Tofacitinib for treating juvenile idiopathic arthritis

3.1 The company positions tofacitinib for people with polyarticular juvenile idiopathic arthritis (JIA) whose disease has responded inadequately to or who are intolerant of, one or more disease-modifying antirheumatic drugs (DMARDs). This corresponds with how biological DMARDs are used in the NHS. The company also positions tofacitinib when biological DMARDs have not controlled disease well enough. The company's cost-comparison case proposes that tofacitinib has similar effects to adalimumab and tocilizumab, which are both recommended in NICE's technology appraisal guidance on abatacept, adalimumab, etanercept and tocilizumab for JIA. The company explained that it selected these comparators because adalimumab is the most frequently used biological DMARD, and tocilizumab represents an alternative mode of action. The ERG's clinical advisers suggested that 50% to 60% of people with JIA currently have adalimumab, 30% to 40% have tocilizumab and around 10% have etanercept. The company's estimates suggested a higher proportion having adalimumab. The committee agreed that adalimumab and tocilizumab are appropriate comparators.

3.2 Tofacitinib has been compared with placebo in a phase 3, randomised, double-blind trial, study A3921104. This showed that tofacitinib was superior to placebo for a range of outcomes at 44 weeks. To compare tofacitinib with adalimumab and tocilizumab, the company carried out indirect comparisons. These suggested that, for the outcomes of disease flare, disease activity (measured by the American College of Rheumatology [ACR] 30, 50 and 70), tofacitinib is similar to the comparators (the exact results are considered confidential by the company and cannot be reported here). The ERG considered it was plausible that tofacitinib is non-inferior to the comparators. However, it noted that tofacitinib follow-up data was only for 44 weeks, while there is longer follow-up data for tocilizumab and adalimumab. The committee concluded that tofacitinib is likely to have similar clinical effectiveness to adalimumab and tocilizumab, although the long-term effectiveness is uncertain.

3.3 Adalimumab biosimilars are available in the NHS at a considerable discount to the list price of the originator product (exact prices are confidential and cannot be reported here). There is also a confidential discount for tocilizumab. When this is applied, tofacitinib has similar overall costs to tocilizumab in both the company and the ERG's modelling. However, tofacitinib has higher costs than adalimumab in both the company and the ERG's modelling. The exact results are confidential and cannot be reported here.

3.4 Although the A3921104 study included a small number of people with juvenile psoriatic arthritis (n=7 tofacitinib, n=8 placebo), this population was not included in the primary end point analysis. Results for people with juvenile psoriatic arthritis favoured tofacitinib for disease flare and ACR response and were similar to those for the polyarticular JIA cohort (exact results are considered confidential by the company and cannot be reported here). The results also favoured tofacitinib for the outcome of body surface area affected by psoriasis. The committee concluded that the results suggest tofacitinib is clinically effective compared with placebo, but the evidence is very limited.

3.5 The only drug with a marketing authorisation for juvenile psoriatic arthritis is etanercept. Etanercept is recommended in NICE's technology appraisal guidance on abatacept, adalimumab, etanercept and tocilizumab (TA373) for juvenile psoriatic arthritis (referred to as psoriatic JIA). In that appraisal the only evidence available for etanercept came from a single-arm open label trial, CLIPPER. Also in the appraisal:

3.6 The company did not present any clinical evidence comparing tofacitinib with etanercept. The committee appreciated that this would have been difficult to do, and any analysis would have been very uncertain. This is because of the small number of patients in the A3921104 study and because the CLIPPER trial was single arm. The company also did not provide a cost-comparison analysis comparing tofacitinib with etanercept. However, the committee was aware that etanercept biosimilars are available in the NHS at a considerable discount to the list price of the originator (exact prices are confidential and cannot be reported here).

3.7 The committee noted that a substantial proportion of people have adalimumab for polyarticular JIA (for more about appropriate comparators, see section 3.1). Although tofacitinib is similarly effective, it costs more than adalimumab. The committee recognised that patients and clinicians would welcome an additional treatment option with an alternative route of administration and mode of action. It noted that if people have already had adalimumab, or it is unsuitable, then tocilizumab may be used. Tofacitinib has similar costs and similar benefits to tocilizumab. Therefore, the committee considered that the cost-comparison case was demonstrated, but only if adalimumab is unsuitable or the condition has not responded well enough to it. The committee considered that the evidence relating to juvenile psoriatic arthritis was limited. But as in TA373 this could be generalised from polyarticular JIA and also from tofacitinib's use in adult psoriatic arthritis. However, the main comparator is etanercept for this population, for which there are low-cost biosimilars. This means tofacitinib is likely to have higher costs than etanercept. So the committee concluded that it could recommend tofacitinib for both polyarticular JIA and juvenile psoriatic arthritis, but only if a tumour necrosis factor (TNF)‑alpha inhibitor (such as adalimumab and etanercept) is not suitable or does not control the condition well enough.