Background/Purpose:

Axial spondyloarthritis (axSpA) is a form of spondyloarthritis (SpA) that includes both ankylosing spondylitis (AS) and non-radiographic axial SpA (nr-axSpA), as defined by the ASAS criteria. Both subgroups of patients (pts) have been shown to have a similar burden on Quality of Life (QoL).¹ A recent survey estimated that SpA may affect up to 1.4% of the US population.² Certolizumab pegol (CZP) is a PEGylated Fc-free anti-TNF that improved patients reported outcomes (PRO) in rheumatoid arthritis (RA).³ RAPID-axSpA (NCT01087762) is the first report of the effect of CZP on PRO in axSpA.

Methods:

The ongoing 158-Wk RAPID-axSpA trial is double-blind and placebo controlled to Wk24, dose-blind to Wk48 and then open label to Wk158. Recruited pts had adult-onset active axSpA as defined by the ASAS criteria,¹ Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4, spinal pain ≥4 on a 10 point NRS, and CRP > upper limit of normal or sacroiilitis on MRI. Pts must have failed ≥1 NSAID. Pts could have been secondary failures to 1 previous TNF inhibitor. The pt population reflected the broad axSpA population, including AS pts also meeting the modified New York criteria and nr-axSpA pts who met the ASAS MRI or clinical criteria. Pts were randomized 1:1:1 to placebo (PBO), or 400mg CZP at week (Wk) 0, 2 and 4 (loading dose, LD) followed by either 200mg CZP every 2 weeks (Q2W) or 400mg CZP every 4 weeks (Q4W). Pts receiving PBO who failed to achieve an ASAS20 response at both Wks14 and 16 were rescued and randomized at Wk16 to receive CZP 200mg Q2W or CZP 400mg Q4W following LD. The primary endpoint was ASAS20 response at Wk12. PRO endpoints included SF-36 physical component summary (PCS), physical function (BASFI), total spinal pain (NRS), fatigue (NRS from BASDAI), Ankylosing Spondylitis Quality of Life (AsQoL), Sleep Problems Index II domains of the MOS Sleep scale (MOS-SPI), and SF-36 mental component summary (MCS) and domains. All PRO were analyzed on the full analysis set using analysis of covariance on change from baseline (CFB) with last observation carried forward imputation.

Results:

325 pts were randomized. Baseline characteristics were similar between groups. Improvements in the CZP-treated groups were observed in pain NRS, fatigue NRS, BASFI and AsQoL from the first measurement at Wk1 through to Wk24 compared to PBO. Pts in both CZP-treated dosage arms had greater improvements in SF-36 PCS. compared to PBO (Table). Improvements were also seen in MOS-SPI, SF-36 MCS and domains.

Conclusion:  

Both dosing regimens of CZP rapidly improved all PRO including pain, fatigue, physical function and QoL of axSpA pts. CZP effectively improved patient-relevant outcomes in the broad population of axSpA pts classified using the ASAS criteria.

References:

1. Rudwaleit M. Arthritis Rheum 2009; 60(3):717-727

2. Reveille JD. Arthritis Care Res 2012; 64(6):905-910

3. Strand VS. Ann Rheum Dis 2011; 70(6):996-1002