TNF inhibitors vs. combination intensive therapy with conventional disease modifying anti-rheumatic drugs in rheumatoid arthritis
As synthetic disease modifying drugs are “slow acting” agents. The combination intensive therapy provides an additional cost benefit and provide better reduction in pain.
Tumor necrosis factor inhibitors are the first biologics for rheumatoid arthritis (RA) that have changed specialist management. Economic modeling used placebo controlled trials to justify their use in patients with active RA who were resistant to methotrexate.
Tumor necrosis factor inhibitors are the first biologics for rheumatoid arthritis (RA) that have changed specialist management. Economic modeling used placebo controlled trials to justify their use in patients with active RA who were resistant to methotrexate. English guidance from the National Institute for Health and Care Excellence (NICE) recommends starting them in patients with persistent active RA that is resistant to methotrexate and one other synthetic disease modifying drug and continuing them as long as the patients maintain good responses.
Tumor necrosis factor inhibitors are expensive. By 2012, international spending exceeded £15bn (€20.5bn, $23bn) a year and England have solely spent over £600 m a year on tumor necrosis factor inhibitors, which has a substantial impact on the National Health Service’s budget.
Rationale behind research
- As healthcare commissioners prefer lower cost alternatives for the disease, provided that patients were not disadvantaged, so the study was evaluated to correlate the economical values
To determine whether intensive combinations of synthetic disease modifying drugs can achieve similar clinical benefits at lower costs to high cost biologics in patients with active RA resistant to initial methotrexate and other synthetic disease modifying drugs
- Primary outcome: Reduction in disability at 12 months, measured with patient recorded heath assessment questionnaires
- Secondary outcome: Quality of life, joint damage, disease activity, adverse events and costs
- Time points:
- Efficacy: Baseline and 12 months
Baseline: Treatment groups were well balanced with no significant baseline differences
- Primary outcomes:
- At week 12, mean reductions were -0.30 (95% CI -0.42 to -0.19) with tumor necrosis factor strategy and -0.45 (-0.55 to -0.34) with disease modifying drug strategy
- The mean difference was -0.14 and 95% CI (-0.29 to 0.01) was below the pre-specified non-inferiority boundary of 0.22
- Secondary outcomes :
- The disease modifying drug strategy reduced costs for months 0-6 by a mean of −£3615 (95% confidence interval −£4104 to −£3182) and for months 6-12 by −£1930 (−£2599 to −£1301)
- At week 12, health and social care costs were £5545 less in patients treated with combined drug strategy
Results showed that triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) achieved similar benefits to etanercept plus methotrexate in incomplete methotrexate responders treated for 12 months. The current trial and RACAT had comparable results, despite differences in patients and trial design, as they highlight the role of head-to-head trials against effective conventional comparators to evaluate expensive treatments.
In patients with RA, the treatment with synthetic disease modifying drugs achieved non-inferior outcomes to the NICE approved strategy of treatment with tumor necrosis factor inhibitor over 12 months. Both strategies improved quality of life similarly and resulted in minimal erosive progression. Over 12 months, health and social care costs were £5545 less in patients who were treated with the combined drug strategy. These reduced costs were associated with reduced scores on the health assessment questionnaire, which have immediate economic benefits.