Probiotic co-administration with berotralstat improves GI tolerability in HAE patients

Berotralstat, the first oral plasma kallikrein inhibitor approved for hereditary angioedema (HAE) prophylaxis, may be associated with gastrointestinal (GI) side effects, particularly during the first three months of therapy. Probiotics have been shown to reduce GI disturbances in several conditions. This pilot study described GI tolerability in patients receiving initiation-phase probiotic co-administration alongside berotralstat and explored whether this supportive strategy merits further controlled evaluation. We analyzed 25 adolescents and adults with HAE treated with berotralstat across six Italian centers (December 2023-November 2025). All patients received probiotics during the early treatment phase. Demographic and clinical data, side effects, and monthly HAE attack rates were collected. Severity of complaints was graded using the Common Terminology Criteria for Adverse Events (CTCAE). Participants were 60% females, and the mean age for the cohort was 45 years (range 12-82). The most common probiotics were Lacteol®, Codex®, and Lactoflorene Plus®. GI complaints occurred in 5/25 patients (20%); only 3/25 (12%) experienced GI side effects while receiving probiotics. 2/25 GI complaints occurred after probiotic discontinuation. No serious side effects were reported. Mean monthly attack rate decreased from 2.6 to 0.8 attacks per month, ~3.3-fold reduction from baseline. Probiotic co-administration during early berotralstat therapy was accompanied by a low incidence of GI side effects, while clinical effectiveness was maintained. These preliminary findings support further controlled studies to validate probiotics as a supportive strategy for improving the tolerability of berotralstat.