NICE has today published final guidance recommending rituximab (MabThera, Roche Products) as an option for inducing remission in adults with the rare autoimmune condition anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitisⁱ.

The guidance applies to adults with types of ANCA-associated vasculitis called severe microscopic polyangiitis or granulomatosis with polyangiitis (also known as Wegener's granulomatosis).

NICE has recommended rituximab in combination with glucocorticoidsⁱⁱ as an option for this patient group, only if:

• more cyclophosphamideⁱⁱⁱ treatment would exceed the maximum amount of cyclophosphamide they can have or
• cyclophosphamide is not suitable for them or they cannot take it or
• they want to have children and treatment with cyclophosphamide may affect their fertility or
• the disease has stayed active or got worse after a course of cyclophosphamide lasting 3-6 months or
• the person has had uroepithelial cancer^iv.

ANCA-associated vasculitis is an inflammatory autoimmune disease affecting blood vessel walls. It can affect many organs and leads to tissue breakdown and damage. Granulomatosis with polyangiitis and microscopic polyangiitis are both types of ANCA-associated vasculitis that affect small blood vessels. ANCA-associated vasculitis usually affects the lungs, kidneys, ears, nose or sinuses. Depending on the organs involved it can cause bleeding, rash, or deafness. It is estimated that around 1200 people are diagnosed with ANCA-associated vasculitis each year in England and Wales, and it is most common in those aged between 60 and 70 years.

The aim of treatment is initially to induce remission, then to maintain remission and treat relapse when necessary. With adequate ongoing care, most people with ANCA-associated vasculitis will have a good quality of life and normal life expectancy.

Rituximab is a manufactured antibody that destroys B cells, which are the part of the immune system thought to be involved in this type of vasculitis.

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE said: “The effects of vasculitis, as well as the stress of the fear of relapse, can often have a significant detrimental impact on patients' quality of life. The introduction of immunosuppressant therapy with cyclophosphamide and corticosteroids has dramatically improved the prognosis from a condition with high mortality to being a chronic disease with a relapsing and remitting course. However, these treatments are associated with substantial side-effects that can further impair patients' quality of life.

“The Committee heard that rituximab is the first effective treatment since the introduction of cyclophosphamide in the 1970s. In addition, they heard from the clinical specialists and patient experts that induction treatment with rituximab was 4 weeks instead of up to 6 months with cyclophosphamide, which was more convenient for patients. The Committee concluded that rituximab is an innovative treatment for vasculitis and that this benefit is important to patients. The Committee also concluded that rituximab is a cost-effective use of NHS resources for those groups specified in the guidance. NICE is pleased, therefore, to recommend rituximab as another treatment option for some people with this condition.”

Ends

For more information, please call the NICE press office on 0845 003 7782, and (out of hours) on 07775 583 813 or email pressoffice@nice.org.uk

The final guidance can be found from 00:01hrs on Wednesday 26 March on the NICE website

Embargoed copies are available on request from the press office.

Notes to Editors

References and explanation of terms

i. ANCA-associated vasculitis is an umbrella term for several related conditions, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). ANCA stands for anti-neutrophil cytoplasmic antibody. ANCAs are autoantibodies that affect neutrophils (a type of white blood cell). The disease mechanisms that cause damage in ANCA-associated vasculitis are not fully understood, but it is thought that neutrophils have an important role. After being activated by ANCAs, neutrophils attack the walls of small vessels in different tissues and organs of the body. This causes vasculitis.

ii.Glucocorticoids are a type of steroid hormone. Glucocorticoid drugs are commonly used to reduce inflammation and suppress the immune system.

iii.Cyclophosphamide belongs to a class of drugs known as alkylating agents, which are used to treat some types of cancer. It can also suppress the immune system. Induction treatment with cyclophosphamide is the standard of care for patients with severe ANCA-associated vasculitis.

iv.Uroepithelial malignancies are cancers affecting the tissue that lines the urethra, bladder, ureters, prostate, and renal pelvis.

About the guidance

1. The guidance is available from 00:01hrs on Wednesday 26 March on the NICE website.

Embargoed copies are available on request; please contact the press office.

2. Rituximab (MabThera, Roche Products) is a genetically engineered chimeric (mouse/human) monoclonal antibody that depletes B cells by targeting cells bearing the CD20 surface marker.

3. Rituximab is priced at £174.63 per 10 ml vial and £873.15 per 50 ml vial (excluding VAT; British national formulary [BNF] edition 67). The manufacturer's estimate of the average cost of a course of treatment is £4889.64 (based on 1.79 m² body surface area and no vial sharing). Costs may vary in different settings because of negotiated procurement discounts.

4. A patient access scheme has not been submitted by the manufacturer.

5. People currently receiving rituximab for ANCA-associated vasculitis, who do not fulfil the criteria in section 1.1 of the recommendations, should have the option to continue therapy until they and their clinicians consider it appropriate to stop.

6. The Committee concluded that a plausible treatment sequence for patients who can receive cyclophosphamide was 2 cycles of cyclophosphamide followed by 1 cycle of rituximab. The Committee noted that 2 cycles of intravenous cyclophosphamide would provide a cumulative dose of 23 g on average, which is below the maximum recommended dose of 25 g.

7. The Committee noted that rituximab was superior to cyclophosphamide in inducing remission in patients with relapsed disease at 6-month follow-up, but the difference between treatments was not significantly different at 18-month follow-up.

8. The Committee heard from the clinical specialists that there may be a small subgroup of people who would benefit from avoiding cyclophosphamide

9. The Committee noted that using rituximab earlier in the treatment sequence, either as a first-line treatment or after 1 course of cyclophosphamide, was not cost effective. It concluded that, for patients for whom further cyclophosphamide treatment would exceed the maximum cumulative dose, rituximab is a cost-effective use of NHS resources and therefore should be recommended.

10. The Committee concluded there was substantial uncertainty regarding the cost effectiveness of rituximab for people who cannot have cyclophosphamide, but on balance the ICER was likely to be lower than £30,000 per QALY gained. The Committee recognised that rituximab is an innovative treatment and the high unmet need of treatment options for people who cannot have cyclophosphamide. Therefore, the Committee concluded that rituximab was a cost-effective use of NHS resources for treating people with severe ANCA-associated vasculitis who cannot have cyclophosphamide, as defined in section 4.8 of the final appraisal determination.

Related published NICE guidance

There is no related guidance for this technology at the time of consultation.

About NICE

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