Patients with systemic lupus erythematosus (SLE) showed reduced antibody responses after Covid-19 vaccination, with researchers involved in a recent study saying drugs for the condition, such as belimumab (Benlysta) and mycophenolate mofetil (MMF), are possibly to blame.
They found that immunoglobulin G (IgG) titers measured two weeks after the second dose of mRNA vaccines were lower by about 20% among 342 lupus patients compared with the average for 1 887 healthcare workers, said Dr Michelle Petri of Johns Hopkins University 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, they reported in Arthritis Care & Research.
But holding MMF for a period of time (typically a week) after vaccination ameliorated the reduction, such that post-immunisation IgG titers were down by about 20% in patients having drug “holidays” relative to the non-SLE group. MedPage Today reports that no increase in SLE flare rates were seen with the holidays.
(No holidays were attempted with belimumab or tacrolimus. The investigators explained that, for belimumab, “past data” showed no impact on vaccine efficacy, while they feared that withholding tacrolimus would be too likely to provoke SLE flares.)
Their report adds to other literature showing that common therapies for rheumatologic diseases can diminish vaccine efficacy, although not by enough to make them useless.
The American College of Rheumatology (ACR) recently published new guidance advising that most vaccines can be given without bothering with drug holidays, albeit with some exceptions.
The guidelines 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 one to two 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 analysed 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 200 days post-vaccination that could be analysed 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 a 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 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.
Study details
Effect of Systemic Lupus and Immunosuppressives on COVID Vaccination Antibody Response
Michelle Petri, Daniel Joyce, Kristin Haag, Andrea Fava, Daniel Goldman, Diana Zhong, Shaoming Xiao, Aaron Milstone, Laurence Magder.
Published in Arthritis Care & Research on 30 January 2023
Abstract
Objective
The risk of Covid-19 infection is increased in SLE vs non-SLE. Some immunosuppressive medications increase Covid infection and decrease the efficacy of vaccination. Consensus documents have suggested management strategies on handling immunosuppressive medications to increase vaccine efficacy, but the benefit of such strategies has not been proven.
Methods
We collected information on Covid infection, vaccination history, and Covid antibodies in the Hopkins Lupus Cohort. A cohort of healthcare workers was used for comparison. Outcome measures included: SARS-CoV-2 antibody IgG levels after vaccination over time in both cohorts; and effect of immunosuppressive medications on post-vaccination IgG levels in SLE patients.
Results
The analysis was based on 365 observations from 334 different patients in the SLE cohort, and 2 235 observations from 1 887 different health care workers. SLE patients on immunosuppressive medications had lower vaccine IgG levels than SLE patients who were not; but both groups had lower levels than healthcare workers. Holding mycophenolate for one week after vaccination increased post-vaccine IgG levels significantly without leading to clinical flares. In multiple variable models, mycophenolate mofetil, tacrolimus, and belimumab all significantly reduced antibody response to vaccination.
Conclusion
SLE patients, regardless of background immunosuppressive therapy, had lower vaccine IgG levels than healthcare workers. Mycophenolate, tacrolimus, and belimumab significantly reduced IgG response to vaccination. Holding mycophenolate for one week improved vaccine efficacy, providing clinical benefit on vaccine response without leading to clinical flares.
COVID-19-Vaccine-Clinical-Guidance-Rheumatic-Diseases-Summary
Medpage Today article – Study: Diminished COVID Vaccine Response in Lupus (Open access)
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