Infectious Risk with B Cell Therapies in Lupus Save

A UK registry study of moderate to severe systemic lupus erythematosus (SLE) patients showed that treatment with rituximab or belimumab was not associated with a greater risk of serious infection, when compared to standard of care therapy.

The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a prospective UK-based register of SLE starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death.

Between 2010 and 2021, 1383 SLE patients were recruited to the BILAG-BR. A total of 1048 participants (1002·7 person-years of follow-up) were includedin this analysis - 71% received rituximab, 11% belimumab, and 17% were on standard of care therapy.

Serious infections occurred in 118 (11.2%) patients; with 76 of these in the first 12-month study period. They found:

• 92 serious infections in 58 individuals on rituximab
• 8 serious infections in five individuals receiving belimumab
• 18 serious infections in 13 individuals on standard of care.

While the overall serious infection crude incidence rate was 117·7 (95% CI 98·3–141·0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1·68 [0·60–4·68]) and belimumab groups (1·01 [0·21–4·80]).

Serious infection risk was associated with prednisolone >10mg (HR 2·38 [95%CI 1·47–3·84]), hypogammaglobulinaemia <6 g/L (HR 2·16 [1·38–3·37]), and multimorbidity (HR 1·45 [1·17–1·80]).

A reduced rate was seen with concomitant immunosuppressive use (HR 0·60 [0·41–0·90]).

Six infection-related deaths occurred at a median of 121 days (IQR 60–151) days from cohort entry.

In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. These findings suggest that immunosupppressives, rituximab, and belimumab should be considered mainstay therapies in SLE management.

(Editor’s note: rituximab is not FDA approved for use in SLE in the USA)