Do mRNA COVID-19 vaccines influence treatment for rheumatic diseases?

In individuals receiving disease-modifying antirheumatic drugs* (DMARDs) for inflammatory rheumatic diseases** (IRD), humoral response remained satisfactory following administration of the second dose of the Pfizer mRNA vaccine against SARS-CoV-2, a study suggests.

“There is very limited data regarding safety, humoral immunogenicity, and impact of two doses of mRNA vaccine against SARS-CoV-2 on patients with IRD treated with immunomodulating agents,” said the researchers. “Concerns were raised whether [patients with IRD] can mount a protective immune response and whether the vaccination may trigger a flare-up of the IRD.”

CD20-depleting antibodies or immunosuppressive agents reportedly blunt humoral response. [Vaccine 2011;29:1643-1648] “Despite continuing chronic immunosuppression, [our participants] mounted significant amounts of protective antibodies,” they continued.

Researchers recruited 264 consecutive patients (mean age 57.6 years, 76 percent female, disease duration 11.06 years) after receiving their first Pfizer vaccine dose. Participants had stable IRD (mean DAS28 CRP*** 2.9, PGA*** 3.4, PhGA*** 2.6) and were re-evaluated 4–6 weeks after receiving the second dose. Immunomodulatory therapy was unchanged pre- or post-vaccination. A comparator arm was also included, which comprised 26 patients with IRD (mean age 47.3 years, 73 percent female, disease duration 6.53 years) who had recovered from COVID-19 within the previous 2 months. [Ann Rheum Dis 2021;80:1317-1321]

Even without altering their immunomodulating regimen, most participants (n=227) mounted a significant humoral response following administration of the second vaccine dose (mean 6,764.27 AU/mL). The corresponding value in the COVID-19-recovered group was lower (mean 2,044.8 AU/mL). A comparison of values from both groups yielded statistical significance (p<0.05).

“It is worth to emphasize that our cohort of recovered COVID-19 patients with IRD included mostly patients with very mild viral disease. The humoral response in patients with severe COVID-19 might be higher than the response in patients with mild disease,” the researchers explained.

On multivariate analysis, humoral response was significantly associated with the type of immunomodulatory treatment, particularly anti-CD20 agents (p=0.0001), abatacept (p=0.003), or mycophenolate mofetil (p=0.0001).

Vaccine side effects were minor, the most common being injection site pain, redness, or swelling (58 percent), followed by fatigue (30 percent) and headache (20 percent). Within 2 months after vaccination, no flare-ups of the underlying IRD were reported (mean DAS28-CRP 2.8, PGA 3.5, PhGA 2.5), suggesting that the IRD remained stable. “[These values imply that] the Pfizer mRNA vaccine against SARS-CoV-2 virus appears safe in our patients,” said the researchers.

Immunomodulating treatment during vaccination: to withhold or not?

“Our results can provide reassurance to patients with IRD receiving immunomodulatory agents and their physicians regarding the immunogenicity and short-term safety of mRNA vaccine against SARS-CoV-2,” said the researchers. “Considering the satisfactory humoral response despite immunomodulatory treatments … we advise not to withhold immunomodulatory treatment around the [time of] vaccination.”

However, the study was not powered to evaluate if antibody titres are relative to improved or diminished protection against COVID-19. This should thus be assessed in future trials, said the researchers. “We plan to continue to follow these patients to assess whether the antibody titres correlate with clinical outcomes … Further studies should [also] assess … whether the timing of anti-CD20 agents’ administration influences the neutralizing antibody titre.”