A patient treated with infliximab for ulcerative colitis associated with COVID-19 reported improvements in the pulmonary picture within a few days. The case described by the gastroenterology team at the ASST Rhodensem Hospital (Milan, Italy) will be published in the journal Gut, and represents a first case that supports the hypothesis of the drug's usefulness in the treatment of COVID-19.
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Many aspects of COVID-19 have not yet been clarified, but it seems now established that, while in most affected patients the disease causes mild flu-like symptoms, in the others it causes serious complications, often fatal, such as progressive pneumonia, acute respiratory distress syndrome (ARDS) and multi-organ failure, sustained by a hyper-inflammatory state and cytokinic storm.
In recent months, numerous studies have been published in gastroenterology journals to analyze inflammatory bowel disease (IBD) in light of this new disease. In the context of IBD, several key issues have been analyzed. For example, the degree of susceptibility of IBD patients to COVID-19 and cytokinic storm syndrome associated with fatal lung lesions. Furthermore, the management of immunosuppression and immunomodulation in IBD patients during the pandemic has been of concern, given the possibility that immunosuppression may affect the progress of COVID-19.
Several issues related to IBD in the COVID-19 context were addressed in the “COVID-19 and Immunomodulation in IBD” review by Markus F. Neurath. The analysis concluded that, excluding particular risk situations (pregnant IBD patients, elderly patients with IBD with comorbidities and patients suffering from malnutrition) there was no evidence of increased risk or aggravated outcomes in IBD patients in the context of COVID-19. Furthermore, the available evidence did not suggest that IBD patients should discontinue IBD-specific drugs.
Also on this issue, the journal Gut published a study coordinated by IG-IBD (Italian Group for Inflammatory Bowel Disease). This analysis assessed the impact of SARS-CoV-2 infection in patients with IBD (mainly affected by Crohn's disease and ulcerative colitis). Between 11 and 29 March 2020, 24 Italian IBD reference units collected and combined their data in a prospective observational cohort study that enrolled patients with an established diagnosis of IBD and confirmed SARS-CoV-2 infection. In total, data from 79 patients with IBD and COVID-19 were analyzed. Research showed that active chronic inflammatory bowel disease, older age and comorbidities are associated with negative outcomes of COVID-19, while treatments to control gastrointestinal disease, including biological drugs, have no worsening influence on the course of new coronavirus infection. The authors emphasized the importance of careful prevention of exacerbations and therefore the non interruption of treatment to decrease the possibility of fatal outcomes from COVID-19.
The main authors of this research are Dr. Cristina Bezzio and Dr. Simone Saibeni, who work at the gastroenterology department of the ASST Rhodense hospital, in the province of Milan, Italy, coordinated by Dr. Gianpiero Manes. "This study of 79 patients with IBD and COVID-19 is highly cited, the data are homogeneous and the results reliable" says Dr. Manes. "Our team is working to better understand the interactions between COVID-19 and IBD. These are patients with autoimmune disease, potentially more exposed to infectious diseases, who also take immunosuppressive drugs”.
The team led by Dr. Manes, together with the COVID Pneumology Department headed by Dr. Bini, recently described the world's first case of a patient treated with infliximab for ulcerative colitis associated with COVID-19. The improvement of the pulmonary picture determined by the drug could support the hypothesis that this drug is useful, as already hypothesized, in the treatment of COVID-19.
"This patient arrived with a diagnosis of ulcerative colitis that did not respond to any medication," Dr. Manes tells us: "The risk was that the patient would have to be operated on for a colon removal. When you have a disease-wide colon that does not respond to medication, colectomy is a treatment option that is considered. Certainly, in a 36-year-old patient, the decision is not an easy one because this surgery has a significant impact on quality of life, resulting in a highly disabling situation. During the hospitalization we gave him a cortisone therapy and, when we seemed to notice a slight improvement, the situation worsened due to the onset of pneumonia. The CT scan showed a typical radiological picture of COVID-19 and the swab test confirmed SARS-CoV-2 infection. We do not know if the infection occurred before or during hospitalization.” The swab test performed at the time of admission, about a week before, was negative.
From the gastroenterology department at the Rho hospital (Lombardy Region, Italy), “which was considered the "clean" ward, the patient was then transferred to the pneumology department of Garbagnate hospital, our "COVID-19" ward”, explains Dr. Manes. Here there was the possibility of guaranteeing the patient with adequate respiratory assistance. The patient, with ulcerative colitis that did not respond to corticosteroids, presented the theoretical conditions for the administration of infliximab.
Infliximab is a chimeric (murine/human) monoclonal antibody of the IgG type, genetically constituted, directed against TNFα. The drug is used to reduce inflammatory states, for example in rheumatoid arthritis and IBD. "There has been much talk about the cytokinic storm caused by COVID-19 and possible therapy with IL-6 inhibitors. IL-6 inhibitors have never been used in ulcerative colitis and therefore infliximab was chosen. The drug was used at standard doses and the patient recovered within a short time. Both respiratory and gastrointestinal symptoms have improved considerably. The patient was discharged and is fine. Dr. Manes believes that this clinical case presents several interesting aspects to be investigated in studies with adequate casuistry. "But fortunately, there is a lack of patients today," he concludes.
The improvement in pulmonary symptoms suggests that anti-TNFα agents may be an effective therapy for COVID-19. Furthermore, the positive outcome is a reassuring message to physicians who consider starting or continuing anti-TNFα therapy in IBD patients with active disease and COVID-19. Here you can download the clinical case description: Infliximab for severe ulcerative colitis and subsequent SARS-CoV-2 pneumonia: a stone for two birds.
Sources:
1. Neurath MF. COVID-19 and immunomodulation in IBD. Gut. 2020;69(7):1335‐1342. doi:10.1136/gutjnl-2020-321269
2. 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(7):1213‐1217. doi:10.1136/gutjnl-2020-321411