This prospective, multicenter, single-arm, open-label phase 3 study aimed to evaluate the efficacy and safety of IqYmune in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients received one induction dose of 2 g/kg and then seven maintenance doses of 1 g/kg at 3-week intervals. The primary endpoint was the responder rate at the end of study (EOS), defined as an improvement of ≥1 point on the adjusted inflammatory neuropathy cause and treatment (INCAT) disability scale. The responder rate was compared with the responder rate of a historical placebo group (33.3%). Secondary endpoints included changes from baseline to EOS of adjusted INCAT disability score, grip strength, Medical Research Council (MRC) sum score, Rasch-modified MRC sum score, Rasch-built overall disability scale score and the clinical global impression. Forty-two patients, including 23 Ig-naïve and 19 Ig-pre-treated, were included in the efficacy set. The overall response rate at EOS was 76.2% (95% confidence interval [60.5%-87.9%]). The superiority of IqYmune compared to the historical placebo control was demonstrated (P < .0001). The responder rate was numerically higher in Ig-pre-treated than in Ig-naïve patients but confidence intervals were overlapping (84.2% [60.4%-96.6%] vs 69.6% [47.1%-86.8%]). All secondary endpoints confirmed this conclusion. The median time to response was 15 weeks [8.9-19.1 weeks]. A total of 156 adverse events including five serious were considered related to IqYmune, 87.2% were mild. Neither hemolysis nor signs of renal or hepatic impairment were observed. These results demonstrate that IqYmune is an effective and well-tolerated treatment in patients with CIDP.

Objective To date, the use of a fibrinogen concentrate (FC) administered in children with inherited fibrinogen deficiency is poorly documented. Treatment modalities may differ from those of adults. The aim of this study was to investigate the pharmacokinetics (PK), efficacy (bleeding/surgery) and safety of a triple-secured FC (FibCLOT, LFB, France) in young patients aged of 12 years or less. Methods This was a prospective, non-comparative, multicentre, phase 2–3 study. Estimated PK parameters were based on population PK modelling. Target fibrinogen levels were 1.2 and 1.0 g/L for major and minor events, respectively. In vivo recovery (IVR) was calculated at study entry to tailor the dose. Results Sixteen afibrinogenaemia patients were treated with FC: 12 included in the PK study (6 aged ≤ 6 years and 6 aged 7–12 years). IVR at 1 hour post-infusion (geometric mean [coefficient of variation]) was 1.91 [20%] mg/dL per mg/kg and results were similar between the two age groups (1.87 [14%]) and (1.96 [27%]) with no statistical differences. Estimated half-life (t 1/2) was 49.0 hours [12%] with no observed differences between groups (46.6 hours [10%] and 51.6 hours [12%]). Overall efficacy was rated as excellent/good in 96.9% of 32 bleeds and in 100% of 11 surgeries. Most of the events (39/43, 90.7%) were managed with one infusion. There was no serious adverse drug reaction. Conclusion Individually tailored dosing was efficacious in children who exhibited a lower IVR and shorter t 1/2 than those previously reported in adolescent and adult patients emphasising the importance of individualised dose optimisation.

Introduction/Aims Treatment response and its timing are variable in chronic inflammatory demyelinating polyneuropathy (CIDP). In this study we assessed the variability using multiple outcome measures. Methods We performed a post hoc analysis of the PRISM trial, a 24‐week prospective, multicenter, single‐arm, open‐label, phase III study of a 10% intravenous immunoglobulin preparation for CIDP. We ascertained timing of response with primary/secondary outcome measures. Results At 6 weeks after treatment initiation, 13 of 40 subjects (32.5%) were defined as responders on the primary outcome measure, the adjusted Inflammatory Neuropathy Cause And Treatment (INCAT) scale. This increased to 20 of 41 (48.8%) at 12 weeks and to 32 of 42 (76.2%) at 24 weeks. Use of minimal important difference (MID)‐determined amelioration of the inflammatory Rasch‐built Overall Disability Scale (I‐RODS), or of the Medical Research Council sum score (MRCSS), or of dominant hand‐grip strength, in addition to the adjusted INCAT, indicated a sensitivity of 41.7% in identifying adjusted INCAT nonresponders at week 12 who subsequently responded at week 24. Specificity was 60% vs INCAT nonresponders at week 24. Consideration of amelioration of any amplitude on any secondary outcome measure indicated a 75% sensitivity, but only 30% specificity vs adjusted INCAT nonresponders at week 24. Discussion Immunoglobulin treatment continuation may be justified for up to 24 weeks in CIDP. Additional outcome measures may help in the early treatment stages to predict delayed response on the adjusted INCAT. However, their use is limited by high false‐positive rates. More robust, reliable, and relevant outcome measures are needed to detect early improvement in immunoglobulin‐treated CIDP.

Introduction: A plasma-derived factor VIII product (pdFVIII, Factane 100 or 200 IU/mL) and a plasma-derived von Willebrand factor product (pdVWF, Wilfactin 100 IU/mL) are approved for replacement therapy by intravenous bolus injections in haemophilia A (HA) and von Willebrand disease (VWD), respectively. However, in situations requiring intensive treatment, continuous infusion (CI) may be desirable to better control target plasma factor levels. Aim: To evaluate the perioperative haemostatic efficacy and safety of these concentrates administered by CI. Methods: Three phase III trials were conducted. Adults with HA (FVIII:C <1%) (Studies 1 and 2) or VWD (VWF:RCo <20%) (Study 3) received a preoperative bolus followed by CI of undiluted concentrate for at least 6 days. Bolus doses and CI rates were based on individual recovery and clearance, respectively. Initial infusion rate had to be higher for 48 hours for HA and 24 hours for VWD patients to anticipate potential fluctuations of factor concentrations during major surgery. Target levels of FVIII:C in HA and VWF:RCo in VWD were 80 and 70 IU/dL, respectively. Efficacy was assessed using a global haemostatic efficacy score. Results: Studies 1, 2, and 3 included 12, 4 and 6 patients, respectively. Efficacy outcomes were excellent/good in all 22 major surgeries including 18 orthopaedic procedures. Most daily measured FVIII and VWF levels (92%) were on target. No safety concerns, thrombotic events or inhibitors were identified. Conclusion: pdFVIII and pdVWF administered by CI represent an effective and safe alternative to bolus injections in patients with severe HA or VWD undergoing surgery.