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

Abstract

PurposeIntravenous 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.MethodsData 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.ResultsThe 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.ConclusionsThese 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.

Fatigue and the wear-off effect in adult patients with common variable immunodeficiency

“…This finding is compatible with previous studies that showed that IVIG and SCIG are equally effective in protecting against infections [21][22][23][24][25]. However, patients on IVIG reported higher infection rates towards the end of the infusion cycle, which was associated with the wear-off effect of IgGRT [26,27], and patients who switched from IVIG to SCIG reported less wear-off effect and less fatigue [28][29][30]. While these data would not provide any rationale for a priority consideration of therapeutic modality, they might equate to the consideration of offering SCIG treatment to patients receiving IVIG can also experience fatigue.…”

“…Studies using longitudinal modelling suggested that retirement was associated with a significant reduction in both mental and physical fatigue, especially in individuals with chronic conditions [17]. However, patients on IVIG reported higher infection rates towards the end of the infusion cycle, which was associated with the wear-off effect of IgGRT [26,27], and patients who switched from IVIG to SCIG reported less wear-off effect and less fatigue [28][29][30]. Previous studies have shown that non-white individuals (e.g.…”

Increased Incidence of Fatigue in Patients with Primary Immunodeficiency Disorders: Prevalence and Associations Within the US Immunodeficiency Network Registry

“…This difference is thought to be due to the lower variability in and more consistently physiological level of serum IgG concentration when Ig is administered via the subcutaneous route [32]. A recent study however showed that the probability of fatigue was greatest in the first week of both the 3- and 4-week dosing cycles and was significantly lower in the subsequent weeks of the treatment cycle, suggesting that fatigue may actually be a result of IVIG administration itself [33]. Further, more specific and prospective studies are needed to identify the relationship between fatigue and IgG replacement therapy.…”

Individualized immunoglobulin treatment in pediatric patients with primary humoral immunodeficiency disease

“…The risk of a first infection in the final week of the IVIG cycle was 26% and 55% higher than in the first week, for patients on a 3-week cycle and 4-week dosing cycles, respectively. 42 These symptoms can be ameliorated by increasing the dose or shortening the interval between IVIG and treating with SCIG. 44 SCIG has increasingly been viewed as an equally acceptable route of administration for IgG replacement therapy for patients with PIDD.…”