Difficulties are encountered in establishing the level and duration of vaccine-induced protection attained among older patients who are receiving treatment with immunosuppressants. Study authors describe the case of a 78-year old woman with rheumatoid arthritis (RA) who was receiving low-dose combination therapy with methotrexate and adalimumab, and who received 2 doses of the mRNA-1273 SARS CoV-2 vaccine. Results of the case report were published in the journal Vaccines (Basel).

Recognizing that treatment with methotrexate and adalimumab may affect a person’s immune response to SARS-CoV-2 vaccines, the investigators sought to illustrate the anti-spike (anti-S) immunoglobulin G (IgG) and neutralizing antibody responses  generated by the mRNA-1273 SARS-CoV-2 vaccine in an older patient with RA. The 78-year-old woman received low-dose methotrexate plus adalimumab shortly before administration of the 2 COVID-19 vaccine doses.

The patient received her initial mRNA-1273 vaccine on January 18, 2021, and a second dose of the vaccine on February 15, 2021. She was treated with adalimumab 4 days before the first vaccine dose and 1 day before the second dose of the vaccine. Further, on the day of vaccination with both of the vaccine doses, the patient received methotrexate.

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A quantitative serologic test was performed on February 25, 2021—that is, 38 days (D-38) after her initial vaccine dose was administered—to determine the patient’s levels of IgG directed against the trimeric form of the SARS-Cov-2 spike protein. Results of this blood test showed that anti-S IgG antibodies were detected at a level of 193 AU (Arbitrary Units)/mL, which was indicative of the presence of a moderate positive response to the first dose of the vaccine. Additional tests performed to determine her level of neutralizing antibodies revealed an anti-S IgG titer of 1366 AU/mL and a neutralizing antibody titer of 106.46 AU/mL.

An additional round of serologic tests was performed on March 15, 2021—that is, 53 days (D-53) following the administration of her first vaccine. These results demonstrated that her level of anti-S IgG at D-53 was similar to that reported at D-38. Further, the neutralizing antibody level remained in the same range as that observed at D-38.

The case study involved a control patient, a 73-year-old woman who was not being treated with any immunosuppressant agents. Her first mRNA-1273 vaccination was administered on March 18, 2021, and her second dose was administered on April 15, 2021. Results of serologic tests performed in the control patient revealed that her neutralizing antibody titers were 10 times higher than those in the patient who was receiving immunosuppressant therapy.

The investigators concluded that the results of the current case report demonstrate that even at low doses, the combination of methotrexate plus adalimumab was associated with a weak immune response to the mRNA-1273 vaccine in an elderly individual.

Additional research is warranted, they maintain, to gather data on the immunogenicity of the various SARS-CoV-2 vaccines in a larger population of patients who are receiving a variety of immunosuppressive therapies at different dosages. Guidance on the administration of an additional vaccine dose, as well as on the timing of administration of immunosuppressant agents—both before and following vaccination—is needed.


Michiels Y, Houhou-Fidouh N, Collin G, Berger J, Kohli E. Impact of low-dose methotrexate-adalimumab combination therapy on the antibody response induced by the mRNA-1273 SARS-CoV-2 vaccine: case of an elderly patient with rheumatoid arthritis. Vaccines (Basel). 2021;9(8):883. doi:10.3390/vaccines9080883