Transition From IVIG to Efgartigimod in Patients With CIDP Could Lead to Worsening of Disease

In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), transitioning from stable treatment with intravenous immunoglobulin (IVIG) to a FcRn inhibiting therapy (FIT), such as efgartigimod (Vyvgart; Argenx SE), could lead to a severe worsening of disease, necessitating further research to understand the immunopathogenesis of these patients.¹

CIDP can lead to muscle weakness and numbness if not treated properly. | Image Credit: © Chinnapong | stock.adobe.com

These results, observed as part of a case series of patients with CIDP treated at the investigator’s clinical practices, are important for guiding clinical treatment recommendations for a condition with limited, but effective, management options.¹

IVIG was approved by the FDA for treatment in patients with CIDP based on study results indicating both the short- and long-term safety and efficacy of IVIG administration. In 2024, efgartigimod joined IVIG as the second approved therapy for CIDP based on the results of the phase 2 ADHERE trial. The study authors demonstrated that efgartigimod was effective in patients with CIDP but were unable to determine whether transitioning patients to efgartigimod after IVIG in a real-world setting is feasible.^2,3

The current study authors treated 9 patients with FIT following IVIG administration in their practice and reported the observations of 4 of those patients who had a severe relapse of CIDP following FIT. Notably, 5 of the other included patients neither declined nor improved with FIT.¹

Case 1 was a 68-year-old woman with a 3-year history of typical CIDP and had been stable on IVIG therapy for 1 year before her initial presentation. Her continued mild distal leg and ankle weakness necessitated a movement to efgartigimod in hopes of further improvement. Efgartigimod was administered 12 days following her last dose of IVIG; 2 days following her infusion, there was a reported increase in sensory dysesthesias that extended from her feet to her calf. Weakness progressed to her arms prior to her third weekly dose, and after her third dose, a fall led to a tibial fracture and hospital admission. Eight weeks following the initiation of efgartigimod, she was assessed with an Inflammatory Neuropathy Cause and Treatment (INCAT) disability score of 5 and needed assistance with routine activities.¹

In case 2, a 74-year-old man with a distal variant of CIDP and had been stable on IVIG for 7 years, presented with leak and arm weakness and numbness with an INCAT score of 4. Stronger IVIG administration led to an improvement to 1 in his INCAT score, and eventually the patient requested a switch to efgartigimod for further improvement. Following a series of doses with efgartigimod, weakness in his hands and proximal arms gradually worsened and spread, with the patient necessitating a walker and reporting an inability to independently care for himself, with an INCAT score of 6. After an urgent switch back to IVIG, the patient improved and regained near-baseline arm strength after 6 weeks of therapy.¹

A 58-year-old female with a 15-year-history of typical CIDP represented case 3, and she reported being stable on IVIG therapy for the last 10 years. Fatigue from sustained infusions of IVIG resulted in her switch to efgartigimod, which was initiated 20 days following her last IVIG infusion. Within 3 days of her first dose, there was an increase in sensory symptoms and worsening gait. A second dose led to a dramatic increase in weakness and necessitated a cane; FIT was stopped and, upon her resumption of IVIG, no longer needed a cane. However, 2 weeks following the beginning of IVIG, she had an INCAT score of 7 which necessitated ongoing treatment in the hospital.¹

Case 4 was a 47-year-old female with a 5-year history of CIDP, with stability on IVIG for the last 4 years. She reported consistent weakness in her hands despite the long-term administration of IVIG, which resulted in a switch to efgartigimod. Numbness and increased weakness in her right arm and both legs was observed within 3 days of her first dose and could not independently drive or work following her second dose, which led to a fall and fracture of her ankle. She reported an INCAT score of 6 and restarted IVIG.¹

The investigators wrote that, at the time of the report being issued, the patients had not yet returned to baseline. Importantly, the worsening of symptoms following transition to FIT was evidence of active disease, with a concern regarding the fast and severe decline observed compared with patients who have their IVIG dose reduced in frequency or dose. It raises questions regarding other factors that may be implicated with FIT in patients with CIDP.¹

“Recognition of the potential for severe worsening during this switch is important to investigate strategies that may prevent severe relapse and irreversible disability,” the study authors concluded.¹

REFERENCES

1. Levine T and Muley S. Early deterioration of CIDP following transition from IVIG to FcRn inhibitor treatment. Journal of the Neurological Sciences. 2025;468:123313. doi:10.1016/j.jns.2024.123313

2. Hughes R, Donofrio P, Bril V, et al. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomized placebo-controlled trial. The Lancet. 2008;7(2):136-144. doi:10.1016/S1474-4422(07)70329-0

3. Siddiqi Z, Allen JA, Basta I, et al. Efficacy, safety, and tolerability of subcutaneous efgartigimod in chronic inflammatory demyelinating polyneuropathy: Results from the ADHERE trial. Canadian Neurological Sciences Federation. 2024;51(s1):S8-S9. doi:10.1017/cjn.2024.92