CIMZIA (certolizumab pegol) is the first therapy to demonstrate positive results in a 52-week, placebo controlled non-radiographic axial spondyloarthritis study. The positive topline results from C-AXSPAND, a Phase 3 multi-centre, randomised, double-blind, parallel-group placebo controlled study to investigate the efficacy of CMIZIA on the signs and symptoms of active non-radiographic axial spondyloarthritis, underscore the potential of the therapy.
The study met the primary objective of achieving a major improvement: 47.2% of CIMZIA-treated patients demonstrated a two-point improvement in ankylosing spondylitis disease activity score (ASDAS-MI) at week 52, compared to just 7% of placebo patients. The study also met assessment of spondyloarthritis international society 40% (ASAS40) response at week 12, a key secondary objective.
The results provide concrete evidence for the high burden of the disease and limitations of current standard of care to provide adequate disease control, a UCB press release states. The company states that it looks forward to quickly submitting the data to the US food and drug administration (FDA), as there are currently no approved biologic treatment options in the US for non-radiographic axial spondyloarthritis.
“People living with non-radiographic axial spondyloarthritis frequently face delayed or incorrect diagnosis, and currently, in the USA, there are no FDA approved options to treat this condition. The C-AXSPAND study results provide important insights into the potential of CIMZIA as an effective and durable treatment option for these patients. Additionally, the study is unique in that it used ASDAS-MI, a rigorous response threshold, and assessed the long-term efficacy of CIMZIA in a one-year, placebo-controlled trial. The study included non-radiographic axial spondyloarthritis patients with objective signs of inflammation, an extended placebo phase, and allowed for modification of background medications to help gain a deeper understanding of the natural history of axial spondyloarthritis and to demonstrate the need for biologic treatment for this disease,” says Atul Deodhar (Oregon Health & Science University, Portland, USA), lead investigator for the study.
The study randomised 317 adult patients. Study participants needed to have evidence of inflammatory disease, defined as sacroiliitis on magnetic resonance imaging (MRI) and/or elevated C-reactive protein levels. Patients must have had an inadequate response to, have a contraindication to, or have been intolerant to at least two non-steroidal anti-inflammatory drugs (NSAIDs). Inadequate response to an NSAID is defined as lack of response to at least 14 days of continuous NSAID therapy at the highest tolerated dose of the administered NSAID.
The primary efficacy variable assessed in C-AXSPAND was ASDAS-MI response at week 52. The ASDAS is a composite index to assess patient disease activity. It is comprised of objective evidence of systemic inflammation, such as C-reactive protein, and patient-reported outcomes, such as back pain, duration of morning stiffness, patient global assessment of the disease, and peripheral pain and/or swelling. The ASDAS is a validated, discriminatory instrument for assessing disease activity in axial spondyloarthritis. In the C-AXSPAND study, the primary outcome was defined as a composite endpoint that was achieved if a patient remained on study treatment through 52 weeks and achieved ASDAS-MI response at week 52. Patients in both the treatment and placebo groups remained on their background therapy for the duration of the study. No new safety signals were observed in the study.
Axial spondyloarthritis is a chronic inflammatory disease that starts in the sacroiliac joints and progresses to the spine, and can ultimately result in patients requiring spinal fusion.
Axial spondyloarthritis is a spectrum of disease that comprises both non-radiographic and radiographic indications, and is also known as ankylosing spondylitis. Non-radiographic axial spondyloarthritis and ankylosing spondylitis share similar symptomology and burden of disease. However, in ankylosing spondylitis there is a definitive structural change of the sacroiliac joints detectable by X-ray; while in non-radiographic axial spondyloarthritis, there is no definitive radiographic sacroiliitis, though there may be magnetic resonance imaging (MRI) evidence of sacroiliitis.
Limited evidence exists regarding the exact prevalence of axial spondyloarthritis, although it is thought to impact a substantial proportion of the population. Recent data suggest that 0.5–1.4% of the adult population have the disease, similar to the prevalence of rheumatoid arthritis, which is 0.5–1%.
CIMZIA is approved by the FDA for adults with active ankylosing spondylitis, but not for non-radiographic axial spondyloarthritis. Most recently, the FDA has approved extending the label for CIMZIA to include a new indication in adults with moderate-to-severe plaque psoriasis.