Certain lupus patients prone to flares after COVID-19 vaccination

Among Asian patients with systemic lupus erythematosus (SLE), those who are younger, male, from ethnic minority backgrounds, and have suboptimal disease control at time of vaccination are at increased risk of flares following mRNA COVID-19 vaccination.

A Singapore study wherein latent class analysis was applied showed that the cluster of patients described above were more likely to experience flares after vaccination, with the flares occurring sooner on average, compared with the cluster of patients who were predominantly Chinese and older, less likely to be men, and had better SLE control in terms of disease activity and medication requirement (hazard ratio [HR], 1.4, 95 percent confidence interval [CI], 1.1–1.9; p=0.014). [Vaccines 2023;12:29]

“To our knowledge, this is the first study to employ latent class analysis in SLE patients to identify different phenotypes predictive of SLE flares after mRNA COVID-19 vaccination,” according to the investigators, stressing the importance of identifying such phenotypic clusters due to the heterogeneity of SLE.

“We have reported previously that younger age, non-Chinese ethnicity, and male gender are associated with higher disease activity. It is thus interesting to observe increased SLE flares following mRNA COVID-19 vaccination in patients with these characteristics likely due to higher baseline disease activity, further contributed to by treatment interruption for vaccination,” they added. [Semin Arthritis Rheum 2022;52:151932]

Malay ethnicity

The uneven ethnic distribution between the two clusters of patients suggests that patients of non-Chinese ethnicity may have unique characteristics that influence the risk of post-COVID-19 vaccination flares, the investigators noted.

Evidence from previous studies point to Malay SLE patients as being more likely to be younger and male and to modify their immunomodulatory/immunosuppressive treatment due to COVID-19 concerns, in line with the current findings. Malay patients in the present study also used higher doses of prednisolone, which is indicative of higher disease activity. [PLoS ONE 2016;11:e0166270; J Rheumatol 2021;48:35-39; Clin Rheumatol 2022;41:3299-3311]

“Hence, younger, male SLE patients of Malay ethnicity with higher disease activity may drive the clustering of our dataset and it will be important for physicians to identify this group of patients for closer monitoring immediately before and after mRNA COVID-19 vaccination,” the investigators said.

Study cohort

The study included 633 SLE patients (median age 52 years, 88.6 percent women, 74.9 percent Chinese) from eight public healthcare institutions in Singapore. These patients were grouped into two, the test and validation cohorts. Two clusters of patients were identified across the test, validation, and combined cohorts.

Across cohorts, the corresponding clusters shared similar baseline characteristics. For example, patients in cluster 1 vs cluster 2 had a higher median age (test cohort: 60.0 vs 41.5 years; validation cohort: 58.0 vs 31.0 years; combined cohort: 60.0 vs 31.0 years; p<0.001), lower proportion of men (test cohort: 10.8 percent vs 23.1 percent, p=0.023; validation cohort: 6.0 percent vs 14.9 percent, p=0.009; combined cohort: 9.7 percent vs 15.2 percent, p<0.043), and higher proportion of patients of Chinese descent (test cohort: 81.6 percent vs 59.6 percent; validation cohort: 83.6 percent vs 58.1 percent; combined cohort: 83.5 percent vs 56.1 percent; p<0.001).

Patients in cluster 1 across cohorts were also less likely to be on prednisolone >7.5 mg/day, hydroxychloroquine, mycophenolate mofetil, and tacrolimus.

After COVID-19 vaccination, flares occurred in 9.0 percent of patients in cluster 1 and in 15.2 percent of those in cluster 2 in the combined cohorts (p=0.021). Significantly more patients in cluster 2 than in cluster 1 had haematological flares (5.6 percent vs 2.1 percent; p=0.020) and had immunomodulatory/immunosuppressive treatment interruption for COVID-19 vaccination (6.6 percent vs 0.2 percent; p<0.001).

“While mRNA COVID-19 vaccination uptake in SLE patients has been hindered by concerns of suboptimal efficacy of vaccination when on immunosuppressive treatment and the possibility of disease flare post-vaccination, this study shows that vaccination remains generally safe. Physicians are recommended to dispel their fears and facilitate informed decision making,” the investigators said. [J Rheumatol 2021;48:35-39]

Meanwhile, mRNA COVID-19 vaccination in SLE patients requires extra attention for high-risk groups, specifically those of ethnic minorities, young males, and those with uncontrolled disease, they added.