Correlation between immunoglobulin dose and incidence of severe and serious infections in secondary immunodeficiencies.

Abstract

e21686 Background: In an interim analysis of an ongoing multicenter observational study on the efficacy and safety of the polyvalent i.v. immunoglobulin product (IVIG) Privigen, we investigated a possible correlation between the two mostly used treatment regimens in Germany - 10 g or 20 g once a month - and the incidence of severe and serious infections in secondary immunodeficiencies (SID). Methods: All patients fulfilling the following criteria were included in this analysis: 1) SID; 2) observation period ≥120 d; 3) ≥6 Privigen infusions; 4) stable dosing, defined as identical doses from the 2nd up to the last administration (a differing loading or test dose at baseline was accepted); 5) a series of at least 4 consecutive dosing intervals each with a duration of at least 21 d and not more than 35 d (any time during the observation period); 6) no other IVIG indication than SID. The cut-off date was Dec. 19, 2016. Results: 835 patients (454 m, 381 f; average 68 years, 76 kg) in 112 centers fulfilled the above criteria. The most frequent underlying diseases were CLL (n = 422), myeloma (175) and NHL (182). The mean observation period was 20.5 mo; the median dosing interval was 28 d. Most patients had a stable Privigen dosing of either 10 g (n = 575; 69%) or 20 g (n = 192; 23%); 68 patients (8%) received other dosages. In order to reduce potential confounding effects of varying dosing intervals, only intervals ( = cycles) complying with the following "steady-state rules" were included in the analysis: 1) duration 21-35 d; 2) each of the 3 preceding intervals also 21-35 d long. 7,858 out of 15,687 treatment cycles (50%, all dosages) complied with these rules and were evaluated for severe and serious infections (acc. to FDA criteria). With the 10 g regimen, 34 severe or serious infections occurred in 5,306 evaluable treatment cycles, while with the 20 g regimen, it was only 2 in 1,851 (p = 0.003). This corresponds to rates of 8.3 vs. 1.4 severe/serious infections per 100 patient years (about half of them pneumonias). There was no increase of reported adverse reactions with the higher dose. Conclusions: With a monthly dose of only 10 g IVIG compared with 20 g, adult SID patients have a considerably higher risk of severe and serious infections.