NICE issues final guidance recommending 7 drugs for rheumatoid arthritis

NICE issues final guidance recommending 7 drugs for rheumatoid arthritis

26 January 2016

In final updated guidance published today NICE recommends a number of drugs called biological disease modifying drugs (DMARDs) as options for treating severei rheumatoid arthritis which has not responded to intensive therapy with a combination of conventional DMARDs. The guidance does not recommend their use for treating moderate active rheumatoid arthritis.

Publication of the guidance follows unsuccessful appeals against the draft guidance.

The guidance recommends adalimumab (Humira, AbbVie), etanercept (Enbrel, Pfizer), infliximab (Remicade, Merck Sharp & Dohme; Inflectra, Hospira UK; Remsima,Napp Pharmaceuticals ) ii, certolizumab pegol (Cimzia, UCB Pharma), golimumab (Simponi, Merck Sharp & Dohme), tocilizumab (RoActemra, Roche) and abatacept (Orencia, Bristol-Myers Squibb), each in combination with methotrexate.

Adalimumab, etanercept, certolizumab pegol or tocilizumab are also recommended as monotherapy for people who cannot take methotrexate.

In the case of certolizumab pegol, golimumab, abatacept and tocilizumab the recommendation is subject to the companies providing them as agreed in their patient access schemes.

The guidance states that treatment should be started with the least expensive drug (taking into account administration costs, dose needed and product price per dose).

The guidance also includes recommendations about when treatment with biological DMARDs should be continued or withdrawn.

Rheumatoid arthritis is an incurable chronic systemic inflammatory autoimmune disease in which the synovial joints (such as those in the hands and feet) become inflamed, causing pain, swelling and stiffness.

The disease affects around 400,000 people in the UK, of whom approximately 15% have severe disease. It is about 2–4 times more common in women than in men. It can develop at any age, but the peak age of onset in the UK is about 40–70 years. Rheumatoid arthritis is associated with increased mortality and increasing disability and can have a severe effect on quality of life.

Professor Carole Longson MBE, Director of the Health Technology Evaluation Centre at NICE said: "This guidance considers at what stage it's clinically and cost effective to start using biological therapies as treatment options for adults with rheumatoid arthritis.

In recommending them as options for people with severe rheumatoid arthritis after previous treatment with conventional DMARDs has been unsuccessful, this guidance reaffirms our previous recommendations on these drugs and confirms their place as an integral part of the rheumatoid arthritis treatment pathway."

Ends

For more information call the NICE press office on 0300 323 0142 or out of hours on 07775 583 813.

Notes to Editors

References

      i.        A disease activity score (DAS28) greater than 5.1. DAS28 is calculated using a formula that includes counts for tender and swollen joints, an evaluation of general health by the person (on a scale of 0–100), and erythrocyte sedimentation rate or C-reactive protein.

     ii.        In addition to the originator infliximab (Remicade, Merck, Sharpe & Dohme) the guidance also considers the biosimilar versions of infliximab - Remsima (Napp Pharmaceuticals) and Inflectra (Hospira UK). A biosimilar medicine is a medicine that is developed to be similar to an existing biological medicine. NICE's approach to evaluating biosimilars is set out on the NICE website.

About the guidance

  1. The guidance is available from the NICE website athttp://www.nice.org.uk/guidance/ta375

  2. The guidance is a review of NICE technology appraisals 130 (Adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis), 186 (Certolizumab pegol for the treatment of rheumatoid arthritis), 224 (Golimumab for the treatment of methotrexate-naive rheumatoid arthritis, terminated appraisal), and 280 (Abatacept for treating rheumatoid arthritis after the failure of conventional DMARDs).

  3. The guidance is a part review of NICE technology appraisals 225 (Golimumab for the treatment of rheumatoid arthritis after the failure of previous DMARDs), and 247 (Tocilizumab for the treatment of rheumatoid arthritis)

 About rheumatoid arthritis

  1. 1.    There is no cure for rheumatoid arthritis. In early disease, management aims to suppress disease activity and induce remission, prevent loss of function, control joint damage, control pain and enhance self-management. In established disease, management should address complications and associated comorbidity, as well as the effect of the condition on the person's quality of life.

  2. 2.    Treatment for rheumatoid arthritis usually includes non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors, which reduce pain, fever, and joint swelling and inflammation, and DMARDs.

    1. DMARDs slow the disease process and reduce joint damage. Traditionally people had DMARDs such as methotrexate, leflunomide and sulfasalazine (referred to as conventional DMARDs).  Also available are a group of drugs including monoclonal antibodies and soluble receptors that modify the disease process by blocking key protein messenger molecules (such as cytokines) or cells (such as B lymphocytes). Such drugs are referred to as biological DMARDs.

    2. 4.    For some people their disease may not respond to DMARDs and for others the response to DMARDs often reduces over time. Therefore people need a sequence of treatments after a combination of conventional DMARDs..

    3. For people with newly diagnosed rheumatoid arthritis, the NICE guideline on rheumatoid arthritis recommends a combination of conventional DMARDs (including methotrexate and at least 1 other conventional DMARD, plus short-term glucocorticoids) as first-line treatment, ideally beginning within 3 months of the onset of persistent symptoms. When combination therapies are not appropriate, conventional DMARD monotherapy is used.

About the technologies

  1. Summary of the marketing authorisations for the technologies:

Technology

MTX-experienced RA

MTX-naive RA

In combination with MTX

Mono-therapy

SC or IV

Adalimumab

+

+

+

+

SC

Etanercept

+

+

+

+

SC

Infliximab

+

+

+

IV

Certolizumab pegol

+

+

+

SC

Golimumab

+

+

+

SC

Abatacept

+

+

IV or SC

Tocilizumab

+

+*

+

+

IV or SC*

Abbreviations: RA, rheumatoid arthritis; MTX, methotrexate; SC, subcutaneous injection; IV, intravenous infusion; +, licensed for use; MTX-experienced, disease previously treated with methotrexate; MTX-naive, disease not previously treated with methotrexate

*Tocilizumab in methotrexate-naive rheumatoid arthritis and the subcutaneous formulation are not part of this appraisal

 

  1. The net price of adalimumab is £352.14 per 40-mg prefilled pen or prefilled syringe, or £352.14 per 40-mg/0.8-ml vial (British national formulary [BNF], July 2015). Assuming 26 doses per year, the annual cost of adalimumab is £9155.64. For adalimumab monotherapy, the dose may be escalated to up to 40 mg per week for people who experience a decrease in response.

  2. The net price of etanercept is £89.38 per 25-mg prefilled syringe, or £178.75 per 50-mg prefilled pen or prefilled syringe (BNF, July 2015). Assuming 52 doses per year, the annual cost of etanercept is £9295.

  3. The NHS list price of originator infliximab (Remicade) is £419.62 per 100 mg vial (BNF, July 2015). Assuming a weight per person of 70 kg, vial wastage and 3 initial doses followed by treatment every 8 weeks, the cost in the first year is £10,070.88, and then £8812.02 per year. Costs may vary in different settings because of negotiated procurement discounts. The NHS list price of infliximab biosimilars (Remsima, Inflectra) is £377.66 per 100‑mg vial (BNF, December 2015). Assuming a weight per person of 70 kg, vial wastage, and 3 initial doses in the first year followed by treatment every 8 weeks, the cost in the first year is £9063.84, and then £7930.86 per year. The infliximab biosimilars are available to the NHS at contract prices negotiated through the Commercial Medicines Unit. These prices are lower than the list price but are commercial in confidence.

  4.  The net price of certolizumab pegol is £357.50 per 200-mg prefilled syringe (BNF, July 2015). Assuming 3 initial doses of 400 mg followed by maintenance doses every 2 weeks, the cost (without the patient access scheme) in the first year is £10,367.50 (or with the patient access scheme, £6793), and then £9295 per year. The company has agreed a patient access scheme with the Department of Health. In the scheme, the first 12 weeks of therapy (currently 10 pre-loaded syringes of 200 mg each) with certolizumab pegol are free of charge.

  5. The net price of golimumab is £762.97 per 50-mg prefilled pen or prefilled syringe (BNF, July 2015). For people weighing less than 100 kg and assuming 12 doses per year, the annual cost of golimumab is £9155.64. The company has agreed a patient access scheme with the Department of Health, in which the 100-mg dose of golimumab will be available to the NHS at the same cost as the 50-mg dose.

  6. The net price of abatacept for intravenous infusion is £302.40 per 250 mg vial (BNF, July 2015). For people weighing between 60 and 100 kg, the cost of treatment for the first year is £12,700.80 and then £11,793.60 per year (without the patient access scheme). The net price of abatacept for subcutaneous injection is £302.40 per 125 mg prefilled syringe (BNF, July 2015). Assuming a weight per person of 70 kg, 1 intravenous loading dose followed by subcutaneous treatment doses every week, the cost (without the patient access scheme) of the initial intravenous dose is £907.20, and then £15,724.80 per year. Costs may vary in different settings because of negotiated procurement discounts. The company has agreed a patient access scheme with the Department of Health in which abatacept will be available with a discount. The level of discount is commercial in confidence.

  7. The net price of tocilizumab is £102.40 per 4-ml (80-mg) vial, £256.00 per 10-ml (200-mg) vial, or £512.00 per 20-ml (400-mg) vial (BNF, July 2015). Assuming an average weight per person of 70 kg, and 13 doses per year, the annual cost (without the patient access scheme) of tocilizumab is £9318.40. Costs may vary in different settings because of negotiated procurement discounts. The company has agreed a patient access scheme with the Department of Health in which tocilizumab will be available with a discount. The level of discount is commercial in confidence.

About NICE

The National Institute for Health and Care Excellence (NICE) is the independent body responsible for driving improvement and excellence in the health and social care system. We develop guidance, standards and information on high-quality health and social care. We also advise on ways to promote healthy living and prevent ill health.

Our aim is to help practitioners deliver the best possible care and give people the most effective treatments, which are based on the most up-to-date evidence and provide value for money, in order to reduce inequalities and variation.

Our products and resources are produced for the NHS, local authorities, care providers, charities, and anyone who has a responsibility for commissioning or providing healthcare, public health or social care services.

To find out more about what we do, visit our website:www.nice.org.uk and follow us on Twitter: @NICEComms.

 

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