Golimumab for treating non-radiographic axial spondyloarthritis

Evidence-based recommendations on golimumab (Simponi) for severe non-radiographic axial spondyloarthritis. This drug is for adults who have tried nonsteroidal anti-inflammatory drugs (NSAIDs), but they have not worked.

# Recommendations
Golimumab is recommended, within its marketing authorisation, as an option for treating severe non-radiographic axial spondyloarthritis in adults whose disease has responded inadequately to, or who cannot tolerate, nonsteroidal anti-inflammatory drugs.
If patients and their clinicians consider golimumab to be one of a range of suitable treatments, including adalimumab, etanercept and certolizumab pegol, the least expensive (taking into account administration costs and patient access schemes) should be chosen.
Assess the response to golimumab 12 weeks after the start of treatment. Continue treatment only 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) score by 2 cm or more.
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.
Why the committee made these recommendations
NICE already recommends adalimumab, etanercept and certolizumab pegol for treating non-radiographic axial spondyloarthritis. An indirect comparison shows that golimumab provides similar overall health benefits to these drugs. The acquisition costs of golimumab are the same as or less than those of adalimumab and etanercept, and in the longer term, would be similar to those of certolizumab pegol.
Because it is has similar overall health benefits and costs to adalimumab, etanercept and certolizumab pegol, golimumab is recommended for treating non-radiographic axial spondyloarthritis in the NHS.# The technology

# Marketing authorisation
Golimumab ((Simponi, Merck Sharp & Dohme) is indicated for the treatment of 'adults with severe, active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated Creactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence, who have had an inadequate response to, or are intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs)'.

# Recommended dose and schedule
Golimumab is administered by subcutaneous injection. The recommended dosage is 50 mg once a month, on the same date each month. The summary of product characteristics recommends that continued golimumab therapy should be reconsidered if there is no evidence of therapeutic benefit within 12 to 14 weeks of starting treatment (that is, after 3 to 4 doses). For patients with a body weight greater than 100 kg whose disease does not respond adequately after 3 or 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 to 4 additional doses of 100 mg, continued golimumab therapy should be reconsidered.

# Price
The list price of golimumab is 762.97 for a 50mg prefilled disposable injection and 1,525.94 for a 100mg prefilled disposable injection (excluding VAT; British national formulary  online ). Merck Sharp & Dohme has agreed a patient access scheme with the Department of Health. This will make the 100mg dose of golimumab available to the NHS at the same cost as the 50mg dose. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS. Assuming a patient has 50 mg every month, the annual cost of treatment with golimumab is estimated at 9,156. 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 50 mg per month and who subsequently have monthly doses of 100 mg.# Committee discussion
The appraisal committee (section 5) considered evidence submitted by Merck Sharp & Dohme and a review of this submission by the evidence review group (ERG). See the committee papers for full details of the evidence.

# Comparators

## The comparison of golimumab with adalimumab, etanercept and certolizumab pegol is appropriate
NICE has already produced technology appraisal guidance on adalimumab, etanercept and certolizumab pegol for non-radiographic axial spondyloarthritis, which recommends that if more than one treatment is suitable then the least expensive treatment (taking into consideration costs and patient access schemes) should be used. The company presented a cost comparison case, in which it proposed that:
the overall health benefits associated with golimumab are similar to or greater than those associated with adalimumab, etanercept and certolizumab pegol
the acquisition cost of golimumab is similar to or lower than those associated with adalimumab, etanercept and certolizumab pegol.The committee understood that treatment with adalimumab, etanercept and certolizumab pegol is standard for non-radiographic axial spondyloarthritis in the NHS. The committee concluded that it was appropriate for the company to compare golimumab with adalimumab, etanercept and certolizumab pegol.

# Clinical effectiveness

## Golimumab is clinically effective compared with placebo
The company presented results of the GOAHEAD trial which compared golimumab with placebo in 198 people with non-radiographic axial spondyloarthritis. Golimumab showed statistically significant improvement in all outcomes at 16 weeks (Assessment in Spondyloarthritis International Society  20, ASAS 40, Bath Ankylosing Spondylitis Disease Activity Index  50 and ASAS partial response) compared with placebo in the full analysis set and in the population with objective markers of active disease (abnormal MRI and/or elevated Creactive protein  at baseline). The committee agreed that golimumab is a clinically effective treatment compared with placebo.

## Golimumab has similar clinical effectiveness to adalimumab, etanercept and certolizumab pegol
The company presented a fixed-effects network meta-analysis, which compared the clinical effectiveness outcomes of golimumab with those of adalimumab, etanercept and certolizumab pegol (all assessed at 12 weeks). The network meta-analysis included the pivotal trial for golimumab (GOAHEAD) and the same trials that were assessed for the NICE technology appraisal of adalimumab, etanercept and certolizumab pegol for the comparator treatments. The network meta-analysis showed a statistically significant benefit for golimumab compared with placebo for all outcomes (ASAS 20, ASAS 40 and BASDAI 50). The clinical effectiveness of golimumab was similar to adalimumab, etanercept and certolizumab pegol for Bath Ankylosing Spondylitis Functional Index (BASFI), BASDAI and Bath Ankylosing Spondylitis Metrology Index (BASMI) scores. Golimumab was statistically significantly superior to etanercept and adalimumab for change from baseline in BASFI score, etanercept for change from baseline in BASDAI score, and adalimumab for change from baseline in BASMI score. The ERG's view was that a random-effects network meta-analysis would have been more suitable for capturing variation between the trials. The point estimates in the ERG's random-effects network meta-analysis were similar to those in the company's submission, but had wider confidence intervals. The committee considered the impact of using 12week outcomes for golimumab in the network meta-analysis (for consistency with the comparator treatments) compared with the 16week outcomes reported in the GOAHEAD trial. An additional analysis conducted by the ERG showed that the network meta-analysis results were robust regardless of whether 12- or 16week outcomes were used. The committee concluded that the clinical effectiveness of golimumab was likely to be similar to those of the comparators.

# Adverse events

## Adverse events with golimumab are likely to be similar to those with adalimumab, etanercept and certolizumab pegol
The adverse event profile for golimumab is well established and is similar to those of adalimumab, etanercept and certolizumab pegol. Patients receiving the 100mg dose of golimumab may or may not have a greater risk of adverse events than those receiving the 50mg dose. The committee concluded that the adverse events associated with golimumab were likely to be similar to those associated with adalimumab, etanercept and certolizumab pegol when treating non-radiographic axial spondyloarthritis.

# Overall health benefits

## Golimumab provides similar overall health benefits to adalimumab, etanercept and certolizumab pegol
The committee agreed that the network meta-analysis provided by the company was suitable for the purpose of decision-making. It considered the clinical effectiveness and adverse event profiles of golimumab to be similar to those of the comparator treatments and that, therefore, golimumab was likely to provide similar overall health benefits.

# Resource use

## It is appropriate to assume that all resource use and costs other than drug acquisition costs are identical across golimumab and the comparators
The company assumed that resource use and costs including drug administration, treatment initiation and monitoring, management of adverse events and long-term disease management are identical across golimumab and the comparators. The committee agreed with the company's assumption.

# Cost comparison results

## Golimumab meets the criteria for a successful cost comparison
The company presented results of a cost comparison analysis for the first and subsequent years of treatment. It showed that the acquisition cost of golimumab is the same as that of adalimumab in the first and subsequent years of treatment (9,156), and lower than the cost of etanercept in the first and subsequent years (9,295). The acquisition cost of certolizumab pegol in the first year (5,720) is lower than that of golimumab because of a patient access scheme which provides the first 10 vials of certolizumab pegol at no cost, but its cost in subsequent years (9,295) is higher than that of golimumab. The committee concluded that the criteria for a positive cost comparison were met, because:
the overall health benefits of golimumab are similar to those of adalimumab, etanercept and certolizumab pegol
the acquisition costs of golimumab are similar to or lower than those of adalimumab, etanercept and certolizumab pegol (taking into account that although certolizumab pegol is approximately half the cost of golimumab in the first year, the subsequent annual cost in the long term is higher than that of golimumab).The committee therefore recommended golimumab as a cost-effective use of NHS resources for treating non-radiographic axial spondyloarthritis in adults.