CIMZIA is the First and Only Biologic Approved in Europe with the Option for a Reduced Maintenance Dose for Patients Across the Full Axial Spondyloarthritis Spectrum
? European label extended to include a dose reduction option for the treatment of adult patients with axial spondyloarthritis (axSpA), including non-radiographic and radiographic axSpA, who are in sustained remission after one year of CIMZIA[?] (certolizumab pegol) treatment,[1]?underpinned by results of the Phase 3b C-OPTIMISE study
? C-OPTIMISE showed that, once axSpA patients are in sustained remission, it is possible to benefit from a reduced CIMZIA dosing regimen without compromising clinical efficacy[2]
Brussels, Belgium ? 5 August 2020 ??UCB today announced that the European Medicines Agency (EMA) has approved a label extension for CIMZIA??(certolizumab pegol) for use in adult patients with axial spondyloarthritis (axSpA) at a reduced maintenance dose of 200 mg every four weeks (Q4W), once sustained remission is achieved after one year of CIMZIA 200 mg every two weeks (Q2W) or 400 mg Q4W.1?The approval makes CIMZIA the only biologic in Europe with a dose reduction option in its label for patients in the broad axSpA population.1?
Clinical remission is recommended as a major treatment target in the Assessment of SpondyloArthritis international Society (ASAS)/European League Against Rheumatism (EULAR) recommendations for axSpA and treat-to-target recommendations for spondyloarthritis.3,4?Additionally, strategies for the maintenance of remission are necessary to prevent future deterioration in disease status.5
Maintenance dose reduction supports the long-term management of patients with axSpA, when sustained disease remission has been achieved.2?This approach offers an additional option that preserves the clinical benefits to patients of remaining on treatment, while responding to specific patient needs, and can optimise the cost of their therapy.2?The extension of CIMZIA?s label in Europe1?addresses an under-recognised unmet need6,7?by providing the first validated dose reduction strategy for patients across the broad axSpA spectrum who have achieved sustained remission.
?AxSpA patients typically experience symptom onset in their mid-twenties and may therefore be concerned about lifelong continuation of therapy. The CIMZIA label extension now offers healthcare providers a validated dose reduction strategy that can meet the needs of patients. Furthermore, the option to reduce the maintenance dose may provide cost reductions, benefiting the wider healthcare system,? said Robert Landew?, MD, PhD, Amsterdam Rheumatology & Clinical Immunology Center, and lead author of the C-OPTIMISE study.
?C-OPTIMISE is the first and only randomised controlled trial to compare both maintenance dose continuation and dose reduction versus placebo in a broad axSpA population. Taken with previous clinical evidence showing that early treatment of axSpA with CIMZIA provides improved clinical outcomes, axSpA patients have a treatment option that can help address their symptoms at every stage of their disease: from initiation of biologic therapy, to remission and maintenance. Our clinical study package in axSpA showed that r-axSpA and nr-axSpA are part of the same disease entity. If treated early, remission is a realistic target and patients can have the flexibility to reduce their dose once they have achieved sustained remission,? said Emmanuel Caeymaex, Executive Vice President Immunology Solutions and Head of US, UCB.
The EMA label extension is based on data from the Phase 3b C-OPTIMISE trial in adults with early active axSpA.2??At week 48 of the induction period, 43.9 percent (323/736) of patients achieved sustained remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 at weeks 32 or 36 and 48). Of those patients, 313 were randomised to full maintenance dose (CIMZIA 200 mg Q2W), reduced maintenance dose (CIMZIA 200 mg Q4W), or placebo.2?At week 96, 84 percent, 79 percent and 20 percent of patients receiving the full maintenance dose, reduced maintenance dose, or placebo, respectively, remained flare-free.2??Of patients who flared in the reduced maintenance dose arm, 60 percent regained remission after 12 weeks of treatment with the full maintenance dose of CIMZIA.2?
There were no differences in responses between radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) patients in both the induction and maintenance periods.2?No new safety signals with CIMZIA were observed over the course of the study compared to previous studies.1,2?In patients who achieve sustained remission, dose reduction is an option, but treatment should not be withdrawn, because of the high risk of flare.2
About Non-Radiographic Axial Spondyloarthritis (nr-axSpA) and Radiographic Axial Spondyloarthritis (r-axSpA)
Non-radiographic axSpA (nr-axSpA) and radiographic axSpA (r-axSpA, also known as ankylosing spondylitis or AS) comprise the axial spondyloarthritis, or axSpA, spectrum of disease, which typically starts in patients in their mid-twenties. Nr-axSpA and r-axSpA share similar symptomology and disease burden. In r-axSpA, there is a definitive structural damage in the sacroiliac joints detectable by x-ray. In nr-axSpA, there is no definitive radiographic sacroiliitis, though magnetic resonance imaging (MRI) testing often shows evidence of active sacroiliitis, visible as inflammation in the sacroiliac joints. Historically, nr-axSpA has not been well-recognised due to a lack of understanding of the disease history, progression, and prognosis, resulting in substantial diagnostic delay. As a result, nr-axSpA is often misdiagnosed and undertreated.
Axial spondyloarthritis is estimated to affect up to 1.4 percent of adults.8,9?Roughly two thirds of nr-axSpA patients are women.10?Yet, axSpA is often overlooked in women, with 89 percent being initially misdiagnosed, leading to a significantly longer time to diagnosis in women compared to men, on average more than two years. Underdiagnosis or misdiagnosis can have long-term consequences for patients with axSpA.11
About the C-OPTIMISE Study2
C-OPTIMISE was a two-part, multicentre Phase 3b trial in adults with early active axSpA (radiographic and non-radiographic). During the 48-week open-label induction period, patients received CIMZIA 200 mg every 2 weeks (Q2W) with loading dose of CIMZIA 400 mg at weeks 0, 2 and 4. At week 48, patients in sustained remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 at weeks 32 or 36 and 48) were randomised to CIMZIA 200 mg Q2W (full maintenance dose), CIMZIA 200 mg every 4 weeks (Q4W; reduced maintenance dose) or placebo (withdrawal) for an additional 48 weeks. The primary endpoint was the proportion of patients remaining flare-free (flare: ASDAS =2.1 at two consecutive visits or ASDAS >3.5 at any time point) during the maintenance period.
C-OPTIMISE is the first and only randomised, interventional, placebo-controlled study in the full axSpA spectrum with three arms (full dose, reduced dose and placebo) that provides strong evidence on the dosing options for healthcare professionals to manage axSpA patients that have achieved sustained remission with CIMZIA treatment.
About CIMZIA??in the EU/EEA
In the EU, CIMZIA??in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active RA in adult patients inadequately responsive to disease-modifying anti-rheumatic drugs (DMARDs) including MTX.
CIMZIA can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. CIMZIA in combination with MTX is also indicated for the treatment of severe, active and progressive RA in adults not previously treated with MTX or other DMARDs.
CIMZIA has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with MTX.
CIMZIA, in combination with MTX, is also indicated for the treatment of active psoriatic arthritis in adults when the response to previous DMARD therapy has been inadequate. CIMZIA can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate.
CIMZIA is also indicated in the EU for the treatment of adult patients with severe active axial spondyloarthritis (axSpA), comprising:
- Ankylosing spondylitis (AS) ? adults with severe active AS who have had an inadequate response to, or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs).
- Axial spondyloarthritis (axSpA) without radiographic evidence of AS ? adults with severe active axSpA without radiographic evidence of AS but with objective signs of inflammation by elevated C-reactive protein (CRP) and/or Magnetic Resonance Imaging (MRI) who have had an inadequate response to, or are intolerant to NSAIDs.
- ? European Medicines Agency (EMA). Certolizumab pegol summary of product characteristics, July 2020:?https://www.ema.europa.eu/en/documents/product-information/cimzia-epar-product-information_en.pdf. Last accessed: August 2020.
- Landew? R, Van der Heijde D, Dougados M, et al. Maintenance of Clinical Remission in Early Axial Spondyloarthritis Following Certolizumab Pegol Dose Reduction. Ann Rheum Dis. 2020;79:920-928.
- Van der Heijde D, Ramiro S, Landew? R, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76(6):978?991.
- Smolen JS, Sch?ls M, Braun J, et al. Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. Ann Rheum Dis. 2018;77(1):3?17.
- Landew? R, Van der Heijde D, Dougados M, et al. Induction of Sustained Clinical Remission in Early Axial Spondyloarthritis Following Certolizumab Pegol Treatment: 48-Week Outcomes from C-OPTIMISE. Rheumatol Ther. 2020; https://doi.org/10.1007/s40744-020-00214-7.
- Wallis D, Holmes C, Holroyd C, et al. Dose reduction of biological therapies for inflammatory rheumatic diseases: what do patients think? Scand J Rheumatol. 2018;00:1-2.
- UCB. Data on file (Qualitative survey, October 2019).
- Reveille JD, Witter JP and Weisman MH. Prevalence of Axial Spondylarthritis in the United States: Estimates From a Cross-Sectional Survey. Arthritis Care Res. 2012;64(6):905-10.
- Hamilton L, Macgregor A, Toms A, et al. The prevalence of axial spondyloarthritis in the UK: a cross-sectional cohort study. BMC Musculoskelet Disord. 2015;21(16):392.
- Baraliakos X, Braun J. Non-radiographic Axial Spondyloarthritis and Ankylosing Spondylitis: What Are the Similarities and Differences? RMD Open. 2015;1(suppl 1):e00005321.
- Feldtkeller E, Bruckel J and Khan MA. Scientific contributions of ankylosing spondylitis patient advocacy groups. Curr Opin Rheumatol. 2000;12(4):239-247.