A recent review discussing immunoglobulin (IG) replacement in hematological malignancies indicates that IG replacement is typically dosed based on actual body weight (ABW). However, due to its small volume of distribution, ideal body weight (IBW) or adjusted body weight (adjBW)-based dosing may be preferable and reduce costs and dose-dependent side effects. While data comparing dosing strategies for RIG are lacking, several observational studies have evaluated the dosing strategies of IG in the setting of hematological malignancies. A single-center retrospective study of 209 adult patients with secondary immunodeficiency (SID) received IG replacement doses using either ABW (n= 125) or IBW or adjBW (n= 84). No difference between the groups was observed in the 30- and 60-day infection rates. Additionally, both groups observed an 86% response rate for improving immunoglobulin G (IgG) levels from below 4 g/L at baseline to greater than 4 g/L within two weeks after treatment (see Table 1). [1], [2]
Similarly, another retrospective study of 297 patients who received IG replacement for various indications (e.g., Immunodeficiency, autoimmune, or infectious diseases) observed no difference in 30-day readmission rate or length of stay between patients who received ABW and IBW-based dosing (see Table 2). Additional benefits observed with the use of IBW or adjBW-based dosing were identified in another retrospective analysis that evaluated 9,918 doses of IG replacement administered to 2,564 patients over 5 years. Benefits included decreased Ig replacement consumption (approximately 22-36%), annual savings (approximately 2.37 to 3.89 million US dollars), and a reduction in annual outpatient infusion time (approximately 841 to 1,366 h or 48 to 78 minutes/patient). [3], [4]
While various factors may alter the pharmacokinetics of IG or the dose required (e.g., high body mass index, lower blood volume, drug clearance, chronic inflammation, increased Ig catabolism, and reduced neonatal Fc receptor recycling), it is suggested that these effects are likely to be minimal and not clinically significant. However, available data show that IG dosing based on IBW or adjBW rather than ABW may be an ideal alternative. Choosing an appropriate dosing strategy is essential as underdosing can potentially decrease the effectiveness of IG replacement, whereas overdosing can increase the cost, infusion time, and risk of adverse events. In light of the potential advantages of IBW or adjBW-based dosing, larger prospective studies comparing IBW or adjBW-based dosing to ABW-based dosing are necessary to help determine the most appropriate approach. [1], [2], [3], [4], [5]
A 2015 retrospective review of medical records assessed the correlation between the three weight-based dosing methods of IVIG and change in serum IgG. A total of 11 adults and 7 adolescent patients were assessed and calculated for their IBW and adjBW, which takes into account the patient’s height and gender. Adolescents had their IBW calculated using a specific formula: IBW= 2.396 e^(0.01863 x height in cm). In adult patients, the correlation was strongest with IBW based upon a correlation coefficient [r] of 0.83 (p<0.05) versus 0.73 for adjBW and 0.70 for ABW (p= 0.005 for both). In adolescent patients, the correlation coefficient was 0.99, 0.99, and 0.95, respectively (p<0.005 for all three). No statistical significance was reported between the three weight-based dosing methods. These findings suggest that IBW dosing of IVIG may be the greatest influencer of serum IgG levels, but the study's retrospective nature and small sample limit the results. IgG peak and trough levels were also measured inconsistently between patients, and certain disease states may alter treatment pharmacokinetics. Unfortunately, this study did not evaluate clinical efficacy or establish an optimal body weight for IVIG dosing. [6]
Available literature also described quality improvement initiatives or IVIG stewardship programs at different health institutions to conserve IVIG usage. A 2013 letter to the editor described a process of standardizing IVIG dosing to use ideal body weight at a single center, given immune globulin’s relatively low volume of distribution, long half-life, and lack of accumulation in tissue. Common indications for IVIG included hypogammaglobulinemia with recurrent infections in oncology, and bone marrow transplants comprised the majority of indications (53.6%), followed by acute organ rejection and antibody desensitization with plasmapheresis (10.6%) and idiopathic thrombocytopenic purpura with bleeding (9.1%). Overall, there was a significant reduction in the mean total dose of IVIG based on IBW compared to the theoretical IVIG dose (58 ± 44.1 g vs. 72.7 ± 62.3 g; p= 0.002), leading to a 20% theoretical reduction in the amount of IVIG dispensed over 12 months. Similarly, another prospective observational study implementing an IVIG stewardship program led by pharmacists found that an estimated 6,088 g of IVIG were saved during the study period using IBW instead of ABW. It should be noted, however, that neither report further evaluated patient outcomes associated with the IBW-based IVIG dosing strategy. [7], [8]