OBJECTIVE: To determine whether intensive combinations of conventional synthetic 
disease-modifying antirheumatic drugs (csDMARDS) achieve similar clinical 
benefits more cheaply than high-cost biologics such as tumor necrosis factor 
inhibitors (TNFi) in patients with active rheumatoid arthritis (RA) whose 
illness has failed to respond to methotrexate and another DMARD.
METHODS: We used within-trial cost-effectiveness and cost-utility analyses from 
health and social care and 2 societal perspectives. Participants were recruited 
into an open-label, 12-month, pragmatic, randomized, multicenter, 2-arm, 
noninferiority trial in 24 rheumatology clinics in England and Wales. Costs were 
linked with the Health Assessment Questionnaire (HAQ; primary outcome) and 
quality-adjusted life years derived from 2 measures (Short-Form 36 health survey 
and EuroQol 5-domain 3-level instrument).
RESULTS: In total, 205 participants were recruited, 104 in the csDMARD arm and 
101 in the TNFi arm. Participants in the csDMARD arm with poor response at 6 
months were offered TNFi; 46 participants (44%) switched. Relevant cost and 
outcome data were available for 93% of participants at 6-month follow-up and for 
91-92% of participants at 12-month follow-up. The csDMARD arm had significantly 
lower total costs from all perspectives (6-month health and social care adjusted 
mean difference -£3,615 [95% confidence interval (95% CI) -4,104, -3,182]; 
12-month health and social care adjusted mean difference -£1,930 [95% CI -2,599, 
-1,301]). The HAQ score showed benefit to the csDMARD arm at 12 months (-0.16 
[95% CI -0.32, -0.01]); other outcomes/follow-ups showed no differences.
CONCLUSION: Starting treatment with csDMARDs, rather than TNFi, achieves similar 
outcomes at significantly lower costs. Patients with active RA and who meet the 
National Institute for Health and Care Excellence criteria for expensive 
biologics can be treated with combinations of intensive csDMARDs in a 
cost-effective manner.