Abstract
Background
Adjusting medication of patients with rheumatoid arthritis (RA) until predefined disease activity targets are met, i.e. Treat-to-Target (T2T), is the currently recommended treatment approach. However, not much is known about long-term cost-effectiveness of different T2T strategies.We model the 5-year costs and effects of a step-up approach (MTX mono - > MTX + csDMARD combination - > Adalimumab - > second anti-TNF) and an initial combination therapy approach (MTX + csDMARD - > MTX + csDMARD higher dose - > anti-TNFs) from the healthcare and societal perspectives, by adapting a previously validated Markov model.Methods
We constructed a Markov model in which 3-monthly transitions between DAS28-defined health states of remission (≤2.6), low (2.6 5.1) were simulated. Modelled patients proceeded to subsequent treatments in case of non-remission at each (3-month) cycle start. In case of remission for two consecutive cycles medication was tapered, until medication-free remission was achieved. Transition probabilities for individual treatment steps were estimated using data of Dutch Rheumatology Monitoring registry Remission Induction Cohort I (step-up) and II (initial combination). Expected costs, utility, and ICER after 5 years were compared between the two strategies. To account for parameter uncertainty, probabilistic sensitivity analysis was employed through Gamma, Normal, and Dirichlet distributions. All utilities, costs, and transition probabilities were replaced by fitted distributions.Results
Over a 5-year timespan, initial combination therapy was less costly and more effective than step-up therapy. Initial combination therapy accrued €16,226.3 and 3.552 QALY vs €20,183.3 and 3.517 QALYs for step-up therapy. This resulted in a negative ICER, indicating that initial combination therapy was both less costly and more effective in terms of utility gained. This can be explained by higher (±5%) remission percentages in initial combination strategy at all time points. More patients in remission generates less healthcare and productivity loss costs and higher utility. Additionally, higher remission percentages caused less bDMARD use in the initial combination strategy, lowering overall costs.Conclusion
Initial combination therapy was found favourable over step-up therapy in the treatment of Rheumatoid Arthritis, when considering cost-effectiveness. Initial combination therapy resulted in more utility at a lower cost over 5 years.