Antibody Response After COVID-19 Vaccine Series Observed in Patients With Rheumatic Disease

Antibody Response After COVID-19 Vaccine Series Observed in Patients With Rheumatic Disease
Antibodies attacking virus, 3d illustration. The body’s own immune system releases immunoglobulin, or antibodies, to attack pathogens.
Study authors described antibody responses among patients with rheumatic and musculoskeletal diseases receiving immunosuppressant therapy 6 months after completing the COVID-19 vaccine series.

The antibody response to SARS-CoV-2 vaccination in patients receiving treatment with immunosuppressive medications for the treatment of rheumatic and musculoskeletal disease was described in a comment published in Lancet Rheumatology. At 6 months after vaccination, the majority of patients maintained a positive antibody titer. Patients with an inadequate immune response reported using lymphodepleting therapies, which are known to significantly delay antibody response.

To assess antibody responses in patients with rheumatic and musculoskeletal disease receiving immunosuppressants after COVID-19 vaccination, study authors assessed data from adults who had received 2 doses of the mRNA vaccine between January 5 and April 28, 2021.

Serial antibody testing was performed at 1, 3, and 6 months after the second vaccine dose to detect antibodies against the receptor binding domain (RBD) of the spike protein. A positive antibody response was defined as an anti-RBD pan immunoglobin (Ig) of at least 0.08 units/mL; a negative response was defined as an anti-RBD pan Ig of less than 0.8 units/mL. Positive antispike titers were stratified into “high” and “low” results, with a high titer exceeding 50.0 units/mL.

Patients with previous SARS-CoV-2 infection and recipients of an additional dose before testing at 6 months were excluded from the analysis. Median values and interquartile ranges were computed for antibody titers at each timepoint.

The study cohort included 326 patients, with a median age of 49 years, among whom 302 (93%) were women. The most common rheumatic disease was inflammatory arthritis, observed in 139 (43%) patients. The majority of patients (n=207; 63%) were receiving combination therapy with 2 or more concomitant immunosuppressive medications.

At a median of 29 days after the second vaccine dose, 312 (96%) patients had positive antispike titers, with a median titer of 1175 units/mL (447.0->2500.0 units/mL). Among patients with a positive titer at 1 month, only 2 (<1%) had a titer below the threshold of positivity at 6 months. At a median of 91 days after the second dose, 311 patients (95%) had a positive antispike titer, with a median of 647.5 units/mL (165.2-1373.0 units/mL). At a median of 181 days days after the second dose, 313 (96%) patients had positive antispike titers, with a median of 419 units/mL (91.9-861.0 units/mL). Based on median titers, antibody response against SARS-CoV-2 decreased between months 1 and 6, but remained above the threshold of neutralizing capacity. Patients who received the mRNA-1273 vaccine were more likely to have high positive antibody titres at 6 months than patients who received the BNT162b2 vaccine (89% vs 72%; P <.001).

Immunosuppressant therapy type also appeared to influence antibody titers. Specifically, a greater percentage of patients receiving monotherapy had a positive antispike titer at 6 months compared with patients receiving combination therapy (94% vs 71%; P <.001). Further, all 13 patients with a negative response at 6 months were receiving lymphodepleting therapy in combination with another immunosuppressive therapy. Specifically, 10 patients were receiving rituximab; 2 abatacept; and 1 belimumab; and 9 patients were receiving concomitant glucocorticoids.

Study limitations included the absence of a control group and lack of data on both memory B cells and cellular response.

“Longitudinal studies evaluating the effects of differential immunosuppression and vaccine platform, as well as clinical correlates of protection, are required to inform the optimal vaccination schedule to ensure durable protective immunity in this susceptible patient population,” the study authors wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Frey S, Chiang TP, Connolly CM, et al. Antibody durability 6 months after two doses of SARS-CoV-2 mRNA vaccines in patients with rheumatic and musculoskeletal disease. Lancet Rheumatol. Published online January 18, 2022. doi:10.1016/S2665-9913(21)00417-3