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