Improving Protection against Infection in People without Enough Immunoglobulin

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The summary below is from the full report titled "The Effect of Two Different Dosages of Intravenous Immunoglobulin on the Incidence of Recurrent Infections in Patients with Primary Hypogammaglobulinemia. A Randomized, Double-Blind, Multicenter Crossover Trial." It is in the 7 August 2001 issue of Annals of Internal Medicine (volume 135, pages 165-174). The authors are HW Eijkhout, JWM van der Meer, CGM Kallenberg, RS Weening, JT van Dissel, EAM Sanders, PFW Strengers, H Nienhuis, and PThA Schellekens, for the Inter-University Working Party for the Study of Immune Deficiencies.

What is the problem and what is known about it so far?

The ability to resist infection depends on many factors, including proteins in the blood, known as immunoglobulins, that help kill bacteria and viruses. Some people cannot make enough immunoglobulin and need regular intravenous injections of immunoglobulin to protect them from infection. Although standard replacement doses of immunoglobulins decrease the number of infections, some infections continue to occur despite this treatment.

Why did the researchers do this particular study?

To see if doubling the standard dose of intravenous immunoglobulin reduces the number and duration of infections in people who do not have enough of these proteins.

Who was studied?

Forty-six people with known immunoglobulin deficiency.

How was the study done?

Before the study began, all patients received regular replacement therapy with immunoglobulin. Patients were then assigned to one of two groups. One group received 9 months of therapy with standard-dose immunoglobulin, followed by 3 months of the same dose they had received before the study, then 9 months of treatment with a double dose of immunoglobulin. In the second group, the order of low-dose and high-dose therapy was reversed. To ensure that patients, doctors, and nurses were unaware which dose was being administered, the pharmacy made the injections look identical. Researchers recorded the number, type, and duration of infections that occurred, as well as the use of antibiotics, for each patient throughout the study. The lowest level of immunoglobulin in the blood ("trough level") was evaluated by measuring immunoglobulin levels immediately before each dose of immunoglobulin was given.

What did the researchers find?

Of the 46 patients in the study, 3 dropped out before receiving the first injection and 2 did not complete the study. One hundred thirty-five infections occurred during standard-dose treatment, and 103 infections occurred during high-dose treatment. Compared with low-dose treatment, high-dose treatment significantly reduced the number of infections (3.5 vs. 2.5 infections per patient). Forty-seven percent of infections during standard-dose treatment were severe, compared with 51% during high-dose therapy. The duration of infections was significantly shorter during high-dose therapy than during standard-dose therapy. The minimum level of immunoglobulin in the blood was significantly higher during high-dose treatment than during low-dose treatment. Side effects, such as headache and fever, occurred slightly more often during high-dose treatment than during low-dose treatment, but the difference was not statistically significant.

What were the limitations of the study?

Since the study was relatively short, it cannot be determined how long the effectiveness of higher doses of immunoglobulin will last. This is important, because the deficiency of immunoglobulin lasts a lifetime. Furthermore, high-dose immunoglobulin therapy is very expensive, and this study did not evaluate the relationship between the cost of the therapy and its potential benefits.

What are the implications of the study?

In patients with immunoglobulin deficiency, doubling the standard dose of intravenous immunoglobulin may significantly reduce the incidence and duration of infections.