Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by joint inflammation, which can lead to chronic pain, reduced quality of life, and irreversible joint deformities. Disease-modifying antirheumatic drugs (DMARDs) play a critical role in RA management by slowing disease progression and preventing structural damage. Conventional synthetic DMARDs (csDMARDs) often prove inadequate, requiring a shift to biologic DMARDs (bDMARDs), which employ various mechanisms of action. Among these bDMARDs are tumor necrosis factor inhibitors (TNFi), interleukin-6 (IL-6) receptor inhibitors, T-cell co-stimulation modulators, and B-cell depleting agents [1]. Despite the similar efficacy of these agents, current guidelines lack specific recommendations on which biologic should be chosen initially [2], highlighting an unmet need for personalized treatment strategies in RA. Personalized selection could benefit RA patients greatly, as many who do not respond to one biologic achieve better outcomes by switching to another with a different mechanism of action [3].

A recent study by Kim et al. [4], titled “Anemia as an indicator of a higher retention rate for tocilizumab versus TNFi in patients with RA from a Korean multi-center registry,” provides a meaningful step toward filling this gap. This study investigates whether simple and accessible laboratory markers can help guide the selection between tocilizumab (TCZ) and TNFi in biologic-naïve RA patients by focusing on their influence on drug retention. Drug retention can offer insight into both the effectiveness and safety of treatments in real-world settings. Higher retention rates can indicate favorable efficacy and tolerability, which are essential for patients’ adherence to long-term RA management [5].

The study analyzed data from the KOrean College of Rheumatology BIOlogics and Targeted Therapy (KOBIO) registry [6], focusing on RA patients who initiated treatment with TCZ or TNFi between March 2013 and December 2021. Anemia was defined as hemoglobin (Hb) <130 g/L for males and <120 g/L for females, C-reactive protein (CRP) elevation as CRP ≥10.0 mg/L, elevated erythrocyte sedimentation rate (ESR) as ESR ≥28 mm/hour, and thrombocytosis as a platelet count >450×10 ⁹/L. To address confounding factors, the authors applied propensity score matching. Among the 893 patients analyzed (315 on TCZ and 578 on TNFi), TCZ was associated with a significantly lower rate of discontinuation compared to TNFi (hazard ratio: 0.53, 95% CI: 0.44~0.66). This difference was particularly pronounced in anemic patients, where the interaction analysis showed statistical significance (p=0.010). In this subgroup, discontinuation due to a lack of efficacy occurred in 35.0% of the TNFi initiators compared to only 7.4% of the TCZ initiators, suggesting that TCZ may offer a distinct benefit for anemic patients by better aligning with IL-6-driven inflammatory pathways [4].

This study’s innovative approach is due to its focus on simple hematological markers, such as Hb, CRP, ESR, and platelet count, which are readily accessible in clinical practice. The authors utilized well-established associations between IL-6 activity and these markers to explore TCZ’s potential effectiveness in specific subgroups. IL-6 is a pivotal cytokine in RA pathogenesis, associated with the induction of anemia, elevation of acute-phase reactants, and stimulation of thrombopoiesis [7-9]. While both TCZ and TNFi are effective, the higher retention rates observed with TCZ, particularly in anemic patients, underscore its potential benefits. The study’s findings align with previous research showing that anemia in RA is closely associated with IL-6 activity, as IL-6 promotes hepcidin production, which reduces iron availability, resulting in anemia [10]. This suggests that patients with IL-6-driven anemia may respond particularly well to IL-6 receptor inhibitors like TCZ. By assessing readily available markers, this study offers a practical and feasible approach to tailoring RA treatment when more advanced cytokine profiling is not feasible in clinical settings.

However, this study has certain limitations. While it emphasizes the higher retention rates of TCZ compared to TNFi, it focuses solely on retention rates and does not directly assess whether TCZ improves disease activity more effectively than TNFi, particularly in anemic patients. This distinction is crucial for fully understanding the clinical implications of TCZ’s use. Additionally, TCZ’s ability to rapidly reduce CRP levels may have influenced retention rates, as patients might continue treatment despite ongoing inflammation. Moreover, the study did not stratify anemia into subgroups based on severity, leaving unanswered whether patients with more severe anemia show distinct responses to TCZ. Future studies are needed to address these gaps, investigating the interplay between anemia severity, IL-6 activity, and treatment response.

In conclusion, this study by Kim et al. [4] makes a significant contribution to the field of RA management by suggesting that TCZ may offer superior retention compared to TNFi in biologic-naïve RA patients, especially among those with anemia. By integrating commonly available laboratory markers as indicators of IL-6 activity, the authors provide a practical framework for guiding initial biologic selection. This approach not only addresses the unmet need for individualized RA treatment strategies but also highlights the potential of accessible biomarkers in optimizing RA care. Future research could expand on these findings, examining other subgroups and additional biomarkers to refine biologic selection further.

None.

No potential conflict of interest relevant to this article was reported.