Observational Study to Determine the Tolerability of Intravenous Immunoglobulin 5% for the Treatment of Patients Diagnosed with Primary Immunodeficiency Disorders

Rationale: Intravenous immunoglobulin (IVIG) is relatively safe, with headaches and fatigue being common side effects. Recently, a subset of patients with common variable immunodeficiency (CVID) and low C1 esterase inhibitor (C1-INH) and/or low C1-INH function (C1-INHF) has been identified. Preliminary data indicates that low C1-INH levels may play a role in adverse drug reactions (ADRs) noted in a subset of CVID patients receiving IVIG. We designed this observational study to determine if 5% IVIG may be an alternative for patients who experience ADRs on 10% IVIG.

Methods: Patients who had previously received 10% IVIG completed 6 infusion visits using 5% IVIG. At each visit, ADRs and data from patient diaries were recorded. Immune-biomarkers, including C1-INH/C1-INHF levels, were also evaluated.

Results: Fifteen subjects completed the study; 12 with CVID and 3 with hypogammaglobulinemia. Switching to 5% IVIG reduced the number of ADRs by 40%. There were also reductions in mean fatigue index, headache score, and neuropathic pain score from IVIG 10% to 5%. Patients experienced an increase in physical function, greater energy, less fatigue, higher emotional rating and an increase in social function. The mean C1-INH|C1-INHF on 10% decreased from 31 to 13 mg/dL (normal 21-29mg/dL)|91% to 59% (normal >67%) while on 5 % the mean C1-INH|C1-INHF decreased from 27 to 21mg/dL|89% -76%.

Conclusions: This study demonstrated that C1-INH/C1-INHF level changes play a role in the incidence of ADRs for IVIG therapy; and a subset of patients may be more susceptible to C1-INH/C1-INHF downregulation by IVIG 10%. Further studies are necessary.