Evaluating nipocalimab for the treatment of chronic inflammatory demyelinating polyneuropathy

Sirs: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy [13] characterized by symmetrical sensory and/or motor symptoms persisting for more than 8 weeks. The disease course may be progressive or relapsing [13]. On the basis of randomized trials, high dose intravenous immunoglobulin (IVIg), corticosteroids and plasma exchange have been established as effective treatments for CIDP. The main limitations of these approaches are lack of long term efficacy, difficulties in their use and high costs; thus, alternative immunosuppressive treatments have been proposed (azathioprine, cyclosporine and cyclophosphamide) [2, 9, 11]. The immune-mechanisms responsible for CIDP resemble those implicated in multiple sclerosis (MS) [13], thus making CIDP the peripheral counterpart of MS. In addition, similar to MS, neuropathological studies support heterogeneity of CIDP pathogenesis, with concomitant demyelination and axonal damage [13]. Some studies have recently been performed to evaluate the usefulness of Interferon (IFN) β1a in CIDP patients unresponsive to conventional therapies [1, 7, 14]. We present the case of a 43year-old woman, who in July 1997 complained of progressive weakness in both lower limbs, as well as sensory symptoms. Clinical symptoms persisted until December 1997 and a diagnosis of CIDP was made according to INCAT criteria [3]. Neurological examination revealed generalized areflexia, while an electrophysiological study showed partial conduction block for stimulation at the fibular head of peroneal nerves (–50 % amplitude on the right and –49 % on the left) and absent F wave on the left median nerve and right peroneal nerve. Cerebrospinal fluid analysis produced evidence of albuminocytological dissociation (total protein 82 mg/dL without cells) and isoelectrofocusing was within normal limit. After a first treatment schedule of IVIg with a good response, she became refractory to this treatment. She presented nine relapses throughout 27 months (treated with plasma exchange with transient and partial response) despite the specific drugs used (Figure). In July 2001 she started IFNβ-1b (Betaferon) 8MUI with subcutaneous injections every other day. No other relapses occurred. At present, she has been relapsefree for 40 months and shows marked improvement in clinical conditions (Table 1). Nerve conduction studies also showed marked improvement in motor and sensory velocities (Figure). In April 2002, serological examination showed the presence of anti-thyreoglobulin and anti-thyroid peroxidase antibodies, with an increase in free triiodothyronine and free thyroxin. Autoimmune thyreopathy was diagnosed, and the patient started treatment with an antithyroid drug. IFN beta has been proven efficient in treating MS [4, 5, 12] reducing the number of relapses. Due to clinical similarities between MS and CIDP, there is emerging interest in the use of IFN in CIDP. As far as we know, this is the first report in which IFNβ-1b has been used to treat a CIDP patient. Our patient showed good clinical and neurophysiological response to long-term IFNβ1b treatment (40 months). The stabilization observed was judged by the absence of relapses. IFN beta acts as an immunomodulatory agent, exerting its action at different levels in the inflammatory process. Two recombinant forms of IFN beta are used in clinical practice: IFNβ-1a and INFβ-1b. The use of IFNβ-1a in the treatment of CIDP is controversial, and contradictory results have been reported in different studies [1, 6, 12]. It should be noted that LETTER TO THE EDITORS

Plasma exchange and intravenous immunoglobulins: Mechanism of action in immune-mediated neuropathies

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a progressive or relapsing disease with a worldwide prevalence of up to nine individuals per 100 000 1. Randomized trials suggest that corticosteroids, plasma exchange and intravenous immunoglobulin (IVIg) can temporarily reduce impairment and disability. Although approximately 60–70% of the patients respond to the initial therapy, reports on long-term experience of IVIg use in CIDP are rare. Corticosteroids, plasma exchange and IVIg are first-line treatment options in CIDP; however, a risk of long-term adverse effects is the main disadvantage of corticosteroids. Long-term plasma exchange may be less tolerated, and expense can be a concern with IVIg. Two Phase III clinical trials proved the efficacy of IVIg for long-term treatment in CIDP. The IVIg CIDP Efficacy (ICE) trial was a large study that evaluated for the first time the long-term efficacy of IVIg in 117 patients with CIDP 2. Of the 57 patients who received IVIg and were first-period or cross-over-period responders, as assessed with the adjusted inflammatory neuropathy cause and treatment (INCAT) scale, 31 were reassigned randomly to IVIg and 26 were assigned randomly to placebo. IVIg-treated patients (13%) showed a significantly lower relapse rate compared to placebo-treated patients (45%), meaning that 55% of those who were re-randomized to placebo in the extension trial did not deteriorate in a time-frame of approximately 24 weeks 2. In the Privigen Impact on Mobility and Autonomy (PRIMA) study, IVIg-pretreated and IVIg-naive CIDP patients were enrolled and treated for 21 weeks 3. Approximately 61% of the patients showed a significant improvement according to the INCAT scale. Fifty per cent of patients responded to IVIg within the first 4 weeks and 88% of patients within 10 weeks. Of the 31 screened patients, only one CIDP patient (9%) failed the IVIg dependency test and did not deteriorate in the wash-out phase 3. Recently, a retrospective study aimed to evaluate the long-term outcomes in 86 CIDP patients treated with IVIg 4. Data were collected at four time-points: baseline (prior to the start of IVIg treatment); at short-term visit (approximately 6 weeks after IVIg initiation); at mid-term visit (approximately 24 weeks after IVIg); and at last follow-up visit (more than 48 weeks after initiating IVIg treatment). At the mid-term visit, 31 patients had only one IVIg course throughout the entire observation period. Twenty CIDP patients did not receive IVIg at all. Of these 20 patients, 12 were stable. At the long-term visit, 22 patients (25·6%) showed no signs of deterioration 4. There are limited data available on the long-term treatment of CIDP and multifocal motor neuropathy (MMN) with subcutaneous immunoglobulin (SCIg). In a recent report, two patients with atypical CIDP (multifocal acquired demyelinating sensory and motor neuropathy – MADSAM), were treated with SCIg over a time-period of 46 months 5. The Medical Research Council (MRC) sum score remained stable during the entire time-period. In a randomized Phase II study, 30 CIDP patients were enrolled and randomized to placebo and SCIg 6. The treatment period was 12 weeks, with twice- or thrice-weekly SCIg injections (30–300 ml/week; 4·8–48 g/week). After 12 weeks, significant increases (P > 0·05) in isokinetic muscle strength were observed in SCIg-treated patients (5·5 ± 9·5%) compared to the decline observed in the placebo group (14·4 ± 20·3%) 6. Two small case series investigated the effect of SCIg in MMN 7,8. SCIg proved its effectiveness in MMN in short- 7 and long-term use 8. It should be noted that the initial SCIg dose should be 100% equivalent to the monthly IVIg dose 7. A Phase III study proving the efficacy of SCIg in treating CIDP (PATH-Study) is still ongoing (ClinicalTrials.gov identifier: NCT01545076). More recently, a cost-effectiveness study comparing IVIg and SCIg was performed in Italy. Assuming that approximately 2100 CIDP patients exist in Italy, and 50% of those patients were prescribed SCIg, the estimated cost-saving in their model was approximately €1·4 million for the health-care sector 9. However, it should be noted that the cost of SCIg differs within Europe. In conclusion, both IVIg and SCIg are safe and well tolerated for long-term treatment in CIDP and MMN. The most common side effects are headaches (IVIg) and local skin reactions (SCIg). Although not very common, haemolysis is a severe side effect seen with IVIg that can potentially lead to hospitalization, especially when higher doses are administered (2 g/kg body weight).

129th ENMC International Workshop: Clinical Trials for Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy, 27th October 2004, Schiphol airport, The Netherlands

Novel Therapeutic Avenues for Chronic Inflammatory Demyelinating Polyneuropathy: The Difficulties of Disease Diversity

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated neuropathy. First-line treatments for CIDP include corticosteroids, intravenous immunoglobulin, and plasma exchange. However, the application is always limited by high costs, effectiveness, and adverse events. This study investigated a new potentially effective and safe therapeutic treatment to alleviate CIDP symptoms and improve the quality of life. In the present case, a 47-year-old rural woman presented with weakness and numbness of progressive extremities. She was diagnosed with CIDP based on abnormal cerebrospinal fluid and electromyography. The patient was treated with intravenous dexamethasone for 1 week and with Huangqi-Guizhi-Wuwu and Bu-Yang-Huan-Wu decoctions for 90 days. Surprisingly, after the treatment, the weakness and numbness were eliminated, and the quality of life improved. The varying INCAT, MRC, and BI scores also reflected the treatment effects. After 8 months of discharge, the symptoms did not relapse during the follow-up. We also searched "traditional Chinese medicine (TCM)" and "CIDP" in PubMed, EMBASE, the Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure Databases, Wanfang Data, and the Chongqing Chinese Science and Technology Periodical Database. Finally, only ten studies were included in the literature review. Three studies were randomized controlled trials, and seven were case reports or case series. There were 419 CIDP patients, but all study sites were in China. Nine TCM formulas involving 44 herbs were reported, with Huang Qi (Astragalus membranaceus) being the most important herb. In conclusion, the case and literature demonstrated that TCM treatment might be a more effective, low-cost, and safe option for treating CIDP. Although these preliminary findings are promising, a larger sample size and higher-quality randomized clinical trials are urgently required to confirm our findings.

Unlike for acute immune-mediated neuropathies (IN), anti-ganglioside autoantibody (aGAAb) testing has been recommended for only a minority of chronic IN yet. Thus, we used a multiplex semi-quantitative line immunoassay (LIA) to search for aGAAb in chronic-inflammatory demyelinating polyneuropathy (CIDP) and its clinical variants. Anti-GAAb to 11 gangliosides and sulfatide (SF) were investigated by LIA in 61 patients with IN (27 typical CIDP, 12 distal-acquired demyelinating polyneuropathy, 6 multifocal-acquired demyelinating sensory/motor polyneuropathy, 10 sensory CIDP, 1 focal CIDP and 5 multifocal-motoric neuropathy), 40 with other neuromuscular disorders (OND) (15 non-immune polyneuropathies, 25 myasthenia gravis), 29 with multiple sclerosis (MS) and 54 healthy controls (HC). In contrast to IgG, positive anti-GAAB IgM against at least one ganglioside/SF was found in 17/61 (27.9%) IN compared to 2/40 (5%) in OND, 2/29 MS (6.9%) and 4/54 (7.4%) in HC (p=0.001). There was a statistically higher prevalence of anti-sulfatide (aSF) IgM in IN compared to OND (p=0.008). Further, aGM1 IgM was more prevalent in IN compared to OND and HC (p=0.009) as well as GD1b in IN compared to HC (p<0.04). The prevalence of aGM1 IgM in CIDP was lower compared to in multifocal motor neuropathy (MMN) (12% vs. 60%, p=0.027). Patients showing aSF, aGM1 and aGM2 IgM were younger compared to aGAAb negatives (p<0.05). Patients with aSF IgM positivity presented more frequently typical CIDP and MMN phenotypes (p<0.05, respectively). The aGAAb LIA revealed an elevated frequency of at least one aGAAb IgM in CIDP/MMN patients. Anti-SF, aGM1 and aGM2 IgM were associated with younger age and anti-SF with IN phenotypes.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous, acquired autoimmune neurological disorder affecting peripheral nerves. CIDP is characterized by progressive weakness, reduced or absent tendon reflexes and impaired sensory function in the lower and upper limbs. CIDP diagnosis is mainly based on clinical, laboratory and electrophysiologic criteria and there are currently no diagnostic or prognostic biomarkers. First-line treatment options include corticosteroids, intravenous immunoglobulin (IVIg) and plasma exchange (PLEX). While IVIg and corticosteroids are the most common therapies administered for CIDP, there are challenges associated with their use, including systemic adverse events (AEs), some of which can be serious. Studies have shown that subcutaneous immunoglobulin (SCIg) may be associated with improved quality of life, which is attributed partially to the patients’ freedom to administer SCIg at home and at their convenience. While AEs with SCIg mostly consist of local site reactions, SCIg is associated with fewer systemic AEs compared with IVIg, and these are commonly mild, though severe reactions may rarely occur. A number of studies in the last decade have assessed SCIg in CIDP. One of these studies, the Polyneuropathy and Treatment with Hizentra® (PATH) study, was a global phase 3, double-blind, randomized, placebo-controlled trial that assessed the efficacy, safety, and tolerability of SCIg treatment in patients with CIDP. Based on the results of the PATH study, the US Food and Drug Administration (FDA) approved SCIg as a maintenance treatment for CIDP in 2018. This review summarizes and discusses the results of the PATH study and its open-label extension (OLE) study and provides an overview of the April 2021 update to the Hizentra® FDA-approved U.S. package insert based on findings from the PATH OLE. In addition, the review highlights key elements of the second revision of the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guideline for the diagnosis and treatment of CIDP. Finally, this review discusses the characteristics of patients with CIDP who may benefit from SCIg treatment.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated neuropathy and patients suffer from muscle weakness and impaired quality of life. Current standard treatments for CIDP include immunoglobulin, corticosteroid, and plasma exchange. Efficacy of these treatments has been demonstrated by high level evidence from several randomized controlled trials. Otherwise, there are some concerns about these treatments such as side effects, CIDP recurrence, unstable drug supply, difficulty of use, and the presence of refractory patients. Novel therapies for CIDP are under development, among which an approach to reduce pathogenic IgG, which is thought to be involved in the pathogenesis of CIDP. Efgartigimod is a human IgG1 antibody fragment designed to reduce IgG including pathogenic IgG by binding to the neonatal Fc receptor and blocking the IgG recycling process. The efficacy and safety of subcutaneous efgartigimod were evaluated in the ADHERE trial, a multicenter, randomized-withdrawal, double-blind, placebo-controlled phase II trial in patients with CIDP, in which subcutaneous efgartigimod significantly suppressed the recurrence of CIDP compared to the placebo and was well-tolerated. Based on these results, subcutaneous efgartigimod was approved for the treatment of CIDP in December 2024 in Japan. Other new therapies targeting complement pathways or B cells are under clinical development. (Received May 9, 2025; Accepted July 23, 2025; Published December 1, 2025).

Should plasma exchange be offered to patients with multiple sclerosis-associated optic neuritis?

Background:Haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) has given rise to an increasing number of neurological complications that cause high morbidity and mortality. Our previous studies have characterized central nervous system complications (Ann Hematol, 2018), although the relatively rare peripheral neuropathies remain poorly understood. Apart from those with clear etiologies, such as treatment toxicity and tumor infiltration, a small subset of posttransplant neuropathies known as immune‐mediated neuropathies (IMNs) is solely relevant to immune factors. Recently, new insights have been proposed for posttransplant IMNs; for instance, diseases such as radiculoplexus neuropathies and multiple mononeuropathies can also be IMN subtypes, which previously included only Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) (J Neurol Neurosurg Psychiatry, 2014). However, the IMNs complicating haplo‐HSCT have not been systematically elucidated at present.Aims:To investigate the incidence, clinical features, risk factors and outcomes of IMNs complicating haplo‐HSCT.Methods:A nested, case‐control study was performed based on 3858 patients who received haplo‐HSCT at Peking University People's Hospital. Transplantation was conducted according to our previous protocols. Cases were defined as patients who developed IMNs after haplo‐HSCT, which were identified by chart review of clinical manifestations, laboratory findings, electrodiagnostic studies, and radiological findings. Individual matching was performed by randomly selecting 3 controls for each identified case from the same cohort considering the time of HSCT (± 90 days), gender, and follow‐up time (± 180 days).Results:Forty cases of IMNs were identified from 3858 haplo‐HSCT patients, for an incidence rate of 1.04%. The median onset time of the IMNs was 78 days after haplo‐HSCT. The identified IMN cases included 10 GBS and 30 peripheral neuropathies that did not meet the diagnostic criteria for GBS or CIDP. The main clinical manifestations were weakness (57.5%), altered sensation (57.5%), hyporeflexia (25%) and pain (10.0%). In the univariate analysis, aGVHD (P = 0.116), cGVHD (P = 0.024), and CMV viremia (P = 0.024) were identified as potential risk factors (P &lt; 0.20) for IMNs. However, only CMV viremia (HR = 4.557, P = 0.024) was identified as an independent risk factor after multivariate analysis. No significant differences in OS (P = 0.619), DFS (P = 0.609), NRM (P = 0.87) or the incidence of relapse (P = 0.583) were found between posttransplant patients with and without IMNs. Eleven (27.5%) of the IMN patients developed cGVHD, which was a significantly higher incidence than that of the patients without IMNs (P = 0.012). All IMN patients received vitamin B1 and B12 therapy once a diagnosis of IMNs was suspected, and 6 of them achieved neurological improvement without further treatment. IVIG/steroids were given to 25 IMN patients, of whom 18 (72%) subsequently achieved clinical improvement.Summary/Conclusion:CMV viremia is the only independent risk factor for rare posttransplant IMNs. Haplo‐HSCT patients with IMNs are at a higher risk of developing cGVHD. Vitamin B and IVIG/steroids can help improve neurological outcomes. In the future, prospective multicenter studies are needed to increase our understanding of the underlying pathogenesis and to propose standardized diagnostic and therapeutic strategies.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic immune-mediated neuropathy: it is clinically heterogeneous (relapsing-remitting form, chronic progressive form, monophasic form or CIDP having a Guillain-Barré syndrome-like onset), but potentially treatable. Although its pathophysiology remains largely unknown, CIDP is considered an immune-mediated neuropathy. Therefore, many immunotherapies have been proposed in this peripheral nervous system disorder, the most known efficient treatments being intravenous immunoglobulin, corticosteroids and plasma exchange. However, these therapies remain unsatisfactory for many patients, so numerous other immunotherapeutic strategies have been evaluated, based on their immunosuppressant or immunomodulatory potency. We have performed a large review of the literature about treatment in CIDP, with a special emphasis on novel and alternative immunotherapeutic strategies.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous immune-mediated peripheral neuropathy with progressive or relapse-remitting course. Incidence of CIDP ranged between 1 and 8.9/100 000. Recently, most frequent therapies for CIDP treatment was glucocorticosteroids, intravenous immunoglobulin and plasma exchange. In cases of ineffectiveness or lack of effectiveness, cytostatics, monoclonal antibodies and others could be used for CIDP treatment. In the article, authors presented an update data on the use of main methods for CIDP therapy, their mechanisms of action, indication for their use and advantages and disadvantages of each of them.

We aimed to identify the target antigens for combined central and peripheral demyelination (CCPD). We screened target antigens by immunohistochemistry and immunoblotting using peripheral nerve tissues to identify target antigens recognized by serum antibodies from selected CCPD and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cases. We then measured the level of antibody to the relevant antigen in 7 patients with CCPD, 16 patients with CIDP, 20 patients with multiple sclerosis, 20 patients with Guillain-Barré syndrome, 21 patients with other neuropathies, and 23 healthy controls (HC) by ELISA and cell-based assays using HEK293 cells. At the initial screening, sera from 2 patients with CCPD showed cross-like binding to sciatic nerve sections at fixed intervals, with nearly perfect colocalization with neurofascin immunostaining at the node and paranode. ELISA with recombinant neurofascin revealed significantly higher mean optical density values in the CCPD group than in other disease groups and HC. Anti-neurofascin antibody positivity rates were 86% in patients with CCPD, 10% in patients with multiple sclerosis, 25% in patients with CIDP, 15% in patients with Guillain-Barré syndrome, and 0% in patients with other neuropathies and HC. The cell-based assay detected serum anti-neurofascin antibody in 5 of 7 patients with CCPD; all others were negative. CSF samples examined from 2 patients with CCPD were both positive. In anti-neurofascin antibody-positive CCPD patients, including those with a limited response to corticosteroids, IV immunoglobulin or plasma exchange alleviated the symptoms. Anti-neurofascin antibody is frequently present in patients with CCPD. Recognition of this antibody may be important, because patients with CCPD who are antibody positive respond well to IV immunoglobulin or plasma exchange.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy that responds to various immunosuppressive treatments. Oral daily prednisone therapy is effective and inexpensive, but the long-term treatment that is usually necessary leads to serious adverse effects. Consequently, intravenous immunoglobulin and plasma exchange have been widely used to treat CIDP, making treatment expensive and inconvenient. A steroid regimen that reduces adverse effects but preserves efficacy would simplify treatment. Pulsed steroids have nongenomic actions not seen with low-dose steroids, including rapid inhibition of arachidonic acid release and of calcium and sodium cycling across plasma membranes of immune cells. To study the efficacy, safety, and tolerability of pulsed oral methylprednisolone therapy in patients with CIDP. Open-label prospective study. University of Minnesota Neuropathy Center, Minneapolis. Ten patients (3 women and 7 men) with CIDP followed up for at least 22 months. Neuromuscular score and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score were used as outcome measures for efficacy; weight, blood pressure, changes in bone density, and steroid-related adverse effect questionnaire were used as outcome measures for safety. This steroid regimen leads to significant improvement in weakness and disability in all patients treated and to off-treatment remission in 60% of patients. Treatment was fairly well tolerated, and only 1 patient discontinued treatment because of adverse effects. Steroid-induced osteoporosis remained a problem, especially in older patients. Pulsed oral methylprednisolone may be efficacious in the long-term treatment of CIDP and is relatively well tolerated. Remission can be induced in most patients, especially those with a shorter duration of disease.