Risk of Adverse Outcomes Due to COVID-19 May Be Lower with TNF Inhibitor Monotherapy

“Our dataset represented patients from 74 countries and multiple immune-mediated disease diagnoses,” says Ms. Izadi. “The findings can guide healthcare professionals on therapeutic approaches in patients with IMIDs during the pandemic.”

A total of 6,077 patients were included in the analyses, 3,441 from GRA, 2,336 from SECURE-IBD and 300 from PsoProtect. Patients had a mean age of 49. Fifty-nine percent were women, and 59% were from Europe. The most common IMID diagnosis was RA, followed by Crohn’s disease. Treatment exposure categories included TNF inhibitor monotherapy, TNF inhibitors combined with methotrexate, TNF inhibitors combined with azathioprine/6-mercaptopurine, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy and Janus kinase (JAK) inhibitor monotherapy.

Of the patients, 21.3% were hospitalized and 3.1% died. Compared with TNF inhibitor monotherapy, a higher risk of COVID-19-related hospitalization and mortality was associated with a TNF inhibitor combined with azathioprine/6-mercaptopurine (odds ratio [OR]: 1.74; 95% confidence interval [CI], 1.17–2.58; P=0.006), azathioprine/6-mercaptopurine monotherapy (OR: 1.84; 95% CI, 1.30–2.61; P=0.001), methotrexate monotherapy (OR: 2.00; 95% CI, 1.57–2.56; P<0.001) and JAK inhibitor monotherapy (OR: 1.82; 95% CI, 1.21–2.73; P=0.004). However, patients who received a TNF inhibitor combined with methotrexate did not have a greater risk of COVID-19-related hospitalization or mortality (OR: 1.18; 95% CI, 0.85–1.63; P=0.33).

Clinician, Patient Reassurance

Dr. Yazdany

“Currently, people taking TNF inhibitors are concerned about getting severely ill should they get COVID-19. This study should provide some reassurance to the thousands of people taking anti-TNF medications during the pandemic,” says senior co-author Jinoos Yazdany, MD, MPH, professor of medicine at the University of California, San Francisco.

“For rheumatologists, although recommendations are to stop anti-TNF drugs if a patient gets COVID-19, practically, this [change] is quite difficult given the long half-life of these drugs. Although more data are needed to advise patients not to skip their next dose of anti-TNF medication in the setting of active COVID-19, hopefully these data provide some reassurance that even when the medications are not stopped, most patients do quite well.”

Dr. Velloso

In an invited commentary, Licio A. Velloso, MD, PhD, professor of medicine at University of Campinas in São Paulo, Brazil, writes that one of the greatest strengths of the study is the inclusion of a large number of patients with distinct ethnic backgrounds and IMIDs.⁶

“The numbers speak for themselves. We are talking about 6,000-plus patients with diverse genetic backgrounds. This [group] is the largest cohort evaluated so far. So indeed, this is very important and impactful data,” Dr. Velloso says. “Patients with COVID-19 present an early surge of inflammatory cytokines. TNF-α is one of the most important cytokines increased in this context. Thus, to be honest, I am not surprised that use of TNF-α inhibitors provides some benefit for this population.