Progress in the treatment of early-stage inflammatory joint disease

Pfizer has announced that the European Commission (EC) has granted a licence extension for Enbrel^® (etanercept) in the treatment of adult patients with severe non-radiographic axial spondyloarthritis (nr-axSpA).

Pfizer has announced that the European Commission (EC) has granted a licence extension for Enbrel^® (etanercept) in the treatment of adult patients with severe non-radiographic axial spondyloarthritis (nr-axSpA).
Nr-axSpA is a subtype of the progressive disease axial spondyloarthritis (axSpA) – a chronic lifelong inflammatory disease for which there is no cure. It affects the spine and sacroiliac (hip and lower spine) joints. ‘Non-radiographic’ describes patients in the early stage of the disease, who experience symptoms before structural changes can be detected by X-ray.(1)

Nr-axSpA symptoms
Sufferers can experience increased lower back pain and inflammation of tendons and ligaments. Nr-axSpA has been described as an early form of ankylosing spondylitis (AS), which is a later stage of the condition that can lead to spinal fusion.(2)
While X-rays of patients with nr-axSpA do not show the inflammation of the sacroiliac joint, the symptoms and disease burden experienced are similar to those with AS where structural changes are visible on an X-ray.(2,3) As many as 12% of nr-axSpA patients progress to AS in a two-year period.(4)
The prevalence of axSpA varies depending on the classification criteria used and a recent US-based study estimated that axSpA could affect up to 1% of adults.(5) The most recent UK study estimates the prevalence of axSpA at 0.3%, including 0.15% for AS,(6) which based on the latest UK population data(7) would equate to around 95,000 patients with nr-axSpA in the UK. The early age of onset of nr-axSpA – most patients are under the age of 45 when symptoms begin – means that it can strike people at their most productive time of life.(8)
Dr Berkeley Phillips, Pfizer UK Medical Director, said “This licence extension reflects Pfizer’s continuing commitment to enhancing the scientific community’s understanding of rheumatic diseases and providing treatment options for patients to address an unmet need in this less well-understood but equally painful form of spondyloarthritis.”

Basis of licence extension
The licence extension was based on data from study 1031 with etanercept, which was a randomised 12 week double-blind, placebo-controlled, clinical trial of 215 adult patients with active nr-axSpA. The primary measure of efficacy was a 40% improvement in at least three of the four Assessment of SpondyloArthritis international Society (ASAS) domains and absence of deterioration in the remaining domain – called ASAS 40. In study 1031 more patients treated with etanercept showed significant improvement compared with placebo (32.4% versus 15.7%; p=0.006)(9) in measures of disease activity and function, and decreases in inflammation on MRI by week 12. Compared with placebo, magnetic resonance imaging assessment of the sacroiliac joint demonstrated a significant improvement for patients receiving Enbrel at week 12. Clinical outcomes improved further after all patients were treated with open-label etanercept between weeks 12–24.(9)
Treatment-related adverse events were reported in 57% and 45% of patients in the etanercept and placebo groups, respectively. In the open-label period, such events were reported in 34% of patients in the etanercept/etanercept group and 50% in the placebo/etanercept group.
The EC approval is for the treatment of adults with severe non-radiographic axSpA with objective signs of inflammation as indicated by elevated C-reactive protein and/or MRI evidence, who have had an inadequate response to non-steroidal anti-inflammatory drugs.

References

1. Kiltz U et al. Do Patients With Non-Radiographic Axial Spondyloarthritis Differ From Patients With Ankylosing Spondylitis? Arthritis Care & Research 2012;64:1415–22.
2. Rudwaleit M et al. The Early Disease Stage in Axial Spondyloarthritis. Arthritis and Rheumatism 2009;60:717–27
3. Bennett A et al. Diagnosing axial spondyloarthropathy. The new Assessment in SpondyloArthritis international Society criteria: MRI entering centre stage. Ann Rheum Dis 2009;68:765–66.
4. Poddubnyy D, Sieper J. Radiographic progression in ankylosing spondylitis/axial spondyloarthritis: how fast and how clinically meaningful? Curr Opin Rheumatol 2012; 24(4):363–9.
5. Reveille J et al. Prevalence of axial spondyloarthritis in the United States: Estimates from a cross-sectional survey. Arthritis Care Res 2012;64:905–10.
6. Hamilton L et al. The Prevalence of Axial Spondyloarthropathy in the UK: a Cross Sectional Cohort Study in a Primary Care Population Rheumatology 2012;53(Suppl. 1) i30.
7. Current UK population estimated at: 64.1 million. Annual Mid-Year Population Estimates for the UK, Office for National Statistics, 2013. (Available at: http://ons.gov.uk/ons/taxonomy/index.html?nscl=Population#tab-overview) accessed 31st July 2014.
8. Rudwaleit, M and Sieper J. Referral strategies for early diagnosis of axial spondyloarthritis. Nature Rev Rheum 2012;8: 262–8.
9. Dougados M et al. The symptomatic efficacy and effect on objective signs of inflammation of etanercept in early nonradiographic axial spondyloarthritis. Arthritis & Rheum 2014 [Epub ahead of print].