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

Patients with immune-mediated inflammatory diseases (IMIDs) receiving tumor necrosis factor (TNF) inhibitor monotherapy have a lower risk of COVID-19-associated hospitalization or death than those on other commonly prescribed immunomodulatory treatment regimens. This finding is according to a cohort study that included data from three international registries.¹

“Our findings are in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs,” says co-first author Zara Izadi, MPharm, MAS, a doctoral candidate and a graduate student researcher at the University of California, San Francisco. “In addition, clinicians would benefit from weighing the risks vs. benefits of de-escalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/mercaptopurine.”

Preliminary Data

TNF inhibitors are widely prescribed for rheumatoid arthritis (RA), Crohn’s disease, ulcerative colitis and psoriasis. However, the effect of COVID-19 on patients with IMIDs who are receiving TNF inhibitors remains poorly understood. Biologic and disease-modifying anti-rheumatic drugs (DMARDs) are risk factors for infection, and they could predispose a patient to severe COVID-19 and increase COVID-19-related mortality. Conversely, because the cytokine storm led by interleukin (IL) 6 and TNF-α is believed to play an important role in the development of many of COVID-19’s serious complications, it has been proposed that biologic inhibitors of these cytokines may decrease the severity of COVID-19.²

In 2020, a study by Brenner et al. found TNF inhibitor use at the time of COVID-19 diagnosis was not associated with severe COVID-19. The researchers analyzed data from the SECURE-IBD registry, which included 525 patients with inflammatory bowel disease (IBD) from 33 countries. Risk factors for severe COVID-19 included increasing age, other comorbidities, systemic corticosteroids and sulfasalazine/5-aminosalicylate use, but not TNF inhibitor use.³ Gianfrancesco et al. studied data from the COVID-19 Global Rheumatology Alliance’s (GRA; a section of the ACR) physician-reported registry of COVID-19 outcomes among people with rheumatic diseases. In 600 patients from 40 countries, prevalent use compared with no use of TNF inhibitors at COVID-19 diagnosis was associated with a lower risk of COVID-19-associated hospitalization, whereas glucocorticoid exposure of 10 mg or more per day was associated with higher odds of hospitalization.⁴

Meanwhile, an analysis of data from the PsoProtect registry by Mahil et al., which included 374 patients with moderate to severe psoriasis from 25 countries, found higher odds of hospitalization among patients treated with non-biologic systemic therapies compared with biologic therapies, including TNF inhibitors.⁵

TNF Inhibitor Safety

Although these studies of international registries have provided preliminary information regarding COVID-19 outcomes among patients who received TNF inhibitor therapies during the pandemic, they were often underpowered to perform detailed analyses of commonly used medications, such as monotherapy vs. combination therapy, or medications that are used less often.¹ To shed light on the safety of TNF inhibitor and DMARD use in patients with IMIDs and COVID-19, Izadi et al. completed a pooled analysis of data from three international COVID-19 registries comprising individuals with rheumatic diseases, IBD and psoriasis from March 12, 2020, to Feb. 1, 2021. The study’s primary outcome was COVID-19-associated hospitalization or death.