Horizon Scanning Centre May 2014 Tabalumab for systemic lupus erythematosus SUMMARY NIHR HSC ID: 5581 Tabalumab (LY-2127399) is intended to be used as second line therapy for the treatment of systemic lupus erythematosus (SLE). If licensed, it would offer an additional treatment option for patients who have active moderate to severe SLE despite treatment with glucocorticoids, anti-malarials, and/or immunosuppressants; a group who currently have few effective therapies This briefing is available. Tabalumab is a human anti-B-cell activating factor (BAFF or B based on lymphocyte stimulator [BLyS]) monoclonal antibody. It is administered information subcutaneously, in contrast to the only existing licensed BAFF antagonist, which is administered via IV infusion. available at the time of research and a The annual incidence of SLE in the UK is between 3 and 4 cases per limited literature 100,000 population, which equates to approximately 1,600 and 2,100 new search. It is not cases in England per year. The estimated prevalence of SLE is 25-28 per intended to be a 100,000 population, commensurate with around 15,000 people in England definitive statement with the disease. SLE is associated with considerable morbidity and on the safety, mortality, with 10-year survival rates ranging from 70% to 92%. Around 40– efficacy or 70% of SLE patients develop renal involvement which confers a worse effectiveness of the prognosis for survival; and approximately 10% of patients with lupus nephritis health technology develop end-stage renal failure requiring dialysis or transplantation. covered and should Neuropsychiatric involvement occurs in 27% of people with SLE, and SLE is not be used for also characterised by haematological features and cardiovascular commercial complications. purposes or commissioning Treatment strategies for SLE depend on the severity of disease and organ without additional involvement. Antimalarials (especially hydroxychloroquine) and non-steroidal information. anti-inflammatory drugs, all in combination with glucocorticoids, are standard therapy for those with mild to moderate skin and joint disease. Immunosuppressive agents such as azathioprine, methotrexate, IV cyclophosphamide or mycophenolate mofetil are considered for refractory moderate skin and joint disease. Biological disease-modifying anti-rheumatic drugs are used in patients with refractory severe disease. Belimumab (Benlysta) is currently the only licensed treatment for active autoantibody- positive SLE which is refractory to standard therapy. Tabalumab is currently in phase III clinical trials comparing its effect on disease activity against treatment with placebo. The first trial is expected to complete in July 2015. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. NIHR Horizon Scanning Centre, University of Birmingham Email: [email protected] Web: http://www.hsc.nihr.ac.uk NIHR Horizon Scanning Centre TARGET GROUP • Systemic lupus erythematosus (SLE): moderate to severe; active; without active lupus nephritis or active central nervous system (CNS) lupus – second line; in combination with standard of care (SOC) treatment. TECHNOLOGY DESCRIPTION Tabalumab (LY-2127399) is a human anti-B-cell activating factor (BAFF or B lymphocyte stimulator [BLyS]) monoclonal antibody. Tabalumab is an antagonist of both soluble- and membrane-bound forms of BAFF, which binds to receptors expressed on B cells. BAFF over-expression may contribute to autoimmune diseases, including SLE, via effects on autoreactive B-lymphocyte activation, proliferation, survival and immunoglobulin (autoantibody) production1,2. Belimumab (Benlysta) is currently the only licensed treatment for active autoantibody-positive SLE which is refractory to standard therapy3. However, many SLE patients fail to clinically improve on belimumab therapy, which targets only soluble BAFF and requires intravenous (IV) administration2. Tabalumab in combination with SOC is intended for the treatment of patients with active moderate to severe SLE (without active lupus nephritis or active CNS lupus) which is refractory to treatment. It is administered by subcutaneous (SC) injection at a loading dose of 240mg, followed by 120mg every 2 weeks or 4 weeks in combination with SOC. Tabalumab has completed a phase II clinical trial in end-stage renal failure and is in a phase II clinical trial for the treatment of multiple myeloma. INNOVATION and/or ADVANTAGES If licensed, tabalumab will offer an additional treatment option for patients who have active moderate to severe SLE despite treatment with glucocorticoids, anti-malarials, and/or immunosuppressants; a group who currently have few effective therapies available. Tabalumab is administered SC in contrast to the only existing licensed BAFF antagonist, which is administered via IV infusion. DEVELOPER Eli Lilly and Company Limited. AVAILABILITY, LAUNCH OR MARKETING In phase III clinical trials. PATIENT GROUP BACKGROUND SLE is a chronic, autoimmune, inflammatory disease which affects the skin, joints, internal organs and serous membranes1. The cause of SLE is unknown, though a combination of genetic, environmental and hormonal factors is thought to play a role in disease 2 NIHR Horizon Scanning Centre development and progression1. Disease activity varies over time and, at the onset, symptoms can be non-specific and include pyrexia, extreme fatigue, myalgia, arthralgia, and skin rash1. Active SLE involves frequent flares and more severe symptoms compared with inactive disease (when the disease is in remission)1. SLE can lead to arthritis, kidney failure, heart and lung inflammation, CNS abnormalities and blood disorders1. NHS or GOVERNMENT PRIORITY AREA This topic is relevant to: • The National Service Framework for Long Term Conditions (2005). • The National Service Framework for Renal Services (2004). • NHS England. 2013/14 NHS Standard Contract for Specialised Rheumatology Services (Adult). A13/S/a. • NHS England. 2013/14 interim Clinical Commissioning Policy Statement: Rituximab for the Treatment of Systemic Lupus Erythematosus in Adults. A13/PS/a. CLINICAL NEED and BURDEN OF DISEASE The annual incidence of SLE in the UK is between 3 and 4 cases per 100,000 population4, which equates to approximately 1,600 and 2,100 new cases in England per year. The estimated prevalence of SLE is 25-28 per 100,000 population, commensurate with around 15,000 people in England with the disease4. Although the severity of SLE is greater in men, it is 8-10 times more common in women, and mainly affects women aged 15-40 years1,5. The majority of people with SLE are of working age and the disease results in most being unable to worka. The prevalence of SLE is significantly higher in African-Caribbean, South Asian and Chinese populations compared with European white populations1. SLE is associated with considerable morbidity and mortality, with 10-year survival rates ranging from 70% to 92%6. Long-term damage accrues as a result of persistent disease activity and the cumulative effects of glucocorticoids1. Various studies have estimated that 40–70% of SLE patients develop renal involvement7, which confers a worse prognosis for survivalb. The prevalence of biopsy-proven lupus nephritis in the northwest of England in 2001 was 4.4 per 100,0007. Approximately 10% of patients with lupus nephritis develop end- stage renal failure requiring dialysis or transplantation8. Neuropsychiatric involvement occurs in 27% of people with SLE and has a wide variety of clinical presentations, including seizures, chronic headache, transverse myelitis, vascular brain disease, psychosis, and neural cognitive dysfunction. SLE is also characterised by haematological features, such as haemolytic anaemia (8%), thrombocytopenia (22%) and lymphadenopathy (12%), and cardiovascular complications, such as thrombosis (14%) and Raynaud's phenomenon (34%)9. Approximately 20-30% of patients with SLE continue to have high disease activity despite standard therapies or have organ involvement particularly associated with a worse prognosis, e.g. renal, neuropsychiatric or haematological involvement8. SLE can lead to a poor quality of life (QoL) and associated psychological disordersb. In one study comparing SLE with rheumatoid arthritis and non-inflammatory rheumatic disorders, physical function was better but general health and mental component QoL summary scores (vitality, social function, role-emotional and mental health) were more impaired in SLE10. In 2012-13 there were 4,038 admissions for SLE (ICD-10 M32) in England, resulting in 9,595 bed days and 4,574 finished consultant episodes11. There were 164 deaths (150 deaths in women) due to SLE (ICD-10 code M32) registered in England and Wales during 201212. a Expert personal communication. b Expert personal communication. 3 NIHR Horizon Scanning Centre PATIENT PATHWAY RELEVANT GUIDANCE NICE Guidance • NICE technology appraisal in development. Systemic lupus erythematosus (autoantibody-positive) - belimumab (ID416). Expected date of issue to be confirmed. • NICE clinical guideline. Chronic kidney disease: Early identification and management of chronic kidney disease in adults in primary and secondary care (CG73). September 2008. • NICE quality standard. Chronic kidney disease (QS5). March 2011. Other Guidance • Arthritis Research UK. Overview of the management of systemic lupus erythematosus. 201313.