Orell Mielke

Efficacy and safety of Privigen® in patients with chronic inflammatory demyelinating polyneuropathy: results of a prospective, single-arm, open-label Phase III study (the PRIMA study)

This prospective, multicenter, single‐arm, open‐label Phase III study aimed to evaluate the efficacy and safety of Privigen® (10% liquid human intravenous immunoglobulin [IVIG], stabilized with l‐proline) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients received one induction dose of Privigen (2 g/kg body weight [bw]) and up to seven maintenance doses (1 g/kg bw) at 3‐week intervals. The primary efficacy endpoint was the responder rate at completion, defined as improvement of ≥1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale. The preset success criterion was the responder rate being ≥35%. Of the 31 screened patients, 28 patients were enrolled including 13 (46.4%) IVIG‐pretreated patients. The overall responder rate at completion was 60.7% (95% confidence interval [CI]: 42.41%–76.43%). IVIG‐pretreated patients demonstrated a higher responder rate than IVIG‐naïve patients (76.9% vs. 46.7%). The median (25%–75% quantile) INCAT score improved from 3.5 (3.0–4.5) points at baseline to 2.5 (1.0–3.0) points at completion, as did the mean (standard deviation [SD]) maximum grip strength (66.7 [37.24] kPa vs. 80.9 [31.06] kPa) and the median Medical Research Council sum score (67.0 [61.5–72.0] points vs. 75.5 [71.5–79.5] points). Of 108 adverse events (AEs; 0.417 AEs per infusion), 95 AEs (88.0%) were mild or moderate in intensity and resolved by the end of study. Two serious AEs of hemolysis were reported that resolved after discontinuation of treatment. Thus, Privigen provided efficacious and well‐tolerated induction and maintenance treatment in patients with CIDP.

Visible infarction on computed tomography is an independent predictor of poor functional outcome after stroke, and not of haemorrhagic transformation

Objectives: To examine a very large dataset to provide a robust answer to the question of whether visible infarction on computed tomography was (a) an independent predictor of functional outcome at all times up to 48 hours after stroke, and (b) independently associated with haemorrhagic transformation, with or without antithrombotic treatment. Methods: The study assessed associations between visible infarction, time to randomisation, baseline neurological deficit, stroke syndrome, allocated aspirin or heparin treatment, recurrent haemorrhagic stroke, early death and six month functional outcome in the International Stroke Trial. Results: Of 12 550 patients, 6267 (50%) had visible infarction up to 48 hours after stroke. The prevalence of visible infarction increased with increasing time from onset and extent of the stroke syndrome. Visible infarction was independently associated with increased death within 14 days (odds ratio (OR) 1.17, 95% CI 1.02 to 1.35), and of death or dependency at six months (OR 1.42, 95% CI 1.31 to 1.55), an absolute increase of 13%, or 130 per 1000 more dead or dependent patients with visible infarction than without it. There was no significant independent relation between visible infarction and fatal or non-fatal haemorrhagic transformation, or interaction between visible infarction and aspirin or heparin treatment allocation with six month functional outcome. Conclusions: Visible infarction on computed tomography up to 48 hours after stroke is an independent adverse prognostic sign.

Hemolysis related to intravenous immunoglobulins is dependent on the presence of anti‐blood group A and B antibodies and individual susceptibility

Patients treated with intravenous immunoglobulins (IVIG) rarely experience symptomatic hemolysis. Although anti‐A and anti‐B isoagglutinins from the product are involved in most cases, the actual mechanisms triggering hemolysis are unclear.

Minimum clinically important difference analysis confirms the efficacy of IgPro10 in CIDP: the PRIMA trial

Dear Editor, The PRIMA (PRivigen Impact on Mobility and Autonomy, NCT01184846) trial, a prospective, multi-center, single-arm, open-label, phase III trial, was designed to assess efficacy and safety of IgPro10 (10% liquid IVIG formulated with L-proline, Privigen®, CSL Behring, Berne, Switzerland) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) (Léger et al., 2013). The primary outcome of the PRIMA study was the responder rate by the 10-point adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score (responders defined as showing an INCAT score improvement ≥1 vs baseline). The success criterion (responder rate ≥35%) was met, making IgPro10 the second IgG product with demonstrated efficacy in CIDP (after IGIV-C) (Hughes et al., 2008; Léger et al., 2013). Here we examine the clinical relevance of the PRIMA study results using the concept of minimal clinically important difference (MCID), which is defined as the smallest difference in clinical score that patients perceive as beneficial and that could lead to a change in the patient’s management (Jaeschke et al., 1989). For this analysis, responder rates for various outcome measures used in the PRIMA trial were recalculated based on MCID cut-off values obtained through selected methods to determine whether the statistically significant results obtained previously also reflect clinically meaningful changes for patients with CIDP. In the PRIMA trial, 28 adult patients with definite or probable CIDP were included. All the enrolled patients first received an IgPro10 induction dose of 2 g/kg body weight in week 1, followed by up to seven infusions of 1 g/kg body weight at 3-week intervals. Outcome measures used in the PRIMA trial were selected based on previous recommendations for assessment in inflammatory neuropathies (Merkies and Lauria, 2006; Lunn et al., 2008). Change in INCAT scores, Medical Research Council (MRC) sum scores,

Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP), a multicenter randomized double-blind placebo-controlled trial: the Path study

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) often require long-term intravenous immunoglobulin (IVIG) maintenance therapy. Subcutaneous immunoglobulin (SCIG) offers an alternative administration option with anticipated improvements in patient quality of life, convenience, and flexibility. To evaluate IgPro20 (SCIG) as a maintenance treatment in CIDP. A randomized, double-blind trial in CIDP patients (n=172) investigated 0.2 and 0.4 g/kg weekly doses of IgPro20 versus placebo. The primary outcome was percentage of patients with CIDP relapse/withdrawal during 24-weeks of treatment determined by Inflammatory Neuropathy Cause and Treatment score. Secondary endpoints included grip strength and patient satisfaction. Both IgPro20 doses significantly reduced rate of CIDP relapse/withdrawal versus placebo. Grip strength remained stable with Hizentra®, but deteriorated with placebo. Most subjects preferred SCIG over IVIG. Local reactions, reported in 33% of IgPro20-treated patients, were mild or moderate in intensity. IgPro20 is efficacious and well-tolerated as maintenance treatment in CIDP. This article is protected by copyright. All rights reserved