Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening condition. In 2018, the nanobody caplacizumab was approved for the treatment of adults experiencing an acute episode of aTTP, in conjunction with plasma exchange (PEX) and immunosuppression for a minimum of 30 days after stopping daily PEX. We performed a retrospective, observational analysis on the use of caplacizumab in 60 patients from 29 medical centers in Germany during acute disease management. Caplacizumab led to a rapid normalization of the platelet count (median, 3 days; mean 3.78 days). One patient died after late treatment initiation due to aTTP-associated complications. In 2 patients with initial disease presentation and in 4 additional patients with laboratory signs of an exacerbation or relapse after the initial therapy, PEX-free treatment regimens could be established with overall favorable outcome. Caplacizumab is efficacious in the treatment of aTTP independent of timing and ancillary treatment modalities. Based on this real-world experience and published literature, we propose to administer caplacizumab immediately to all patients with an acute episode of aTTP. Treatment decisions regarding the use of PEX should be based on the severity of the clinical presentation and known risk factors. PEX might be dispensable in some patients.

Objectives. To evaluate the prevalence and association of antineutrophil cytoplasmic antibodies (ANCA) and their subtypes [proteinase 3 (PR3)‐ANCA, myeloperoxidase (MPO)‐ANCA] with distinct clinical features in various clinicopathological syndromes. Methods. All consecutive ANCA‐positive patients seen at the combined unit for rheumatology for Bad Bramstedt and the University of Lübeck between 1989 and 1999 were analysed. ANCA were detected by an immunofluorescence technique and ANCA subspecificities were determined by ELISA. Clinical features at presentation and diagnoses were recorded according to standardized procedures. Results. Among 4620 patients tested, 333 were cytoplasmic ANCA‐positive and 291 were perinuclear ANCA‐positive. cANCA/PR3‐ANCA were strongly associated with Wegener's granulomatosis (WG), whereas pANCA/MPO‐ANCA were associated with a diverse disease spectrum. Further investigation of PR3‐ANCA‐positive (n=80) and MPO‐ANCA‐positive patients (n=40) revealed a greater extent of disease [disease extent index (DEI); median 8 vs 5, P<0.01] and more frequent involvement of the upper/lower respiratory tract and the eyes in PR3‐ANCA‐positive than in MPO‐ANCA‐positive patients. Fewer than 5% of WG patients were MPO‐ANCA‐positive. Compared with matched PR3‐ANCA‐positive WG patients, the MPO‐ANCA‐positive WG patients had a lower DEI (median 5 vs 8) and had a lower frequency of peripheral neuropathy. Conclusions. ANCA testing is useful due to its high sensitivity and specificity, especially for cANCA/PR3‐ANCA in WG. We found a divergence in the disease spectrum between PR3‐ and MPO‐ANCA‐positive patients, characterized by higher DEI and extrarenal manifestations in the PR3‐ANCA group. MPO‐ANCA was rarely found in WG and was associated with less organ involvement.

Steroid-resistant focal segmental glomerulosclerosis (FSGS) often recurs after renal transplantation. In this international survey, we sought to identify genotype–phenotype correlations of recurrent FSGS. We surveyed 83 patients with childhood-onset primary FSGS who received at least one renal allograft and analyzed 53 of these patients for NPHS2 mutations. The mean age at diagnosis was 6.7 years, and the mean age at first renal transplantation was 13 years. FSGS recurred in 30 patients (36%) after a median of 13 days (range, 1.5 to 152 days). Twenty-three patients received a second kidney transplant, and FSGS recurred in 11 (48%) after a median of 16 days (range, 2.7 to 66 days). None of the 11 patients with homozygous or compound heterozygous NPHS2 mutations developed recurrent FSGS compared with 45% of patients without mutations. These data suggest that genetic testing for pathogenic mutations may be important for prognosis and treatment of FSGS both before and after transplantation.

Introduction of the nanobody caplacizumab was shown to be effective in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP) in the acute setting. The official recommendations include plasma exchange (PEX), immunosuppression, and the use of caplacizumab for a minimum of 30 days after stopping daily PEX. This study was a retrospective, observational analysis of the use of caplacizumab in 60 patients from 29 medical centers in Germany. Immunosuppressive treatment led to a rapid normalization of ADAMTS13 activities (calculated median, 21 days). In 35 of 60 patients, ADAMTS13 activities started to normalize before day 30 after PEX; in 11 of 60 patients, the treatment was extended beyond day 30; and in 5 patients, it was extended even beyond day 58 due to persistent autoimmune activity. In 34 of 60 instances, caplacizumab was stopped before day 30 with a favorable outcome whenever ADAMTS13 activities were >10%. In contrast, 11 of 34 patients with ADAMTS13 activities <10% at the time of stopping caplacizumab treatment developed a nonfavorable outcome (disease exacerbation or relapse). In some cases, prolongation of the treatment interval to every other day was feasible and resulted in a sustained reduction of von Willebrand factor activity. ADAMTS13 activity measurements are central for a rapid diagnosis in the acute setting but also to tailor disease management. An ADAMTS13 activity–guided approach seems safe for identifying the individual time point when to stop caplacizumab to prevent overtreatment and undertreatment; this approach will result in significant cost savings without jeopardizing the well-being of patients. In addition, von Willebrand factor activity may serve as a biomarker for drug monitoring.