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Patients suffering from potentially fatal forms of vasculitis could benefit from first ever licensed treatment, UK

(rituximab) is now licensed as the first and only treatment for two potentially life-threatening auto-immune diseases, GPA and MPA, which result in the inflammation and damage of small blood vessels and frequently involve multiple organs. The two diseases affect over 13,000 people in the UK and are characterised by the decaying inflammation of specific areas of tissue in the body that, if not treated, can lead to organ damage, organ failure and even death.[1]

MabThera, which selectively targets CD20, a cell surface marker that is expressed on certain B cells and leads to B cell depletion, has been shown to offer similar efficacy to the chemotherapy agent cyclophosphamide.[2] In a subset of patients with relapsing disease, it has been shown to offer greater efficacy.[2]

MabThera is licensed in combination with glucocorticoids, a type of steroid, to induce remission in adult patients with severe, active GPA or MPA. The licence is based on data, which compared MabThera versus cyclophosphamide and found that treatment with MabThera provided effective induction of complete remission at 6-months in 64% of patients vs. 53% with cyclophosphamide (p=0.09).[2] Achieving complete remission is important for patients, as it means that their disease is kept at bay.

“This licence is much welcomed news for patients suffering from these rare diseases. GPA and MPA can strike suddenly and have a serious impact on a person’s life and overall health, with the likelihood of relapse high,” said Dr. David Jayne, Consultant in Nephrology and Vasculitis at Addenbrookes Hospital. “In the management of these two conditions, remission and keeping patients from relapsing is the goal of treatment. MabThera, as the first and only licensed treatment for these debilitating conditions, not only means that more patients will have an additional treatment option, but will also have a chance of achieving remission or getting patients back into remission when their disease has relapsed.”

The rate of relapse is higher in patients with GPA compared to those with MPA, with up to 50% of GPA patients relapsing within 5 years and each episode carries a high risk of organ damage.[1] Data have shown that treatment with MabThera is more efficacious than a cyclophosphamide-based regimen to induce remission among those with relapsing disease, 67% vs. 42% respectively (p=0.01).[2]

MabThera has an established safety profile across a number of disease areas, as demonstrated in over 3.5 million patient exposures, 14,000 patient years, of up to ten years duration with up to 19 courses of treatment in clinical trials[3],[4] The most common adverse reactions reported in clinical studies were upper respiratory tract infections, urinary tract infections, infusion related reactions and headaches.[5]

GPA and MPA in the UK:
Facts and Figures

  • GPA and MPA affects over 13,000 people in the UK[1]
  • GPA and MPA affects men and women equally[1]
  • Average age of onset is between 60-70 years old[1]
  • GPA and MPA are usually fatal if not treated[1]
  • 80% of patients with GPA and/or MPA who are treated will be alive after two years[1]

About GPA, MPA and ANCA-Associated Vasculitis
Granulomatosis with Polyangiitis (GPA) and Micoscopic Polyangiitis (MPA) are two diseases under the types of ANCA-associated vasculitis, a term given to a group of auto-immune inflammatory disorders associated with autoantibodies known as antineutrophil cytoplasmic antibodies (ANCAs). These abnormal antibodies interact with neutrophils, which then cause damage to the walls of small and medium blood vessels in various tissues and organs in the body, whereby the tissue necrotises and can cause failure to the kidney, ENT/respiratory tract and nervous system. Management of the GPA/MPA involves three phases: induction of remission, remission maintenance, treatment of flares and keeping patients from relapsing, which carries a risk of subsequent organ damage.[1]

RAVE study
The RAVE trial was a 6-month, multicentre, randomised, double-blind, double-dummy, non-inferiority trial to compare MabThera with cyclophosphamide (CYC) followed by azathioprine (AZA) for remission induction.

RAVE enrolled 197 ANCA positive GPA and MPA patients (newly diagnosed or relapsing), who were randomised to either MabThera 375mg/m2 of body surface area intravenously (IV) once weekly for 4 weeks plus daily cyclophosphamide-placebo, or MabThera-placebo IV plus daily cyclophosphamide 2mg/kg.[2] Those with severe renal disease or severe alveolar haemorrhage were excluded. The primary endpoint was remission, defined as BVAS/GPA of 0 and successful oral steroid withdrawal at month [6]. Groups were matched for disease severity, subtype, organ involvement and ANCA type and approximately 50% in each group had relapsing disease.[2] Remission rates were comparable in the two treatment arms, with 64% in the MabThera arm and 53% of the control arm reaching the primary endpoint (p=0.09). In a planned subgroup analysis, the MabThera-based regime (67%) was more efficacious than the cyclophosphamide-based regimen (42%) for inducing remission of relapsing disease (P=0.01).[2]

About MabThera
MabThera was first licensed by the FDA in 1997 and in 1998 in Europe to treat B cell non-Hodgkin lymphoma resistant to other chemotherapy regimens and in 2006 for rheumatoid arthritis. It is a monoclonal antibody that targets CD20, a cell surface marker that is expressed on B cells, leading to B cell depletion. MabThera is the first and only B cell targeted therapy for rheumatoid arthritis and provides a different treatment approach compared with traditional anti-TNF and DMARD treatments. B cells play a key role in the development of RA and by selectively targeting and depleting a sub-set of these B cells, MabThera can prevent some of the effects that cause the disease symptoms and can lead to other long-term benefits for the patient.[5] MabThera is now licensed for the induction of remission of severe, active GPA and MPA in adult patients in the UK and is currently funded in certain circumstances by NHS England.[1]

Source

[1] NHS Commissioning Board Clinical Commissioning Policy: Rituximab for Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis. Reference : NHSCB/ A13/P/a – April 2013

[2] Stone John H et al. Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis. The New England Journal of Medicine, Vol.363; 221-232, July 2010

[3] Van Vollenhoven RF, et al. Ann Rheum Dis 2012; 71(Suppl 3): 195 and poster number 459 at ACR 2012

[4] Roche data on file RXUKDONF00294, February 2013

[5] Summary of Product Characteristics. MabThera 100mg and 500mg concentrate for solution for infusion. http://www.medicines.org.uk/emc/medicine/2570/SPC/Mabthera+100mg+and+500mg+concentrate+for+solution+for+infusion [last accessed June 2013]

Roche Products Ltd

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