Certolizumab pegol (Cimzia) for the treatment of ankylosing spondylitis second or third line

Transcription

1 Certolizumab pegol (Cimzia) for the treatment of ankylosing spondylitis second or third line August 2011 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The National Horizon Scanning Centre Research Programme is part of the National Institute for Health Research

2 Certolizumab pegol (Cimzia) for the treatment of ankylosing spondylitis second or third line Target group Ankylosing spondylitis (AS): active - second or third line; after intolerance or inadequate response to at least one non-steroidal anti-inflammatory drug (NSAID). Background AS is a chronic inflammatory condition that is strongly associated with the HLA-B27 genotype. It is a progressive disease with onset typically in late teenage years and early 20s, and is most prevalent in young men of working age. Diagnosis is based on clinical criteria, the modified New York Criteria 1, and evidence of sacro-iliitis and/or inflammatory spinal disease on imaging (x-ray, MRI, bone scan). Principal features are inflammation of the sacro-iliac joints and the vertebral bodies, affecting the whole spine in the worst cases. A significant number of patients have systemic involvement, including inflammation of the eyes (uveitis) in 30%; microscopic colitis; peripheral joint involvement in 30%; heart and lung involvement; as well as weight loss, fatigue, and fever. Untreated disease results in pain, restriction of movement, spinal stiffness and postural changes, and in the longer term; fusion of the spinal vertebrae, increased risk of spinal fractures and osteoporosis causing considerable disability a. Technology description Certolizumab pegol (Cimzia, CDP870, PHA ) is a pegylated, Fab fragment humanised monoclonal antibody directed against tumour necrosis factor alpha (TNFα). Currently there are several TNFα inhibitors already on the market for the treatment of AS. It is intended as a substitute therapy for the second or third line treatment of active AS, after failure of NSAIDs. Certolizumab is presented in a pre-filled syringe and administered via a subcutaneous route at 400mg fortnightly for the first 4 weeks (3 doses) and 200mg fortnightly after that. An autoinjector device for the administration of certolizumab is also being developed by the manufacturer and may be approved before the anticipated launch date. Certolizumab is licensed in the USA and EU for the second line treatment of moderateto-severe active rheumatoid arthritis and in the USA and Switzerland for the treatment of Crohn s disease. Common reported side effects include: bacterial and viral infections, eosinophilic disorders, leukopenia, headaches, hypertension, hepatitis, rash and injection site reactions. Certolizumab is in phase III development for axial spondyloarthropathy (SpA) and psoriatic arthritis, and in phase II development for juvenile rheumatoid arthritis. Innovation and/or advantages If licensed, certolizumab would provide an alternative therapy for the treatment of AS in patients with an intolerance or inadequate response to at least one NSAID. Developer UCB Pharma Ltd. a Personal communication with expert. 2

3 Availability, launch or marketing dates, and licensing plans In phase III clinical trials. NHS or Government priority area The Musculoskeletal Services Framework (2006). Relevant guidance NICE technology appraisal in development. Golimumab for the treatment of ankylosing spondylitis. Expected October NICE technology appraisal. Certolizumab pegol for the treatment of rheumatoid 3 arthritis NICE technology appraisal. Adalimumab, etanercept and infliximab for ankylosing spondylitis Assessment of SpondyloArthritis International Society. ASAS Handbook: a guide to assess spondyloarthritis Assessment of SpondyloArthritis International Society and European League Against Rheumatism (ASAS/EULAR). Recommendations for the management of ankylosing 6 spondylitis ASAS International Working Group. Consensus statement for the use of anti-tnf 7 agents in patients with ankylosing spondylitis British Society for Rheumatology. Guidelines for prescribing TNFα blockers in adults with ankylosing spondylitis Clinical need and burden of disease An estimated 2% of patients each year present to General Practice with back pain, and up to 5% of these will show features of AS 9. SpAs as a group are one of the most common rheumatic diseases with a prevalence of %, making them roughly as common as rheumatoid arthritis 3. The most common SpA subgroups are AS and undifferentiated SpA. NICE estimate the prevalence of clinically significant AS at 0.15% of the population with an annual incidence of 6.9 per 100,000, representing approximately 2,300 new cases each year in England and Wales 6. AS is more common in men than women, with men more likely to develop severe spinal disease. About a third of people with AS may be unable to work altogether, with a further 15% reporting some changes to their working lives 6. Patients with AS have an increased mortality risk, with a standardised mortality ratio of 1.5. Causes of death include cardiovascular disease, amyl oidosis and fractures 6. Existing comparators and treatments As AS manifestations can be varied, treatment choice depends on the patient s symptoms and their severity. Guidelines for the management of AS 6 suggest a combination of patient/family education, exercise, physical therapy and surgery, as well as pharmacological treatments. Pharmacological therapies for AS include 6,7 : NSAIDs first line. Analgesics for patients in whom NSAIDs are insufficient, contraindicated and/or poorly tolerated. Corticosteroid injections to the site of local musculoskeletal inflammation. Disease-modifying antirheumatic drugs (DMARDs) no evidence for efficacy in axial disease, but may be considered in patients with peripheral arthritis. 3

4 TNF-α antagonist therapy for persistently high disease activity. Efficacy and safety Trial AS001, EudraCT , NCT ; certolizumab pegol at two doses versus placebo; phase III. Sponsor UCB Inc. Status Ongoing. Source of information Trial registry 10. Location EU (inc UK), USA, Canada and other countries. Design Randomised, placebo-controlled. Participants and n=315 (planned); adults; active axial SpA, including AS; diagnosis 3 schedule mths; intolerance or inadequate response to 1 NSAID. Randomised to 3 treatment arms: Arm 1 Week 0-4: certolizumab 400mg SC every 2 weeks, week 6-48: certolizumab 200mg SC every 2 weeks. Arm 2 Week 0-4: certolizumab 400mg SC every 4 weeks, week 8-48: certolizumab 400mg SC every 4 weeks. Arm 3 Week 0-24: placebo SC given every two weeks. At week 16, patients not achieving minimal response will be given certolizumab 400mg SC every 2 weeks. At week 24, patients will be randomised to arms 1 or 2 (no placebo arm) until week 48. Week all patients can enter open-label extension (OLE), continuing study allocated treatment. Follow-up Treatment period 24 weeks, possibly continuing in OLE until week 156. Follow-up till end of week 156. Primary outcome Response at week 12 assessed using ASAS20 b criteria. Secondary outcomes Response at week 24 (ASAS20); change in BASFI c, BASDI d and BASMI e at week 12 and 24; change in spine and sacroiliac (SPARCC f ) score at week 12. Expected reporting date September Estimated cost and cost impact The cost of certolizumab for the treatment of AS is not yet known. For the treatment of rheumatoid arthritis, certolizumab costs for a 200mg pre-filled syringe. The following comparator anti-tnfα drugs are recommended for the treatment of severely active AS in patients after failure of NSAIDs due to non-response or intolerance 11 : Drug Dose Period: 1 yr Adalimumab 40mg every other week. 9,295 (Humira) Etanercept (Enbrel) 50mg once weekly. 9,296 b ASAS - Assessment of SpondyloArthritis International Society. Improvement 20 criteria - Improvement of >20% and >1 unit in at least 3 of 4 domains on a scale of 10. c BASFI - Bath Ankylosing Spondylitis Functional Index. d BASDAI - Bath Ankylosing Spondylitis Disease Activity Index. e BASMI - Bath Ankylosing Spondylitis Metrology Index. f SPARCC - Spondyloarthritis Research Consortium of Canada. 4

5 Claimed or potential impact speculative Patients Reduced mortality or increased length of survival Other: Reduction in associated morbidity or Improved quality of life for patients and/or carers Quicker, earlier or more accurate diagnosis or identification of disease None identified Services Increased use Service organisation Staff requirements Decreased use Other: None identified Costs Increased unit cost compared to alternative Increased costs: more patients coming for treatment Increased costs: capital investment needed New costs: Savings: Other: uncertain unit cost compared to alternative treatment options (NB: PAS proposed). Other issues Clinical uncertainty or other research question identified: The long term effects of certolizumab are currently uncertain. None identified References 1 National Institute for Health and Clinical Excellence. Adalimumab, etanercept and infliximab for ankylosing spondylitis. Technology appraisal TA143. London: NICE; May National Institute for Health and Clinical Excellence. Golimumab for the treatment of ankylosing spondylitis. Technology appraisal in development. Expected October National Institute for Health and Clinical Excellence. Certolizumab pegol for the treatment of rheumatoid arthritis. Technology appraisal TA186. London: NICE; February National Institute for Health and Clinical Excellence. Adalimumab, etanercept and infliximab for ankylosing spondylitis. Technology appraisal TA143. London: NICE; May Sieper J, Rudwaleit M, Baraliakos X et al. The Assessment of SpondyloArthritis International Society (ASAS) Handbook: a guide to assess spondyloarthritis. Annals of the Rheumatic Diseases 2009;68:ii1-ii44. 6 Zochling J, van der Heijde D, Burgos-Vargas R et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Annals of the Rheumatic Diseases 2006;65: Braun J, Davis J, Dougados M et al. First update of the international ASAS concensus statement for the use of anti-tnf agents in patients with ankylosing spondylitis. Annals of the Rheumatic Diseases 2006;65: Keat A, Barkham N, Bhalla A et al., on behalf of the British Society for Rheuamtology Standards, Guidelines and Audit Working Group. BSR guidelines for prescribing TNF-α blockers in adults with ankylosing spondylitis - report of a working party of the British Society for Rheumatology. Rheumatology 2005;44: NHS Clinical Knowledge Summaries (CKS). Ankylosing Spondylitis Background Information. Accessed 25 March ClinicalTrials.gov. Certolizumab pegol in subjects with active axial spondyloarthritis. Accessed 6 June British Medical Association and Royal Pharmaceutical Society of Great Britain, British National Formulary. BMJ Group and RPS Publishing. London; March

6 The National Institute for Health Research National Horizon Scanning Centre Research Programme is funded by the Department of Health. The views expressed in this publication are not necessarily those of the NHS, the NIHR or the Department of Health The National Horizon Scanning Centre, Department of Public Health and Epidemiology University of Birmingham, 90 Vincent Drive, Edgbaston, Birmingham, B15 2SP, England Tel: +44 (0) Fax +44 (0)