IGRT is widely used to treat PID, as IVIG or SCIG and its use has been increasing. IGRT is also used as an anti-inflammatory and immunomodulatory medication. However, there are insufficient data on the frequency of administration of SCIG therapy in children. Furthermore, there are no data on use of this therapy in children with LBW. This is one of largest studies in the literature on the effects of SCIG administration in pediatric patients with PID and reveals that SCIG can be safely used in children with LBW.
IVIG therapy has been used globally, including in our country, for a long period of time, while SCIG therapy has been safely used as a treatment modality in both adults and children since 2006 in Europe and the U.S. There are two main routes of administration for SCIG. In recent years, SCIG therapy has become a preferred route of administration that utilizes an infusion pump or rapid push method at home. While it is possible for IGRT to be initially administered as IVIG and then continued as SCIG therapy, there are some patients who begin treatment with the SCIG method. However, SCIG therapy requires 6−12 weeks to reach stable IgG levels compared to IVIG therapy. Therefore, intravenous administration of the first few doses is recommended for patients undergoing initial IGRT [13]. To evaluate family compliance in our patients, IVIG therapy was initiated in all our patients, and SCIG administration was started 12 months later. With this method, we hypothesized that higher serum IgG values would be observed in patients undergoing SCIG administration at the beginning and during follow-up.
The monthly SCIG dose used in our study was the same for both IVIG and SCIG in European countries [14]. However, it was recommended we multiply the IVIG dose by 1.37, as per studies in the U.S. [15,16], and administer the monthly dose subcutaneously every week [15]. In contrast to the peaks and low levels of serum IgG observed during IVIG infusions, SCIG therapy has been shown to provide levels that are more stable and closer to physiological serum IgG levels [11]. Karakoç-Aydıner et al. reported no significant difference in the stability of serum IgG levels, reactions, and infection incidence when patients were administered the monthly total SCIG dose over three or four partial doses [17]. After recalculating the monthly immunoglobulin dose by using the coefficient of 1.37, we administered the total dose in three or four partial doses in 75% and 25% of the patients, respectively. While no significant difference in the infection incidence was detected, higher serum IgG levels were observed in patients administered the total SCIG dose over four divided doses, although this was not statistically significant. This indicates that weekly SCIG administration leads to serum IgG levels that are closer to physiological levels. However, we suggest considering long-term compliance to therapy when deciding on either a weekly or 10-day administration regime.
The incidence of infections has been shown to decrease linearly with increasing IgG levels during SCIG therapy [18]. Therefore, regular measurement of serum IgG levels is an important marker in evaluating clinical efficacy. While most infections in our patients were controlled after initiation of IVIG, 10 patients had a high incidence of infections despite increasing IVIG doses, and serum IgG levels could not be increased above 600 mg/dL. Three of these patients had LBW. Eight of the 10 patients produced serum IgG levels > 600 mg/dL after switching to SCIG therapy. Although the IgG levels of the other two patients also increased, the serum IgG levels persisted below 600 mg/dL. After switching to SCIG administration, infections in all our patients were controlled and hospitalizations decreased significantly. We believe that switching to SCIG treatment improved the clinical follow-up of our patients by providing an incremental increase in serum IgG levels.
The side effects observed during IVIG administration are more severe and frequent than those of SCIG therapy. Side effects that may be seen during SCIG administration are mainly local and include pain, swelling, and redness at the site of injection. While these findings are often temporary, the frequency of local side effects decreases with repeated infusions [19,20]. Local tissue reactions were reported in 2.1−20% of patients, while the rate of systemic side effects in patients receiving SCIG is between 0.3% and 3.3% [21]. A Scandinavian retrospective study evaluated more than 33,000 subcutaneous infusions in PID patients and reported 100 mild and less moderate systemic reactions, with no serious or anaphylactic reactions observed [22]. In this study, 4,540 subcutaneous administrations were performed, and no systemic side effects were observed. However, mild side effects were observed in 153 administrations (3.3%). The rate of side effects after SCIG administrations in our study was found to be consistent with the literature.
Our study shows that SCIG administration on a weekly or 10-day interval increased serum IgG levels, making it more stable than IVIG therapy. It also indicates that SCIG therapy can be administered safely in younger age groups, especially in children with LBW. Using this approach, hospitalizations and family visits were also reduced, allowing for less interruptions in the daily lives of patients and their parents, and resulting in improved quality of life. For this reason, we believe that it is beneficial to switch to SCIG therapy, especially for those patients undergoing IVIG therapy whose IgG levels do not increase or those with uncontrolled infections, even if they have LBW.