Reply to comment: Screening for active COVID-19 infection prior to biologic therapy in IBD patients: primum non nŏcēre

Abstract

We have read with interest the comments to our article [[1]Zingone F. Buda A. Savarino E.V. Screening for active COVID-19 infection and immunization status prior to biologic therapy in IBD patients at the time of the pandemic outbreak.Dig Liver Dis. 2020; 52 (604-05 2020/05/04)https://doi.org/10.1016/j.dld.2020.04.004Abstract Full Text Full Text PDF Scopus (17) Google Scholar] written by Festa et al “Screening for active COVID-19 infection prior to biologic therapy in IBD patients: let's not increase our uncertainty without reducing our concerns [[2]Festa S. Aratari A. De Biasio F. et al.Screening for active COVID-19 infection prior to biologic therapy in IBD patients: let's not increase our uncertainty without reducing our concerns.Dig Liver Dis. 2020; (2020/06/13)https://doi.org/10.1016/j.dld.2020.05.037Abstract Full Text Full Text PDF Scopus (5) Google Scholar]” recently published on Digestive and Liver Disease. The authors criticized our suggestion to expand the screening commonly recommended prior to the beginning of biologic therapy in Inflammatory Bowel Disease (IBD) patients, to include SARS-CoV-2 RT-PCR and, when available, antibody testing. Although available data do not support an increased risk of contracting COVID-19 infection in IBD patients, a recent report from Italy showed a case fatality rate of 8% and an hospitalization rate of 28% among 79 IBD patients with confirmed COVID-19 followed-up at 24 IBD referral units [[3]Bezzio C. Saibeni S. Variola A. et al.Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study.Gut. 2020; 69 (1213-17 2020/05/02)https://doi.org/10.1136/gutjnl-2020-321411Crossref PubMed Scopus (212) Google Scholar]. The British Society of Gastroenterology and the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) recommendation that IBD patients do not have to stop their current medications in order to prevent infection or adverse outcome with COVID-19 [[4]Kennedy N.A. Jones G.R. Lamb C.A. et al.British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic.Gut. 2020; 69 (984-90 2020/04/19)https://doi.org/10.1136/gutjnl-2020-321244Crossref PubMed Scopus (170) Google Scholar,[5]IOIBD Update on COVID19 for Patients with Crohn's Disease and Ulcerative Colitis [cited 2020 13 July 2020]; Available from: https://www.ioibd.org/ioibd-update-on-covid19-for-patients-with-crohns-disease-andulcerative-colitis/.Google Scholar has recently been incorporated in the expert commentary commissioned by the American Gastroenterology Association institute [[6]Rubin D.T. Feuerstein J.D. Wang A.Y. et al.AGA clinical practice update on management of inflammatory bowel disease during the COVID-19 pandemic: expert commentary.Gastroenterology. 2020; (2020/04/14)https://doi.org/10.1053/j.gastro.2020.04.012Abstract Full Text Full Text PDF Scopus (152) Google Scholar]. Considerations on specific drugs were also provided, although robust evidence on the impact of different immunosuppressive medications on IBD patients during COVID-19 outbreak are lacking. However, there was no specific guidance with respect to COVID-19 testing in patients starting immunosuppressive treatment. Festa et al listed some considerations, which we would like to address point by point. First, the authors underline the need “to have in mind the strategies to adopt in case of positivity”. Currently, there is not a standard approach to adopt in case of COVID-19 positivity, in particular when it is necessary to start a biological therapy, and the decision should be carefully made case by case. In the event of a SARS-CoV-2 positivity, an informed decision can be made to either postpone the start of the biologic therapy by a few days or, if an immediate start is necessary because of a severe disease flare, a multidisciplinary approach with the involvement of infectious disease specialists and/or respiratory physicians should be considered. Indeed, any event occurring after the start of biologic would be better managed if all the information regarding the health status of the subject is known. Another important aspect to consider is the contribution of glucocorticoids to the risk of a negative outcome in patients with COVID-19 active infection [[7]Lukin D.J. Kumar A. Hajifathalian K. et al.Baseline disease activity and steroid therapy stratify risk of COVID-19 in patients with inflammatory bowel disease.Gastroenterology. 2020; (2020/06/02)https://doi.org/10.1053/j.gastro.2020.05.066Abstract Full Text Full Text PDF Scopus (76) Google Scholar], since they are used concomitantly with Infliximab during the induction regimen or often as a bridge therapy before induction to biologic drugs of different class. Second, the authors expressed concerns about the possibility that COVID-19 testing could result in a delay of starting biologic therapy in patients with moderate-severe activity. We are somewhat surprised by this consideration. All IBD centres should follow the recommended pre-biologic screening guidelines [[8]Lamb C.A. Kennedy N.A. Raine T. et al.British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults.Gut. 2019; 68 (s1-s106 2019/09/29)https://doi.org/10.1136/gutjnl-2019-318484Crossref PubMed Scopus (765) Google Scholar] which include latent tuberculosis infection (LTBI) testing and relevant viruses immunization status. These tests require days to be completed (e.g. interferon gamma release assay (IGRA) for LTBI) which is more than the time required to obtain the results from the current widely available rapid oropharyngeal swab tests (less than 24 hours) or serological tests (less than 6 hours). Third, the authors criticised the different approach between patients starting immunomodulatory therapies and those already receiving biological or immunomodulatory agents. We acknowledge that it remains uncertain whether the use of IBD immunosuppressive medications increase the risk for SARS-CoV-2 infection and subsequent COVID-19 [[5]IOIBD Update on COVID19 for Patients with Crohn's Disease and Ulcerative Colitis [cited 2020 13 July 2020]; Available from: https://www.ioibd.org/ioibd-update-on-covid19-for-patients-with-crohns-disease-andulcerative-colitis/.Google Scholar] and that now data from SECURE-IBD, not available at the time of writing the manuscript, do not suggest an increased risk complications of COVID-19 in IBD patients on biologics. However, we did not rule out the opportunity of testing patients on biological therapies. Recently new insights on the contribution of pre-symptomatic and asymptomatic subjects with active infection into transmission dynamics have been highlighted [[9]Lavezzo E. Franchin E. Ciavarella C. et al.Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo'.Nature. 2020; (2020/07/01)https://doi.org/10.1038/s41586-020-2488-1Crossref PubMed Scopus (563) Google Scholar]. Patients receiving immunosuppressive medications could have a delay in viral clearance and thus prolong their transmission potential. This could be particularly important given that most of these patients regularly attend infusion centres and in the near future control measures may be eased. In conclusion, at the time when the understanding of transmission should be improved and active interventions strategies implemented, we strongly believe that all patients should be tested for SARS-COV-2 by oropharyngeal swab before starting immunosuppressive (and immunomodulatory) therapies to avoid potential complications and make informed decisions [[1]Zingone F. Buda A. Savarino E.V. Screening for active COVID-19 infection and immunization status prior to biologic therapy in IBD patients at the time of the pandemic outbreak.Dig Liver Dis. 2020; 52 (604-05 2020/05/04)https://doi.org/10.1016/j.dld.2020.04.004Abstract Full Text Full Text PDF Scopus (17) Google Scholar,[10]Zingone F. Buda A. Savarino E.V. Starting a biologic therapy in IBD patients amidst COVID-19: hold, careful monitoring or testing?.J Crohns Colitis. 2020; (2020/05/20)https://doi.org/10.1093/ecco-jcc/jjaa102Crossref PubMed Scopus (4) Google Scholar,[11]Zingone F. Savarino E.V. Viral screening before initiation of biologics in patients with inflammatory bowel disease during the COVID-19 outbreak.Lancet Gastroenterol Hepatol. 2020; (2020/03/30)https://doi.org/10.1016/s2468-1253(20)30085-6Abstract Full Text Full Text PDF PubMed Google Scholar in line with the “primum non nŏcēre” principle. Fabiana Zingone, MD, PhD: design of the study, writing of the manuscript, approving final version Andrea Buda, MD: design of the study, writing of the manuscript, approving final version Edoardo Savarino, MD, PhD: design of the study, writing of the manuscript, approving final version None All authors declare no conflict of interest for the letter to the Editor titled “Reply to comment: Screening for active COVID-19 infection prior to biologic therapy in IBD patients: primum non nŏcēre” Screening for active COVID-19 infection prior to biologic therapy in IBD patients: Let's not increase our uncertainty without reducing our concernsDigestive and Liver DiseaseVol. 52Issue 11PreviewWe have read with interest the article of Zingone et al. “Screening for active COVID-19 infection and immunization status prior to biologic therapy in IBD patients at the time of the pandemic outbreak” recently published on Digestive and Liver Disease [1]. The authors, using a pragmatic approach, suggest updating the screening commonly recommended prior to the beginning of biological therapy in Inflammatory Bowel Disease (IBD) patients, adding SARS-CoV-2 RT-PCR and, when available, antibody testing. Full-Text PDF Screening for active COVID-19 infection and immunization status prior to biologic therapy in IBD patients at the time of the pandemic outbreakDigestive and Liver DiseaseVol. 52Issue 6PreviewCoronavirus disease 2019 has been recently classified as pandemic infection by the World Health Organization. Patients with inflammatory bowel disease (IBD) are invited to follow the national recommendations as any other person. It is unclear whether a more aggressive clinical course might develop in asymptomatic COVID-19 infected subjects during biological therapy and current evidence does not support treatment suspension. However, during pandemic, the start of treatment with immunosuppressive drugs and biologics should be postponed whenever possible and based on an individual risk assessment. Full-Text PDF