By: Sang Hyo Kim, Staff Editor
This year, on July 23rd, FDA advisers voted 7 to 6, with one abstention, in favor of approving the drug certolizumab (Cimzia®) for the indication of axial spondyloarthritis (axSpA). axSpA is a chronic imflammatory condition that includes ankylosing spondylitis (AS) and non-radiographic axial spndyloarthristis (nr-axSpA).1,2 axSpA, AS and nr-axSpA, are forms of inflammatory arthritis that mainly affects the spine and pelvic joints.1 The main feature that distinguishes axSpA from nr-axSpA is that nr-axSpA cannot be diagnosed by utilization of radiographic imaging.2
Certolizumab (Cimzia®), marketed by UCB Inc., belongs to the tumor necrosis factor (TNF) inhibitor class of drugs, which are used to treat autoimmune diseases such as rheumatoid arthritis (RA) and Crohns Disease.2,3 Rheumatoid arthritis is a form of inflammatory arthritis, while Crohn’s Disease is a form of inflammatory bowel disease that usually affects the intestines.4,5 Certolizumab, approved for Crohn’s disease and RA in 2008 and 2009, respectively, is administered by subcutaneous injection every four weeks for Crohn’s disease and every other week or every four weeks for RA as maintenance therapy.3 Certolizumab is a breakthrough drug because although there are four other TNF inhibitors that are approved for ankylosing spondylitis (AS), these medications are not approved for treating nonradiographic axial spondyloarhtritis (nr-axSpA).3
The approval of certolizumab came from a study of 325 patients: 178 patients with AS and 147 patients with nr-axSpA.3 The pivotal study compared two dosing regimens of certolizumab against placebo for patients who had an inadequate response or a contraindication to NSAIDS.3 Like the regimens currently approved to treat rheumatoid arthritis, the recommended dosing is 400 mg in weeks 0, 2, and 4, followed by either 200 mg every 2 weeks (Q2W) or 400 mg every 4 weeks (Q4W). 58% of patients on the Q2W regimen and 64% on the Q4W regimen had achieved an ASAS (Assessment of SpondyloArthritis International Society) 20 response, a primary endpoint at 12 weeks, compared with 38% of those on placebo; ASAS 20 response is defined as an improvement of at least 20% and absolute improvement of at least 10 units on a 0-100mm scale in at least 3 of the following domains (See for criteria: (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003425.pdf ).3,6 The differences also remained significant at 24 weeks, in which the ASAS20 response in the two subpopulations, AS and nr-axSpA, also favored those treated with certolizumab.3 The rates of serious adverse events were similar in the certolizumab-treated and placebo groups, and the safety profile of certolizumb corresponded to that of other TNF inhibitors.3
Although with the approval, many concerns were raised. Advisory panels of the FDA, who voted against it, say that the indication is too broad, especially for those treated with nr-axSpA, since the number of patients in the clinical trial was too small.3Additionally, the panels believe that there is a lack of clear definition of active disease in the nr-axSpA indication, as well as the possibility of primary care physicians prescribing the biologic drug for patients with lower back pain.3 However, panelists supporting the approval say that adequate prescribing information will result in appropriate use for patients with active disease in clinical practice .3 Dr.Janet Maynard, a clinical team leader in the FDA’s Division of Pulmonary, Allergy, and Rheumatology Products, further states that the FDA did not base the efficiency of the drug solely on the subgroups and that the data for AS appear reasonable.3 With its debate, certolizumab will be keenly observed.
- Ail P. FDA panel narrowly backs new use of UCB’s arthritis Drug. Reuters. http://www.reuters.com/article/2013/07/23/us-ucb-fda-idUSBRE96M11S20130723. Published July 23rd, 2013. Accessed August 19th, 2013
- The AdverseEvents Research Team. FDA Advisory Panel to Evaluate Adequacy of Safety Data for New Indication for Humira. Drug Safety Monitor. http://www.adverseevents.com/monitor/2013/07/22/fda-advisory-panel-to-evaluate-adequacy-of-safety-data-for-new-indication-for-humira/ . Published July 22nd, 2013. Accessed August 20th, 2013
- Mechcatie,E. Proposed axial spondyloarthritis indication for certolizumab divides FDA panel. Internal Medicine News. http://www.internalmedicinenews.com/single-view/proposed-axial-spondyloarthritis-indication-for-certolizumab-divides-fda panel/f16248620eef54c52ba0d34251962acf.html. Published July 24th, 2013. Accessed August 20th, 2013.
- Rheumatoid Arthritis. Arthritis Foundation. http://www.arthritis.org/conditions-treatments/disease-center/rheumatoid-arthritis/. Accessed August 24th, 2013
- Crohn’s Disease. The New York Times. http://health.nytimes.com/health/guides/disease/crohns-disease/. Accessed August 24th, 2013
- Committee for Medical Products for Human Use. emeA. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003425.pdf. Published June 23rd, 2005. Accessed September 1st, 2013