Background/Purpose:

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-years costs and effects of a step-up approach (MTX mono -> MTX + csDMARD combination -> Adalimumab -> second anti-TNF-α) and an initial combination therapy approach (MTX + csDMARD + prednisone if needed -> MTX + csDMARD high dose -> anti-TNF-α’s) 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<DAS28≤3.2), moderate (3.2<DAS28≤5.1), and high disease activity (DAS28>5.1) were simulated. Hypothetical 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 the ICER after 5 years were compared between the two strategies. To account for parameter uncertainty, probabilistic sensitivity analysis was employed through Beta, 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 €16226.3 and 3.552 QALY vs €20183.3 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 means less healthcare and productivity loss costs and more accumulated utility. Additionally, higher remission percentages caused less bDMARD use in the initial combination strategy, again lowering overall costs.

Conclusion:

Initial combination therapy was found to be 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.

Figure 1: Cost-effectiveness plane comparing initial combination and step-up therapy

X-axis: incremental effect (Quality-Adjusted Life Years). Y-axis: Incremental cost (€’s).  Probabilistic sensitivity analysis shows initial combination strategy is cost-effective.