Certain rheuma therapies tied to poorer COVID-19 outcomes, impaired vaccine response

Certain therapies used for rheumatic diseases, including rituximab, are associated with worse outcomes for COVID-19 and reduced immune response after COVID-19 vaccination in patients with rheumatic diseases, according to two studies presented at the virtual EULAR 2021 Congress. 

“Targeted DMARDs* may dampen the hyperinflammatory response in COVID-19, perhaps leading to a less severe clinical course. However, some DMARD targets may impair viral immune defence leading to more severe course,” explained Dr Jeffrey Spark from Brigham and Women’s Hospital in Massachusetts, Boston, US, who presented on the findings from the COVID-19 Global Rheumatology Alliance physician registry.

“There has been a lot of interest in repurposing immune-modulating drugs used in rheumatic diseases for COVID-19 treatment,” he continued. “There’s as much of an opportunity to look at rheumatic patients who are on these medications and wonder if baseline use could alter their course of disease as far as COVID-19 outcomes are concerned.”

Taking TNF** inhibitor treatment as a reference comparator, patients with rheumatoid arthritis (RA) who received rituximab therapy had a fourfold significantly increased risk for more severe COVID-19 illness (adjusted odds ratio [OR], 4.15, 95 percent confidence interval [CI], 3.16–5.44). [EULAR 2021, abstract OP0006]

Similarly, patients on JAK*** inhibitors were twice more likely to have a worse COVID-19 disease course than those receiving TNF inhibitors (OR, 2.06, 95 pecent CI, 1.60–2.65).

The primary endpoint of COVID-19 outcome was assessed using an ordinal scale ranging from 1–4 for disease severity: with “1” indicating no hospitalization, to hospitalization without oxygen to hospitalization requiring oxygen or ventilation to death for each step up the scale.

The risk for worse disease outcome remained elevated in sensitivity analyses after excluding patients with comorbid interstitial lung disease or cancer (ORs, 4.34 for rituximab use and 2.14 for JAK inhibitor use) and propensity score matching (ORs, 4.70 for rituximab and 2.09 for JAK inhibitors). 

The increased risk persisted with both rituximab and JAK inhibitor when analysed specifically by each level of outcome on the ordinal scale.

Participants in the multinational large registry study were 1,673 RA patients (mean age 56.7 years, 79.6 percent female) who were receiving DMARDs at baseline, including rituximab, abatacept, JAK inhibitors, interleukin-6 (IL-6) inhibitors, or TNF inhibitors at the time of COVID-19 diagnosis. Overall, 34.3 percent of the patients were hospitalized and 6.7 percent had died.

Unlike rituximab or JAK inhibitors, neither abatacept (OR, 1.26, 95 percent CI, 0.88-1.80) nor IL-6 inhibitors (OR, 0.81, 95 percent CI, 0.56-1.18) was significantly associated with worse COVID-19 outcomes compared with TNF inhibitors.

“The very elevated odds for poor COVID-19 outcomes in rituximab users highlights the urgent need for risk-mitigation strategies, such as the optimal timing of vaccination,” said Spark.

RA meds on vaccination

In a separate prospective multicenter study, researchers found that some immunomodulatory medications used for treating autoimmune inflammatory rheumatic diseases (AIIRD) may dampen immune response induced by the BNT162b2 vaccine. [EULAR 2021, abstract LB0003]

Overall, the rate of seropositivity measured 2–6 weeks after the second dose of vaccination was significantly lower in AIIRD patients compared with controls (86 percent vs 100 percent; p<0.0001).

Of note, patients who were treated with the anti-CD20 antibody rituximab showed the lowest seropositivity rate of 39 percent, among the AIIRD therapies studied — indicating that the treatment was associated with impaired immunogenicity of vaccine.   

Other therapies associated with significantly lower seropositivity after vaccination included glucocorticoids, mycophenolate mofetil, and abatacept.

“Postponing administration of rituximab, when clinically feasible, seems to be reasonable to improve vaccine-induced immunogenicity,” suggested the researchers.

 

*DMARDs: Disease-modifying antirheumatic drugs

**TNF: Tumour necrosis factor

***JAK: Janus kinase