Neuro News Roundup: Chronic Demyelinating Polyneuropathy Awareness Month – Expert Insight and Latest Literature

The NeurologyLive^® team has been hard at work in the year conducting interviews with thought leaders and covering the news on the latest updates in the clinical care of individuals with neuromuscular disorders such as chronic demyelinating polyneuropathy (CIDP), and others.

For Chronic Demyelinating Polyneuropathy Awareness Month — May 2024 —our team offers an update on those new developments in the literature and insight into the expert opinions about how they’re shaping the ever-changing care paradigm in CIDP into one place.

Click here for more coverage of the latest neuromuscular news from NeurologyLive.

EXPERT INSIGHTS

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At the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, investigators presented data from a preliminary conceptual model of CIDP based on targeted literature review sources. Using interviews from 12 patients with the disease, the most frequently reported symptoms were muscle weakness (n =12), neuropathic sensations (n = 12), numbness (n = 10), fatigue (n = 10), difficulties with balance, and pain (n = 6). CIDP most commonly negatively impacted mobility (n = 12), activities of daily living (n = 12), emotional wellbeing (n = 11), work (n = 9), hobbies/leisure (n = 9), and fine motor skills (n = 8).¹

Lead investigator Kayla Scippa, associate director, Patient Reported Outcomes, Johnson & Johnson, sat down with NeurologyLive following the meeting to provide greater clarity on the data and the major unmet needs for patients with CIDP. She spoke about how these findings will help inform drug development for the future, gearing efforts towards the symptoms that are most prevalent in CIDP. In addition, she touched upon some of the research goals and how to expand on this data going forward.

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In January 2024, a study recently published in the European Journal of Neurology on the 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines for CIDP showed that the criteria provided a better characterization of CIDP variants, allowing their distinction from typical CIDP and more appropriate treatments for patients.² According to the clinical criteria from the 2021 EAN/PNS guidelines, 245 patients were diagnosed with typical CIDP or a CIDP variant (66%). Investigators identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), 4 sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and 8 motor-predominant CIDP (2%).

Researchers observed that those with multifocal, distal, and sensory CIDP showed milder impairment and symptoms. In the analysis, investigators reported that patients with multifocal CIDP demonstrated less frequently reduced conduction velocity (14%) and prolonged F-wave latency (4%). Additionally, patients with multifocal CIDP also exhibited lower levels of CSF protein (55%). Coauthor Giuseppe Liberatore, MD, assistant in Neuromuscular and Neuroimmunology Service at Humanitas Clinical and Research Institute in Milan, Italy, provided some commentary on the results in an interview with NeurologyLive.

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Findings from the ongoing global phase 2 ADHERE trial (NCT04281472) assessing subcutaneous (SC) efgartigimod PH20 as a treatment for CIDP were presented at the 2023 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held November 1-4, in Phoenix, Arizona, by lead author Richard Lewis, MD, professor of neurology at Cedars-Sinai Medical Center, and colleagues. In the trial, the primary objectives included investigating evidence of clinical improvement (stage A) and efficacy of efgartigimod PH20 SC compared with placebo based on time to occurrence of clinical deterioration (stage B).³

At the meeting, Lewis sat down in an interview with NeurologyLive to discuss the presented findings from the trial as well as how the rapid reduction of IgG antibodies in patients with CIDP contributes to the potential effectiveness of FcRn inhibitors. He talked about the considerations that healthcare professionals should keep in mind when discussing the use of this novel treatment with patients who live with CIDP, especially in comparison with the existing available therapies. In addition, Lewis spoke about how the presence of antibodies resistant to traditional treatments might influence the global response rate of FcRn inhibitors in CIDP.

LATEST LITERATURE

Combination Therapy of Corticosteroids and Immunosuppressants Shows Efficacy in Rare Case of Overlapping CIDP and NMOSD

A rare case study of a 49-year-old woman who presented with an overlap of CIDP and neuromyelitis optica spectrum disorder (NMOSD) showed that a combination of corticosteroids and immunosuppressants treatment may improve clinical outcomes.⁴

Following the diagnosis of both CIDP and NMOSD, the woman was administered pulse therapy with high-dose corticosteroids (1000 mg, q.1.d) for 3 days. After the completion of those doses, the authors reported a marked improvement in the extremities. To serve as a disease-modifying therapy for NMOSD, the authors had the patient on a regimen of methotrexate (25 mg each week), azathioprine (50 mg TID), and prednisone (5 mg TID). Researchers noted that the patient’s vertigo, nausea, and vomiting subsided, and then 7 days following hospitalization, the woman became discharged from the facility.

Conducted by lead author Baarid Luqman Hamidi, MD, a neurologist at Rumah Sakit Umum Daerah Dr. Moewardi Surakarta in Indonesia, and colleagues, the patient was brought to the emergency department with severe acute-onset vertigo 4 days before admission. Her condition developed suddenly while watching television and was felt throughout the day. Thereafter, the woman reported experiencing nausea, recurrent vomiting, hiccups, and blurry vision. The patient also had progressive weakness in the lower and upper extremities 10 weeks prior to admission, requiring a wheelchair for mobilization as weakness worsened. The woman also experienced a tingling sensation that ascended from the lower to the upper extremities and had weakness that persisted until arrival at the emergency room.

Rozanolixizumab Shows No Clinical Impact on CIDP in Long-Term Phase 2 Study

Results from a phase 2a study (NCT03861481) and its open-label extension (OLE) showed that rozanolixizumab, an approved medication for myasthenia gravis and immune thrombocytopenia, did not show evidence of efficacy in patients with CIDP. Investigators noted that the lack of efficacy could be a result of the relatively high disease stability rate in the placebo group.⁵

Otherwise known as CIDP01, the placebo-controlled, investigator-blinded study comprised of 34 patients with definite or probable CIDP who were randomly assigned to once-weekly subcutaneous infusions of rozanolixizumab 10 mg/kg (n = 17) or placebo (n = 17) in addition to subcutaneous or intravenous immunoglobulin (IgG) maintenance therapy. After 85 days of treatment, investigators observed no significant between-group differences in inflammatory Rasch-built Overall Disability Scale (iRODS) score, the primary end point (rozanolixizumab: least square mean [LSM], 2.0 [SE, 3.2] vs placebo: LSM, 3.4 [SE, 2.6]; difference, –1.5; 90% CI, –7.5 to 4.5).

Led by Luis Querol Gutierrez, MD, PhD, a neurologist at the Hospital de la Santa Creu, in Barcelona, Spain, the study results may have been impacted by the high disease stability rate in patients on placebo. “This stability rate could be the consequence of recruiting a low proportion of patients with active immunoglobulin-dependent disease or the use of an endpoint of disease deterioration, which has been shown to be associated with higher placebo response rates. Similar disease stability rates have been seen in other CIDP trials that required patients to have immunoglobulin-dependent disease, indicating that improved methods for identifying immunoglobulin dependency may be needed,” the study authors wrote.

Patient Sera Screening Confirms Dihydrolipoamide S-Acetyltransferase Antibodies in Immune-Mediated Neuropathies

Findings from a newly published cross-sectional study in Neurology confirmed the presence of dihydrolipoamide S-acetyltransferase (DLAT) antibodies in the serum of patients with immune-mediated neuropathies, significantly in those with CIDP.⁶ These results suggest that the anti-DLAT antibody, which was highly expressed in dorsal root ganglion (DRG), may serve as a diagnostic biomarker for sensory-predominant neuropathies including a subset of patients with CIDP.

Among 78 sera from patients with CIDP screened, findings demonstrated a positive band around 60-70 kDa identified as DLAT, also known as PDC-E2. Investigators observed a relatively high reactivity in 29 of 160 (18%) patients with CIDP, followed by in 6 of 58 patients with sensory neuropathy (10%) and in 2 of 47 patients with multiple sclerosis (MS)(4%). High reactivity was not observed in patients with Guillain-Barré syndrome (n = 27), patients with hereditary neuropathy (n = 40), and healthy controls (n = 26). Notably, authors noted that both the cell-based and tissue-based assays confirmed reactivity in 26 of 33 (78%) patients with CIDP.

In this study, investigators had proteins extracted from mouse brain tissue and used them to react with sera from patients with CIDP by western blotting to determine the presence of common bands. The bands reported as positive were then characterized by mass spectrometry and confirmed for reactivity with the patient sera utilizing using enzyme-linked immunosorbent assay and western blotting. In further testing, the serum immunoglobulin G (IgG) and IgM antibodies' reactivity to recombinant DLAT was then confirmed by cell-based and tissue-based indirect immunofluorescence assays. Authors also analyzed the clinical characteristics of patients with candidate autoantibody-positive CIDP and their association with other neurologic diseases.

REFERENCES
1. Scippa K, Macey J, Batista A, et al. Recognizing unmet need in chronic inflammatory demyelinating polyneuropathy: development of a conceptual model characterizing patient experiences and perspectives. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.
2. De Lorenzo A, Liberatore G, Doneddu PE, et al. Impact of 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria on diagnosis and therapy of chronic inflammatory demyelinating polyradiculoneuropathy variants. Eur J Neurol. Published online January 2, 2024. doi:10.1111/ene.16190
3. Lewis R, Allen J, Dysgaard T, et al. Efficacy, Safety, And Tolerability Of Efgartigimod In Patients With Chronic Inflammatory Demyelinating Polyneuropathy: Results From The Adhere Trial. Presented at: American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting; November 1-4, 2023; Phoenix, AZ. Abstract 143.
4. Hamidi BL, Mirawati DK, Rahayu RF, Prabaningtyas HR, Hafizhan M, Putra SE. Chronic inflammatory demyelinating polyradiculoneuropathy associated with neuromyelitis optica spectrum disorder: A rare case report. Prev Med Rep. 2024;42:102702. Published 2024 Apr 27. doi:10.1016/j.pmedr.2024.102702
5. Querol L, De Seze J, Dysgaard T, et al. Efficacy, safety, and tolerability of rozanolixizumab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a randomized, subject-blind, investigator-blind, placebo-controlled, phase 2a trial and open-label extension study. Neurol, Neurosurg & Psych. Published online May 10, 2024. doi:10.1136/jnnp-2023-333112
6. Fukami Y, Iijima M, Koike HH, et al. Autoantibodies Against Dihydrolipoamide S-Acetyltransferase in Immune-Mediated Neuropathies [published correction appears in Neurol Neuroimmunol Neuroinflamm. 2024 Mar;11(2):e200224]. Neurol Neuroimmunol Neuroinflamm. 2024;11(2):e200199. doi:10.1212/NXI.0000000000200199