Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura

Abstract

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with PEX and immunosuppression. The objective of this study is to analyze and compare the safety and efficacy of caplacizumab versus the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 iTTP patients (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5% p<0.05) and less refractoriness (4.5% vs 14.1% p<0.05) than those that were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after plasma exchange (PEX) was associated with a lower number of PEX (OR 7.5, CI 2.3-12.7; p<0.05) and days of hospitalization (OR 11.2, CI 5.6-16.9; p<0.001) compared to standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared to the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared to standard of care regimens. When administered within the first 3 days after PEX it also provided a faster clinical response, reducing hospitalization time and the need for PEX.

CD38-specific nanobodies allow in vivo imaging of multiple myeloma under daratumumab therapy

“…Furthermore, the risk of allergic infusion reactions is reduced when using nanobodies as opposed to conventional antibodies, owing to their low immunogenicity ( 43 ). This possibly explains the lack of infusion reactions in patients receiving caplacizumab, the first FDA-approved nanobody ( 44 ).…”

Evidence-Based Minireview: Should caplacizumab be used routinely in unselected patients with immune thrombotic thrombocytopenic purpura?

“…15 Another series reported that 1 of 77 patients treated with caplacizumab expe ri enced fatal intra cranial hem or rhage soon after receiv ing the drug. 6 By contrast, no episodes of intracranial hemorrhage were observed in 219 consecutive episodes of iTTP treated with TPE during 13 years of data collected by the Harvard registry. 11 In the TITAN and HERCULES stud ies, caplacizumab use was asso ci ated with fewer TPE treat ments and a more than 4-fold increase in iTTP relapse com pared to pla cebo.…”

“…Second, 3 obser va tional stud ies uti liz ing his tor i cal con trols did not iden tify a sta tis ti cally sig nifi cant improve ment in all -cause mor tal ity with the use of caplacizumab. [4][5][6] Third, caplacizumab was asso ci ated with a sig nifi cantly increased risk of iTTP relapse in the US Food and Drug Administration reg is tra tion tri als, with the rate of fatal relapses not reported in any study to date. Unmeasured deaths from relapses linked to caplacizumab could cause the true mor tal ity rate in patients receiv ing the drug to be underestimated.…”

“…3 All large obser va tional stud ies of caplacizumab to date confirm the high rate of hem or rhagic com pli ca tions in patients receiv ing the drug, though non stan dard or incom plete reporting lim its the util ity of these expe ri ences in assessing risk. [4][5][6]14 Concerns around bleed ing were fur ther high lighted by 2 recent case series. In 20 patients treated ini tially with caplacizumab instead of TPE, 1 indi vid ual expe ri enced a sub dural hema toma requir ing neu ro sur gi cal inter ven tion and res cue ther apy with von Willebrand fac tor con cen trate.…”

More on the use of frontline caplacizumab in immune-mediated thrombotic thrombocytopenic purpura

“…Importantly, "frontline" caplacizumab refers to caplacizumab as part of the initial treatment of an acute iTTP episode, i.e., at the same time or within the very first days after the first therapeutic plasma exchange (TPE) 2,7 . It has indeed been repeatedly shown that patients receiving caplacizumab in a delayed manner had worse outcomes [8][9][10] . Notably, in the UK study included in the metaanalysis, caplacizumab initiation was delayed >48 hours after TPE initiation for 5 out of 6 deceased patients (up to 21 days) 9 .…”