Ustekinumab for the treatment of moderate to severe psoriasis.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of ustekinumab for the treatment of moderate to severe psoriasis based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's main evidence came from three randomised controlled trials (RCTs), of reasonable methodological quality and measuring a range of clinically relevant outcomes. Higher proportions of participants treated with ustekinumab (45 mg and 90 mg) than with placebo or etanercept achieved an improvement on the Psoriasis Area and Severity Index (PASI) of at least 75% (PASI 75) after 12 weeks. There were also statistically significant differences in favour of ustekinumab over placebo for PASI 50 and PASI 90 results, and for ustekinumab over etanercept for PASI 90 results. A weight-based subgroup dosing analysis for each trial was presented, but the methodology was poorly described and no statistical analysis to support the chosen weight threshold was presented. The manufacturer carried out a mixed treatment comparison (MTC); however, the appropriateness of some of the methodological aspects of the MTC is uncertain. The incidence of adverse events was similar between groups at 12 weeks and withdrawals due to adverse events were low and less frequent in the ustekinumab than in the placebo or etanercept groups; however, statistical comparisons were not reported. The manufacturer's economic model of treatments for psoriasis compared ustekinumab with other biological therapies. The model used a reasonable approach; however, it is not clear whether the clinical effectiveness estimates from the subgroup analysis, used in the base-case analysis, were methodologically appropriate. The base-case incremental cost-effectiveness ratio for ustekinumab versus supportive care was 29,587 pounds per quality-adjusted life-year (QALY). In one-way sensitivity analysis the model was most sensitive to the number of hospital days associated with supportive care, the cost estimate for intermittent etanercept 25 mg and the utility scores used. In the ERG's scenario analysis the model was most sensitive to the price of ustekinumab 90 mg, the proportion of patients with baseline weight > 100 kg and the relative risk of intermittent versus continuous etanercept 25 mg. In the ERG's probabilistic sensitivity analysis ustekinumab had the highest probability of being cost-effective at conventional NICE thresholds, assuming the same price for the 45-mg and 90-mg doses; however, doubling the price of ustekinumab 90 mg resulted in ustekinumab no longer dominating the comparators. In conclusion, the clinical effectiveness and cost-effectiveness of ustekinumab in relation to other drugs in this class is uncertain. Provisional NICE guidance issued as a result of the STA states that ustekinumab is recommended as a treatment option for adults with plaque psoriasis when a number of criteria are met. Final guidance is anticipated in September 2009.