Heart Failure as an Adverse Outcome With the Use of Biologic Medications for Crohn’s Colitis: A Pharmacovigilance Study
Background:
Many adverse effects have been associated with biologic agents used for Crohn’s disease, including heart failure. Anti-TNF specifically has been related to new onset heart failure or worsening of existing disease. FDA adverse reporting system (FAERS) is a useful tool to look for new safety concerns that might be related to a marketed product. We aimed to highlight this relation with the newer biologic agents which have been approved in recent years and looked at new cases of HF with these biologics.
Methods:
We utilized FAERS database (until June 30, 2023) to look up adverse effect of heart failure. The biologics included were infliximab, adalimumab, vedolizumab, ustekinumab, natalizumab, tofacitinib, certolizumab, and risankizumab. We did not include upadacitinib as it was recently approved for Crohn’s in May 2023 and had limited data available on the database. Adverse effects were identified using the Medical Dictionary for Regulatory Activities (MedDRA) terminology and the following terms were identified: Cardiac failure/Cardiac failure Congestive/Cardiac Failure Acute/Right Ventricular Failure/Left Ventricular Failure/Cardiac Failure Chronic, Ventricular Failure, Chronic right ventricular Failure, Chronic Left Ventricular Failure/cardiogenic shock. We looked for number of cases, disparities in age and sex, and outcomes including hospitalization and mortality.
Results:
A total of 176025 adverse effects were reported for patients using biologic agents for Crohn’s disease with a total of 1041 cases of heart failure. A high percentage of HF was seen in patients of the age group 18-64 years (43.3%) followed by patients above 65 years of age (27.7%). Some of the cases did not have age reported. Female had the higher percentage of HF (53.1%). The majority of the cases were reported with Infliximab (48.1%), followed by adalimumab (41.8%) vedolizumab (4.8%) and ustekinumab (4.6%) respectively. There were only 5 reported cases with natalizumab, one reported case with tofacitinib and no cases reported so far for certolizumab or Risankizumab. Regarding the ratio for HF among all adverse events for the biologics, tofacitinib had the highest at (0.025), followed by Infliximab (0.009), natalizumab and adalimumab (0.003), and ustekinumab/vedolizumab (0.002). We also looked at outcomes of the patients who had HF as an adverse event due to biologics, including hospitalizations and it showed it was highest with adalimumab, followed by Infliximab and vedolizumab. The other outcome we looked at was mortality for patients who had HF with biologics, it was highest in patients who had used adalimumab, followed by Infliximab and ustekinumab.
Conclusions:
Our study adds further to the literature regarding biologics adverse events, specifically heart failure. Tofacitinib had the highest ratio of heart failure among all adverse effects, followed by the already-established Infliximab. All other newer biologics had a relatively lower ratio. Despite tofacitinib having the highest ratio for heart failure, we cannot attribute significance to this due to this drug having only one reported case compared to other drugs. Furthermore, we can conclude that newer biologics have a relatively very small ratio for the risk of heart failure compared to Infliximab. Further data is needed for the newer biologics.
