Decreasing COVID-19 Antibody Levels Among Patients With Rheumatic, Musculoskeletal Disease

A cohort study published in Lancet Rheumatology found that antibody response against COVID-19 among people with rheumatic and musculoskeletal disease decreased within 6 months after full vaccination, but most still had high positive titer levels at that point.

“Although we previously described overall stability of SARS-CoV-2 antibody titres at 3 months in patients with rheumatic and musculoskeletal disease, few longitudinal data exist beyond 3 months in immunosuppressed patients with rheumatic and musculoskeletal disease,” the authors explained.

The authors collected data on 326 adults with rheumatic and musculoskeletal disease who received 2 doses of either the Pfizer (BNT162b2) or Moderna (mRNA-1273) COVID-19 vaccine between January 5, 2021, and April 28, 2021. Most (93%) participants were female, and the median (interquartile range) age was 49 (39-59) years.

The most common condition was inflammatory arthritis, which was present in 139 (43%) patients. The most frequently reported conventional synthetic disease-modifying antirheumatic drug (sDMARD) was hydroxychloroquine, a prescription drug used to treat various autoimmune diseases, which was reported by 135 (41%) patients. Tumor necrosis factor (TNF) inhibitors were the most common biological therapy, used by 84 (26%) patients. Most participants (207 [63%]) were on combination therapy, defined as at least 2 concomitant immunosuppressive medications.

Antibody tests were conducted 1, 3, and 6 months after the second vaccine dose, using an anti–SARS-CoV-2 S enzyme immunoassay. This study did not include individuals who received additional doses.

The authors found that antibody response against COVID-19 decreased by 2.8 times between months 1 and 6.

At 1 month, 312 (96%) patients had positive antispike titers with a median of 1175 units/mL. At 3 months, 311 (95%) patients had positive antispike titers with a median of 647.5 units/mL. At the 6-month antibody test, 313 participants (96%) had positive antispike titers with a median of 419 units/mL and, of those with a positive titer at month 1, only 2 patients went below the threshold of positivity at month 6.

Overall, 313 patients had positive antibody titers 6 months after receiving 2 doses of an mRNA vaccine. Of 287 patients with a high positive titer level at 1 month, 250 continued to have a high positive level at 6 months, while the other 37 had a low positive value at that time.

A small group of 12 patients saw an increase in antibody response over 6 months. All 12 used antimetabolites, with 10 using mycophenolate and 2 using methotrexate. For 4 of these participants, titer values decreased between months 3 and 6.

Additionally, the investigators noted that all 13 patients with negative antibody response at 6 months were on lymphodepleting therapy in combination with another immunosuppressive therapy. Ten patients used rituximab, 2 used abatacept, and 1 used belimumab. Nine of these 13 were also receiving concomitant glucocorticoid therapy.

The data also showed that 89% of participants had high positive antibody titers after receiving 2 doses of the Moderna vaccine—a greater proportion compared with those who received the Pfizer vaccine (72%).

The study, however, did not include a control group or data on memory B cells and cellular response. The authors also did not conduct antinucleocapsid tests and did not know whether participants had COVID-19 at any point during the study.

With FDA authorization of a third COVID-19 vaccine dose and the ongoing conversations on the potential need for further booster doses, the authors said these findings can help develop an appropriate vaccination timeline for people who are immunosuppressed.

“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 authors wrote.

Reference

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