Etanercept, Infliximab and Adalimumab for the Treatment of Psoriatic Arthritis: A Systematic Review and Economic Evaluation

BACKGROUND: Etanercept, infliximab and adalimumab are licensed in the UK for the treatment of active and progressive psoriatic arthritis (PsA) in adults who have an inadequate response to standard treatment. OBJECTIVE: To determine the clinical effectiveness, safety and cost-effectiveness of these biologic agents in the treatment of active and progressive PsA. DATA SOURCES: Systematic reviews were performed, with data sought from 10 electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, Conference Proceedings Citation Index - Science, ClinicalTrials.gov, metaRegister of Current Controlled Trials, NHS Economic Evaluation Database, Health Economic Evaluations Database and EconLit) up to June 2009. REVIEW METHODS: Full paper manuscripts of titles/abstracts considered relevant were obtained and assessed for inclusion by two reviewers according to criteria on study design, interventions, participants and outcomes. Data on study and participant characteristics, efficacy outcomes, adverse effects, costs to the health service and cost-effectiveness were extracted, along with baseline data where reported. The primary efficacy outcomes were measures of anti-inflammatory response, skin lesion response and functional status, and the safety outcome was the incidence of serious adverse events. The primary measure of cost-effectiveness was incremental cost per additional quality-adjusted life-year (QALY). Standard meta-analytic techniques were applied to efficacy data. Published cost-effectiveness studies and the economic analyses submitted to the National Institute for Health and Clinical Excellence (NICE) by the biologic manufacturers were reviewed. An economic model was developed by updating the model produced by the York Assessment Group for the previous NICE appraisal of biologics in PsA. RESULTS: Pooled estimates of effect demonstrated a significant improvement in patients with PsA for all joint disease and functional status outcomes at 12-14 weeks' follow-up. The biologic treatment significantly reduced joint symptoms for etanercept [relative risk (RR) 2.60, 95% confidence interval (CI) 1.96 to 3.45], infliximab (RR 3.44, 95% CI 2.53 to 4.69) and adalimumab (RR 2.24, 95% CI 1.74 to 2.88), with 24-week data demonstrating maintained treatment effects. Trial data demonstrated a significant effect of all three biologics on skin disease at 12 or 24 weeks. Evidence synthesis found that infliximab appeared to be most effective across all outcomes of joint and skin disease. The response in joint disease was greater with etanercept than with adalimumab, whereas the response in skin disease was greater with adalimumab than with etanercept, although these differences are not statistically significant. Under base-case assumptions, etanercept was the most likely cost-effective strategy for patients with PsA and mild-to-moderate psoriasis if the threshold for cost-effectiveness was �20,000 or �30,000 per QALY. All biologics had a similar probability of being cost-effective for patients with PsA and moderate-to-severe psoriasis at a threshold of �20,000 per QALY. LIMITATIONS: Limited available efficacy data and difficulty in assessing PsA activity and its response to biologic therapy. CONCLUSIONS: The data indicated that etanercept, infliximab and adalimumab were efficacious in the treatment of PsA compared with placebo, with beneficial effects on joint symptoms, functional status and skin. Short-term data suggested that these biologic agents can delay joint disease progression and evidence to support their use in the treatment of PsA is convincing. Future research would benefit from long-term observational studies with large sample sizes of patients with PsA to demonstrate that beneficial effects are maintained, along with further monitoring of the safety profiles of the biologic agents. FUNDING: The National Institute for Health Research Health Technology Assessment programme.