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

7 August 2001 | Volume 135 Issue 3 | Pages 165-174

Background: In patients with hypogammaglobulinemia, substitution with immunoglobulin is the treatment of choice to reduce both frequency and severity of bacterial infections. Even with treatment, however, infections still occur in these patients.

Objective: To determine whether doubling the standard dose of intravenous immunoglobulin would affect the incidence and duration of infections.

Design: Multicenter, double-blind, randomized, crossover study.

Setting: 15 outpatient clinics in the Netherlands.

Patients: 43 patients with primary hypogammaglobulinemia, 41 of whom completed the protocol.

Intervention: Patients received standard-dose immunoglobulin therapy for 9 months, followed by a 3-month washout period, and high-dose intravenous immunoglobulin therapy for 9 months, or vice versa.

Measurements: The primary outcome measures were total number and duration of infections. Other measures were periods of fever, hospital admissions, use of antibiotics, absence from school or work, and trough levels of serum immunoglobulin. Side effects from the study medication were also recorded.

Results: Compared with the standard dose of intravenous immunoglobulin (adults, 300 mg/kg of body weight every 4 weeks; children, 400 mg/kg every 4 weeks), high-dose therapy (adults, 600 mg/kg every 4 weeks; children, 800 mg/kg every 4 weeks) significantly reduced the number (3.5 vs. 2.5 per patient; P = 0.004) and duration (median, 33 days vs. 21 days; P = 0.015) of infections. Trough levels of IgG increased significantly during high-dose therapy. The incidence and type of side effects did not differ significantly for the two dosages.

Conclusion: In patients with hypogammaglobulinemia, doubling the standard dose of intravenous immunoglobulin significantly reduced the number and duration of infections.

Author and Article Information

From CLB, Academic Medical Center, and Parexel Mirai, Amsterdam; University Hospital Nijmegen, Nijmegen; University Hospital Groningen, Groningen; Leiden University Medical Center, Leiden; and University Hospital for Children, Utrecht, the Netherlands.

Acknowledgments: The authors thank the internists, pulmonologists, and pediatricians who participated in the study; the nurses who provided medical care to the patients, the pharmacists who provided study medication, and the patients who participated. They also thank Professor W.G. van Aken for commenting on the manuscript; Machteld Tissing and Angelique van den Broek for data entry; and T.H. The, K. Brinkman, J.C.C. Borleffs, C.A.J.J. Jaspers, A.J.P. Veerman, P.J. van den Broek, M.C. Wallis-Spit, A.M. Hemmes, E.J.F.M. ten Berge, J.J.M. Peters, F.A.E. Nabben, L. Ausema, J.W. van 't Wout, and H.H.M. Hassing for provision of study materials or patients.

Grant Support: By Sanquin Blood Supply Foundation, Amsterdam, the Netherlands.

Requests for Single Reprints: Heleen W. Eijkhout, MD, CLB, Medical Department, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands; e-mail, H_Eijkhout{at}CLB.nl.

Current Author Addresses: Drs. Eijkhout and Strengers: CLB, Medical Department, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands.

Dr. van der Meer: Department of Medicine, University Hospital Nijmegen, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, the Netherlands.

Dr. Kallenberg: Department of Clinical Immunology, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands.

Dr. Weening: Department of Paediatrics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.

Dr. van Dissel: Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.

Dr. Sanders: Department of Immunology, University Hospital for Children, Lundlaan 6, 3584 EA Utrecht, the Netherlands.

Ms. Nienhuis: Parexel Mirai, Herman Heijermansweg 20, Box 75079, 1070 AB Amsterdam, the Netherlands.

Dr. Schellekens: Department of Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.

Author Contributions: Conception and design: H.W. Eijkhout, J.W.M. van der Meer, C.G.M. Kallenberg, R.S. Weening, J.T. van Dissel, P.Th.A. Schellekens.

Analysis and interpretation of the data: H.W. Eijkhout, C.G.M. Kallenberg, J.T. van Dissel, E.A.M. Sanders, H. Nienhuis, P.Th.A. Schellekens.

Drafting of the article: H.W. Eijkhout, H. Nienhuis, P.Th.A. Schellekens.

Critical revision of the article for important intellectual content: J.W.M. van der Meer, C.G.M. Kallenberg, E.A.M. Sanders, P.F.W. Strengers, P.Th.A. Schellekens.

Final approval of the article: H.W. Eijkhout, J.W.M. van der Meer, C.G.M. Kallenberg, R.S. Weening, J.T. van Dissel, E.A.M. Sanders, P.F.W. Strengers, H. Nienhuis, P.Th.A. Schellekens.

Provision of study material or patients: J.W.M. van der Meer, C.G.M. Kallenberg, R.S. Weening, J.T. van Dissel, E.A.M. Sanders, P.Th.A. Schellekens.

Statistical expertise: H. Nienhuis.

Obtaining of funding: H.W. Eijkhout, J.W.M. van der Meer.

Collection and assembly of data: H.W. Eijkhout, P.F.W. Strengers.