Study: Diminished COVID Vaccine Response in Lupus

Patients with systemic lupus erythematosus (SLE) showed reduced antibody responses following COVID-19 vaccination, with drugs for the condition such as belimumab (Benlysta) and mycophenolate mofetil (MMF) likely to blame, researchers said.

Immunoglobulin G (IgG) titers measured 2 weeks after the second dose of mRNA COVID vaccines were lower by about 20% among 342 lupus patients compared with the average for 1,887 healthcare workers, according to Michelle Petri, MD, MPH, of Johns Hopkins University in Baltimore, and colleagues.

The effect was most pronounced for patients taking broad-spectrum immunosuppressants, including MMF and tacrolimus, with reductions in IgG response of about 30% relative to the healthcare workers, the researchers reported in Arthritis Care & Research.

But holding MMF for a period of time (typically a week) after vaccination ameliorated the reduction, such that post-immunization IgG titers were down by about 20% in patients having drug “holidays” relative to the non-SLE group. And no increase in SLE flare rates were seen with the holidays, Petri and colleagues indicated. (No holidays were attempted with belimumab or tacrolimus. The investigators explained that, for belimumab, “past data” showed no impact on COVID vaccine efficacy, while they feared that withholding tacrolimus would be too likely to provoke SLE flares.)

Their report adds to considerable literature showing that common therapies for rheumatologic diseases can diminish vaccine efficacy, although not by enough to make them useless. Indeed, earlier this month, the American College of Rheumatology (ACR) published new guidance indicating that most vaccines can be given without bothering with drug holidays, albeit with some exceptions.

Those guidelines, however, deliberately excluded COVID vaccines because the evidence is still evolving. An ACR guideline issued last August on COVID vaccination for rheumatologic disease patients called for many drugs to be paused for 1 to 2 weeks. These included MMF and other broad-spectrum immunosuppressants, as well as more targeted therapies such as belimumab, rituximab (Rituxan), and Janus-activated kinase inhibitors. Holding MMF for at least 10 days was found to be optimal in a study reported at ACR’s annual meeting in 2022 by a different Hopkins group.

For the current study, Petri and colleagues analyzed data collected at Hopkins in a specifically assembled cohort of lupus patients, as well as from workers at five hospitals in the university’s healthcare system. All provided serial blood samples over a period of 200 days post-vaccination that could be analyzed for SARS-CoV-2 spike protein antibody titers.

Roughly two-thirds of the lupus cohort were not taking immunosuppressants during the study period. The rest were evenly divided between those continuing them as normal and those having them withheld for 1 week after each vaccine dose.

Although there was considerable scatter among individuals, mean titers in most groups (stratified in the lupus cohort according to whether they received immunosuppressant drugs normally, not at all, or with brief holidays) declined in parallel up to about day 120 after the second vaccine dose, becoming nearly equal by day 200 at about half their early peaks.

However, since the group taking immunosuppressants with no holiday had only weak responses to begin with, the subsequent decline was less steep, and mean IgG titers at day 200 were similar to those in the other groups.

Withholding MMF or other immunosuppressants, versus continuing them as normal, appeared to have no effect on SLE disease activity. Trajectories for standard ratings including the SLE Disease Activity Index and Physician’s Global Assessment from pre- to post-vaccination were similar, as were counts of disease flares.

One surprise in the new data was that, despite the expectation that belimumab wouldn’t affect antibody responses, in fact, patients taking the drug did show some diminution (mean 2.7 vs 5.7 among other patients at peak, P=0.018). Of those on belimumab, 67% showed IgG responses, compared with 90% of lupus patients treated otherwise (P=0.18).

Despite this finding, Petri and colleagues argued against a belimumab holiday, based on the drug’s pharmacodynamics. “Holding for one weekly subcutaneous dose would not be long enough to allow a rebound in B cells,” they wrote.

Limitations in the study included that it only covered two vaccine doses without the third (or further) booster, and clinical vaccine efficacy in terms of COVID-19 infection or symptoms was not evaluated. The restriction to the Hopkins patient and worker populations was also a potential limitation. In addition, since essentially all the SLE patients were on some type of therapy, it was impossible to determine how much the disease itself versus its treatments may have contributed to the diminished antibody responses.