Efficacy, tolerability, safety and pharmacokinetics of a nanofiltered intravenous immunoglobulin: studies in patients with immune thrombocytopenic purpura and primary immunodeficiencies

Wolf, Hans‐Heinrich; Davies, S.V.; Borte, Michael; Caulier, Mathieu; Williams, Paul; Bernuth, Horst von; Egner, William; Sklenar, I.; Adams, Carolyn E.; Späth, Peter; Morell, A.; Andresen, Irmgard

doi:10.1046/j.1423-0410.2003.00255.x

Cited by 39 publications

(34 citation statements)

References 35 publications

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“…In fact, a phase I study as well as unpublished data from two additional studies with IVIG-F10 and Sandoglobulin in healthy subjects suggest that the t1/ 2 values for IgG and anti-HBsAg of the two products are similar [11, ZLB Behring, data on file]. Interestingly, in the present study the anti-HBsAg of both products had a shorter t1/ 2 than the total IgG, which confirms results of a recent study, but differs from others [11,26,34]. Possibly, the difference reflects the IgG subclass composition of this antibody.…”

Section: Discussionsupporting

confidence: 88%

“…As in previous investigations, we attempted to document a correlation between IVIG-induced release of cytokines and the occurrence of inflammatory AE, selecting TNF-α as a protagonist of a pro-inflammatory cytokine [18,19,26]. Interestingly, in patients with chronic ITP, IVIG-F10 induced on average a more pronounced TNF-α increase than Sandoglobulin.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with chronic ITP, the most frequently used IVIG regimen consists of one or two infusions of 0. within 3 days [14,25]. In this study, we applied the original dosage of 0.4 g/kg on 5 consecutive days for reasons of comparability with another recently published trial [26]. The results showed that there were no significant differences between IVIG-F10 and Sandoglobulin in the numbers of responders as well as in the time to platelet response or its magnitude.…”

Section: Discussionmentioning

confidence: 99%

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Clinical Properties of a Novel Liquid Intravenous Immunoglobulin: Studies in Patients with Immune Thrombocytopenic Purpura and Primary Immunodeficiencies

Borte¹,

Davies²,

Touraine³

et al. 2004

Transfus Med Hemother

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Background: We have developed a novel liquid intravenous immunoglobulin (IVIG-F10). It consists of a nanofiltered 12% immunoglobulin G (IgG) solution, stabilized with nicotinamide, L-proline and L-isoleucine. The efficacy, tolerability, safety, and pharmacokinetics of this product were assessed in patients with chronic immune thrombocytopenic purpura (ITP) and primary humoral immunodeficiencies (PID). Patients and Methods: 33 chronic ITP patients with platelet counts of < 20 × 10⁹/l were treated with IVIG-F10 or Sandoglobulin at doses of 0.4 g/kg body weight on 5 consecutive days. The primary efficacy endpoint was an increase in platelet counts to ≧50 × 10⁹/l. Secondary endpoints were time to and duration of platelet response and regression of bleeding. 34 PID patients with X-linked agammaglobulinemia, common variable immunodeficiency or IgG subclass deficiency were treated for 6 months with IVIG-F10 or Sandoglobulin at doses of 0.3–0.8 g/kg, infused at 3- or 4-week intervals. The primary efficacy endpoint was the number of days absent from school/work. Secondary endpoints were feeling of well-being, days of hospitalization, and use of antibiotics. Results: In ITP patients, the primary endpoint was met by 12/16 patients on IVIG-F10 and by 12/17 patients on Sandoglobulin (p = 1.000). Results of the secondary endpoints were comparable in the two study groups. In the PID study, 10/17 patients on IVIG-F10 and 9/17 patients on Sandoglobulin missed days at school/work, with monthly mean absences of 0.7 and 0.6 days (p = 0.746), respectively. There were no significant differences in the outcome of the secondary endpoints. Pharmacokinetics showed constant peak and trough serum IgG levels in PID patients. The median half-life (t_1/2) of IgG was 33 days in the IVIG-F10 group and 41 days in the Sandoglobulin group. For anti-HBsAg, median t_1/2 values were shorter, i.e. 17 and 19 days for IVIG-F10 and Sandoglobulin, respectively. In the ITP study, adverse events related to study drug were suspected in 9 and 14 patients treated with IVIG-F10 and Sandoglobulin, respectively; in the PID study adverse events occurred in 8 and 9 patients, respectively. Viral safety was ascertained in both studies by serology supplemented with nucleic acid amplification testing. Serum levels of the stabilizers transiently increased after infusion of IVIG-F10, but were back to baseline at the following day. Conclusions: The clinical studies in patients with chronic ITP and PID showed that the efficacy, tolerability, safety, and pharmacokinetics of IVIG-F10 were comparable to the properties of Sandoglobulin.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Clinical Properties of a Novel Liquid Intravenous Immunoglobulin: Studies in Patients with Immune Thrombocytopenic Purpura and Primary Immunodeficiencies

Borte¹,

Davies²,

Touraine³

et al. 2004

Transfus Med Hemother

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“…In a similar study in adults with chronic ITP, treatment response defined as platelet increase to ≥50 × 10 9 /l was achieved in 73.4% of the subjects [35]. A platelet increase to ≥50 × 10 9 /l was attained in 75% of the subjects who received a nanofiltered preparation as reported in a study comparing 2 different IGIV preparations [36]. In a study comparing two 12% immunoglobulin preparations, a platelet increase to ≥50 × 10 9 /l was seen in 75 and 71% of the subjects [37].…”

Section: Discussionmentioning

confidence: 58%

Efficacy and Safety of the New Intravenous Immunoglobulin IGIV 10% in Adults with Chronic Idiopathic Thrombocytopenic Purpura

Varga

Volková

Leibl

et al. 2006

Transfus Med Hemother

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Background: Intravenous immunoglobulin (IGIV) 10% is a newly developed 10% liquid immunoglobulin preparation for intravenous use where 3 dedicated virus reduction steps have been integrated into the manufacturing process. The efficacy and safety of this product were assessed in a prospective multicenter study in chronic ITP (idiopathic thrombocytopenic purpura) patients with platelet counts of =20 × 109/l. Patients and Methods: 23 adult ITP patients received the product at a total dose of 2 g/kg body weight administered over 2-5 days, and were followed for 4 weeks. Results: Of the 21 subjects included in the Per-Protocol Analysis Data Set, 15 responded successfully to treatment (71.4%). Eleven subjects in this group attained a platelet count increase to >100 × 109/l, and 8 reached a platelet count of >200 × 109/l. All 15 responders achieved a platelet count of =50 × 109/l by day 8, and 14 of them reached this level by day 5. The median duration of platelet response was 25 days, and the highest median platelet count in the responders was 182 × 109/l. A total of 81 infusions were administered to the 23 subjects in the Safety Analysis Data Set over the course of the study. There were 40 non-serious adverse events related to the use of the study drug - 35 mild, 3 moderate, and 2 severe. The most frequent related adverse events were headache and pyrexia. Conclusion: The results obtained in this study demonstrate that IGIV 10% is effective in the treatment of adult subjects with chronic ITP and indicate a good safety profile.

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“…ha messo a confronto, in uno studio di fase II/III, la sicurezza, la farmacocinetica e l'efficacia delle preparazioni nanofiltrate (IVIG-N) e delle IVIG tradizionali, in pazienti affetti da porpora trombocitopenica idiopatica ed immunodeficienza primitiva. Le IVIG-N si sono dimostrate sicure dal punto di vista virologico e comparabili in termini di efficacia e farmacocinetica alle IVIG tradizionali (66).…”

Section: Effetti Indesideratiunclassified

Indications for intra-venous immunoglobulin treatment in rheumatic diseases

Pasini¹,

Capecchi²,

Bellisai³

et al. 2011

Reumatismo

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Con l'immissione in commercio delle Immunoglobuline per uso endovenoso (IVIG), che risale ormai al 1981, è stato possibile ampliarne enormemente le utilizzazioni terapeutiche, dimostrando l'efficacia di tale trattamento in condizioni cliniche le più diverse. In particolare, sulla base della progressiva acquisizione di conoscenze circa la capacità delle IVIG ad alte dosi di interferire a vari livelli col sistema immunitario, ne è stato proposto l'impiego in moltissime patologie su base autoimmunitaria o comunque dipendenti da meccanismi di tipo flogistico-immunitario. Ci limiteremo in questa sede a riportare le indicazioni al trattamento con IVIG, di quelle situazioni cliniche, di stretta competenza reumatologica, per le quali l'evidenza di efficacia sia sufficientemente solida, sia cioè basata su sperimentazioni cliniche allargate e adeguatamente controllate. Prima di procedere alla disamina degli aspetti terapeutici è tuttavia opportuno ricordare brevemente i meccanismi invocati per spiegare la potente attività immunomodulante di cui sono dotate le IVIG. I meglio conosciuti e documentati sono i seguenti. 1) Interazioni con i recettori per la porzione Fc (FcR)Questo meccanismo, operante in una ormai classica indicazione all'uso di Immunoglobuline endovena quale è la Porpora Trombocitopenica Idiopatica (PTI), può essere influenzato a più livelli dalla somministrazione di IVIG: a. blocco del recettore per il frammento Fc (FcR) (1); b. stimolazione (ed induzione della espressione) del recettore Fc inibitorio (FcγRIIB) capace di contrastare l'attivazione indotta dal legame dell'autoanticorpo con il FcR (2) e di inibire attivamente la proliferazione e la funzione delle cellule B (3); c. saturazione del recettore FcRn intracellulare con accellerato catabolismo degli auto-Ab (IgG) (4). 2) Innesco di reazioni idotipo-antiidiotipoL'idiotipo delle molecole anticorpali è dotato di proprietà antigeniche in grado di innescare la produzione, limitata ma continua, di altrettanto specifici anticorpi anti-idiotipo. Questi ultimi, contenuti in abbondanza nel pool delle IVIG, hanno il compito di prevenire l'innesco di reazioni autoimmunitarie attraverso diversi possibili meccanismi: a. neutralizzazione di auto-anticorpi: Nelle IVIG sono stati dimostrati anticorpi antiidiotipo capaci di riconoscere specificatamente diversi auto-anticorpi importanti in patologia umana, tra cui gli Ab anti-tireoglobulina, gli Ab anti-DNA, gli Ab anti-recettore dell'acetilcolina, gli ANCA, gli Ab anti-fattore VIII, gli Ab anti-MAG, gli ab anti-endotelio (AECA), gli Ab anti-fosfolipidi e gli Ab anti-antigeni retinici (5-9). Recentemente, è stato evidenziata la presenza nelle preparazioni di IVIG di anticorpi anti-idiotipo capaci di reagire con anticorpi anti-LDL ossidate (aventi un ruolo chiave nel processo immuno-flogistico che sostiene la formazione della placca aterosclerotica) suggerendo un possibile meccanismo immunomodulante attraverso cui potrebbe esplicarsi il dimostrato (in modelli murini) effetto anti-aterogeno delle IVIG (10). b. riduzione d...

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Efficacy, tolerability, safety and pharmacokinetics of a nanofiltered intravenous immunoglobulin: studies in patients with immune thrombocytopenic purpura and primary immunodeficiencies

Abstract: IVIG-N is efficacious, well tolerated and safe in patients with ITP and PID. Its pharmacokinetic properties were comparable to those of Sandoglobulin.

Cited by 39 publications

References 35 publications

Clinical Properties of a Novel Liquid Intravenous Immunoglobulin: Studies in Patients with Immune Thrombocytopenic Purpura and Primary Immunodeficiencies

Clinical Properties of a Novel Liquid Intravenous Immunoglobulin: Studies in Patients with Immune Thrombocytopenic Purpura and Primary Immunodeficiencies

Efficacy and Safety of the New Intravenous Immunoglobulin IGIV 10% in Adults with Chronic Idiopathic Thrombocytopenic Purpura

Indications for intra-venous immunoglobulin treatment in rheumatic diseases

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