The National Institute for Health and Clinical Excellence (NICE) has opened a consultation on the use of Savient's Krystexxa (peglioticase) in treating severe gout, after publishing draft guidance which does not recommend the drug for this use.

Considering the evidence present for peglioticase within its marketing authorisation for the treatment of severe debilitating chronic tophaceous gout in adults, NICE's independent appraisal committee has concluded that the drug effectively lowers the level of uric acid in the blood for a significant proportion of patients with severe gout.

However, the panel also noted the risk of severe adverse reactions, and concluded that there was considerably uncertainty about the drug’s long-term efficacy and safety. 

The committee noted the initial risk of increased flare with the drug, and that in the three months after the initial period, the number of patients with flares and the number of flares per patient were lower in those receiving peglioticase compared with placebo. The panel concluded that this initial risk does not seem to override the effectiveness of peglioticase.

Evidence presented to the committee by the manufacturer included a pooled analysis of the results from two Phase III trials, which indicated that the proportion of patients who had a response to peglioticase was 42%. Pooled analysis is not normally considered a robust method for combining data from two trials, but the panel accepted that the data was sufficient for its deliberations, says NICE.

The committee concluded that there was uncertainty about the predictability of infusion-related reactions in the patients receiving peglioticase in clinical practice, and was concerned that antibodies against peglioticase may cross-react with other drugs. It also concluded that treatment duration with peglioticase might be substantially longer than six months, and that aspects of the drug's long-term safety remain uncertain at this stage.

The acquisition cost of a single vial containing 8mg of pegloticase concentrate for one infusion is £1,770, excluding value-added tax (VAT), and the average cost of a six-month course of treatment is £23,010, although costs may vary in different settings because of negotiated procurement discounts.

As the drug's cost per quality-adjusted life-year (QALY) was estimated to be over £66,000 -  above the £20,000-£30,000 range normally considered cost-effective - the committee's provisional recommendation is that it would not represent a cost-effective treatment option for the NHS.

"We recognise that severe debilitating chronic tophaceous gout can be an extremely difficult condition, treating affecting a person's quality of life," said Professor Carole Longson, director of the health technology evaluation centre at NICE. "However, the evidence available to the committee showed that there was considerable uncertainty about the long-term efficacy and safety of pegloticase, and a very high cost compared with the known benefit, so the committee concluded that pegloticase had not been shown to be a cost-effective use of NHS resources as a treatment option for this condition."

NICE’s draft recommendations are: - (a) pegloticase is not recommended within its marketing authorisation - for treating severe debilitating chronic tophaceous gout in adults who may also have erosive joint involvement and in whom xanthine oxidase inhibitors at the maximum medically-appropriate dose have failed to normalise serum uric acid or for whom these medicines are contraindicated; and - (b) people who are currently receiving peglioticase in circumstances where it is not recommended according to (a)  should be able to continue treatment until they and their clinician consider it appropriate to stop.

NICE also points out that it has previously recommended Takeda's Uloric (febuxostat) as an option for the management of chronic hyperuricaemia (raised uric acid levels in the blood) in gout only for people who are intolerant of allopurinol or for whom allopurinol is contraindicated.

Prof Longson added that NICE would welcome comments on its draft recommendations as part of the consultation, which runs to February 22.

- It is estimated that, overall, one in 70 adults in the UK have gout. Symptoms of the condition usually occur after the age of 30 in men, and after 60 in women.