Clinical InsAIghts: The ADVANCE-CIDP 1 Trial

Study Overview

  • Study Acronym: ADVANCE-CIDP 1 (1)

  • Study Design: Phase 3, prospective, randomized, double-blind, multicenter, placebo-controlled study.

  • Study Phase: Phase 3

  • Population Under Investigation: Adults with definite or probable CIDP.

  • Intervention Under Investigation: Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase).

  • Control Group: Placebo (0.25% albumin solution with rHuPH20).

  • Number of Patients: 132 (fSCIG 10%: 62; Placebo: 70).

  • Duration of Follow Up: 6 months or until relapse/discontinuation.

  • Main Efficacy Outcomes: CIDP relapse was reduced in the fSCIG 10% group (9.7%, 95% CI: 4.5%–19.6%) compared to placebo (31.4%, 95% CI: 21.8%–43.0%), with an absolute difference of -21.8% (95% CI: -34.5% to -7.9%, p = .0045). Sensitivity analyses supported these findings.

  • Main Safety Outcomes: Adverse events were more frequent in the fSCIG 10% group (79.0%) than the placebo group (57.1%), but severe (1.6% vs 8.6%) and serious adverse events (3.2% vs 7.1%) were less common in the fSCIG group.

Clinical InsAIghts Report

The recent approval of Takeda's HyQvia by the European Commission (EC) and the US Food and Drug Administration (FDA) (January 16, 2024) for maintenance therapy in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) adds a significant dimension to the management of this neuromuscular disorder. HyQvia, an immune globulin infusion 10% (human) with recombinant human hyaluronidase, represents an advancement in the delivery of immunoglobulin therapy, a cornerstone in CIDP treatment.

CIDP is a condition characterized by immune-mediated damage to the myelin sheath of peripheral nerves (2). This damage leads to progressive weakness and sensory dysfunction, primarily affecting the limbs. The epidemiology of CIDP, though variable, suggests an estimated prevalence of 1-9 cases per 100,000, with a slight male predominance and onset typically in the sixth decade of life (3). It has been traditionally managed with intravenous immunoglobulin (IVIG) (4). While IVIG remains a standard treatment, its administration can be challenging due to long infusion times, venous access issues, and the necessity of a clinical setting. The approval of HyQvia, based on the positive results from the ADVANCE-CIDP 1 study, signifies a shift towards more patient-friendly treatment options.

The ADVANCE-CIDP 1 study's findings, demonstrating a significant reduction in relapse rates with HyQvia compared to placebo, align with the therapy's proposed benefits. HyQvia's subcutaneous administration allows for up to monthly dosing and can be self-administered following appropriate training. This method could enhance patient compliance, reduce healthcare burden, and improve overall quality of life for CIDP patients.

In the context of seminal studies like the ICE (5) and PATH (6) trials, which established the efficacy of IVIG and SCIG in CIDP, HyQvia's approval offers a more practical and potentially more tolerable alternative. This is particularly relevant given the chronic nature of CIDP and the need for long-term management.

The clinical implications of HyQvia's approval are far-reaching. It provides a new maintenance therapy option that addresses some of the limitations associated with traditional IVIG treatment. The potential for at-home administration not only improves accessibility but also aligns with a growing trend in healthcare towards patient-centric and individualized treatment approaches.

In conclusion, HyQvia's approval represents a significant advancement in CIDP management. Its efficacy, combined with the convenience of subcutaneous administration, positions it as a valuable addition to the therapeutic arsenal against CIDP, potentially transforming the standard of care in this chronic, debilitating condition.

References

  1. Bril V, Hadden RDM, Brannagan TH, 3rd, Bar M, Chroni E, Rejdak K, et al. Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial. J Peripher Nerv Syst. 2023;28(3):436-49.

  2. Mathey EK, Park SB, Hughes RA, Pollard JD, Armati PJ, Barnett MH, et al. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype. J Neurol Neurosurg Psychiatry. 2015;86(9):973-85.

  3. Van den Bergh PY, Hadden RD, Bouche P, Cornblath DR, Hahn A, Illa I, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - first revision. Eur J Neurol. 2010;17(3):356-63.

  4. England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, et al. Practice Parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology. 2009;72(2):185-92.

  5. Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, et al. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol. 2008;7(2):136-44.

  6. van Schaik IN, Bril V, van Geloven N, Hartung HP, Lewis RA, Sobue G, et al. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2018;17(1):35-46.