Baseline Characteristics and Predictive Factors of Intravenous Immunoglobulin Response in Drug and Device Refractory Gastroparesis Symptoms

Abstract

Introduction: Intravenous immunoglobulin (IVIG) has been shown in a small pilot series to be helpful for some patients with gastroparesis that is refractory to drugs, devices, and surgical therapies. Many but not all patients have serologic neuromuscular markers. We hypothesize that those patients with serologic markers and/or longer duration of therapy would have better responses to IVIG. Materials and Methods: We studied 47 patients with a diagnosis of gastroparesis and gastroparesis-like syndrome that had all failed previous therapies including available and investigational drugs, devices, and/or pyloric therapies. Patients had a standardized 12-week course of IVIG, dosed as 400 mg/kg per week intravenously. Symptom assessment was done with Food and Drug Administration (FDA) compliant traditional patient-reported outcomes. Success to IVIG was defined as 20% or greater reduction in average symptom scores from baseline to the latest evaluation. Results: Fourteen patients (30%) had a response, and 33 (70%) had no response per our definition. Patients responding had a higher glutamic acid decarboxylase 65 positivity (64% vs. 30%, P=0.049, missing=3) and longer duration of therapy (>12 wk/continuous: 86% vs. 48%, P=0.09). Conclusions: In this moderately sized open-label series of refractory patients with gastroparesis symptoms treated with IVIG, 30% of patients responded. While serologic markers and extended therapies show a trend to greater response, neither was statistically significant, except for glutamic acid decarboxylase 65 which showed a higher positivity rate in responders. We conclude that a clinical trial of IVIG may be warranted in severely refractory patients with gastroparesis symptoms.

Gastroparesis and Gastroparesis Syndromes as Neuromuscular Disorders

“…Glutamic acid decarboxylase-65 (GAD-65) autoantibodies have been well studied and noted to have a strong association with gastroparesis, not only in patients with diabetes but also in individuals with idiopathic gastroparesis. 16 Anti-GAD autoantibodies work against the GAD enzyme, essential for forming gamma amino butyric acid (GABA) neurotransmitters and associated with CNS and neuroendocrine autoimmunity disorders, including neuro-GI dysmotility syndromes. 5 Several other autoantibodies that interfere with the synaptic transmission in the enteric nervous system have been implicated in the pathogenesis of autoimmune gastroparesis.…”

“…Modalities like parenteral immunoglobulin infusions have produced symptomatic improvement in these patients when used alone or in conjunction with other modalities, such as gastric electrical stimulation and pyloroplasty. 16,21 The results of responders and nonresponders to IVIG in one study are detailed in ►Fig. 2.…”