Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre randomised trial

Abstract

Introduction: For patients with rheumatoid arthritis (RA) whose treatment with a tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment options are available. Often, another TNFi or a biological with another mode of action is prescribed. The objective of this study was to compare the effectiveness and cost-effectiveness of three biologic treatments with different modes of action in patients with RA whose TNFi therapy is failing.

Methods: We conducted a pragmatic, 1-year randomised trial in a multicentre setting. Patients with active RA despite previous TNFi treatment were randomised to receive abatacept, rituximab or a different TNFi. The primary outcome (Disease Activity Score in 28 joints) and the secondary outcomes (Health Assessment Questionnaire Disability Index and 36-item Short Form Health Survey scores) were analysed using linear mixed models. Cost-effectiveness was analysed on the basis of incremental net monetary benefit, which was based on quality-adjusted life-years (calculated using EQ-5D scores), and all medication expenditures consumed in 1 year. All analyses were also corrected for possible confounders.

Results: Of 144 randomised patients, 5 were excluded and 139 started taking abatacept (43 patients), rituximab (46 patients) or a different TNFi (50 patients). There were no significant differences between the three groups with respect to multiple measures of RA outcomes. However, our analysis revealed that rituximab therapy is significantly more cost-effective than both abatacept and TNFi over a willingness-to-pay range of 0 to 80,000 euros.

Conclusions: All three treatment options were similarly effective; however, when costs were factored into the treatment decision, rituximab was the best option available to patients whose first TNFi treatment failed. However, generalization of these costs to other countries should be undertaken carefully.

Trial registration: Netherlands Trial Register number NTR1605. Registered 24 December 2008.

Figure 1

Inclusion and exclusion of patients in the study. aba, abatacept; rit, rituximab; TNF, Tumour necrosis factor; TNFi, Tumour necrosis factor inhibitor; toc, tocilizumab.

Figure 2

Effectiveness outcomes over time with standard deviations. (a) Disease Activity Score in 28 joints (DAS28). (b) Health Assessment Questionnaire Disability Index (HAQ-DI). (c) EQ-5D. (d) 36-item Short-Form Health Survey (SF-36). PCS, Physical Component Summary. Month 0 represents the start of the treatment.

Figure 3

Percentages of patients in remission, with low disease activity and with good or moderate European League Against Rheumatism response criteria [30]. DA, Disease activity; EULAR, European League Against Rheumatism; TNFi, Tumour necrosis factor inhibitor.

Figure 4

Mean quality-adjusted life-years and medication-related costs in a 1-year period. Error bars represent the upper bars of the 95% confidence intervals. QALY, Quality-adjusted life-year.

Figure 5

Mean incremental net monetary benefit (iNMB) with 95% confidence intervals (CIs). The location of the 95% CI lines below an INMB of zero indicates that the two treatment groups differed significantly with respect to cost-effectiveness.