The draft guidance re-affirms previous NICE guidance¹ recommending adalimumab, etanercept and golimumab2 as treatment options for adults with ankylosing spondylitis. The draft guidance also now recommends certolizumab pegol as an additional treatment option for adults with anklylosing spondylitis.

Non-radiographic axial spondyloarthritis is also covered by the draft guidance and adalimumab, certolizumab pegol and etanercept are provisionally recommended as treatment options for adults with this condition.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 clinically diverse 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 joints³ 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 progressive and irreversible and can cause people with them 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 add certolizumab pegol to the list of clinically and cost effective treatment options for adults with ankylosing spondylitis, as well as recommending for the first time, treatment options for adults with non-radiographic axial spondyloarthritis.” 

Further recommendations in the draft guidance are given on how the response to treatment should be monitored

The draft guidance does not recommend infliximab as a treatment option for ankylosing spondylitis.

This is draft guidance – NICE has not yet issued final guidance to the NHS. Stakeholders, including the companies that market the procedures, healthcare professionals, patient groups and members of the public are now able to comment on this draft guidance. The consultation is open until 19 June 2015 and any comments received will be fully considered by the Committee. Until final guidance is issued to the NHS, NHS organisations should make decisions locally on the funding of specific treatments.

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

1. Adalimumab, etanercept and infliximab for ankylosing spondylitis and Golimumab for the treatment of ankylosing spondylitis
2. 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.
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 29 May 2015.
   2. The draft guidance states:
      1.                i.        Adalimumab, certolizumab pegol, etanercept and golimumab are recommended within their marketing authorisations, as treatment options for active ankylosing spondylitis.
      2.               ii.        Adalimumab, certolizumab pegol and etanercept are recommended within their marketing authorisations, as treatment options for non-radiographic axial spondyloarthritis.
      3.              iii.        The choice of treatment should be made on an individual basis after discussion between the responsible clinician and the patient about the advantages and disadvantages of the treatments available, and may include consideration of associated conditions. If more than 1 treatment is suitable, the least expensive should be chosen.
      4.              iv.        The response to adalimumab, certolizumab pegol, etanercept or golimumab 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:
         1. reduction of the Bath Ankylosing Spondylitis Disease Activity Index            (BASDAI) score to 50% of the pre-treatment value or by 2 or more    units
                    and

About the draft guidance

b.reduction of the spinal pain visual analogue scale (VAS) by 2 cm or     more.

1.               v.        For people who cannot tolerate adalimumab, certolizumab pegol, etanercept or golimumab and are unable to take it for long enough to assess response at 12 weeks, another TNF‑alpha inhibitor is recommended within its marketing authorisation.
2.              vi.        Treatment with another TNF‑alpha inhibitor is not recommended for people whose disease has not responded to treatment with the first TNF-alpha inhibitor, or those who had an initial response which was then lost.
3.             vii.        Infliximab is not recommended within its marketing authorisation for the treatment of ankylosing spondylitis.
4. 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.
5. 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.
6. 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)’.
7. 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.
8. Golimumab and infliximab do not currently have a marketing authorisation in the UK for non-radiographic axial spondyloarthritis.
9. 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.
10. 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.
11. 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
12. 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).
13. 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.
14. 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.