To evaluate the clinical effectiveness, safety, tolerability and cost-effectiveness of etanercept and efalizumab for the treatment of moderate to severe chronic plaque psoriasis.
Major electronic databases and several Internet resources were searched up to April 2004.
Systematic reviews were undertaken of the efficacy, safety and economic reviews of etanercept and efalizumab. An existing systematic review of the efficacy and safety of other treatments was also updated. Economic models supplied by the manufacturers of etanercept and efalizumab were critiqued. An economic model was then developed of etanercept and efalizumab in the treatment of moderate to severe chronic plaque psoriasis.
The review of the clinical evidence identified a total of 39 published and three unpublished studies: eight randomised controlled trials (RCTs) of the efficacy of etanercept (three trials) and efalizumab (five); 10 studies of the adverse effects of the interventions; and 24 RCTs of the efficacy of the other treatments for moderate to severe psoriasis. The trials of the efficacy of the interventions were all double-blind and placebo-controlled trials and generally of good quality, but three of the five efalizumab trials were poorly reported. A total of 1347 patients were included in the etanercept trials and 2963 in the efalizumab trials. Data on the efficacy of etanercept 25 mg twice a week for 12 weeks were available from three RCTs. On average, active treatment resulted in 62% of patients achieving a Psoriasis Area and Severity Index (PASI) 50, 33% achieving a PASI 75, 11% achieving a PASI 90 and 40% were assessed as clear or almost clear. These figures are not adjusted for changes relative to placebo. Improvement in quality of life as assessed by mean percentage change in Dermatology Life Quality Index (DLQI) was around 59% with etanercept 25 mg twice a week compared with 9% with placebo, and all mean differences that could be calculated were statistically significantly in favour of etanercept. Data on the efficacy of etanercept 50 mg twice a week for 12 weeks were available from two RCTs. Across the two trials, the proportion of patients achieving PASI 50, 75 and 90 was 76, 49 and 21%, respectively; the pooled relative risks were all statistically significantly in favour of etanercept. The findings for mean PASI after treatment, mean percentage change in PASI from baseline and mean percentage change in DLQI also demonstrated the efficacy of etanercept treatment. Evidence from one RCT indicates that the response to etanercept is maintained post-treatment, at least in the medium term, and data from uncontrolled follow-up phases reflect and extend these findings. Efalizumab at a dose of 1 mg/kg once a week subcutaneously was studied in five RCTs. Across these trials, 12 weeks of active treatment resulted in an average of 55% of patients achieving PASI 50, 27% PASI 75, 4.3% PASI 90 and 27% clear or minimal psoriasis status. These figures are not adjusted for changes relative to placebo. There is no evidence from RCTs that the response to efalizumab 1 mg/kg once a week is maintained when treatment continues beyond 12 weeks, and long-term follow-up data relate to a range of doses and are poorly reported and so cannot be used to draw even tentative conclusions regarding the long-term efficacy of efalizumab. Uncontrolled data from trial follow-up suggest that time to relapse may be around 60 days. No data indicating the existence or absence of any rebound in psoriasis after discontinuation of efalizumab were identified. There is no evidence relating to the efficacy of efalizumab upon retreatment. A mixed treatment comparison analysis found a higher response rate in terms of PASI 50, 75 and 90 with etanercept than with efalizumab. Injection site reactions appear to be the most common adverse effects of etanercept. Overall, etanercept appears to be well tolerated in short- and long-term use, although many of the long-term data are not from patients with psoriasis. Headache, chills and, to a lesser extent, nausea, myalgia, pain and fever are the common adverse events associated with efalizumab. Overall, withdrawal rates due to adverse events are low. Longer term data for efalizumab are not readily available for evaluation, but the adverse events data up to 3 years appear to reflect those over 12 weeks and to remain stable. Unfortunately, few data for serious infections and serious adverse events with efalizumab are available. For the primary analysis comparing etanercept, efalizumab and supportive care, the results of the York Model suggest that the biological therapies would only be cost-effective for all patients with moderate to severe psoriasis if the NHS were willing to pay over pound 60,000 per QALY gained. In patients with poor baseline quality of life (fourth quartile DLQI), efalizumab, etanercept 25 mg (intermittent), etanercept 25 mg (continuous) and etanercept 50 mg (intermittent) would be cost-effective as part of a treatment sequence if the NHS were willing to pay pound 45,000, pound 35,000, pound 45,000 and pound 65,000 per QALY gained, respectively. In patients who are also at high risk of inpatient hospitalisation (21 days per annum), these therapies would be cost-effective as part of a sequence as long as the NHS were willingness to pay pound 25,000, pound 20,000, pound 25,000 and pound 45,000 per QALY gained, respectively. As part of a secondary analysis including a wider range of systemic therapies as comparators, the York Model found that it would only be cost-effective to use etanercept and efalizumab in a sequence after methotrexate, ciclosporin and Fumaderm.
Clinical trial data indicate that both etanercept and efalizumab are efficacious in patients who are eligible for systemic therapy, but the economic evaluation demonstrates that these biological therapies are likely to be cost-effective only in patients with poor baseline QoL and who are at risk of hospitalisation. Efficacy trials conducted in the specific population for which etanercept and efalizumab are licensed are required, as are long-term comparisons of etanercept and efalizumab with other treatments for moderate to severe psoriasis. Long-term efficacy trials and safety/tolerability data for patients treated with etanercept or efalizumab are required, as are trials on the response of specific subtypes of psoriasis to different drugs. Research on the rate of inpatient hospitalisation in patients with moderate to severe psoriasis is warranted, and the effect of treatment on this rate.