Do Some Arthritis, IBD Drugs Put Patients at Greater COVID Risk?

For people with immune-mediated inflammatory diseases (IMIDs) who contracted COVID-19, those on tumor necrosis factor (TNF) inhibitors fared better when it came to serious COVID-19 outcomes, data from three international registries suggested.

Across more than 6,000 such patients, a higher risk of COVID-19 related hospitalization and mortality was associated with methotrexate (OR 2.00, 95% CI 1.57-2.56, P<0.001), JAK inhibitors (OR 1.82, 95% CI 1.21-2.73, P=0.004), azathioprine/6-mercaptopurine (OR 1.84, 95% CI 1.30-2.61, P=0.001), or a TNF inhibitor with azathioprine/6-mercaptopurine (OR 1.74, 95% CI 1.17-2.58, P=0.006) versus TNF inhibitor monotherapy, reported Zara Izadi, MPharm, of the University of California San Francisco, and colleagues.

IMID patients who received a TNF inhibitor combined with methotrexate did not have any greater risk of COVID-19-related hospitalization or mortality, the authors wrote in JAMA Network Open.

“The emergence of COVID-19 has created questions regarding both the safety and potential therapeutic applicability of several anti-inflammatory agents, including TNF inhibitors,” wrote Licio A. Velloso, MD, PhD, of the University of Campinas in São Paulo, Brazil, in an accompanying editorial. “The safety concerns rely on the fact that immunobiological and disease-modifying antirheumatic drugs are important risk factors for infections, and, in the context of COVID-19, they could predispose a patient to severe illness and increased mortality.”

“The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients,” added Velloso.

Izadi and colleagues evaluated data on three international COVID-19 registries — SECURE-IBD; the Psoriasis Patient Registry for Outcomes, Therapy, and Epidemiology of COVID-19 infection (PsoProtect); and the Global Rheumatology Alliance (GRA).

They noted that their study was “the first to pool data across registries to evaluate COVID-19 outcomes among patients with IMIDs.”

Izadi and colleagues evaluated data on 6,077 IMID patients in 74 countries from Mar. 12, 2020 to Feb. 1, 2021: 3,441 from GRA, 2,336 from SECURE-IBD, and 300 from PsoProtect. The primary outcome was hospitalizations and deaths from COVID-19.

Patients had a mean age of 49, almost 60% were women, 59% were from Europe, and a third were from North America. The most common diagnoses were rheumatoid arthritis (35%), Crohn’s disease (25%), ulcerative colitis (13%), spondyloarthritis (10.3%), and psoriatic arthritis (9.3%). About 22% of patients had hypertension. More patients in the GRA registry were current smokers and had obesity versus those in PsoProtect or SECURE-IBD.

Overall, 72% of patients in the PsoProtect registry were on TNF inhibitor monotherapy, as were 62% and 24% in the SECURE-IBD and GRA registries, respectively. Methotrexate monotherapy was most common among patients in the GRA registry, at 42%, the authors noted.

A total of 1,297 patients (21%) were hospitalized and 189 (3%) died from COVID-19. Hospitalizations and deaths were more common among patients in the GRA registry (27% and 5%, respectively).

Additional risk factors associated with higher hospitalizations and mortality included chronic kidney disease (OR 3.10, 95% CI 1.70-5.66), oral budesonide use (OR 2.86, 95% CI 1.20-6.84) and obstructive lung disease (OR 2.34, 95% CI 1.69-3.24). As has been described in other settings with COVID-19, female sex appeared protective (OR 0.79, 95% CI 0.66-0.96).

The analysis had several limitations, the researchers acknowledged, including registry reporting bias, different thresholds for COVID-19 hospitalization, as well as varying treatments for the disease across regions and other unmeasured confounders, such as prior IMID therapy.