBM versus placebo plus NBBM 15.2% [95% confidence interval 7.3–31.6]) [Figure 2].²

Figure 2.
Proportion of patients achieving major improvement in the Ankylosing Spondylitis Disease Activity Score (ASDAS-MI). P < 0.0001 for certolizumab pegol (CZP) versus placebo (PBO) at week 12 and week 52 for ASDAS-MI. NBBM = nonbiologic background medication.

Adapted from: Deodhar et al., 2019 

A post hoc analysis stratified patients into cohorts who had experienced symptoms ≥5 years and patients with less than 5-year symptom history at screening. ASDAS-ID was achieved in 40.5% (32/79) patients with <5 years symptom duration and in 17.9% (14/78) patients with ≥5 years symptom duration, in the CZP and NBBM group [Figure 3].^1,2

Figure 3.
Clinical outcomes in patients treated with Placebo (PBO) and NBBM or Certolizumab (CZP) and NBBM stratified by symptom duration. Missing values imputed using double-blind last observation carried forward.

Adapted from: Rudwaleit et al., 2019 

Secondary efficacy endpoint

The key secondary endpoint was achievement of 40% improvement according to the ASAS (ASAS40) at weeks 12 and 52.²

Figure 4.
Proportion of patients achieving 40% improvement in disease activity according to Assessment of Spondyloarthritis international Society criteria (ASAS40) by week 52. P < 0.0001 for certolizumab pegol (CZP) versus placebo (PBO) at week 12 and week 52 for ASAS40. NBBM = nonbiologic background medication.

Adapted from: Deodhar et al., 2019 

At week 12, 47.8% (76 of 159) of Cimzia plus NBBM patients had achieved an ASAS40 response, compared to 11.4% (18 of 158) of placebo plus NBBM patients (P < 0.0001). By week 52, 56.6% (90 of 159) of Cimzia plus NBBM patients and 15.8% (25 of 158) of placebo plus NBBM patients had achieved an ASAS40 response (P < 0.0001) [Figure 4].²

• Clinically meaningful and statistically significant responses for the BASDAI and the BASFI were achieved in Cimzia plus NBBM–treated patients. Mean ± SD BASDAI score of 6.88±1.40 in Cimzia treated population at baseline to 2.64± 2.08 at week 52, compared to 6.79± 1.28 in the placebo-treated population at baseline to 3.47± 1.73 at week 52 (p<0.0001). Mean ± SD BASFI score of 5.41± 2.12 in Cimzia treated population at baseline to 2.13±2.09 at week 52, compared to 5.44± 2.18 in the placebo-treated population at baseline to 2.88± 1.94 at week 52 (p<0.0001).²
• MRI inflammation in the sacroiliac joints significantly improved in Cimzia plus NBBM–treated patients, decreasing from a mean ± SD sacroiliac joint SPARCC score of 7.79 ± 10.82 at baseline to 1.92 ± 3.96 at week 52, compared to 8.46 ± 12.31 in the placebo-treated population at baseline to 5.84 ± 10.99 at week 52 (P < 0.0001).²
• There were corresponding improvements in nocturnal spinal pain in Cimzia plus NBBM–treated patients that were maintained to week 52. Mean ± SD Nocturnal spinal pain 6.6± 2.3 at baseline to 2.0± 2.1 at week 52 (p<0.0001).²
• Improvements and sustained responses were observed in health-related quality of life outcomes such as the ASQoL and SF-36. Mean ± SD ASQoL score 11.70± 4.34 at baseline to 4.14± 4.67 at week 52 (p<0.0001). Mean ± SD SF-36 PCS 34.6± 7.1 at baseline to 47.4± 7.8 at week 52. Mean ± SD SF-36 MCS 42.0 ± 11.0 at baseline to 48.2± 10.4 at week 52 (Both not included in statistical analysis).²
• Post-baseline uveitis was observed in 2.5% (4 of 159) of Cimzia  plus NBBM-treated patients compared to 5.1% (8 of 158) of placebo plus NBBM-treated patients, but this difference did not achieve statistical significance.²

SPARCC - Spondyloarthritis Research Consortium of Canada

BASFI - Bath Ankylosing Spondylitis Functional Index

ASQoL- Ankylosing Spondylitis quality of life

Cimzia in nr-axSpA: Key Safety Data

One malignancy was reported in the placebo plus NBBM group, and two malignancies were reported in the Cimzia plus NBBM group. There were no deaths, serious cardiovascular events, or opportunistic infections (including tuberculosis) during the trial. The adverse events reported were consistent with those already identified for Cimzia and other anti-TNF agents [Table 1].²

Safety outcomes for all patients (n = 317)

Table 1.
Safety outcomes for all patients (n=317)*

Adapted from: Deodhar et al., 2019 

*The safety set consisted of all patients treated with ≥1 dose of study medication. Values are the number (%). NBBM = nonbiologic background medication; TEAE = treatment-emergent adverse event.

† Certolizumab pegol (CZP) 200mg every 2 weeks.

Improvements in clinical efficacy and objective signs of inflammation were maintained to week 52 in Cimzia treated non-radiographic axSpA patients. Adding Cimzia to background medication demonstrated a significant improvement in ASDAS-MI and ASAS40 at week 52 compared to adding placebo in patients with active non-radiographic axSpA. Post hoc analysis indicate that early Cimzia treatment for nr-axSpA may be beneficial to patients.^1,2

Cimzia can be used with adults with severe active axial spondyloarthritis without radiographic evidence of AS but with objective signs of inflammation by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), who have had an inadequate response to, or are intolerant to NSAIDS^3. Treating early is conditional to the above mentioned factors.