Certolizumab pegol in axial spondyloarthritis

Abstract

The axial spondyloarthritis (SpA) classification criteria cover both patients with ankylosing spondylitis and non-radiographic axial SpA. After failure of NSAIDs TNF-α-inhibitors (TNF-blockers) can be given to patients with active axial SpA. Until recently, the TNF-blockers infliximab, adalimumab, etanercept and golimumab are labeled for the treatment of active ankylosing spondylitis while for active nr-axSpA only adalimumab has been approved in Europe. The TNF-blocker certolizumab pegol has recently been evaluated in the RAPID-axSpA trial which is the first placebo-controlled randomized-controlled trial in the entire group of axial SpA. An elevated C-reactive protein and/ or evidence of bone marrow edema on MRI of the sacroiliac joints were required for inclusion in RAPID-axSpA, and patients could have been preexposed to TNF-blockers. The interesting data of this important trial in the context of the emerging therapeutic field of non-radiographic axial SpA therapy is discussed in this review.

Keywords::

• ankylosing spondylitis
• axial spondyloarthritis
• TNF-α inhibitor

Financial & competing interests disclosure

I-H Song has received honoraria for consultancies and/ or scientific presentations at symposia or meetings from AbbVie, Pfizer, and Roche/Chugai. M Rudwaleit has received honoraria for consultancies and/ or scientific presentations at symposia or meetings from AbbVie, BMS, Janssen & Cilag, MSD, Pfizer, Novartis, Roche/Chugai, and UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • The Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (SpA) encompass both patients with ankylosing spondylitis (AS) and non-radiographic axial SpA (nr-axSpA), and are being used in clinical trials.

• • According to the ASAS recommendations tumor-necrosis-factor alpha-blocking agents can be given to patients with active axial SpA after failure of at least two NSAIDs given for a total of 4 weeks.

• • Until 2012, four TNF-blockers including infliximab, adalimumab, etanercept and golimumab were labelled for the treatment of ankylosing spondylitis. For the treatment of nr-axSpA only adalimumab was approved in Europe.

• • The TNF-blocker certolizumab pegol (CZP) is a unique compound among the TNF-blockers due to the absence of a Fc fragment.

• • Based on the data from the RAPID-axSpA trial, CZP has been approved in 2013 for AS (in the USA and Europe) and for nr-axSpA (in Europe only). The RAPID-axSpA trial is the first placebo-controlled randomized controlled trial which evaluated a total of 325 axial SpA patients according to the ASAS classification criteria including patients with AS (54.8% of patients) and nr-axSpA (45.2% of patients).

• • CZP was applied in two different regimes (400 mg CZP at weeks 0, 2 and 4 [loading dose] followed by either 200 mg CZP every 2 weeks or 400 mg CZP every 4 weeks), and tested against placebo.

• • The primary outcome of the RAPID-axSpA trial, ASAS20 response at week 12, was significantly more often reached by CZP-treated patients compared to placebo-treated patients. Similar improvements could be observed for ASAS40 and ASAS partial remission at weeks 12 and 24, respectively.

• • In line with the observed clinical efficacy there was also a significant effect in the reduction of active inflammation on MRI of the sacroiliac joints and the spine which was statistically greater in CZP-treated as compared to placebo-treated patients.

• • Both subgroups, AS and nr-axSpA, responded similarly well in RAPID-axSpA. Yet, there was a tendency for a slightly better response in nr-axSpA patients compared to AS patients, possibly due to shorter disease duration in nr-axSpA patients.

• • CZP showed a beneficial safety profile in RAPID-axSpA.

• • Arguments in favour of CZP could be a good efficacy that appears comparable to other TNF blockers, a lower rate of injection site reactions and potentially greater safety in pregnancy based on preliminary data suggesting that PEGylated Fab fragments may not actively cross the placenta.

• • Long-term data on the efficacy and safety in the future must be obtained.

Notes