Title: Avacopan for treating anti-neutrophil cytoplasmic antibody-associated vasculitis [ID1581]
Funder: Department of Health and Social Care

Abstract: Systemic vasculitis is an autoimmune condition characterised by damage to and inflammation of blood vessels. Anti-neutrophil cytoplasmic autoantibody (ANCA)- associated vasculitis is an umbrella term for several related conditions, including granulomatosis with polyangiitis (GPA; Wegener's granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). ANCAassociated vasculitis mostly affects small and medium sized blood vessels, particularly those in the respiratory and renal systems. One of the primary mediators of ANCA-associated vasculitis pathology is thought to be B-lymphocytes, but the precise mechanism is unknown._x000D_ _x000D_ The annual UK incidence of GPA is estimated to be around 11 per million population, and the prevalence is between 135 and 146 per million.[1],[6] The annual incidence and prevalence of MPA is around 6 and 63 per million respectively. [1] This implies that fewer than 970 people are diagnosed with GPA and MPA each year in England, and there are about 12,200 people currently living with these conditions.[2] The incidence of ANCA-associated vasculitis increases with age and the peak age of onset is between 60 and 70 years.[3]_x000D_ _x000D_ The aim of treatment is initially to induce remission (to reduce the risk of organ damage), then to maintain remission and treat relapse as needed while avoiding drug toxicity. Without treatment, the condition is fatal._x000D_ _x000D_ Clinical practice guidelines (BSR and BHPR 2014[4] and EULAR/EUVAS 2015[5] ) recommend clinical management strategies based on disease progression. Methotrexate or mycophenolate mofetil with corticosteroids are recommended for non-organ-threatening disease, and cyclophosphamide or rituximab with corticosteroids are recommended for organ or life-threatening disease. After induction of remission, maintenance therapy with low dose corticosteroids and either azathioprine, rituximab, methotrexate or mycophenolate mofetil is recommended for at least 2 years._x000D_ _x000D_ NICE TA308 recommends rituximab, in combination with glucocorticoids, as an option for inducing remission in adults with ANCA-associated vasculitis (severely active GPA and MPA) if there is disease progression with cyclophosphamide, or if cyclophosphamide is not appropriate or not tolerated. Rituximab is currently commissioned by NHS England as a treatment option for maintenance therapy in a specific subgroup of adults with ANCA-associated vasculitis._x000D_ _x000D_ References_x000D_ _x000D_ 1 Watts, R. A., Mooney, J., Skinner, J., et al. (2012). The contrasting epidemiology of granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis. Rheumatology, 51(5), 926-931._x000D_ _x000D_ 2 Office for National Statistics (2020) Mid-year population estimates for England in 2019. Accessed August 2020._x000D_ _x000D_ 3 NHS England (2015). Clinical commissioning policy: rituximab for the treatment of ANCA-associated vasculitis in adults. Accessed August 2020._x000D_ _x000D_ 4 Ntatsaki, E., Carruthers, D., Chakravarty, K., et al. (2014). BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology 53 (12):2306-2309. Accessed August 2020._x000D_ _x000D_ 5 Yates M, Watts RA, Bajema IM et al. (2016) EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Annals of rheumatic Disease 75(9):1583-1594. Accessed August 2020._x000D_ _x000D_ 6 Pearce, F. A., Grainge, M. J., Lanyon, P. C., Watts, R. A., & Hubbard, R. B. (2017). The incidence, prevalence and mortality of granulomatosis with polyangiitis in the UK Clinical Practice Research Datalink. Rheumatology, 56(4), 589-596.

Lay abstract: To appraise the clinical and cost effectiveness of avacopan within its marketing authorisation for treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM