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Clinical, Real-World Data Support Importance Of Tocilizumab For RA
Tocilizumab has emerged as a key treatment for rheumatoid arthritis, showing efficacy, safety, and potential cardiovascular benefits in recent studies.
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
TNF Inhibitor Use In RA With Early-Stage Cancer Does Not Decrease Survival
Patients with rheumatoid arthritis (RA) who receive tumor necrosis factor (TNF) inhibitors after being diagnosed with early-stage colorectal, lung, or prostate cancer have similar survival outcomes as those who receive conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or no DMARDs, according to study results published in The Lancet Rheumatology.
Researchers assessed the impact of TNF inhibitor use during the 3 years after being diagnosed with early-stage cancer among patients with RA.
Data for the retrospective cohort study were sourced from the Surveillance, Epidemiology, and End Results Medicare-linked dataset. Patients aged 66 years or older who were diagnosed with localized or regional colorectal, lung, or prostate cancer between 2008 and 2019 were eligible for inclusion. Patients were grouped based on their treatment within the first year after cancer diagnosis: TNF inhibitors, csDMARDs, or no DMARDs. The study employed Cox regression models, adjusted by propensity scores, to compare 5-year overall and cancer-specific survival estimates.
Among the 1981 included patients with RA, 514 (mean age, 76.1 years; 75% women; 79% White) had colorectal cancer, 864 (mean age, 74.8 years; 73% women; 86% White) had lung cancer, and 603 (mean age, 73.1 years; 82% White) had prostate cancer. The use of TNF inhibitors during the first year postdiagnosis was observed among 16%, 12%, and 20% of patients with colorectal, lung, and prostate cancer, respectively.
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Patients with these early-stage cancers might be able to continue or start treatment with TNF inhibitors after discussion with their health-care providers.
Across all 3 cancer types, TNF inhibitor use was not linked to worse survival outcomes at any of the 3 key time points — 1-, 2-, or 3-years postdiagnosis.
For colorectal cancer, 5-year overall survival estimates were 62% for csDMARD users, 68% for no DMARD use, and 71% for TNF inhibitor users (P =.22). The adjusted hazard ratio (HR) for overall survival during the first year of treatment was 0.72 (95% CI, 0.43-1.21), when comparing TNF inhibitor users vs the other treatment groups.
Among patients with lung cancer, the 5-year survival estimates were 39%, 38%, and 49% across the TNF inhibitor, csDMARD, and non-DMARDs groups, respectively (P =.25), with an HR of 0.70 (95% CI, 0.49-1.00). Notably, in the 3-year analysis, TNF inhibitor use was associated with improved survival (HR, 0.58; 95% CI, 0.34-0.96). For prostate cancer, no significant survival differences were observed among treatment groups (HR, 0.80; 95% CI, 0.44-1.44).
Glucocorticoid use, particularly at doses of 7.5 mg/day or higher, was linked to significantly worse survival outcomes across all cancer types. The HRs for overall survival ranged from 1.75 to 2.91, depending on the cancer type.
Study limitations include the observational design and reliance on administrative data, potential residual confounding, and the inability to assess disease activity or cancer progression metrics beyond mortality.
"Patients with these early-stage cancers might be able to continue or start treatment with TNF inhibitors after discussion with their health-care providers," the study authors concluded.
This article originally appeared on Rheumatology Advisor
JAK Inhibitors Linked To Increased Lung Cancer Risk In Older Patients With RA
Janus kinase (JAK) inhibitors are associated with an increased risk for lung cancer but not overall cancer among older patients in the United States with rheumatoid arthritis (RA), according to study findings published in Rheumatology.
Rheumatoid arthritis is a chronic autoimmune disease that requires long-term immunosuppressive therapy, raising concerns about its impact on cancer risk. Therefore, researchers conducted a retrospective case-control study comparing cancer risks among patients with RA who received JAK inhibitors, tumor necrosis factor (TNF) inhibitors, and other biologic disease-modifying antirheumatic drugs (bDMARDs).
Data were sourced from the Surveillance, Epidemiology, and End Results-Medicare database. Patients with RA aged at least 65 years who were diagnosed with cancer between 2014 and 2019 (cases) were eligible for inclusion, along with cancer-free controls.
The study included 12,463 patients with RA and cancer and 38,345 cancer-free controls. The median patient age at cancer diagnosis or control selection was 76 years. The majority of patients from the cancer and control groups were women (70.8% and 80.5%) and White (85.7% and 80.5%); the median RA duration was 4.8 years among both groups.
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The inverse association between breast cancer and [JAK inhibitor] exposure should be interpreted cautiously due to lack of a clear mechanism and support from randomized trials, and it warrants further investigation.
Among all participants, 95.3% had received conventional synthetic DMARDs. Janus kinase inhibitors were prescribed to 1.9% of patients with cancer and 2% of controls, with a median exposure duration of 1.8 years. Tumor necrosis factor inhibitors were used among 27.6% of patients with cancer and 28.0% of controls, while 10.9% and 11.3% received other bDMARDs, respectively.
Overall, JAK inhibitor exposure was not associated with an increased risk for cancer (adjusted odds ratio [aOR], 1.04; 95% CI, 0.87-1.26). Similarly, TNF inhibitors (aOR, 0.98; 95% CI, 0.92-1.05) and other bDMARDs (aOR, 0.98; 95% CI, 0.90-1.07) showed no significant association with total cancer incidence.
However, JAK inhibitor use was linked to a significantly increased risk for lung cancer (OR, 1.40; 95% CI, 1.06-1.87). This risk was particularly elevated among men (OR, 2.12; 95% CI, 1.14-3.94) and patients with more than 2 years of JAK inhibitor exposure (OR, 1.52; 95% CI, 1.01-2.28).
Conversely, JAK inhibitor exposure was associated with a decreased risk for breast cancer among women (OR, 0.62; 95% CI, 0.39-0.97). This reduction was more pronounced among estrogen receptor-positive cases, though further research is needed to confirm these findings.
TNF inhibitor use was not associated with an increased risk for any specific cancer type. Exposure to other bDMARDs was linked to a decreased risk for non-Hodgkin lymphoma (OR, 0.75; 95% CI, 0.59-0.95).
Study results are limited by the observational design and reliance on Medicare claims data, which lack information on key confounding factors such as smoking status. Additionally, JAK inhibitor exposure duration was relatively short, making it difficult to assess long-term cancer risks.
"The inverse association between breast cancer and [JAK inhibitor] exposure should be interpreted cautiously due to lack of a clear mechanism and support from randomized trials, and it warrants further investigation," the researchers concluded.
This article originally appeared on Rheumatology Advisor
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