Worse COVID-19 Severity Among Patients With RA Receiving Rituximab or JAK Inhibitors vs TNF Inhibitors

nurse checking on hospitalized patient, ventilator, COVID19
Nurse is checking a covid patient’s drip needle at the ICU
Using data from the COVID-19 Global Rheumatology Alliance registry, researchers assessed the association between baseline use of DMARDs and COVID-19 outcomes in patients with rheumatoid arthritis.

The use of certain disease-modifying antirheumatic drugs (DMARDs), including rituximab and Janus kinase inhibitors (JAKi), compared with tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) may be associated with worse COVID-19 severity and outcomes, according to study results published in Annals of the Rheumatic Diseases.

Researchers sought to evaluate the baseline use of biologic or targeted synthetic (b/ts) DMARDs and COVID-19 outcomes among patients with RA.

The analysis included patients with rheumatic diseases and COVID-19 (based on rheumatologist diagnosis) from the COVID-19 Global Rheumatology Alliance physician registry and the European Alliance of Associations for Rheumatology (EULAR) COVID-19 database between March 2020 and April 2021. Researchers assessed the baseline use of a b/ts DMARD at the time of COVID-19 in patients with RA. The study was limited to patients receiving treatment with abatacept, rituximab, interleukin (IL)-6 inhibitors, JAKi, or TNFi.

The primary study outcome was a mutually exclusive ordinal COVID-19 severity outcome – no hospitalization; hospitalization without oxygen; hospitalization with oxygenation or mechanical ventilation; or death.

Among a total of 6132 patients with RA who were reported to the registry, 2869 were receiving b/ts DMARDs at COVID-19 onset: abatacept (n=237), rituximab (n=364), IL-6 inhibitors (n=317), JAK inhibitors (n=563), and TNFi (n=1388). Overall, 80.8% of the patients were women; the mean age was 56.7±13.4 years. Most of the patients were from Europe and North America (51.8% and 35.0%, respectively).

The majority of patients (78.6%) were not hospitalized; 4.8% were hospitalized without oxygenation; 11.1% were hospitalized and required oxygenation or ventilation; and 5.5% died. Among patients receiving rituximab vs TNFi, 22.0% vs 7.4%, respectively, required hospitalization with oxygenation or ventilation and 14.8% vs 2.6%, respectively, died. Among patients receiving JAKi, 15.3% were hospitalized with oxygenation/ventilation and 7.1% died. On the other hand, 2.8% of patients receiving IL-6 inhibitors died.

Patients receiving rituximab vs TNFi had a 4.15-greater likelihood of worse COVID-19 severity (95% CI, 3.40-3.80). Patients receiving JAKi vs TNFi had a 2.06-greater odds of worse COVID-19 severity (95% CI, 1.60-2.65). The primary analysis did not demonstrate any significant associations between abatacept or IL-6 inhibitors and COVID-19 severity.

Researchers concluded, “The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights [prioritization] of risk mitigation strategies for [patients with RA].”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Sparks JA, Wallace ZS, Seet AM, et al; COVID-19 Global Rheumatology Alliance. Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: results from the COVID-19 Global Rheumatology Alliance physician registry. Ann Rheum Dis. Published online May 28, 2021. doi:10.1136/annrheumdis-2021-220418