Caplacizumab 10mg powder and solvent for solution for injection vials

AbstractThrombotic thrombocytopenic purpura (TTP) is a rare, potentially fatal thrombotic microangiopathy caused by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13) deficiency. Prompt treatment improves survival; however, reference standard enzyme-linked immunosorbent assay and FRETS-VWF73 ADAMTS13 activity assays have long turnaround times (TATs) that necessitate empiric treatment of many patients who ultimately are found not to have TTP. Rapid assays with analytical TATs <1 hour have recently become available. We conducted a systematic review and meta-analysis of the performance characteristics of rapid assays relative to reference standard assays for ADAMTS13 activity for patients with suspected or confirmed TTP. Nineteen studies representing 3 rapid ADAMTS13 assays and 4207 patient samples were included. The HemosIL AcuStar chemiluminescence immunoassay (CLIA) demonstrated high sensitivity (0.98; 95% confidence interval [CI], 0.94-1.00), specificity (0.99; 95% CI, 0.97-1.00), and positive (PPV) (0.96; 95% CI, 0.90-0.98) and negative predictive values (NPV) (0.99; 95% CI, 0.99-1.00). The Technofluor fluorescence resonance energy transfer (FRET) and Technoscreen assays had sensitivity of 0.93 (95% CI, 0.86-0.96) and 0.98 (95% CI, 0.42-1.00), specificity of 0.98 (95% CI, 0.95-0.99) and 0.87 (95% CI, 0.76-0.94), PPV of 0.97 (95% CI, 0.85-1.00) and 0.71 (95% CI, 0.59-0.80), and NPV of 0.96 (95% CI, 0.93-0.98) and 0.99 (95% CI, 0.72-1.00), respectively. The proportion of discrepant results (relative to reference standard assays) was 0.04 (95% CI, 0.03-0.05) for HemosIL AcuStar, 0.04 (95% CI, 0.02-0.06) for Technofluor FRET, and 0.11 (95% CI, 0.07-0.16) for the Technoscreen assay. With rapid TAT and high sensitivity, the HemosIL AcuStar CLIA seems able to reliably avert empiric plasma exchange, corticosteroids, and caplacizumab in patients without TTP.

Abstract licence: CC BY-NC-ND

BackgroundImmune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disorder caused by anti-ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) antibodies. Although therapeutic plasma exchange (TPE) and corticotherapy have long been the standard of care (SOC), rituximab and caplacizumab are increasingly incorporated into clinical practice. Given that these drugs significantly increase the costs of iTTP treatment, synthesizing the available evidence is important for coverage decisions in resource-limited settings.ObjectivesTo summarize and critically appraise systematic reviews with meta-analyses (SRMAs) evaluating effectiveness and safety of rituximab and caplacizumab for iTTP treatment.MethodsPubMed, EMBASE, the Cochrane Library, and LILACS were searched up to August 2025. Two reviewers screened citations, with disagreements resolved by a third reviewer. Data extraction was performed by one reviewer and verified by another. Findings were synthesized narratively.ResultsSeven SRMAs were included: two evaluated rituximab and five caplacizumab. SRMAs of rituximab included non-randomized studies and reported reductions in mortality and relapse when added to SOC, although exacerbation and safety were not assessed. SRMAs of caplacizumab included two randomized and nine non-randomized studies. Mortality reduction with caplacizumab was not demonstrated in randomized trials, although real-world data suggested a survival benefit. Randomized trials showed reduced risk of exacerbation and increased risk of bleeding, but no consistent effect on relapse. All SRMAs were rated as critically low methodological quality.ConclusionAlthough SRMAs suggest rituximab and caplacizumab may improve clinical response and survival, with more consistent evidence favoring rituximab, their critically low methodological quality highlights limitations in the current evidence base.

Abstract licence: CC BY

Background Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy characterized by severe ADAMTS13 deficiency and accumulation of ultralarge von Willebrand factor multimers. Although therapeutic plasma exchange (PEX), corticosteroids, rituximab, and caplacizumab have improved outcomes, refractory and relapsing disease remain important clinical challenges. N-acetylcysteine (NAC) has been explored as an adjunctive therapy because of its ability to reduce disulfide bonds within von Willebrand factor multimers.Objective This systematic review aimed to summarize the published clinical experience with NAC in TTP, including treatment strategies, reported outcomes, and safety.Methods A systematic search of PubMed was performed from database inception until December 31, 2025, using combinations of the terms "thrombotic thrombocytopenic purpura", "TTP", "N-acetylcysteine", and "acetylcysteine". Two reviewers independently screened records, assessed full texts against predefined eligibility criteria, and extracted study-level data. Eligible studies included case reports and case series describing therapeutic NAC use in patients with TTP. The review was conducted in accordance with PRISMA 2020 guidance. The protocol was not prospectively registered.Results Six publications comprising 22 adult patients were included. NAC was used as adjunctive therapy, predominantly in refractory or relapsing TTP, alongside PEX, corticosteroids, rituximab, and/or other immunosuppressive therapies. Platelet recovery was reported following NAC initiation in the included cases, with concurrent improvement in hemolysis markers and neurologic symptoms described in some reports. No serious NAC-related adverse events were reported in the included cases. Because all evidence was derived from uncontrolled reports with concomitant therapies, the independent contribution of NAC cannot be established.Conclusions The available case-based literature suggests that NAC is a biologically plausible and generally well-tolerated adjunctive therapy in refractory or relapsing TTP. However, the current evidence remains hypothesis-generating and is insufficient to establish efficacy. Prospective studies are needed to clarify its therapeutic role, optimal dosing, and patient selection.

Abstract licence: CC BY