Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study

Abstract

Objectives: To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-axSpA (NCT01087762), an ongoing Phase 3 trial in patients with axial spondyloarthritis (axSpA), including patients with ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA).

Methods: Patients with active axSpA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). In total 325 patients were randomised. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society 20) response at week 12. Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index (BASMI) linear.

Results: Baseline disease activity was similar between AS and nr-axSpA. At week 12, ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo (57.7 and 63.6 vs 38.3, p≤0.004). At week 24, combined CZP arms showed significant (p<0.001) differences in change from baseline versus placebo in BASFI (-2.28 vs -0.40), BASDAI (-3.05 vs -1.05), and BASMI (-0.52 vs -0.07). Improvements were observed as early as week 1. Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA subpopulations. Adverse events were reported in 70.4% vs 62.6%, and serious adverse events in 4.7% vs 4.7% of All CZP versus placebo groups. No deaths or malignancies were reported.

Conclusions: CZP rapidly reduced the signs and symptoms of axSpA, with no new safety signals observed compared to the safety profile of CZP in RA. Similar improvements were observed across CZP dosing regimens, and in AS and nr-axSpA patients.

Figure 1

Study design and patient disposition. A. RAPID-axSpA trial design to week 24 of an ongoing 204-week trial. B. Disposition of patients in the overall axSpA population (RS). axSpA, axial spondyloarthritis; CZP, certolizumab pegol; LD, loading dose; Q2W, every 2 weeks; Q4W, every 4 weeks; sc, subcutaneous. *All patients received the allocated treatment. Discontinuations for placebo patients are detailed for time periods prior to and after escape at week 16.

Figure 2

ASAS response rates in axSpA patients at week 12 (A) and up to week 24 (B). A. ASAS20, ASAS40, ASAS5/6 and ASAS partial remission response rates at week 12. * p<0.001; § p=0.004 CZP versus PBO (2-sided Wald asymptotic test). B. ASAS20 response rate in the three treatment groups from week 0 to week 24. * p<0.001; § p=0.004 CZP versus PBO (2-sided Wald asymptotic test). ‡ Placebo patients escaping at week 16 (n=56) were considered non-responders at weeks 16–24. Data corresponds to the RS (non-responder imputation). PBO, placebo; CZP, certolizumab pegol; Q2W, every 2 weeks; Q4W, every 4 weeks; ASAS20, assessment of Axial SpondyloArthritis international Society 20% response criteria; ASAS40, assessment of Axial SpondyloArthritis international Society 40% response criteria; ASAS5/6: assessment of Axial SpondyloArthritis international Society at least 20% improvement in 5 of 6 domains (including spinal mobility and c-reactive protein).

Figure 3

Change from baseline in BASFI, BASDAI, BASMI linear and ASDAS, and response rates for BASDAI50 and ASDAS major improvement or inactive disease at weeks 12 and 24. Change from baseline in A, BASFI; B, BASDAI; C, BASMI linear; and D, ASDAS. E, BASDAI50 response rates expressed as the % of patients achieving ≥50% improvement in BASDAI from baseline. F, ASDAS response rates expressed as the percentage of patients achieving major improvement and inactive disease state. Data are presented for the placebo (PBO), CZP 200 mg Q2W or CZP 400 mg Q4W at week 12 and week 24. * p<0.001; † p<0.05 CZP versus PBO (2-sided Wald asymptotic test). ‡ Placebo patients escaping at week 16 (n=56) were considered non-responders at weeks 16–24. ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BASMI, Bath Ankylosing Spondylitis Metrology Index linear; CZP, certolizumab pegol.

Figure 4

Efficacy in AS and nr-axSpA subpopulations at weeks 12 and 24. Responses for the three treatment groups (placebo (PBO), CZP 200 mg Q2W or CZP 400 mg Q4W) at weeks 12 and 24 in: A, ASAS20; B, ASAS40 and C, ASDAS. Change from baseline at weeks 12 and 24 in: D, BASDAI; E, BASFI and F, BASMI linear. All response rates are presented as % of patients. * p<0.001; † p<0.05 CZP versus PBO (2-sided Wald asymptotic test). Escaping PBO patients were considered non-responders week 24. N values for the AS subpopulation are 57, 65 and 56 for the placebo, CZP 200 mg Q2W and CZP 400 mg Q4W. AS, ankylosing spondylitis; ASAS20, assessment of Axial SpondyloArthritis international Society 20% response criteria; ASAS40, assessment of Axial SpondyloArthritis international Society 40% response criteria; ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BASMI, Bath Ankylosing Spondylitis Metrology Index linear; CZP, certolizumab pegol.