Success of infliximab discontinuation depends on disease activity at the start of treatment

This tailored treatment strategy did not statistically increase sustained remission after 1 year discontinuation.

Rheumatoid arthritis is a chronic inflammatory disease that affects a person’s joints, causing pain and possible disability. Rheumatoid arthritis affects people of all ages, and is more common in women than men. Treatments for rheumatoid arthritis aim to improve symptoms and stop joint damage from happening. This includes a specific treatment goal called remission. This means a person no longer has any evidence of rheumatoid inflammation. Remission is measured by monitoring symptoms and looking at what the patient reports about their disease and how it is affecting them.

Targeted biologic drugs (also called bDMARDs) have been developed for the treatment of rheumatoid arthritis. These include TNF inhibitors such as adalimumab, etanercept, infliximab, golimumab and certolizumab-pegol. These drugs 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. TNF inhibitors are given as an injection or infusion. Once people have achieved remission, it is possible to consider reducing the dose, or stopping taking the TNF inhibitor. This reduces costs and minimises the risk of getting side effects.

What did the authors hope to find?
The authors hoped to find out whether people could achieve clinical remission with a “programmed” treatment, compared to the standard treatment.

Who was studied?
The study looked at 337 people with rheumatoid arthritis being treated in 50 hospitals in Japan. Everyone was over the age of 18, and they all had active disease despite taking at least 6 mg per week of methotrexate. People could not take part if they had tried infliximab before, if they were taking high doses of steroids, if they had an infection, or if they had a different type of rheumatic disease other than rheumatoid arthritis.

How was the study conducted?
This was a randomised, open-label trial, which means that patients were assigned by chance to one of two treatment groups to receive the programmed or standard treatment. Using chance in this way means that the groups are similar and allows the variable or treatment under investigation to be compared objectively. During the study, both the patients and their doctors knew which treatment they were taking.

The standard treatment group was given infliximab at the normal dose. The normal dose is worked out depending on a person’s weight, with 3 mg given for every kilogram of bodyweight. This standard dose was given at the start of the study, after 2 and 6 weeks, and then once every 8 weeks until they had received 54
weeks of treatment.

The people in the programmed group were also given a normal dose of 3 mg/kg at weeks 0, 2 and 6, but after this time they got a different dose depending on the levels of TNF in their blood. If TNF levels were low, they stayed on the standard infliximab dose. People with intermediate levels of TNF had their infliximab dose increased to 6 mg/kg every 8 weeks. And people with high levels of TNF in their blood had their infliximab dose increased to 6 mg/kg until 22 weeks into the study, and then increased again to 10 mg/kg until 54 weeks.

After 54 weeks, people in both groups could stop treatment if they had achieved remission. The authors carried on monitoring these off-treatment people until 158 weeks to see whether they would stay in remission, or if their disease would come back. The main measurement the authors were looking at was how many people
were still able to stay off treatment at 106 weeks.

What were the main findings of the study?
After 54 weeks, more people in the programmed group achieved remission than in the standard group (39.4% compared to 32.3%). The main finding was at week 106, the sustained discontinuation rate was not significantly different between the two groups: 23.5% for the programmed group, and 21.6% for the standard group. They
also found that people’s disease activity at the start of the study could be used to predict whether they would have successful long-term remission when they came off treatment. Finally, the authors found that people did better on infliximab when their disease was already under some control with methotrexate before they started.
Overall, the results suggest that it is possible to stop taking infliximab after 1 year of treatment in about 60 to 70% of people who have achieved remission. This means some people will be able to have breaks from treatment.

Are these findings new?
No, tapering studies have been done before, but many of the details and implications are new.

What are the limitations of the study?
The way the study was designed meant that it was not possible to increase a person’s dose until week 14. This was because of rules put in place by the Japanese government about how these drugs are used. It is possible that this limited how well the programmed treatment strategy worked, because the early weeks of treatment may be the most important period. In addition, there were some technical problems with the different numbers of vials that had to be prepared when people were treated with different doses.

What do the authors plan on doing with this information?
The authors are working on another study to investigate dose reductions and withdrawal of different types of drugs in people with rheumatoid arthritis.

What does this mean for me?
If you have rheumatoid arthritis, there are a lot of different treatments available for you. In the future, it may be possible to tailor these better rather than using the same approach for everyone. In this study, blood tests were used to measure TNF levels and then decide on the best dose to use in an individual, rather than just using one standard dose for everybody. This study also suggests that it might be possible to have treatment holidays when your disease is in remission. However, more research is needed to work out who this will suit, and exactly how it should be done.

If you have any concerns about your disease or its treatment, you should talk to your doctor. It is very important that you do not stop taking any medicine you have been prescribed without getting proper medical advice.

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Date prepared: January 2020
Summary based on research article published on: 19 October 2019
From: Summary from Tanaka Y, et al. Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: the RRRR study, a randomised controlled trial. AnnRheum Dis 2020;79:94–102. doi:10.1136/annrheumdis-2019-216169

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