PURPOSE: Inhaled human insulin (EXU; Exubera® (insulin human [rDNA origin]) Inhalation Powder] has been shown to be more immunogenic than subcutaneous (SC) comparator insulins in patients with type 1 diabetes and in insulin-using patients with type 2 diabetes (Fineberg SE, et al. J Clin Endocrinol Metab. 2005;90:3287-3294). This study was designed to address concerns that discontinuation and reinstitution of SC therapy after EXU treatment might lead to enhanced immunologic responses.
METHODS: In 2 open-label, parallel-group trials lasting up to 24 months, adult patients with type 1 diabetes received EXU (n = 290) or SC insulin (n = 290); patients with type 2 diabetes received EXU (n = 316) or SC (n = 311). Following up to 24 months of therapy (comparative phase), EXU was discontinued and replaced with SC for 6 months (run-out phase), then the original therapy was resumed for 6 months (EXU resumption phase). Throughout, insulin antibody (IAb) levels were assessed using a quantitative assay, and pulmonary function was assessed by standardized measures of forced expiratory volume in 1 second (FEV1 [L]) and carbon monoxide diffusing capacity (DLCO [mL/min/mm Hg]).
RESULTS: Initially, antibody levels in the EXU group increased, then decreased during the run-out phase. When EXU therapy was resumed, IAb levels increased to similar levels as seen during the comparative phase (Table). An anamnestic response was not seen after EXU resumption. Small mean treatment group differences in change from baseline FEV1 and DLCO were apparent after 3 months of EXU treatment, remained stable throughout the 24-month comparative phase, resolved upon discontinuation, and recurred to the same magnitude upon readministration of EXU. No significant intrasubject correlations with IAb response could be shown with changes in FEV1 or DLCO. Samples with the highest IAb levels consisted predominantly of immunoglobulin G for both treatment groups.
CONCLUSION: No correlation was found between IAb response and changes in lung function.
CLINICAL IMPLICATIONS: Immunologic safety was demonstrated with long-term EXU therapy, discontinuation, and readministration.
DISCLOSURE: Richard Riese, No Product/Research Disclosure Information; Employee Employee of Pfizer Inc which funded this study