As well as re-affirming previous NICE guidance³ recommending adalimumab, etanercept and golimumab as treatment options for adults with ankylosing spondylitis, the draft guidance also now recommends infliximab and certolizumab pegol as additional treatment options for adults with anklylosing spondylitis.

Non-radiographic axial spondyloarthritis is also covered by the draft guidance and adalimumab, certolizumab pegol and etanercept are provisionally recommended as treatment options for adults with this condition.

Ankylosing spondylitis and axial spondyloarthritis are part of a group of inflammatory rheumatologic diseases known as spondyloarthritis. They cause inflammation mainly in the lower spine, which results in back pain and stiffness. Inflammation at the sites where ligaments and tendons attach to bone can lead to new bone development and joint fixation (ankylosis), where joints and bones fuse together.

Disease is classified as ankylosing spondylitis if changes to the sacroiliac joints⁴ or the spine, or both, can be seen on X-ray. Where there is no X‑ray evidence of the disease, it is classified as non-radiographic axial spondyloarthritis.

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE, said: “Both these conditions are irreversible and can cause a great deal of pain and discomfort and have a significant negative impact on quality of life.

“We are therefore pleased to be able to recommend for the first time, treatment options for adults with non-radiographic axial spondyloarthritis, as well as add infliximab and certolizumab pegol to the list of clinically and cost effective treatment options for adults with ankylosing spondylitis.

“At its meeting to consider responses to the consultation on the first draft of the guidance the Comiittee heard from patient experts who highlighted that not being able to try a second TNF-alpha inbibitor would leave people reliant either on NSAIDs which had already proved inadequate to control symptoms, and are associated with long-term adverse effects, or to continue on their sub-optimal TNF-alpha inhibitor indefinitely. The Committee acknowledged that predicting how the condition would respond to an initial TNF-alpha inhibitor was not possible, and that this could have a major impact on a lifelong condition. The Committee therefore agreed there was a clinical need to be able to consider further TNF-alpha inhibitor treatments as options and this is now recommended in the draft guidance.”

This is draft guidance – NICE has not yet issued final guidance to the NHS. The draft guidance is now with consultees, who have the opportunity to appeal against it. Once NICE issues its final guidance on a technology, it replaces local recommendations across the country.

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 and explanation of terms

1. The draft 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.The Committee noted that the companies marketing biosimilar versions of infliximab had presented new ICERs, in response to the appraisal consultation document, using lower prices for their products to reflect the tendering process that was taking place during the consultation period. The Committee noted that as a result the cost-effectiveness of infliximab was within the range considered to be a cost-effective use of NHS resources. The Committee therefore concluded that infliximab could be recommended as an option for treating adults with ankylosing spondylitis whose disease has responded inadequately to, or who cannot tolerate, NSAIDs only if the infliximab product with the lowest acquisition cost is used.

NICE’s approach to evaluating biosimilars is set out on the NICE website.

1. Golimumab is recommended only when the company provides the 100 mg dose of golimumab at the same cost as the 50 mg dose, in accordance with the discount agreed in the patient access scheme
2. Adalimumab, etanercept and infliximab for ankylosing spondylitis and Golimumab for the treatment of ankylosing spondylitis
3. The sacroiliac joint is located in the lower spine where the sacrum (base of spine) is joined to the ilium (part of the pelvis)
   1. The draft guidance is available at http://www.nice.org.uk/guidance/indevelopment/gid-tag355 from Friday 11 September 2015. The draft guidance states:

About the draft guidance

1.1                   Adalimumab, certolizumab pegol, etanercept,golimumab and infliximab are recommended, within their marketing authorisations, as options for treating severe active ankylosing spondylitis in adults whose disease has responded inadequately to, or who cannot tolerate, non-steroidal anti-inflammatory drugs.

Infliximab is recommended only if the product with the lowest acquisition cost is used.

1.2                   Adalimumab, certolizumab pegol and etanercept are recommended, within their marketing authorisations, as options for treating severe non-radiographic axial spondyloarthritis in adults whose disease has responded inadequately to, or who cannot tolerate, non-steriodal anti-inflammatory drugs..

1.3                   The choice of treatment should be made after discussion between the clinician and the patient about the advantages and disadvantages of the treatments available. This may include considerating associated conditions such as extra-articular manifestations. If more than 1 treatment is suitable, the least expensive (taking into account administration costs and patient access schemes) should be chosen.

1.4                   The response to adalimumab, certolizumab pegol, etanercept, golimumab or infliximab treatment should be assessed 12 weeks after the start of treatment. Treatment should only be continued if there is clear evidence of response, defined as:

• a reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score to 50% of the pre-treatment value or by 2 or more units and
• a reduction in the spinal pain visual analogue scale (VAS) by 2 cm or more.

1.5                   Treatment with another tumour necrosis factor (TNF) alpha inhibitor is recommended for people who cannot tolerate, or whose disease has not responded to, treatment with the first TNF‑alpha inhibitor, or whose disease has stopped responding after an initial response.

1.6                   When using BASDAI and spinal pain VAS scores, healthcare professionals should take into account any physical, sensory or learning disabilities, or communication difficulties that could affect the responses to the questionnaires, and make any adjustments they consider appropriate.

1.7                   People whose treatment with a TNF‑alpha inhibitor is not recommended in this NICE guidance, but was started within the NHS before this guidance was published, should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

1. TNF-alpha inhibitors work by inhibiting the pro-inflammatory cytokine, tumour necrosis factor alpha. TNF‑alpha inhibitors may modify the inflammatory process of the disease.
2. Adalimumab, etanercept, golimumab and infliximab have marketing authorisations in the UK for the treatment of adults with severe active ankylosing spondylitis that has responded inadequately to conventional therapy.
3. Certolizumab pegol has a marketing authorisation in the UK for the treatment of ‘adults with severe active ankylosing spondylitis who have had an inadequate response to, or are intolerant to, nonsteroidal anti-inflammatory drugs (NSAIDs)’.
4. Adalimumab, certolizumab pegol and etanercept are also licensed for the treatment of adults with severe axial spondyloarthritis without radiographic evidence of ankylosing spondylitis (non‑radiographic axial spondyloarthritis) but with objective signs of inflammation by elevated C‑reactive protein and/or magnetic resonance imaging, whose disease has responded inadequately to, or who cannot tolerate, NSAIDs.
5. Golimumab is now also licensed for people with severe non-radiographic axial spondyloarthritis who have not responded adequately or are intolerant to NSAIDs. This marketing authorisation was granted recently (June 2015). Because this was relatively late in the appraisal process, the evidence for golimumab for severe non-radiographic axial spondyloarthritis was not included in the assessment report and no recommendations are made for golimumab in this indication in the draft guidance.
6. Infliximab does not currently have a marketing authorisation in the UK for non-radiographic axial spondyloarthritis.
7. Adalimumab is administered by subcutaneous injection. The recommended dose regimen for patients with ankylosing spondylitis, and for patients with non-radiographic axial spondyloarthritis, is 40 mg (given as 1 injection) every other week. The price of adalimumab is £352.14 for a 40 mg pre-filled pen or pre-filled syringe, or a 40 mg/0.8 ml vial (excluding VAT; ‘British National Formulary’ [BNF] edition 68). The annual cost of treatment with adalimumab is estimated at £9156, assuming the patient has 40 mg every other week.
8. Etanercept is administered by subcutaneous injection. The recommended dosage for patients with ankylosing spondylitis, and for patients with non-radiographic axial spondyloarthritis, is 25 mg administered twice weekly or 50 mg administered once weekly. The summary of product characteristics recommends that continued etanercept therapy should be carefully reconsidered in patients whose disease does not respond within 12 weeks of starting treatment. The price of etanercept is £89.38 for a 25 mg pre-filled syringe or a 25 mg vial containing powder for reconstitution (with solvent), and £178.75 for a 50 mg pre-filled pen or pre-filled syringe (excluding VAT; BNF edition 68). The annual cost of treatment with etanercept, using either twice weekly or once weekly dosage frequency is estimated at £9296.
9. Golimumab is administered by subcutaneous injection. The recommended dose regimen for patients with ankylosing spondylitis is 50 mg once a month, on the same date each month. The summary of product characteristics recommends that continued golimumab therapy should be carefully reconsidered if there is no evidence of therapeutic benefit within 12–14 weeks of starting treatment (that is, after 3–4 doses). For patients with a body weight greater than 100 kg whose disease does not respond adequately after 4 doses (50 mg each), the summary of product characteristics states that increasing the dosage of golimumab to 100 mg once a month may be considered. If there is still no evidence of therapeutic benefit after 3–4 additional doses of 100 mg, continued golimumab therapy should be carefully reconsidered. The price of golimumab is £762.97 for a 50 mg pre-filled pen or pre-filled syringe and £1525.94 for a 100 mg pre-filled pen (excluding VAT; BNF edition 68). Merck Sharp & Dohme has agreed a patient access scheme with the Department of Health. This will make the 100 mg dose of golimumab available to the NHS at the same cost as the 50 mg dose. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS. Assuming the patient has 50 mg every month, the annual cost of treatment with golimumab is estimated at £9156. Because of the patient access scheme, this cost would remain the same for patients with a body weight greater than 100 kg whose disease does not respond adequately to the 50 mg per month dosage and who subsequently have monthly doses of 100 mg
10. Infliximab is administered by intravenous infusion. The recommended dosage for patients with ankylosing spondylitis is a 5 mg/kg infusion at weeks 0, 2 and 6, then every 6–8 weeks. The summary of product characteristics states that if there is no response by 6 weeks (that is, after 2 doses), no additional treatment with infliximab should be given. The price of infliximab is £419.62 for a 100 mg vial containing powder for reconstitution (excluding VAT; BNF edition 68). For a patient with a body weight of 73 kg, the annual cost for first year of treatment with infliximab therapy (including 3 induction doses) is estimated at between £16,785 and £13,428 (depending on whether the maintenance infusions are repeated every 6 or 8 weeks).
11. Biosimilar versions of infliximab (Inflectra, Hospira; Remsima, Celltrion) have a marketing authorisation in the UK for the same indications. The therapeutic indications, dosage and method of administration for Remsima and Inflectra are identical to those for Remicade. Adverse reactions are similar too. The price of Remsima is £377.66 for a 100 mg vial (price confirmed by Celltrion Healthcare and Napp Pharmaceuticals). For a patient with a body weight of 73 kg, the annual cost for first year of treatment with Remsima therapy is estimated at between £15,106 and £12,085 (depending on whether the maintenance infusions are repeated every 6 or 8 weeks). Inflectra did not have an approved list price in the UK at the time of the appraisal.
12. Infliximab is available to the NHS at contract prices negotiated through the Commercial Medicines Unit. These prices are lower than the list prices but are commercial in confidence.
13. Certolizumab pegol is administered by subcutaneous injection. The recommended induction dosage for patients with ankylosing spondylitis, and for patients with non-radiographic axial spondyloarthritis, is 400 mg (given as 2 injections of 200 mg each) at weeks 0, 2 and 4. The recommended maintenance dose regimen is 200 mg every other week or 400 mg every 4 weeks. The summary of product characteristics recommends that continued certolizumab pegol therapy should be carefully reconsidered if there is no evidence of therapeutic benefit within 12 weeks of starting treatment. The price of certolizumab pegol is £357.50 for a 200 mg pre-filled syringe (excluding VAT; BNF edition 68). Assuming the recommended dosage is followed the annual cost for first year of treatment with certolizumab pegol is estimated at £10,368.