Immune deficiencies, infection, and systemic immune disorders
Infection outcomes in patients with common variable immunodeficiency disorders: Relationship to immunoglobulin therapy over 22 years

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Background

Common variable immunodeficiency disorders (CVIDs) are the most common forms of symptomatic primary antibody failure in adults and children. Replacement immunoglobulin is the standard treatment, although there are few consistent data on optimal dosages and target trough IgG levels required for infection prevention.

Objective

To provide data to support the hypothesis that each patient requires an individual dose of therapeutic immunoglobulin to prevent breakthrough infections and that efficacious trough IgG levels vary between patients.

Methods

Data, collected prospectively from a cohort of 90 patients with confirmed CVIDs from 1 center over a follow-up period of 22 years, was validated and analyzed. Immunoglobulin doses had been adjusted in accordance with infections rather than to achieve a particular trough IgG level. Doses to achieve infection-free periods were determined and resultant trough levels analyzed. A smaller group of patients with X-linked agammaglobulinemia was analyzed for comparison.

Results

Patients with a CVID had a range of trough IgG levels that prevented breakthrough bacterial infections (5-17 g/L); viral and fungal infections were rare. Doses of replacement immunoglobulin to prevent breakthrough infections ranged from 0.2 to 1.2 g/kg/mo. Those with proven bronchiectasis or particular clinical phenotypes required higher replacement doses. Patients with X-linked agammaglobulinemia showed a similar range of IgG levels to stay infection-free (8-13 g/L).

Conclusion

These data offer guidance regarding optimal doses and target trough IgG levels in individual patients with CVIDs with or without bronchiectasis and for particular clinical phenotypes. The goal of replacement therapy should be to improve clinical outcome and not to reach a particular IgG trough level.

Section snippets

Inclusion criteria

Patients that met the CVID criteria30 were selected, namely those with a reduced serum IgG level (<6.0 g/L) and either a serum IgA level <0.8 g/L or a serum IgM level <0.5 g/L or both, over 4 years of age at diagnosis, and exclusion of other conditions or therapies associated with antibody failure. Of these patients with CVIDs, 73 had serum IgG levels <3.5 g/L at diagnosis, and therefore, specific antibody testing was not essential for the diagnosis.29 Of the remaining 17 patients, 12 had

Patient characteristics

One hundred and fifteen patients with confirmed CVIDs and 17 with XLA, seen regularly in the past 25 years (1982-2007), were included initially. Of these, 25 patients with CVIDs were excluded, 10 for noncompliance with therapy, poor infection history or missing serum IgG data, and 15 with less than 1 year available since stabilization of trough IgG. Two patients with XLA were excluded, 1 for noncompliance and 1 for <1 year of follow-up. Patient characteristics are shown in Table I. Diagnostic

Discussion

This is the first study to determine the relationships between doses of replacement therapy, infection rates, and trough IgG levels and to compare these for patients with different clinical CVIDs phenotypes or common complications. Furthermore, this is a substantial group of patients with CVIDs followed over 741 patient-years in 1 center using validated data over 22 years. The policy of adjusting the dose of replacement therapy to reduce the infection rate to a minimum in a given patient has

References (32)

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Supported by the NIHR Oxford Biomedical Research Centre; unrestricted gifts from Baxter Healthcare, Talecris, and the Jeffrey Modell Foundation; the Centre of Excellence award from the Primary Immunodeficiency Association; and a 7th Framework grant, EURO-PADnet no. 201549, from the European Commission.

Disclosure of potential conflict of interest: S. Misbah is on advisory boards for CSL Behring, Baxter, and Biotest. The rest of the authors have declared that they have no conflict of interest.

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