Tocilizumab vs. Rituximab: Similar Outcomes in RA-ILD Over 5 Years
March 11, 2026
2 min read
Comparable Mortality Risks Seen with Tocilizumab and Rituximab in Rheumatoid Arthritis-Associated Interstitial Lung Disease
Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) experience similar risks of death, hospitalization, and the need for mechanical ventilation whether treated with tocilizumab or rituximab, a recent study indicates. The findings, published in CHEST, suggest both medications offer comparable effectiveness in managing this complex condition. However, researchers noted potential differences based on baseline inflammatory markers and sex, warranting further investigation.
The study, led by Zewen Wu, MD, of the Third Hospital of Shanxi Medical University, analyzed data from over 2,300 patients within the TriNetX U.S. Collaborative Network database. Researchers employed propensity score matching to create comparable groups of patients receiving either tocilizumab or rituximab, accounting for a range of factors including age, sex, race, lab results, lifestyle, existing health conditions, and medication use. RA-ILD biomarkers are an area of ongoing research.
No Significant Difference in Overall Mortality
The primary outcome of the study – all-cause mortality – showed no statistically significant difference between the two treatment groups. Approximately 16% of patients receiving tocilizumab died over a five-year follow-up period, compared to 17.7% of those receiving rituximab. This consistency extended to hospitalization rates and the need for mechanical ventilation, suggesting a similar overall clinical burden for patients on either therapy.
While the overall risks were comparable, a closer look revealed some intriguing nuances. Researchers found a significantly reduced risk of hospitalization among women receiving tocilizumab compared to rituximab. Conversely, men receiving tocilizumab had a significantly increased risk of requiring mechanical ventilation. However, the authors cautioned that these findings were based on smaller sample sizes and wider confidence intervals, limiting their definitive interpretation.
Inflammation Levels May Influence Treatment Response
Interestingly, the study highlighted the potential importance of baseline inflammatory markers. Patients with elevated levels of these markers at the start of treatment appeared to have a higher risk of mortality and mechanical ventilation when treated with tocilizumab compared to rituximab. This suggests that rituximab might be preferable in individuals presenting with significant inflammation.
The researchers also observed that patients who were treatment-naive to tumor necrosis factor inhibitors (TNFis) experienced a higher risk of mechanical ventilation when treated with tocilizumab versus rituximab. This finding adds another layer of complexity to treatment decisions, suggesting that prior TNFi exposure could influence the relative effectiveness of the two drugs.
Study Limitations and Future Directions
The authors acknowledge several limitations inherent to the retrospective nature of the study. As an emulated target trial using observational data, the findings are susceptible to confounding factors and selection bias. Specifically, the study could not account for variations in RA-ILD subtype (such as usual interstitial pneumonia versus other patterns) or the severity of lung disease as measured by pulmonary function tests. The Lancet Respiratory Medicine has published related research on RA-ILD treatment.
“Given the inherent limitations of retrospective data, these findings should be interpreted cautiously, emphasizing the need for prospective, randomized trials to confirm these observations,” Wu and colleagues wrote. Future research should focus on identifying biomarkers that can predict individual treatment response and tailoring therapy accordingly.
The findings underscore the ongoing challenge of managing RA-ILD, a serious complication of rheumatoid arthritis that can lead to significant morbidity and mortality. While both tocilizumab and rituximab appear to be viable treatment options, careful consideration of individual patient characteristics, including inflammatory markers and prior treatment history, may be crucial for optimizing outcomes. Patients should discuss the risks and benefits of each medication with their rheumatologist and pulmonologist to determine the most appropriate course of treatment. Hospitalization and mortality risks are key considerations in RA-ILD management.
Expert Perspective
Amir A. Razmjou, MD, MSc, Assistant Professor, Division of Rheumatology, UCLA David Geffen School of Medicine, and Greater Los Angeles Veterans Affairs, offered perspective on the study. “There is a significant paucity of high-quality data informing treatment decisions for patients with RA-ILD, with only one published randomized controlled trial in patients with RA-ILD (TRAIL1 study).”
Dr. Razmjou noted that professional societies recommend tocilizumab as a treatment option for RA-ILD, based largely on its effectiveness in systemic sclerosis-associated ILD. He added that the current study’s findings generally align with other observational studies suggesting tocilizumab’s effectiveness.
“However, You’ll see important limitations… including a lack of control for several important variables, including RA-ILD subtype, ILD severity, and RA disease activity.” Dr. Razmjou emphasized that the observed differences based on inflammatory markers warrant further investigation.
References:
Frideres H, et al. Semin Arthritis Rheum. 2025;doi:10.1016/j.semarthrit.2025.152735.
Amir A. Razmjou, MD, MSc
Disclosures: Razmjou reports no relevant financial disclosures.
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