CLARITY

Lead researcher: Dr Tariq Ahmad (Royal Devon & Exeter Hospital)

What is the trial looking at?
What are antibodies?
What are T cells?
Why are the researchers looking at vedolizumab and infliximab?
What has the research found so far?
What does this mean for people with Crohn’s or Colitis?
What does this mean for vaccination?
What if I don’t make antibodies after vaccination?
Can I have my second vaccine dose sooner?
I’ve only had my first vaccine dose - is it safe for me to go to work?
Should I stop taking my infliximab or other medicines?
Should I switch from infliximab to vedolizumab?
Can I have an antibody test?
Can I have a T cell test?
What is Crohn’s & Colitis UK doing in response to this research?
Next steps for this research


What is the trial looking at?

The CLARITY trial is looking at the impact of two biologic medicines (infliximab and vedolizumab) on COVID-19 infection, vaccination and immune response in people with Crohn’s or Colitis. The study also takes into account other medicines that people may be taking alongside their infliximab or vedolizumab, for example azathioprine or methotrexate. The researchers want to see if people on these medicines produce the same immune response to coronavirus and to coronavirus vaccines.

CLARITY is a one year study led by the IBD research team at the Royal Devon and Exeter NHS Foundation Trust and the University of Exeter Medical School. The study involves 6,935 patients from 92 UK hospitals. Crohn’s & Colitis UK are supporting this research.

Researchers are using blood samples collected since the start of 2020 to look at differences in positive antibody rates between people with Crohn’s or Colitis on different drugs, and then look at what happens people have the first and second doses of their coronavirus vaccines. 


What are antibodies?

Your body makes antibodies when you get an infection, like coronavirus, or after you have had a vaccination. Antibodies, along with other parts of the immune system, help your body to fight the infection. If antibodies stay in your blood, the next time your body comes into contact with coronavirus, they may help to fight the infection off and keep you well. You need a good level of antibodies in your blood to help fight off an infection.

But not everyone makes antibodies in response to infection or being vaccinated. Some people test positive to coronavirus but do not make antibodies. And some people might not make antibodies after being vaccinated. Even without antibodies, you may still be protected against coronavirus by other parts of the immune system. 


What are T cells?

T cells are a type of white blood cell that, along with other parts of the immune system, play an important role in helping your body to fight infections, such as coronavirus. There are different types of T cells. Each works in a different way to help your immune system. They help to recognise an infection and alert other parts of the body. Some T cells help the body to produce antibodies. Other T cells attack infected cells, stopping the virus spreading to healthy cells. Your body makes T cells when you get an infection, like coronavirus, and when you are vaccinated. It is not known how long the T-cell response to the virus or vaccination lasts, but it is likely that it will last longer than the antibody response.


Why are the researchers looking at vedolizumab and infliximab?

Vedolizumab and infliximab are both types of biologic medicine. Biologic medicines work by blocking some parts of the immune system – which reduces the inflammation in Crohn’s and Colitis.

The researchers will compare the level of antibodies made by people taking vedolizumab with people taking infliximab. This is because vedolizumab works specifically on immune cells in the gut, whereas infliximab can affect the immune response throughout the whole body.
 


What has the research found so far?

Making antibodies after coronavirus infection

The researchers found that people on infliximab and vedolizumab were just as likely to catch coronavirus as the general population.

People taking vedolizumab were more likely to have antibodies to coronavirus than people taking infliximab. People taking an immunomodulator, like azathioprine, as well as infliximab were the least likely to have antibodies after being infected with coronavirus.

Making antibodies after coronavirus vaccination

After one vaccine dose:

People taking vedolizumab were more likely to make a good level of antibodies after their first vaccine dose than people taking infliximab. Only around 1 in 3 people taking infliximab made a good level of antibodies after their first vaccine dose.

People that had been infected with COVID-19 before their vaccine were more likely to produce a higher level of antibodies after their first dose of vaccine.

After two vaccine doses with no previous COVID-19 infection:

After two doses of vaccine, people taking vedolizumab generally had a good antibody response which lasted up to 16 weeks after their second vaccine dose. This is similar to the response seen in the general public so far.

However, people taking infliximab had much lower antibody levels after their second dose. Their antibody levels were five times lower than the levels seen in those taking vedolizumab. By 14 weeks after their second dose, these antibody levels had dropped to very low levels.

In about 1 in 20 people taking infliximab an antibody response was not detected after two vaccine doses. In comparison, an antibody response was not detected in about 1 in 100 people taking vedolizumab after two vaccine doses.

In this study people aged 60 years or over, those taking thiopurine or methotrexate as well as their infliximab or vedolizumab, and current smokers generally had lower antibody levels after two vaccines. However, people from non-white ethnicities made more antibodies than people of white ethnicities after their first and second vaccine doses.

It was also noted that people with Crohn’s, rather than Colitis or unclassified IBD (IBDU), tended to have slightly lower antibody level concentrations. It is difficult to say if it is the Crohn’s itself that caused a lower antibody response or if other complicating factors were involved, such as flare ups or anaemia.

After two vaccine doses and previous COVID-19 infection:

In both groups, people who had previously been infected with COVID-19 had higher levels of antibodies after their second vaccine. The response in these people also lasted longer than in those who had not been previously infected.

T cell response

T cell response, another part of the immune system, is more difficult to test than antibody response. T cell response was only tested in a percentage of the whole group in the study (about 1 in 5) and was only tested in the group that had not been previously infected with COVID-19. After two doses of vaccine T cell levels were about the same in both the infliximab and vedolizumab groups. For both groups, 1 in 5 people did not develop a T cell response.

There did not seem to be a connection between antibody and T cell response. Some people that had no antibody response, had a good T cell response, and vice versa. 

A small minority of people had both a low antibody and a poor T cell response after two vaccines.


What does this mean for people with Crohn’s or Colitis?

The CLARITY results are an important step in helping us understand how different medicines for Crohn’s and Colitis affect a person’s response to coronavirus and to coronavirus vaccines.

Reassuringly, the CLARITY study has found no evidence that people taking infliximab are more likely to catch coronavirus, or have more serious illness from coronavirus, even if antibodies are lower. 

The results mean that people taking vedolizumab may be better able to fight off coronavirus than people taking infliximab or other anti-TNF medicines. But there is not enough evidence to say for certain if this is true, as antibodies cannot necessarily tell us whether someone is protected against coronavirus.

We still don’t know what a reduced antibody response means in real life. We don’t know if having a higher antibody response makes you less likely to catch or be ill from COVID-19. The groups that have higher antibody and T cell response are more likely to have better protection, but this does not mean that those with no response have no protection. It is not known if having antibodies stops you getting the virus again. People who produce antibodies may still be vulnerable to coronavirus.

Though the study showed 1 in 5 people taking infliximab or vedolizumab did not produce a T cell response after the two doses of vaccine, we don’t know how this compares to the general public yet. It is reassuring though that the majority did have a T cell response.

We know that antibody response increases after a second dose of vaccine. People taking infliximab may want to take extra precautions or follow social distancing measures until two weeks after their second dose. You may also want to carry on taking some precautions after your second dose as well.

What is also important is that antibody response is highest after a third exposure (infection with the virus and two doses of vaccine). This means that a booster programme is likely to increase the chances of people taking infliximab having a good antibody response.

We know that a very small group of people will not make an antibody or T cell response after two doses of vaccine. Unfortunately, it is not possible to predict who will or won’t respond to the vaccine. We don’t yet know yet if this small group would make a response after three doses.  


What does this mean for vaccination?

It is strongly recommended that you have both coronavirus vaccine doses when offered (if you have not already done so), regardless of which medicine you take or if you have had coronavirus before.

People taking infliximab have much better antibody response after two vaccines which means it is important to take get your second dose when you can. You may also want to take extra precautions until two weeks after your second dose, as this is the time when your antibody response is likely to kick in.

This study strongly suggests that having three exposures gives a much higher level of antibodies. Those antibody levels also seem to last longer. This was seen in both the infliximab and vedolizumab groups. This suggests that a vaccine booster programme, giving people a third vaccine dose will result in a higher and longer lasting antibody response.

A booster programme has been recommended by the Joint Committee on Vaccination and Immunisation (JCVI) but not yet finalised by the UK government. See more information here.

This study does not tell us the best length of time to wait between a second and third dose. Nor does it tell us if mixing different types of vaccine gives someone a better chance of an immune response. These are both areas that need further research before we can give more information.

We do know that no vaccine is 100% effective for everyone. Even if the vaccine works less well for a small number of people, it will still offer far greater protection than not having the vaccine.

To find out more about the coronavirus vaccine for people with Crohn’s or Colitis, please see our vaccine information.  


What if I don’t make antibodies after vaccination?

As discussed above, antibodies are not the only way your body can protect you from viruses.

No vaccine is guaranteed to work for everyone. All adults in the UK are being offered the vaccine, meaning that you are less likely to come into contact with coronavirus.  Some people with Crohn’s or Colitis will still be at increased risk of getting coronavirus or developing severe illness if they do catch it. Find out more about your level of risk, and what you can do to lower your risk of getting COVID-19.


Can I have my second vaccine dose sooner?

It is recommended that your second vaccine dose is given eight weeks after your first vaccine dose. This is based on guidance set out by the JCVI.

Currently, it’s unlikely you’ll be able to have your second vaccine dose earlier than when you are invited. If you are about to start taking an immunosuppressant medicine, it’s advised that you have both vaccine doses before starting treatment. In this case you should have your second vaccine dose sooner than eight weeks, so your immunosuppressant treatment is not delayed. You can read more about this here.

We understand that you may be worried about having to wait for your second vaccine dose. It’s advised that you continue to take all possible precautions to keep safe – such as social distancing and good hygiene measures (such as frequent handwashing). Additionally, all those who live with people at high risk (clinically extremely vulnerable) can now get their first vaccination. 


I’ve been vaccinated - is it safe for me to go to work?

Not everyone with Crohn’s or Colitis is at higher risk of complications from coronavirus. Check your risk using our decision tree.

If you’re at high risk or moderate risk, your employer must take extra precautions to keep you as safe as possible at work. See our detailed information on going to work, including a letter of support you can share with your employer. 


Should I stop taking my infliximab or other medicines?

No. Stopping your medicine could result in a flare-up, which puts you at high risk of serious complications from COVID-19. There has been no strong evidence to suggest that people taking infliximab or any other biologic medicine have worse outcomes from coronavirus, even if antibodies are lower. 


Should I switch from infliximab to vedolizumab?

Some people who take infliximab may be wondering whether they should change medications. For the moment it is not advised to change but you may want to speak to your IBD team about this. There is not any guidance yet on this issue as the research is so new. This may change and we will update our information if it does.

It is important to remember that vedolizumab does not work for everyone. If infliximab is working for you at the moment it may be more risky to change to another drug.


It is worth remembering that most people on infliximab do get some antibody or T cell response from having two doses of the vaccine, even if the levels do start to drop. There is no evidence at the moment to suggest you are at more risk of developing serious complications from COVID-19 if you are taking infliximab or vedolizumab.


Can I have an antibody test?

Antibody tests are not widely available yet on the NHS. You can pay to have a test at a private clinic if you want to. To read more about antibody testing, see our information here.


Can I have a T cell test?

Testing T cell response is technically very difficult and not widely available.  Like antibody testing, it cannot tell you your level of immunity.


What is Crohn’s & Colitis UK doing in response to this research?

Crohn’s & Colitis UK will use the results to make sure the needs of people with Crohn’s and Colitis are heard at the highest levels. This includes prioritising the booster vaccine for those who are on immunosuppressants or are high risk and protection in the workplace. See our recent news story for more information. 


Next steps for this research

The CLARITY researchers will be monitoring how long the antibodies last after coronavirus vaccination in people taking infliximab or vedolizumab.

If you would like more information on this study please contact: rde-tr.clarityibd@nhs.net or visit @CLARITYIBD