IBD-ENC Group updated position statement on SARS-CoV2 Vaccination in patients with IBD - 30/04/2021

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Introduction: 

The WHO (World Health Organization) on 11th March 2020 declared coronavirus disease COVID-19 as a Global Pandemic, triggering widespread safety measures being adopted by nations all across1. In the last 10 months, the pandemic has caused over 1.9 million deaths and almost 100 million lives got affected, significantly impacting all demographics especially those with comorbidities. Recently, multiple vaccines have been approved for emergency use.

Vaccination rates in IBD patients have not been encouraging in the past. This was due to a perceived lack of benefit, as well as concerns regarding side-effects, risk of disease flares, needle aversion and inconvenience 2,3 Majority of the patients are immune compromised and are on immunosuppressants. Initial data from the SECURE-IBD registry displayed a negative association of corticosteroids with COVID-19 outcomes.4

Understandably, there is a lack of clarity and dilemma regarding the Covid-19 vaccines in IBD patients. The IBD- ENC, therefore, felt the need for a position statement for this highly populous region on the use of Covid-19 vaccination in IBD patients in the light of emerging information.5 As more data becomes available, IBD-ENC will update this position document.

Currently Available Vaccine in the IBD- ENC region

COVISHEILD

COVAXIN

PFIZER

MODERNA

SINOPHARM

SPUTNIK

RECOMMENDATION 1: IBD patients > 16 years’ age should be vaccinated for COVID-19 irrespective of the severity of the disease. Immunosuppression is not a contraindication.

The ChAdOx1 nCoV-19 (Oxford/AstraZeneca) vaccine is approved for use in those aged ≥18 years; however, the UK Joint Committee on Vaccination and Immunisation (JCVI) states that it may be used in 16–17 years of age where there is no access or availability to an alternative approved COVID-19 vaccine.6 Although suboptimal antibody responses are noted in IBD patients with a single dose of vaccination, protective antibody levels are achieved with two doses of vaccination in the majority of IBD patients even those on anti-TNF and anti-integrin agents.7,8


 

RECOMMENDATION 2: All vaccine types appear to be suitable and can be decided on basis of availability and local regulatory approval.

Most of the vaccines have been shown to be safe and effective in IBD patients based on studies. Published data on the efficacy of vaccination in IBD patients is present with mRNA BNT162b2 (Pfizer-BioNTech),ChAdOx1 nCoV-19 (Oxford/AstraZeneca). mRNA-1273 (NIH- Moderna) vaccines. Vaccination leads to protective antibody levels after 2 doses of vaccination in IBD patients irrespective of the type of vaccine.6,7,8


 

RECOMMENDATION 3: In the highly populous IBD-ENC region, vaccine distribution across the general population may have inordinate delays. In view of the immunocompromised state of many IBD patients, a priority status should be given for vaccination.

Since the mortality of COVID-19 infection increases exponentially with age, most of the prioritization of vaccination strategy is based on age alone. Elderly (>60-65 years ) are given priority for vaccination in most countries. IBD is an underlying health condition that puts patients at higher risk of serious disease and mortality and hence vaccination should be prioritised in IBD patients aged 16-64 years.6


 

RECOMMENDATION 4: Active efforts should be taken to disseminate this information across all IBD care providers, practicing physicians, gastroenterologists, and local government authorities.

The uptake of recommended vaccines amongst patients with IBD has been sub-optimal historically.9 There is concerns among IBD patients and physicians regarding the safety and long-term effects of COVID-19 vaccination in IBD. Perceived risk of increased adverse events, the interaction between IBD medications and vaccine, scepticism about long term safety, and lack of typical scrutiny for COVID 19 vaccination are barriers to vaccination in IBD patients.10 Hence dissemination of proper information to IBD patients, all IBD care providers, practicing physicians, gastroenterologists, and local government authorities are required to improve vaccination drive in this subgroup of patients.


 

RECOMMENDATION 5: The risk of an adverse event to COVID 19 vaccination in IBD patients is very low and similar to that of the general population.

In a longitudinal vaccine registry of 246 IBD patients with m-RNA COVID19 vaccination, no increased risk of adverse events was noted. Adverse events were more frequent in patients with prior COVID 19 or young age. Adverse events were less frequent in patients on immunomodulator therapy specially biologics.11


 

RECOMMENDATION 6: IBD patients on immunomodulators have suboptimal antibody responses to vaccination specially after single dose of vaccine. Two doses of vaccine leads to seroconversion in most patients. Delayed second dosing of vaccination should be avoided specially in patients receiving infliximab.

Two recent studies have shown that IBD patients on infliximab and vedolizumab have suboptimal antibody responses to COVID19 vaccination with SARS-CoV-2 spike (S) mRNA BNT162b2 (Pfizer-BioNTech),ChAdOx1 nCoV-19 (Oxford/AstraZeneca) & mRNA-1273 (NIH- Moderna) vaccines. Kennedy NA et al. showed that elderly ( ≥60 years), immunomodulator use, Crohn disease and smoking were associated with lower seroconversion rates. Seroconversion rates were low after single dose if vaccination in patients on infliximab. Seroconversion after a single dose of vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of vaccine.7 Another recent study he showed that despite achieving protective antibody levels, lower antibody levels were seen in patients with vedolizumab for all antibodies tested and with anti-TNFs for anti- receptor binding protein (RBD) total Immunoglobulin only.8

RECOMMENDATION 7: There is need for active research on efficacy of vaccines based on disease severity and type of vaccine

Most of the COVID19 vaccines have not been specifically studied in patients with IBD. Emerging data based on serological data from vaccination registry is shedding some light on efficacy of vaccination in IBD patients specially those on immunosuppressants.7,8 There are, however, no randomized data so far regarding the efficacy of these vaccines in the context of immunosuppression. In view of impaired responses to pneumococcal, influenza, and other vaccines in patients with IBD on immunosuppression, there is a need for studies to understand whether different immunosuppressive regimens impair the development of anti- SARS-CoV-2 immunity in this high-risk population. Studies are also required to aspects whether there is requirement of booster doses of vaccine based on antibody levels. Precision vaccination strategy based on baseline features can predict response to vaccination. Future multi-platform research based on germline genetics, host transcriptional responses, microbiome, metabolome can identify biomarkers predicting vaccination outcome.6


 

References

1. World Health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020

2. Huth K, Benchimol EI, Aglipay M, Mack DR. Strategies to improve influenza vaccination in pediatric inflammatory bowel disease through education and access. Inflamm Bowel Dis 2015; 21: 1761–68.

3. Brenner EJ ,Ungaro RC, Gearry RB et al.Corticosteroids, but not TNF antagonists, are associated with adverse COVID-19 outcomes in patients with inflammatory bowel diseases: results from an international registry.Gastroenterology. 2020; 159: 481-491

4. Kumar A, Quraishi MN, Segal JP, Raine T, Brookes MJ. COVID-19 vaccinations in patients with inflammatory bowel disease. Lancet Gastroenterol Hepatol. 2020 Nov;5(11):965-966.

5. James L. Alexander1,2, Gordon Moran et al . British Society of Gastroenterology on behalf of the IBD section of the British Society of Gastroenterology and the CRG.Inflammatory Bowel Disease section and IBD Clinical Research Group position statement on SARS-CoV2 Vaccination

6. Alexander JL, Moran GW, Gaya DR, Raine T, Hart A, Kennedy NA, Lindsay JO, MacDonald J, Segal JP, Sebastian S, Selinger CP, Parkes M, Smith PJ, Dhar A, Subramanian S, Arasaradnam R, Lamb CA, Ahmad T, Lees CW, Dobson L, Wakeman R, Iqbal TH, Arnott I, Powell N; Inflammatory Bowel Disease section of the British Society of Gastroenterology and the the Inflammatory Bowel Disease Clinical Research Group. SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement. Lancet Gastroenterol Hepatol. 2021 Mar;6(3):218-224. doi: 10.1016/S2468-1253(21)00024-8. Epub 2021 Jan 26. PMID: 33508241; PMCID: PMC7834976.

7. Kennedy NA, Lin S, Goodhand JR, Chanchlani N, Hamilton B, Bewshea C, Nice R, Chee D, Cummings JF, Fraser A, Irving PM, Kamperidis N, Kok KB, Lamb CA, Macdonald J, Mehta S, Pollok RC, Raine T, Smith PJ, Verma AM, Jochum S, McDonald TJ, Sebastian S, Lees CW, Powell N, Ahmad T; Contributors to the CLARITY IBD study. Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD. Gut. 2021 Apr 26:gutjnl-2021-324789. doi: 10.1136/gutjnl-2021-324789. Epub ahead of print. PMID: 33903149; PMCID: PMC8076631.

8. Wong SY, Dixon R, Pazos VM, Gnjatic S, Colombel JF, Cadwell K; ICARUS-IBD Working Group. Serological response to mRNA COVID-19 vaccines in IBD patients receiving biological therapies. Gastroenterology. 2021 Apr 19:S0016-5085(21)00648-X. doi: 10.1053/j.gastro.2021.04.025. Epub ahead of print. PMID: 33887219; PMCID: PMC8055494.

9. Malhi G, Rumman A, Thanabalan R, et al. Vaccination in inflammatory bowel disease patients: attitudes, knowledge, and uptake. J Crohns Colitis 2015; 9: 439–44.

10. Dalal RS, McClure E, Marcus J, Winter RW, Hamilton MJ, Allegretti JR. COVID-19 Vaccination Intent and Perceptions Among Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2021 Feb 4:S1542-3565(21)00105-1. doi: 10.1016/j.cgh.2021.02.004. Epub ahead of print. PMID: 33549869; PMCID: PMC7859624.

11. Botwin GJ, Li D, Figueiredo J, Cheng S, Braun J, McGovern DPB, Melmed GY. Adverse Events Following SARS-CoV-2 mRNA Vaccination Among Patients with Inflammatory Bowel Disease. medRxiv [Preprint]. 2021 Mar 31:2021.03.30.21254607. doi: 10.1101/2021.03.30.21254607. PMID: 33821287; PMCID: PMC8020989