A syndrome of progressive muscle spasm, alopecia, and diarrhea

Aims Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; previously ‘AR101’) is a once-daily oral immunotherapy approved by the FDA (Palforzia®) to mitigate allergic reactions that may occur with accidental peanut exposure in peanut-allergic individuals aged 4-17 years. Previously, safety data from trial participants receiving PTAH over ≤3.5 years were pooled/described; analyses including an additional year of data (totaling ≤4.5 years) are presented here. Methods Safety data from six PTAH clinical trials (n=3, controlled; n=3, open-label extension) were pooled and assessed (cut-off July 31, 2021). Results Of 1127 individuals receiving ≥1 PTAH dose, representing 2323 exposure-years, most participants experienced ≥1 treatment-related adverse event (TRAE; n=1021; 90.6%). Median duration of PTAH exposure was 21.0 (IQR 10.3-41.3) months. Maximum AE severity was predominantly mild (n=395; 35.0%) or moderate (n=662; 58.7%); 62 (5.5%) participants reported severe or life-threatening AEs. Serious AEs (SAEs) occurred in 44 (3.9%) participants; seven (0.6%) experienced treatment-related SAEs. Overall, 149 (13.2%) participants discontinued due to AEs. Exposure-adjusted AE and TRAE rates were 73.6 and 56.4 events/exposure-years, respectively, during updosing and decreased to 13.6 and 7.6 events/exposure-years during 300-mg maintenance. Exposure-adjusted rates of systemic allergic reactions of any severity and of epinephrine use were low during Year 1 (0.26; 0.19) and decreased in Years 2 (0.16; 0.11), 3 (0.07; 0.07), and 4 (0.07; 0.05) of maintenance. Conclusion PTAH safety data, characterized over up to 4.5 years, consistently show AEs trend downward during continued maintenance dosing. Furthermore, systemic allergic reactions and epinephrine use occur less frequently, also trending downwards as treatment continues.