CLARITY

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

What is the trial looking at?
What are antibodies?
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?
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 COVID-19 on people with Crohn’s and Colitis who are taking either infliximab or vedolizumab. 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 antibodies to coronavirus and to coronavirus vaccines.

The CLARITY study is 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 will use serum 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 also look at what happens over the next 12 months as people have their coronavirus vaccines.
 

What are antibodies?

Your body makes antibodies when you get an infection, like coronavirus. 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. Your body also makes antibodies after you’ve had a vaccination.

If you have coronavirus antibodies in your blood, it's likely you've had the virus before. But antibodies cannot always tell you if you have had the virus – 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.
 

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 were least likely to have antibodies if they also take a thiopurine, like azathioprine, alongside their infliximab.

Making antibodies after coronavirus vaccination

People taking vedolizumab were more likely to make a good level of antibodies after their first vaccine dose than people taking infliximab. This was the case for both the Pfizer vaccine and the Oxford/AstraZeneca vaccine. Only around 1 in 3 people taking infliximab made a good level of antibodies after their first vaccine dose.

But, 4 in 5 people taking infliximab made a good level of antibodies after:

  • they'd had their second vaccine dose
  • they'd had one vaccine dose but had previously been infected with coronavirus

So, people taking infliximab needed to ‘see’ the virus twice to trigger a good antibody response – whether that was through two vaccine doses, or through an infection with coronavirus and one vaccine dose.

So far the researchers have only looked at the data for a small number of people taking a second dose of the Pfizer vaccine.

Interestingly, the researchers found that people from non-white ethnicities made more antibodies after their first vaccine dose. Making fewer antibodies after the first vaccine dose was linked to taking an immunomodulator (like azathioprine) in combination with infliximab or vedolizumab, being over 60 years old or being a current smoker.

Watch a video from the research team sharing the results of this study.  
 

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

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. And people taking infliximab made a good antibody response after two vaccine doses.

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

The results may mean that people taking vedolizumab will 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:

  • Antibodies are not the only way your body can protect you against coronavirus. For example, T cells are another important part of the immune system which help to fight off infection. T cells are important for long-term protection against the virus. So people who did not produce antibodies may still be able to fight off coronavirus if they have made T cells.
  • It's not known if having antibodies stops you getting the virus again. People who produced antibodies may still be vulnerable to coronavirus.
  • It’s not known how long antibodies stay in your body. People who produced antibodies may still be vulnerable to coronavirus later.

Because it is not known how well antibodies can protect you, the general population are also being asked to continue to follow government guidance on reducing the risk of infection.

Dr Nick Powell said the CLARITY team is now exploring the role of other elements of the immune system, which may still protect against reinfection. “Although we clearly observed diminished antibody responses in patients taking infliximab, we haven’t yet looked at T-cell or other protective immune responses against the virus. I would expect that even in the presence of less efficient antibody production, infliximab-treated patients will mobilise some protective aspect of their immune system to defend themselves.” 
 

What does this mean for vaccination?

It is strongly recommended that you have both coronavirus vaccine doses when offered, regardless of which medicine you take or if you have had coronavirus before.

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. Even without vaccination, there is no evidence that people with Crohn’s or Colitis are more at risk from coronavirus than the general population.

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. Plus some form of distancing, mask wearing and increased hygiene measures are still likely to be in place in the longer term. These measures are in place to protect the most vulnerable.

If you’re a current smoker and you’re thinking about stopping smoking, see the NHS website for help and advice. You can also read our general information on smoking and Crohn’s and Colitis
 

Can I have my second vaccine dose sooner?

Your second vaccine dose has to be given between 3 and 12 weeks after your first vaccine dose. But, most people will be offered their second vaccine dose closer to 12 weeks after their first – this is based on guidance set out by the Joint Committee on Vaccination and Immunisation (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 12 weeks, so your immunosuppressant treatment is not delayed.

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 hand washing hygiene. Additionally, all those who live with people at high risk (clinically extremely vulnerable) can now get their first vaccination. 
 

I’ve only had my first vaccine dose - 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 safe 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?

There is not enough evidence to recommend switching from infliximab to vedolizumab at this time. Vedolizumab does not work for everyone, and so you may be risking a flare-up if you decide to try it when infliximab is already working well for you. 
 

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. Find out more about antibody testing on GOV.UK
 

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. 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