ADHERE Data Support FcRn Blockade With Efgartigimod as Effective Option in CIDP

A plain language summary of the ADHERE trial, recently published in Therapeutic Advances in Neurological Disorders, highlighted the clinical efficacy, durability, and safety of efgartigimod (Vyvgart; argenx), a first-in-class neonatal Fc receptor (FcRn) antagonist, in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).¹

Efgartigimod, approved in the United States in 2024 for CIDP, works by reducing circulating immunoglobulin G (IgG), including pathogenic autoantibodies implicated in peripheral nerve damage.¹ This mechanism represents a shift from traditional therapies, which broadly modulate immune activity rather than selectively targeting IgG recycling.

ADHERE Trial Design and Population

Led by Jeffrey Allen, MD, a professor in the department of neurology at the University of Minnesota, and others, the ADHERE study was a multicenter, 2-stage trial evaluating subcutaneous efgartigimod in adults with active CIDP. Stage A was an open-label run-in phase designed to identify treatment responders, followed by a randomized, double-blind, placebo-controlled Stage B evaluating relapse prevention and long-term outcomes.¹

A total of 322 patients were enrolled in Stage A, with a mean age of 54 years and a predominance of men (65%).¹ Notably, the cohort included both treatment-experienced and treatment-naïve individuals, with 51% previously treated with intravenous immunoglobulin (IVIg) and nearly 30% untreated or off therapy for at least 6 months.¹

Of these participants, 221 responders advanced to Stage B, where they were randomized to receive weekly subcutaneous efgartigimod (1000 mg) or placebo for up to 48 weeks.

Rapid and Meaningful Clinical Improvement

In Stage A, 66% of participants (214 of 322) demonstrated clinical improvement based on established endpoints, including adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), and grip strength measures.¹

Clinical responses were observed early, with 40% of patients improving within 4 weeks and a median time to first improvement of approximately 22 days.¹ Overall, the study authors concluded that these findings suggested a relatively rapid onset of action for FcRn inhibition in CIDP.

Reduced Relapse Risk and Functional Preservation

In Stage B, efgartigimod significantly reduced the risk of disease relapse compared with placebo. Patients receiving efgartigimod experienced a 61% lower risk of relapse, defined as worsening on the aINCAT scale. In addition, relapse occurred in 28% of patients treated with efgartigimod compared with 54% of those receiving placebo. Correspondingly, mean aINCAT scores remained largely stable in the treatment group (increase of 0.1 points) versus greater worsening in the placebo group (increase of 0.9 points).¹

Functional outcomes also favored efgartigimod. A greater proportion of treated patients maintained or improved their ability to perform daily activities, as measured by I-RODS, while fewer experienced clinically meaningful decline compared with placebo. Grip strength data further supported these findings, with patients receiving efgartigimod maintaining strength in both dominant and non-dominant hands, whereas those on placebo experienced notable declines.¹

Favorable Safety Profile

Across both stages of the study, efgartigimod demonstrated a favorable safety profile. The majority of adverse events (AEs) were mild to moderate in severity, with similar rates observed between treatment and placebo groups. In Stage B, AEs occurred in 56% of patients receiving efgartigimod compared with 64% in the placebo group, while serious AEs were reported in 5% of both groups.¹ Treatment-related AEs were reported in 20% of efgartigimod-treated patients versus 24% with placebo.¹

Overall, the authors concluded that these findings align with prior studies of FcRn inhibition, supporting its tolerability in chronic autoimmune conditions.

Clinical Implications and Evolving Treatment Landscape

The ADHERE trial represented a significant advancement in CIDP, demonstrating that targeted FcRn inhibition can provide both symptomatic improvement and sustained disease control.¹ Importantly, these benefits were observed with a subcutaneous formulation that can be administered in 30 to 90 seconds, offering a more convenient alternative to infusion-based therapies.¹

Current standard treatments such as IVIg, corticosteroids, and plasma exchange remain effective but are associated with logistical burdens and incomplete response in a subset of patients. Approximately one-third of patients may not respond adequately to existing therapies, underscoring the need for additional options

Looking Ahead

Ongoing studies, including phase 4 and real-world analyses, are expected to further define the role of efgartigimod in CIDP, including its use in patients transitioning from IVIg and its effectiveness in routine clinical practice.¹

As the first novel mechanism introduced in CIDP in decades, FcRn inhibition represents a meaningful addition to the therapeutic armamentarium, with the potential to reshape long-term management strategies for this chronic and often disabling disease.¹

REFERENCE
1. Allen JA, Querol L, Suresh N, et al. Efgartigimod as a treatment for people with chronic inflammatory demyelinating polyradiculoneuropathy: plain language summary of publication of the ADHERE trial. Ther Adv Neurol Disord. 2025.