Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in July 2013. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

Subcutaneous canakinumab 150 mg reduced pain intensity and the risk of new attacks of gout compared with intramuscular triamcinolone 40 mg. However, patients who used canakinumab experienced more adverse effects than those who used triamcinolone, including infections, neutropenia and thrombocytopenia. Canakinumab is considerably more expensive than other treatments.

Effectiveness

  • Compared with triamcinolone, the mean pain score on a 100 mm visual analogue scale was 10.7 mm lower in the canakinumab group (95% confidence interval [CI] 6.0 mm to 15.4 mm, p<0.0001). Specialists have advised that this is of borderline clinical importance.

  • Over 12 weeks, canakinumab reduced the risk of a new attack of gout by 62% (hazard ratio 0.38, 95% CI 0.26 to 0.57, p<0.0001).

  • 16% of patients using canakinumab experienced at least 1 new attack of gout in 12 weeks, compared with 36% using triamcinolone (p value not reported).

Safety

  • Over 24 weeks, serious adverse events were reported in 7.6% of patients using canakinumab and 3.1% of patients using triamcinolone (p value not reported).

  • Infections were seen more commonly in the canakinumab group (20% compared with 12% in the triamcinolone group; p value not reported).

  • Neutropenia and thrombocytopenia have been reported with canakinumab.

Patient factors

  • Patients may prefer their gout to be managed optimally using standard oral treatments (non-steroidal anti-inflammatory drugs, colchicine and urate-lowering therapy) and oral corticosteroids before trying injectable treatments.

  • Canakinumab is injected subcutaneously, whereas triamcinolone and other corticosteroids are generally injected intramuscularly or intra-articularly.

Resource implications

  • The cost of 1 dose of canakinumab 150 mg is £9927.80.

  • The cost of 1 dose of triamcinolone 40 mg is £1.49.

Key points

Gout is a disorder of purine metabolism characterised by a raised uric acid level in the blood and the deposition of urate crystals in joints and other tissues. These crystals trigger macrophages to produce interleukin-1 beta, producing an acute, painful inflammatory response. Canakinumab is a human monoclonal antibody that binds to human interleukin-1 beta, blocking its effects and preventing the production of inflammatory mediators.

In February 2013, the marketing authorisation for canakinumab was extended to include the symptomatic treatment of frequent gouty arthritis attacks (at least 3 attacks in the previous 12 months) in adults in whom non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate.

This evidence summary is based on 2 randomised controlled trials (β-RELIEVED and β-RELIEVED-II) and their extension studies, the results of which were all published in 1 paper (Schlesinger et al. 2012).

In the studies, subcutaneous canakinumab 150 mg was statistically significantly more effective than intramuscular triamcinolone 40 mg at reducing pain intensity in the most affected joint at 72 hours post dose and delayed the time to first new attack of gout over 12 weeks (the co-primary outcomes). In the pooled analysis of β-RELIEVED and β-RELIEVED-II, at 72 hours mean pain scores were lower for canakinumab than for triamcinolone (25.0 mm compared with 35.7 mm; mean difference on 100 mm visual analogue scale 10.7 mm, 95% confidence interval [CI] 6.0 mm to 15.4 mm, p<0.0001). Although statistically significant, specialists have advised that this is of borderline clinical significance. Also, this dose of triamcinolone is considered to be low by specialists (including those informing the European public assessment report for canakinumab) and may be a suboptimal dose to use as a comparator.

Compared with triamcinolone, canakinumab statistically significantly reduced the risk of a new attack of gout by 62% (hazard ratio 0.38, 95% CI 0.26 to 0.57, p<0.0001) over the 12-week period. Of patients treated with canakinumab, 16.0% experienced at least 1 new attack of gout, compared with 35.8% of those treated with triamcinolone (statistical significance of difference not reported).

In the pooled analysis of the initial and extension studies, over 24 weeks, adverse events were reported in 149 (66.2%) patients treated with canakinumab 150 mg and 121 (52.8%) patients treated with triamcinolone 40 mg. They were reported to be serious but not fatal in 17 (7.6%) patients using canakinumab and 7 (3.1%) using triamcinolone. There was 1 death in each group; neither was considered by the investigators to be related to the study. Infections were reported in 46 (20.4%) patients using canakinumab and 28 (12.2%) patients using triamcinolone. The statistical significance of these differences was not reported.

The European public assessment report for canakinumab states that neutropenia and thrombocytopenia have been observed with canakinumab, with a possible dose-response relationship.

Around 20−30% of people affected by gout are women; however, only 9% of patients in the studies were female. Similarly, the peak prevalence of gout occurs in those aged 75 years or more; however in the study, the mean age of the participants was 53 years and only limited data were available for patients aged 75 years or more (Mickuls et al. 2005). Both colchicine and NSAIDs had been judged as unsuitable for 35% of patients in the studies. This means that 65% of patients still had at least 1 usual first-line treatment option open to them. Only 42% of patients had contraindications to, intolerance of, or were unresponsive to colchicine. Similarly, only 42% of patients were on urate-lowering therapy, suggesting suboptimal management of gout.

The cost of 1 vial of canakinumab 150 mg is £9927.80.

Specialists have advised that is important to ensure that standard treatments for gout, including NSAIDs, colchicine and corticosteroids have been optimised before canakinumab is considered. Also, longer term, adequate urate-lowering therapy should be used to reduce the risk of ongoing attacks occurring. If this is done, the number of people with severe gout who may be eligible for treatment is likely to be very small.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.