Delayed ADAMTS13 normalisation in caplacizumab/PEX treated patients associated with anti-ADAMTS13 IgG antibody boosting

Delayed ADAMTS13 normalisation was previously reported in a subgroup of caplacizumab/PEX-treated patients. To further explain this finding, we analysed anti-ADAMTS13 IgG antibody levels at multiple time points during the acute TTP episode in 59 caplacizumab/PEX and 50 non-caplacizumab/PEX cases. Caplacizumab/PEX cases required fewer PEX, taking longer to achieve ADAMTS13 activity >20% than non-caplacizumab/PEX cases (median 33 days vs 17.5 days, p<0.0001). More caplacizumab/PEX cases increased anti-ADAMTS13 IgG antibody after stopping PEX (40% vs 25.5% in non-caplacizumab/PEX cases, p=0.14). Cases requiring more than thirty days of caplacizumab had a higher presenting anti-ADAMTS13 IgG antibody compared to less than 30 days (63.5% vs 25%, p=0.02). 50% of cases requiring more than 30 days of caplacizumab, increased anti-ADAMTS13 IgG antibody post PEX, with median 101 days to ADAMTS13 activity >20%, compared to 28 days (p<0.0001) in patients without an antibody increase. Fifty-four percent of all caplacizumab cases had presenting anti-ADAMTS13 IgG antibody >40% and 47% had an increased antibody post PEX, taking longer to achieve an ADAMTS13 activity >20%. 33% with presenting anti-ADAMTS13 IgG antibody <40% increased their antibody following PEX, taking 97.5 days to achieve ADAMTS13 activity >20%. Cases with presenting anti-ADAMTS13 antibody <40% and no increase in antibody post PEX took a median of 14 days (p=0.0005). Therefore, delayed normalisation of ADAMTS13 activity in a subgroup of caplacizumab/PEX cases was associated with antibody boosting, more common with a higher presenting anti-ADAMTS13 IgG antibody and subsequently, longer caplacizumab use. These findings were subsequently confirmed in 93 cases receiving caplacizumab/PEX over 3 years.