A Retrospective Cohort Study on the Risk of Serious Infections in Rheumatoid Arthritis Patients Receiving Tocilizumab

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether the risk of serious infections in rheumatoid arthritis patients with tocilizumab is higher than in those with tumor necrosis factor inhibitors using the nationwide real-world data.

Detailed Description
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This observational, retrospective cohort study using the Korean National Health Insurance (NHI) data will evaluate whether the risk of serious infections (SIs) in rheumatoid arthritis patients treated with tocilizumab is higher than in those with tumor necrosis factor inhibitors. We will compare incidence rates between two groups and estimate relative risks of SIs in tocilizumab users using the time-dependent Cox proportional hazard regression. Various covariates potentially related to RA severity and occurrence of infection will be assessed and used for adjustment.

Official Title
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A Retrospective Cohort Study to Examine the Risk of Serious Infections in Rheumatoid Arthritis Patients Receiving Tocilizumab Compared With Tumor Necrosis Factor Inhibitors Using the National Health Insurance Database

Conditions
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Infection, Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Tocilizumab
* Drug: Tumor Necrosis Factor Inhibitor (etanercept, infliximab, adalimumab, and golimumab)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who had a diagnosis of rheumatoid arthritis (ICD-10 codes: M05-06) between 2013 and 2018 Exclusion Criteria: Individuals less than 18 years of age Having no records of prescription of tocilizumab or TNFi at least once between 2013 and 2018

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tocilizumab initiators<br>Patients over 18 years of age with a diagnosis of RA (ICD-10 codes: M05-06) and receiving tocilizumab at least once from January 2013 to December 2018. Tocilizumab initiators are required to have no record of tocilizumab within 1 year prior to the first prescription of tocilizumab. | Drug: Tocilizumab<br>* A humanized monoclonal antibody against the interleukin-6 receptor, which is mainly for the treatment of rheumatoid arthritis.<br>* Other names: ACTEMRA;|
| Tumor necrosis factor inhibitors (TNFi) users<br>Patients over 18 years of age with a diagnosis of RA (ICD-10 codes: M05-06) and receiving TNFi at least once from January 2013 to December 2018. TNFi users will be patients who had no record of tocilizumab and given specific TNFi during 1 year before the first prescription of TNFi. | Drug: Tumor Necrosis Factor Inhibitor (etanercept, infliximab, adalimumab, and golimumab)<br>* Tumor Necrosis Factor inhibitors (TNFi) are a group of medicines that suppresses the physiologic response to TNF, a protein involved in early inflammatory events. We will include etanercept, infliximab, adalimumab, and golimumab as TNFis since these drugs are commercialized in Korea.<br>* Other names: ENBREL, REMICADE, HUIMIRA, and SIMPONI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hazard ratio for serious infections | The ratio of the hazard rates of the serious infections in tocilizumab initiators vs. TNFi users | January 2013 to December 2018 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hazard ratio for six subdivided groups of serious infections by organ class | The ratio of the hazard rates of six subdivided organ-specific serious infections (respiratory tract, gastrointestinal tract, urological and gynecological infections, skin and subcutaneous tissue, sepsis, and others) in tocilizumab initiators vs. TNFi users | January 2013 to December 2018 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tocilizumab, Serious Infection, Rheumatoid Arthritis, Tumor necrosis factor inhibitors