From the Journals

Lower SARS-CoV-2 vaccine responses seen in patients with immune-mediated inflammatory diseases



Ten percent of patients with immune-mediated inflammatory diseases (IMIDs) fail to respond properly to COVID-19 vaccinations regardless of medication, researchers report, and small new studies suggest those on methotrexate and rituximab may be especially vulnerable to vaccine failure.

Dr. Anne R. Bass is the rheumatology fellowship program director at the Hospital for Special Surgery, New York

Dr. Anne R. Bass

Even so, it’s still crucially vital for patients with IMIDs to get vaccinated and for clinicians to follow recommendations to temporarily withhold certain medications around the time of vaccination, rheumatologist Anne R. Bass, MD, of Weill Cornell Medicine and the Hospital for Special Surgery, New York, said in an interview. “We’re not making any significant adjustments,” added Dr. Bass, a coauthor of the American College of Rheumatology’s COVID-19 vaccination guidelines for patients with rheumatic and musculoskeletal diseases.

The findings appear in a trio of studies in Annals of the Rheumatic Diseases. The most recent study, which appeared May 25, 2021, found that more than one-third of patients with IMIDs who took methotrexate didn’t produce adequate antibody levels after vaccination versus 10% of those in other groups. (P < .001) A May 11 study found that 20 of 30 patients with rheumatic diseases on rituximab failed to respond to vaccination. And a May 6 study reported that immune responses against SARS-CoV-2 are “somewhat delayed and reduced” in patients with IMID, with 99.5% of a control group developing neutralizing antibody activity after vaccination versus 90% of those with IMID (P = .0008).

Development of neutralizing antibodies somewhat delayed and reduced

Team members were surprised by the high number of vaccine nonresponders in the May 6 IMID study, coauthor Georg Schett, MD, of Germany’s Friedrich-Alexander University Erlangen-Nuremberg and University Hospital Erlangen, said in an interview.

Prof. Georg Schett

The researchers compared two groups of patients who had no history of COVID-19 and received COVID-19 vaccinations, mostly two shots of the Pfizer-BioNTech vaccine (96%): 84 with IMID (mean age, 53.1 years; 65.5% females) and 182 healthy controls (mean age, 40.8 years; 57.1% females).

The patients with IMID most commonly had spondyloarthritis (32.1%), RA (29.8%), inflammatory bowel disease (9.5%), and psoriasis (9.5%). Nearly 43% of the patients were treated with biologic and targeted synthetic disease-modifying antirheumatic drugs and 23.9% with conventional synthetic DMARDSs. Another 29% were not treated.

All of the controls developed anti–SARS-CoV-2 IgG, but 6% of the patients with IMID did not (P = .003). The gap in development of neutralizing antibodies was even higher: 99.5% of the controls developed neutralizing antibody activity versus 90% of the IMID group. “Neutralizing antibodies are more relevant because the test shows how much the antibodies interfere with the binding of SARS-CoV-2 proteins to the receptor,” Dr. Schett said.

The study authors concluded that “our study provides evidence that, while vaccination against SARS-CoV-2 is well tolerated and even associated with lower incidence of side effects in patients with IMID, its efficacy is somewhat delayed and reduced. Nonetheless, the data also show that, in principle, patients with IMID respond to SARS-CoV-2 vaccination, supporting an aggressive vaccination strategy.”


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