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Biological disease-modifying antirheumatic drugs are recommended for use particularly in rheumatoid arthritis patients who had an inadequate response to methotrexate but they are costly. In this article, we estimated the number needed to treat and treatment costs associated with the use of baricitinib and adalimumab in moderate to severe rheumatoid arthritis patients who are inadequate responders to methotrexate. We used Efficacy data (American College of Rheumatology indices) from the RA-BEAM trial. For both DMARDs, the number needed to treat was calculated with reference to placebo, using the (American College of Rheumatology indices (ACR20, ACR50, and ACR70 response at 24 weeks)). Direct medical costs (therapy costs of medication) were the only costs considered in the base case analysis. However, administration and monitoring costs were included in the sensitivity analyses. Baricitinib had a lower cost per number needed to treat (ACR20: €10,846.08; ACR50: €12,942.72; and ACR70: €18,506.88) compared to adalimumab (ACR20: €21,124.45; ACR50: €23,945.22; and ACR70: €45,445.77). The most significant cost difference in favor of baricitinib was observed using ACR70 index (−€26,938.89). Sensitivity analysis confirmed these results. This analysis demonstrates that baricitinib represents a more cost-effective option in comparison to adalimumab in the treatment of rheumatoid arthritis patients with an inadequate response to methotrexate in Italy and based on Italian costs.