medwireNews: Findings from two studies suggest that the type of immunomodulatory therapy, and whether agents are used as monotherapy or in combination, may impact how well patients with immune-mediated inflammatory diseases (IMIDs) respond to COVID-19 vaccines.
In the first study, published in The Lancet Rheumatology, the researchers analyzed serum samples from 2339 people in the Netherlands who were vaccinated against SARS-CoV-2. A total of 1692 were on immunomodulatory therapy for an IMID – including rheumatic, inflammatory bowel, neurologic, and dermatologic diseases – and the control group comprised 473 IMID patients not taking immunosuppressants plus 174 healthy controls.
Filip Eftimov (University of Amsterdam, the Netherlands) and team found that receipt of anti-CD20 therapy, sphingosine 1-phosphate receptor (S1P) modulators, or mycophenolate mofetil–corticosteroid combination therapy was associated with a significantly reduced risk for seroconversion 28 days after complete vaccination, with relative risks of 0.32, 0.35, and 0.61, respectively.
A complete vaccination course was defined as two doses of the Pfizer–BioNTech (BNT162b2), Oxford–AstraZeneca (ChAdOx1 nCoV-2019), or Moderna (mRNA-1273) vaccine, or a single dose of Johnson & Johnson’s Janssen (JNJ-78436735) vaccine. Seroconversion was defined as anti-receptor binding domain (RBD) immunoglobulin G antibodies of more than 4 AU/mL.
In patients treated with mycophenolate mofetil–corticosteroid combination therapy, administration of a third vaccine dose significantly increased seroconversion rates from 52.6% after the second dose to 89.5% after the third dose. On the other hand, the researchers say that “the effect of a third vaccination in patients on anti-CD20 therapy and S1P modulators was limited,” with nonsignificant improvements from 36.8% to 45.6% and from 35.5% to 48.4%, respectively.
Eftimov et al report that patients on most other monotherapy and combination therapy options had “moderately reduced” antibody titers, but had similar seroconversion rates to those in the control group. They say that “the clinical relevance of this observation is uncertain,” because a “formal minimal antibody threshold for protection after vaccination has not been established.”
Writing in an accompanying commentary, Caoilfhionn Connolly and Julie Paik, both from Johns Hopkins University School of Medicine, Baltimore, USA, say that “the findings add credence to existing data that the type and intensity of immunosuppressive therapy is of major relevance for humoral responses following SARS-CoV-2 vaccination.”
Moreover, the study highlights “the continued need for non-medical and medical countermeasures, including additional vaccine doses, in immunosuppressed patients,” they add.
The second study included 1505 IMID patients from Norwegian healthcare centers and 1096 healthy controls who received a standard two-dose vaccination schedule. In accordance with Eftimov and colleagues’ results, median anti-RBD titers were significantly lower in patients versus controls (619 vs 3355 AU/mL), but overall seroconversion rates were comparable (≥70 AU/mL; 91 vs 98%).
There were “relatively high response rates” in the majority of medication groups, albeit patients on anti-CD20 therapies were excluded from this study, report Guro Løvik Goll (Diakonhjemmet Hospital, Oslo, Norway) and team.
Nevertheless, they found that certain therapies were associated with reduced response rates. Specifically, patients on abatacept had a significantly lower likelihood of seroconversion than those on tumor necrosis factor (TNF) inhibitor monotherapy (53 vs 95%), as did those on Janus kinase inhibitors (78%) or TNF inhibitor combination therapy (86%).
The researchers note that 153 patients who had a weak antibody response to two vaccine doses (anti-RBD <100 AU/mL) were given a third dose at a median of 70 days after the second dose, and 84% of these people achieved an increase in antibody levels, with a median improvement of 362 AU/mL.
“These data facilitate identification of patient groups at risk of attenuated vaccine response, and support administering a third vaccine dose to poorly-responding IMID-patients,” write Goll et al in Arthritis & Rheumatology.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group
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Lancet Rheumatol 2022; 4: e338–e350
Lancet Rheumatol 2022; 4: e307–e308
Arthritis Rheumatol 2022; doi:10.1002/art.42153