For Better COVID Vax Response in Rheumatology Patients, Hold the MMF Longer

— Small study suggests at least a 10-day holiday

MedicalToday

PHILADELPHIA -- Patients taking mycophenolate mofetil (MMF) for rheumatologic conditions had much stronger antibody responses to vaccination against COVID-19 when the immunosuppressant was stopped for 10 days or more, a retrospective study indicated.

Some 64% of patients for whom MMF was held for at least 10 days attained antibody titers of at least 250 U/mL targeting the SARS-CoV-2 spike protein, compared with 29% among those who had MMF held for less than that or not at all, reported Sarah Frey, BS, of Johns Hopkins School of Medicine in Baltimore, and colleagues.

In a poster presentation at the American College of Rheumatology (ACR) annual meeting, Frey said there was no suggestion that disease flares were more common in patients with the longer drug stoppages.

At a press conference following the presentation, co-author Caoilfhionn M. Connolly, MD, MSc, said the study focused on MMF because it appears to be "one of the greatest offenders in terms of blunting the SARS-CoV-2 vaccine response."

Guidelines have recommended that the drug and others like it be stopped temporarily when COVID-19 vaccines are given. Until a few months ago, the ACR had set the interval at 1 week, although an modified the recommendation to 1-2 weeks.

However, little evidence was given regarding the recommended holiday for immunosuppressant agents. The optimal duration is not really known, Connolly said.

The researchers drew on a prospective cohort study involving individuals with rheumatologic diseases receiving COVID-19 vaccines. It included 220 participants who were taking MMF for conditions such as inflammatory arthritis, lupus, Sjogren's syndrome, and systemic sclerosis.

Mean age in this group was about 50 and more than 80% were women. The median daily MMF dose prior to vaccination was 2,000 mg among those having it stopped for less than 10 days (n=21) and 2,500 mg for participants with longer holds (n=22). The vast majority of participants (177) did not have the drug held at all. Most patients were taking other drugs, but the three groups did not differ substantially in the types and proportions involved.

Median duration of MMF stoppage was 5 days for those in the <10-days group (interquartile range 2-7) and 21 days (IQR 14-30) for the longer-hold group. Antibody titers were measured serially after the second COVID-19 vaccine dose (no patients receiving the one-dose Johnson & Johnson vaccine were included) and the highest at any point was the one used for the outcome analysis.

Rates of disease flares requiring new treatment were as follows:

  • No hold: 6.8%
  • Less than 10 days: 9.5%
  • ≥10 days: 4.5%

Also, no flares in any group required admission or IV therapy.

These findings suggest that flare risk was not increased with the longer hold. But with barely 20 patients in each of the hold groups, chance was a likely factor: only one patient having a longer hold suffered a flare, as did two in the short-hold group.

Frey and colleagues were suitably cautious in their interpretation. "Certain patients may benefit from longer perivaccination MMF hold; further research is needed to quantify the optimal hold duration," the team concluded.

Besides the small numbers, limitations to the study included its reliance on participants to report flares and other clinical information.

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    John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.

Disclosures

The study was funded by the NIH, the Ben-Dov and Trokhan Patterson families, and the Jerome L. Greene Foundation Discovery Fund.

Frey disclosed no relationships with industry; co-authors disclosed relationships with, and/or support from, multiple entities, including vaccine makers.

Primary Source

American College of Rheumatology

Frey S, et al "Increased duration of mycophenolate hold improves antibody response to SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal disease" ACR 2022; Abstract 0797.