Dataset Information

Quantitative Evidence of Wear-Off Effect at the End of the Intravenous IgG (IVIG) Dosing Cycle in Primary Immunodeficiency.

ABSTRACT: Intravenous IgG (IVIG) treatment wear-off is commonly experienced by patients, who report increased susceptibility to infection, and decreased quality of life towards the end of their 3- or 4-week dosing cycle, when serum IgG levels approach their trough. We quantified IVIG wear-off in terms of treatment efficacy and patient well-being.Data were collected from patients enrolled in three Phase III trials of Sandoglobulin NF Liquid or Privigen, treated every 3- or 4- weeks. Pooled analyses of raw patient data compared the rate of infection and other clinical outcomes during the course of the dosing cycle. Subjective symptoms of wear-off were quantified by comparing patient-reported overall well-being scores.The probability of a first infection in the final week of the IVIG cycle was 1.26 (95% confidence intervals [CI]: 0.76-2.11; p = 0.3621) and 1.55 (95% CI: 1.04-2.32; p = 0.0314) times higher than in the first week, for patients on a 3-week cycle and 4-week dosing cycles, respectively. Wear-off, as manifested by a decrease in overall well-being, was experienced in 10% of all cycles and reported at least once by 61% of the patients on a 3-week cycle, and 43% of those on a 4-week cycle.These findings confirm the existence of decreased efficacy (treatment wear-off) towards the end of a 3-4 week IVIG dosing cycle, and provide a quantifiable evaluation to a phenomenon typically reported anecdotally. For patients experiencing wear-off, increasing the IgG dose or shortening the dosing interval and/or a switch to SCIG may be beneficial.

SUBMITTER: Rojavin MA

PROVIDER: S-EPMC4792336 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Quantitative Evidence of Wear-Off Effect at the End of the Intravenous IgG (IVIG) Dosing Cycle in Primary Immunodeficiency.

Rojavin Mikhail A MA Hubsch Alphonse A Lawo John-Philip JP

Journal of clinical immunology 20160224 3

<h4>Purpose</h4>Intravenous IgG (IVIG) treatment wear-off is commonly experienced by patients, who report increased susceptibility to infection, and decreased quality of life towards the end of their 3- or 4-week dosing cycle, when serum IgG levels approach their trough. We quantified IVIG wear-off in terms of treatment efficacy and patient well-being.<h4>Methods</h4>Data were collected from patients enrolled in three Phase III trials of Sandoglobulin NF Liquid or Privigen, treated every 3- or 4 ...[more]

PMID: 26910102

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Project description:BackgroundPatients with primary immunodeficiency disease (PIDD) and antibody deficiency require lifelong immunoglobulin replacement therapy. While both subcutaneous immunoglobulin (SCIG) and intravenous immunoglobulin (IVIG) replacement therapy are effective in preventing infection, patients with PIDD still experience worse health-related quality of life (hrQOL) outcomes.ObjectiveAssess differences in hrQOL for PIDD patients receiving home SCIG versus IVIG.MethodsSF-36 surveys were administered by a specialty pharmacy to 630 PIDD patients receiving home SCIG and IVIG at baseline and then every 3 months between 2014 and 2016. Results were analyzed using two-sample t tests and linear mixed effects model. Analysis was repeated for different age categories and trended over time.ResultsPatients receiving SCIG reported statistically significant higher energy fatigue scores (+ 9 points, p < 0.001) but lower perceived role limitations due to physical health scores (- 14 points, p < 0.001). These differences were only observed in patients > 36 years of age. There were no differences in the composite SF-36 score for patients receiving SCIG versus IVIG (+ 1, p = 0.66). Immunoglobulin-naïve patients all improved their hrQOL, but a larger improvement was seen in those initiating SCIG versus IVIG.ConclusionPatients with PIDD on home IVIG versus SCIG have similar composite hrQOL scores as measured by the SF-36. In the adult population, initiating immunoglobulin replacement with SCIG may result in more hrQOL improvement compared with IVIG, although personal preferences should also be considered.Clinical implicationsPatients with PIDD on home IVIG versus SCIG have similar composite health-related quality of life scores as measured by the SF-36. Patients with primary immune-deficiency on home IVIG versus SCIG have similar composite health-related quality of life scores as measured by the SF-36. Personal preferences are important in deciding whether to treat with IVIG or SCIG.

Project description:Ischemic stroke causes a high rate of deaths and permanent neurological damage in survivors. Ischemic stroke triggers the release of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1), which activate toll-like receptors (TLRs) and receptor for advanced glycation endproducts (RAGE) in the affected area, leading to an exaggerated inflammatory response and cell death. Both TLRs and RAGE are transmembrane pattern recognition receptors (PRRs) that have been shown to contribute to ischemic stroke-induced brain injury. Intravenous immunoglobulin (IVIg) preparations obtained by fractionating human blood plasma are increasingly being used as an effective therapeutic agent in the treatment of several inflammatory diseases. Its use as a potential therapeutic agent for treatment of stroke has been proposed, but little is known about the direct neuroprotective mechanisms of IVIg. We therefore investigate whether IVIg exerts its beneficial effects on the outcome of neuronal injury by modulating HMGB1-induced TLR and RAGE expressions and activations.Primary cortical neurons were subjected to glucose deprivation or oxygen and glucose deprivation conditions and treated with IVIg and recombinant HMGB1. C57/BL6J mice were subjected to middle cerebral artery occlusion, followed by reperfusion, and IVIg was administered intravenously 3 h after the start of reperfusion. Expression of TLRs, RAGE and downstream signalling proteins in neurons and brain tissues were evaluated by immunoblot.Treatment of cultured neurons with IVIg reduced simulated ischemia-induced TLR2, TLR4, TLR8 and RAGE expressions, pro-apoptotic caspase-3 cleavage and phosphorylation of the cell death-associated kinases such as c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) as well as the p65 subunit of nuclear factor kappa B (NF-?B). These results were recapitulated in an in vivo model of stroke. IVIg treatment also upregulated the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) in cortical neurons under ischemic conditions. Finally, IVIg protected neurons against HMGB1-induced neuronal cell death by modulating TLR and RAGE expressions and signalling pathways.Taken together, these results provide a rationale for the potential use of IVIg to target inappropriately activated components of the innate immune system following ischemic stroke.

Dataset Information

Quantitative Evidence of Wear-Off Effect at the End of the Intravenous IgG (IVIG) Dosing Cycle in Primary Immunodeficiency.

Publications

Quantitative Evidence of Wear-Off Effect at the End of the Intravenous IgG (IVIG) Dosing Cycle in Primary Immunodeficiency.

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