Thread by @charlie_lees

What is the impact of immunosuppression on COVID?

Follow along; I will describe:
• serological response to infection
• vaccines: antibody and T cell responses
• durability of response to vaccine

Data from the 7000 person @clarityibd study
• infliximab vs vedolizumab in IBD

Breakdown of the questions asked and answered in this dataset

Full publications available online
gut.bmj.com/content/70/5/8…
gut.bmj.com/content/early/…
researchsquare.com/article/rs-755…

20 minute video with full explanation here

2 persons on infliximab (anti-TNF) recruited for every 1 on vedolizumab (anti-integrin: no impact on systemic immunity)

= 7000 persons from 92 sites
= 10 weeks of recruitment in q4 2020

All masterminded by @ClaireBewshea

IFX & VEDO pts had similar COVID experiences

We have established above that IFX & VEDO patients had the same COVID experiences

Despite this patients on IFX were
• less like to have antibodies to SARS-CoV-2
• had lower seroconversion rates
• effect was great with combo therapy

Thus attenuated response to infection

What is the impact of infliximab on the immune response to vaccination?

We studied fully vaccinated patients
• 2052 on IFX
• 925 on VEDO

50% had Pfizer / BioNtech (PZ)
50% had Oxford / Astra (AZ)

Different antibody:
Anti-SARS-CoV-2 spike (S) receptor binding domain (RBD)

After one dose of vaccine (5a: left panel)
• patients on IFX do not have protective levels of anti-S RBD antibodies

After two doses of vaccine (5b: right panel)
• patients on IFX have protective levels of antibodies

Antibody levels are 4-5 fold lower on IFX than VEDO

What factors are associated with anti-spike RBD antibody concentration?

Lower levels with:
• infliximab (vs vedo)
• Crohn's disease
• age >60 years
• current smoking
• thiopurines & methotrexate (PZ only)

Durability of anti-spike RBD antibody responses over time:

• antibody levels decay to the seroconversion threshold on IFX after 14 (AZ - top right panel) to 18 weeks (PZ - top left panel)
• no decay seen on vedo

• no decay with prior infection on vedo or IFX (bottom panels)

Vedolizumab responses over time (green boxes) were equivalent to a healthy population without IBD (blue/purple boxes)

Here you can see the lower levels of antibodies to infliximab (orange boxes) and decay over time

Note logarithmic scale

T cells responses are not affected by infliximab

In both IFX and VEDO patients about 20% of persons have no measurable T cell response

Do T cell responses correlate with antibodies?
• yes with PZ
• no with AZ

T cell responses are uncoupled from antibody responses

Here patients are lined up left to right from low to high antibody levels

Most patients with low antibody responses have good T cells responses and so have some protection

To summarise:

Patients with IBD on infliximab
• have protective antibodies after 2 doses of vaccine
• these decay rapidly (14-18 weeks)
• T cell responses are not affected by IFX

Most people with low antibody responses have protective T cells

This likely affects all anti-TNF drugs (infliximab and adalimumab in IBD)

It may affecte azathioprine and mercaptopurine and methotrexate alone but we need to study this

It likely also applies to anti-TNF drugs in inflammatory joint and skin diseases

If you are taking infliximab or adalimumab as monotherapy or in combination with a thiopurine (aza or mp) or methotrexate

• please do not be worried
• continue to take your medicines
• get vaccinated

These data indicate you will need a booster (3rd) dose
• this should work

We are now studying the affect of ustekinumab and tofacitinib and drug combinations in IBD as part of the @VIPStudy1

https://twitter.com/VIPStudy1/status/1418236375363694601?s=20

To learn more please watch the 20 minute video I made explaining these data

If you found this thread helpful please go back to the top and share

https://twitter.com/charlie_lees/status/1424407890014703620?s=20

If you found this helpful please go back to the top and share

https://twitter.com/charlie_lees/status/1424407890014703620