Arthritis (juvenile idiopathic) - etanercept

4. Evidence

4.1. Clinical effectiveness

4.1.1. Only one randomised controlled trial of etanercept in children with JIA was identified and this was of high quality. The trial had a unique design to satisfy ethical considerations. There was an initial open-label phase in which all 69 patients, who had not responded to NSAIDs and methotrexate, received etanercept for 3 months. This was followed by randomisation of responders to a double-blind phase, in which they received either etanercept or placebo for a further 4 months.

4.1.2. In the initial phase, 74% of children achieved a JRA30 response (see Appendix E). In the second phase, 28% of children receiving etanercept experienced a flare up of symptoms compared with 81% receiving placebo (p = 0.003). At the end of the study, the proportion of children who still met the JRA30 definition of improvement was significantly higher in the group receiving etanercept than in the placebo group (80% vs 35%, p < 0.01). At the end of the double-blind phase, the JRA50 definition of improvement was met by 72% of children who had received etanercept compared with 23% who had received placebo; the JRA70 definition of improvement was met by 44% who had received etanercept compared with 19% who had received placebo.

4.1.3. In the ongoing open-label extension study, after 2 years (median duration of treatment of 26 months), 83% of children had achieved a JRA30 response, 78% a JRA50 response, and 63% a JRA70 response. Children whose disease had flared while receiving placebo regained their initial response.

4.1.4. There were no statistically significant differences in adverse events per patient month between the etanercept and placebo groups. The most common adverse events seen with etanercept were mild to moderate injection site reactions (39%), which were self-limiting and caused no withdrawals, upper respiratory tract infections (35%), headache (20%), rhinitis (16%), abdominal pain (16%), vomiting (14%), pharyngitis (14%), nausea (12%) and rash (10%).

4.1.5. In the etanercept group, functional ability measured by Child Health Assessment Questionnaire (CHAQ) score (see Appendix E) improved from 1.6 at baseline to 0.8 at month 7, whereas there was little change in the placebo group (from 1.3 at baseline to 1.2 at month 7).

4.2. Cost-effectiveness

4.2.1. No published economic evaluations were identified. A cost–utility analysis was undertaken as part of the manufacturer's submission, based upon an economic model developed for adult rheumatoid arthritis. The model is based on a number of uncertainties but was included as a starting point for future research.

4.2.2. The main assumptions are that the measures of clinical response used in children and adults are comparable, that the CHAQ is equivalent to the adult version, the Health Assessment Questionnaire (HAQ), and that the HAQ relationship to utility and mortality also applies in children.

4.2.3. The model gives a base-case incremental cost-effectiveness ratio (ICER) of £16,082 per quality adjusted life year (QALY) for etanercept versus placebo (range £3900 to £34,000).

4.2.4. The Assessment Group did not develop an economic model because the lack of empirical information precluded the construction of a model with greater validity.

4.3. Considerations

4.3.1. The Committee reviewed the available evidence on the clinical and cost effectiveness of etanercept, and considered evidence from user representatives and clinical experts on the nature of the condition and the benefits of drug therapy. They took into account that:

• no DMARDs are licensed currently for use in children
• at present, best practice is limited to methotrexate prescribed off licence
• there was convincing evidence of the clinical effectiveness of etanercept in the short to medium term
• the disease is arrested by drug therapy in a small proportion of children.

4.3.2. The Committee accepted that given the relative robustness of the manufacturer's estimate of cost-effectiveness to changes in key parameters, the ICER for etanercept is likely to be in the region of £15–30,000 per QALY.