Risk of some types of serious bacterial infection are higher with tocilizumab than TNFi

Serious bacterial infection, skin and soft tissue infection, and diverticulitis are more common with tocilizumab than TNFi, but there is no overall difference in the rates of serious infection including bacterial, viral or opportunistic infection.

Rheumatoid arthritis is a chronic inflammatory disease that affects a person’s joints, causing pain and disability. It can also affect internal organs. Rheumatoid arthritis is more common in older people, but there is also a high prevalence in young adults, adolescents and even children, and it affects women more frequently than men. People with rheumatoid arthritis are more at risk of getting infections than people who do not have the disease. This is because of the way rheumatoid arthritis affects the immune system.

Biologics are a group of medicines that work by targeting specific molecules that cause inflammation. By doing so, they reduce inflammation in the joints and decrease pain and disease worsening in rheumatoid arthritis. Because of the way they work, biologic medicines can increase the risk of getting both viral and bacterial infections. Some types of infections are described as ‘serious’ or ‘opportunistic’. Serious infections include septicaemia (blood poisoning) or pneumonia. Opportunistic infections include tuberculosis, some types of lung infection, and herpes zoster (shingles). It is important for both doctors and their patients to understand the risks of getting these types of infections when taking biologic medicines.

What did the authors hope to find?
The authors wanted to find out how often people with rheumatoid arthritis get serious or opportunistic infections when they are taking different types of biologic medicine.

Who was studied?
The study looked at over 60,000 people with rheumatoid arthritis treated in clinics in the US between 2010 and 2015. Everyone was over the age of 18 and had already tried at least one other medicine for their rheumatoid arthritis. People who had already had a recent infection or a malignancy (cancer) before they started biologic treatment were not included.

How was the study conducted?
This was a retrospective observational study, which means that the authors used existing databases of patient records to look back and find people for each group. There was no interventional treatment given as part of this study.

The authors used three healthcare insurance databases and looked at the records of people with rheumatoid arthritis who started taking either tocilizumab, abatacept, or a tumour necrosis factor inhibitor (often shortened to TNFi) after they had already used another biologic or a drug called tofacitinib, one of the so called targeted synthetic DMARDs. From the patient records, the authors worked out how many people had been hospitalised for a serious infection, and what the specific types of infection were.

What were the main findings of the study?
In total there were 618 serious infections in 16,074 patients taking tocilizumab and 1,155 in 33,109 patients taking TNFi. The authors found that there was no difference in the risk having to stay in hospital with a serious infection in people who started taking tocilizumab or a TNFi. However, there was a higher risk of getting a very specific serious bacterial infection, namely a skin or soft tissue infection, or a gut infection called diverticulitis with tocilizumab compared to TNFi. The risk of serious infections was also higher in people taking tocilizumab than in those taking abatacept.

Are these findings new?
To the best of our knowledge, this is the largest study directly comparing the serious infection risk of tocilizumab versus other biologics in people with rheumatoid arthritis.

What are the limitations of the study?
The authors used a statistical method to take into account more than 70 variables, but it is possible that there could still be some bias in the results. This is because the infection risk might be affected by things other than the medicines being studied. For example, how long people had rheumatoid arthritis for and how severe it was, as well as things like whether they smoked and drank, or were overweight. However, not all of this information was available in the databases used, so it was not possible to include it in the analysis. It is also possible that people on tocilizumab had taken more previous medicines than the people in the TNFi group, which could also have affected the results. A further limitation is that the study relied on the historical information in the patient records, and it is possible that the wrong diagnosis codes could have been used for infection types. There could also be bias if doctors had decided to hospitalise patients with infections because they were taking certain medicines, rather than because of how serious the infection was. Finally, the study did not look at how long infections took to get better, or whether they came back.

What do the authors plan on doing with this information?
The authors are planning a new study to look at the risk of serious infection in people taking either biologics or a other so called targeted-synthetic DMARDs.

What does this mean for me?
If you have rheumatoid arthritis, the disease means that you have a higher risk of getting some types of infections. Some of the medicines used to treat rheumatoid arthritis – such as tocilizumab and other drugs – can increase that risk. It is important to understand that the numbers of people who get serious infections are small. Your doctor should talk to you about the risks as well as the benefits, and you should decide together which medicine is right for you. People who have an increased risk of infection (such as those who have had certain infections in the past, or who get repeat infections) will be closely monitored by their doctor while they are taking biologic medicines.

It is very important that you do not just stop taking any medicines you have been prescribed. If you have any concerns about your disease or its treatment, you should talk to your doctor.

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Date prepared: April 2019
Summary based on research article published on: 24 January 2019
From: Pawar A, et al. Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study.
Ann Rheum Dis 2019;78:456–464. doi:10.1136/

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