Clinical, Real-World Data Support Importance of Tocilizumab for RA

A slew of research has positioned tocilizumab as a cornerstone of rheumatoid arthritis (RA) treatment, according to insights from a narrative review.1

Tocilizumab has emerged as a key treatment for rheumatoid arthritis, showing efficacy, safety, and potential cardiovascular benefits in recent studies.

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Published in Frontiers in Immunology, the review includes a range of data showing favorable efficacy, both as an infusion and an injection. Available data on the IL-6 receptor–targeting monoclonal antibody include those from randomized controlled trials and from real-world use, including some studies that have hinted at benefits that extend past RA alone.

Favorable long-term data of tocilizumab date back to 2009, when the STREAM study showed improved efficacy and safety for up to 5 years in patients with active disease. Since STREAM, 2 additional longer-term studies—AMBITION and ENTRACTE—have published data on 5-year findings.

Across the clinical data portfolio, tocilizumab has demonstrated efficacy and safety compared with tumor necrosis factor (TNF) inhibitors and other biologic disease-modifying antirheumatic drugs, including a comparable risk of cardiovascular disease (CVD) compared with TNF inhibitors.

In the 2019 ENTRACTE study, patients receiving either tocilizumab or etanercept, a TNF inhibitor, had no significant differences in risk of major adverse cardiovascular events (HR, 1.05; 95% CI, 0.077-1.43) or cardiovascular-related death (HR, 1.03; 95% CI, 0.64-1.63). Other findings included a lower but insignificant trend of myocardial infarction (HR, 0.89; 95% CI, 0.54-1.49) with tocilizumab, a higher but nonsignificant incidence of nonfatal stroke (HR, 1.53; 95% CI, 0.80-2.92) with tocilizumab, and a small nonsignificant difference in incidence of hospitalized heart failure (HR, 1.50; 95% CI, 0.61-3.67).

Data also show favorable safety in RA-associated interstitial lung disease and that tocilizumab is fit for people with overweight or obesity. Data remain unclear on whether tocilizumab is suitable for patients who are pregnant or breastfeeding.

Complementary data coming from the real-world use of tocilizumab has pointed to the impact of certain behaviors on treatment response. For example, one real-world study found that smoking is not associated with a worse response to the treatment.

These studies also add insight into types of patients more likely to have a better response to treatment. The same retrospective observational study, which assessed data from patients visiting 5 academic centers in France in 2014, found that younger age, high baseline C-reactive protein level, and no history of CVD were predictors of better treatment response.2

More recently, a 2022 observational study of 337 real-world patients in Europe showed that the monoclonal antibody is more likely to yield a better response in patients younger than 75 years and in patients who had never before received a biologic treatment.3

Notable adverse events of tocilizumab include serious infections, neutropenia, and diverticulitis, all of which, explain the researchers, are expected due to the treatment’s mechanism of action.

The researchers also highlighted emerging data pointing to a broader impact of tocilizumab.

“Emerging evidence suggests that [tocilizumab] may exert significant cardiovascular benefits beyond its established role in managing RA,” noted the researchers. “By targeting IL-6, [tocilizumab] not only reduces systemic inflammation but also influences key mediators of cardiovascular risk, such as endothelial dysfunction, monocyte activity, neutrophil extracellular trap (NET) formation (NETosis), and oxidative stress—principal drivers of atherosclerosis and CVD.”

In one study, tocilizumab showed improvements in endothelial function and reduced oxidative stress and reduced low-density granulocytes.

References

1. Parisi S, Ditto MC, Ghellere F, et al. Update on tocilizumab in rheumatoid arthritis: a narrative review. Front Immunol. Published online February 23, 2025. doi:10.3389/fimmu.2025.1470488
2. Pers Y-M, Fortunet C, Constant E, et al. Predictors of response and remission in a large cohort of rheumatoid arthritis patients treated with tocilizumab in clinical practice. Rheumatology. 2024; 53(1):75-84.
3. Nagy G, Géher P, Tamási L, et al. Real-world evidence on methotrexate-free subcutaneous tocilizumab therapy in patients with rheumatoid arthritis: 24-week data from the SIMPACT study. Rheumatol Adv Pract. 2022;6(2):1-13