To determine whether a strategy based on methylenetetrahydrofolate reductase (MTHFR) genotype screening is more cost-effective than the conventional strategy in reducing the risk of methotrexate (MTX)-related toxicity in patients with rheumatoid arthritis (RA).
We consecutively enrolled 385 patients with RA (355 female, 30 male) who had received MTX and identified toxicity associated with MTHFR C677T genotypes. We designed a hypothetical decision model to compare the genotype-based strategy with the conventional strategy. The time horizon was set as 1 year, and direct medical costs were used. The measured outcomes were the total expected cost, the effectiveness, and the incremental cost-effectiveness ratio.
MTHFR genotype distribution revealed 133 patients (34.6%) with 677CC, 193 (50.1%) with 677CT, and 59 (15.3%) with 677TT. A total of 154 patients (40.0%) exhibited MTX-related toxicity. Compared to RA patients with the CC genotype, the odds ratio (95% confidence interval) for risk of toxicity was 3.8 (2.29-6.33) for the CT genotype, and 4.7 (2.40-9.04) for the TT genotype. In the base-case model, the total expected cost and the probability of continuing MTX medication for the conventional and genotype-based strategies were 851,415 Korean won (710 US dollars) and 788,664 Korean won (658 US dollars), and 94.03% and 95.58%, respectively.
The MTHFR C677T polymorphism may be an important predictor of MTX-related toxicity in patients with RA. The cost-effectiveness analysis suggests that the genotype-based strategy is both less costly and more effective than the conventional strategy for MTX therapy.