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Mycophenolic Acid Treatment Not Associated with More Severe COVID-19 Infection

Throughout the pandemic, rheumatologists have been concerned that their patients may be at risk of developing more severe forms of the COVID-19 disease as a result of their rheumatic disease or treatment.

Mycophenolic acid (MPA) therapy was not linked to more a severe form of COVID-19 infection. However, investigators not that careful consideration should be taken in patients with inflammatory rheumatic and musculoskeletal diseases (iRMD), who are likely to be treated with MPA, due to an increased risk of developing severe COVID-19, according to a study published in Rheumatic and Musculoskeletal Diseases.1

“Throughout the pandemic, physicians who treat patients with iRMD have been concerned their patients would develop more severe forms of the COVID-19 disease due to the disruption of their immune systems as a result of their illness or treatment,” investigators stated. “Currently, treatment with MPA is used under very specific conditions in iRMD, which is characterized by a higher risk of poor prognosis, including connective tissue disorders, with pulmonary or renal involvement. Whether iRMD patients treated with MPA have a higher risk of developing severe COVID-19 is still unclear.”

This observational, multicenter study analyzed patients with iRMD with and without MPA treatment who had confirmed or highly suspected COVID-19. The primary endpoint was the death rate from COVID-19 and the secondary objective evaluated the severity of infection and length of hospital stay. Comparisons were evaluated using regression models both with and without adjustment on prespecified confounding factors. Additionally, odds ratios (ORs), sub hazard ratio (sHR), and 95% confidence intervals (CIs) were analyzed utilizing patients who were not treated with MPA as a reference group.

In total, 1977 patients were included in the analysis, of which 1928 were not treated with MPA and 49 patients were placed in the MPA cohort. Most patients in the MPA-treated group were diagnosed with systemic lupus erythematosus (44.9%, n = 22) and systemic sclerosis (SSc) (36.7%, n = 18). Across all cohorts, patients were predominately female (66.6%), had a mean age of 55 years, and 68.1% reported 1 or more comorbidities.

Initially, MPA-treated patients had more severe infection (18.4%, n = 9/49) when compared with 11.1% (n = 219/1928) in those not treated with MPA. In the age-sex adjusted analyses, a higher death rate from COVID-19 and longer hospital stays were also observed in the MPA-treated cohort when compared with non-MPA patients.

However, using the adjusted propensity score overlap weighting (PSOW) method, none of the outcomes were independently associated with MPA therapy. Severity, death rate, and length of hospital stay were not significantly different between MPA-treated patients and those not treated by MPA-eligible (n = 393).

The most vulnerable patients were those with lupus and SSc, particularly for those with interstitial lung disease (ILD), in which limited treatment options are available and the efficacy of MPA has been established. Further, rituximab (RTX), the “gold standard” for alternative treatment in these patient populations, has been associated with worse COVID-19 outcomes. The analysis focused on the risk of mortality and severe outcomes in patients treated with MPA. Future studies should examine the safety of MPA treatment and efficacy of the COVID-19 vaccine with concurrent treatment, which was not evaluated within the current analysis.

“In the present study, we demonstrate that there was no difference among our three study groups in terms of severity, length of hospital stay or death rate from COVID-19,” investigators concluded. “Based on our findings, we claim that the overall excess risk of poor outcome of COVID-19 in patients treated with MPA in an iRMD population after age and sex adjustment is likely due to confounding factors… MPA use should be continued in patients requiring the treatment for autoimmune disease, without fear of an increased risk of severe COVID-19.”


Truchetet ME, Drumez E, Barnetche T, et al. Outcome of COVID-19 in patients with rheumatic and inflammatory diseases treated with mycophenolic acid: data from the French RMD COVID-19 cohort. RMD Open. 2022;8(2):e002476. doi:10.1136/rmdopen-2022-002476