# Managing Primary Immunodeficiency Immunoglobulin Replacement Therapy‐Related Adverse Events With Recombinant Human C1 Esterase Inhibitor Prophylaxis: A Case Report

## TL;DR

A patient with severe side effects from immunoglobulin therapy improved after using C1 esterase inhibitor before treatment.

## Contribution

Demonstrates C1-INH prophylaxis as a novel strategy to manage IRT-related adverse events.

## Key findings

- C1-INH administration prior to SCIG reduced severe neuropathy and other AEs.
- The patient tolerated the recommended SCIG dose with C1-INH prophylaxis.
- C1-INH may improve IRT tolerability in patients with adverse event challenges.

## Abstract

Immunoglobulin replacement therapy (IRT) for primary immunodeficiency reduces infection risk and subsequent complications and can be lifesaving. However, IRT can cause severe systemic adverse events (AEs) that may limit adequate dosing. These AEs may be caused, in part, by activation and/or consumption of complement proteins, thereby lowering C1 esterase inhibitor (C1‐INH) levels. Data suggest that C1‐INH administration prior to intravenous immunoglobulin (IVIG) may reduce IVIG‐related AEs. This case describes an adult with common variable immunodeficiency unable to tolerate IRT therapy (subcutaneous immunoglobulin [SCIG] 20% solution once weekly). She experienced AEs of severe neuropathy, described as burning and pins‐and‐needles sensation in the extremities and muscle twitching for several days post‐treatment. Dose decreases of SCIG to 0.5 g did not improve the AE profile. Inability to tolerate IRT caused suboptimal dosing and inadequate primary immunodeficiency management, resulting in hospitalizations for pneumonia and sepsis. A trial of recombinant human C1‐INH 4200 U was administered intravenously over approximately 5 min, 1 h prior to SCIG 1 g (Day 1). This dose was well tolerated with minimal AEs reported. SCIG 3 g was administered on Days 2 and 3 with no AEs reported. By continuing routine recombinant human C1‐INH 4200 U prophylaxis, the patient was able to tolerate the recommended dose of SCIG 20 g once weekly without the debilitating neuropathy and other AEs previously experienced with SCIG alone. This case suggests that a patient with IRT‐related AEs may benefit from C1‐INH replacement therapy prior to SCIG/IVIG administration to improve tolerability.

This case suggests that a patient with severe immunoglobulin replacement therapy‐related adverse events might benefit from C1 esterase inhibitor (C1‐INH) replacement therapy prior to immunoglobulin replacement therapy for primary immunodeficiency. In appropriate patients, a trial of C1‐INH replacement therapy as part of an adverse event management strategy might improve tolerability.