Treatment Of Chronic Inflammatory Demyelinating Polyneuropathy Research Articles

Whole-body magnetic resonance neurography in patients with chronic inflammatory demyelinating polyneuropathy.

Whole-body magnetic resonance neurography (MRN) is an imaging modality that shows peripheral nerve signal change in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We aimed to explore the diagnostic potential of whole-body MRN and its potential as a monitoring tool after immunotherapy in treatment-naïve CIDP patients. Whole-body MRN using coronal 3-dimensional short tau inversion recovery (STIR) sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) techniques was performed in patients being investigated for CIDP and in healthy controls. Baseline clinical neuropathy scales and electrophysiologic parameters were collected, and MRN findings were compared before and after CIDP treatment. We found highly concordant symmetrical thickening and increased T2 signal intensities in the brachial/lumbosacral plexus, femoral, or sciatic nerves in five of the eight patients with a final diagnosis of CIDP and none of the healthy controls. There were no treatment-related imaging changes in five patients with CIDP who completed a follow-up study. Diffuse, symmetrical thickening, and increased T2 signal in root, plexus, and peripheral nerves were found in two patients ultimately excluded due to a diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome in addition to signal changes in the muscles, bony lesions, organomegaly, and lymphadenopathy. Whole-body MRN imaging shows promise in detecting abnormalities in proximal nerve segments in patients with CIDP. Future studies evaluating the role of MRN in assessing treatment response should consider follow-up scans after treatment durations of more than 4 months.

Subcutaneous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy: A Historical Perspective.

The therapeutic administration of subcutaneous immunoglobulin (SCIg) offers various advantages over intravenous immunoglobulin (IVIg). This narrative review examines and compares SCIg versus IVIg in chronic inflammatory demyelinating polyneuropathy (CIDP). SCIg is as effective as IVIg but is better tolerated and easier to administer, as intravenous access is not required. Furthermore, SCIg administration is more convenient and cost-effective than IVIg, enabling flexible treatment scheduling at home and improving patients' overall quality of life. The availability of highly concentrated immunoglobulin G (IgG) subcutaneous solutions, such as IgPro20, a 20% IgG solution stabilized with L-proline, allows for the administration of larger volumes in a single session, while the parallel development of new technological devices enables the delivery of higher doses over a shorter time. Based on the results of the PATH study, SCIg has become a well-established therapy in CIDP. In addition to discussing the advantages of SCIg, this review summarizes the evolution of SCIg by discussing all the relevant clinical studies which have considered its use in the treatment of CIDP.

How I Treat Chronic Inflammatory Demyelinating Polyneuropathy Podcast.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated neuropathy that typically presents with progressive or relapsing, symmetric, proximal, and distal weakness of upper and lower limbs, sensory involvement of at least two limbs, and decreased or absent deep tendon reflexes. The symptoms of CIDP can be similar to those of other neuropathies, making diagnosis difficult, which can often lead to delays in correct diagnosis and treatment. The updated European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) 2021 guideline outlines a set of diagnostic criteria that help to identify CIDP with high accuracy and provides recommendations for the treatment of CIDP. The aim of this podcast, featuring Dr. Urvi Desai (Professor of Neurology, Wake Forest School of Medicine and Atrium Health Neurosciences Institute Wake Forest Baptist, Charlotte), is to discuss how the new guideline impacts diagnosis and treatment decisions in her everyday clinical practice. Using a patient case study example, the updated guideline recommends assessing a patient for clinical, electrophysiological, and supportive criteria for CIDP, enabling a more straightforward diagnosis of either typical CIDP, a CIDP variant, or an autoimmune nodopathy. A second patient case study highlights how the new guideline no longer considers autoimmune nodopathies as CIDP, as patients with these disorders do not meet hallmark CIDP criteria. This leaves an unmet need in terms of guidance on how to treat this subset of patients. Although the new guideline has not necessarily changed treatment preference in clinical practice, the addition of subcutaneous immunoglobulin (SCIG) into the guideline now better reflects clinical practice. The guideline helps to define and categorize CIDP more simply and consistently, allowing quicker and more accurate diagnosis, leading to a positive impact on treatment response and prognosis. These real-world insights into the diagnosis and management of patients with CIDP could help guide best clinical practice and help facilitate optimization of patient outcomes.

A Budget Impact Model of Maintenance Treatment of Chronic Inflammatory Demyelinating Polyneuropathy with IgPro20 (Hizentra) Relative to Intravenous Immunoglobulin in the United States.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, progressive autoimmune disease causing peripheral nervous system dysfunction. Guidelines recommend immunoglobulin (IG) therapy as an immunomodulatory agent in CIDP. Drawbacks and unmet needs with intravenous immunoglobulin (IVIG) include adverse effects and wear-off effects, along with the burden of administration based on site of care. Subcutaneous administration of Hizentra, a subcutaneous immunoglobulin (SCIG) reduces patient burden by allowing self-administration outside the hospital setting and has fewer adverse events (AEs). We aimed to compare the expected cost of treatment and the budget impact of Hizentra compared with IVIG for maintenance treatment of CIDP in the United States. A decision tree model was developed to estimate the expected budget impact of maintenance treatment with Hizentra for US stakeholders. The model adopts primarily a US integrated delivery network perspective and, secondarily, a commercial perspective over a 1-year time horizon. Pharmacy costs were based on a payment mix of average sales price (73%), wholesale acquisition cost (2%), and average wholesale price (25%). Costs in the model reflect 2022 US dollars. In accordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines and recommendations for budget impact modeling, no discounting was performed. The PATH clinical study of Hizentra maintenance in CIDP was used to determine clinical inputs for relapse rates at initial assessment (24 weeks) and at 52 weeks for Hizentra. The ICE clinical study of Gamunex maintenance in CIDP was the basis of relapse rates for Gamunex (and other IVIGs). Literature-based estimates were obtained for infusion costs by site of care, costs of IVIG infusion-related complications, and significant IVIG AE rates. Hizentra AE rates from the US Hizentra prescribing information were assessed but were not included in the model as the AEs in CIDP were mild, easily treated, and self-limited. Sensitivity analyses and scenario analyses were conducted to evaluate variations from the base case. The model showed that a Hizentra starting dose of 0.2 g/kg is expected to result in annual cost savings of US$32,447 per patient compared with IVIG. For a hypothetical 25-million-member plan, the budget impact of a 10% market share shift from IVIG to Hizentra is expected to result in savings of US$2,296,235. This analysis projects that Hizentra is likely associated with favorable economic benefit compared with IVIG in managing CIDP.

Optimizing chronic inflammatory demyelinating polyneuropathy care with subcutaneous immunoglobulin: The Polyneuropathy and Treatment with Hizentra Open-Label Extension (PATH OLE) study and beyond

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 Polyneuropathy (CIDP): Current Therapies and Future Approaches.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated polyradiculoneuropathy leading to disability via inflammatory demyelination of peripheral nerves. Various therapeutic approaches with different mechanisms of action are established for the treatment of CIDP. Of those, corticosteroids, intravenous or subcutaneous immunoglobulin, or plasma exchange are established first-line therapies as suggested by the recently revised EAN/PNS guidelines for the management of CIDP. In special cases, immunosuppressants or rituximab may be used. Novel therapeutic approaches currently undergoing clinical studies include molecules or monoclonal antibodies interacting with Fc receptors on immune cells to alleviate immune-mediated neuronal damage. Despite various established therapies and the current development of novel therapeutics, treatment of CIDP remains challenging due to an heterogeneous disease course and the lack of surrogate parameters to predict the risk of clinical deterioration. This review summarizes established therapies for CIDP and provides an outlook on future therapeutic approaches.

Contemporary challenges in the diagnosis and management of chronic inflammatory demyelinating polyneuropathy

ABSTRACT Introduction Despite extensive research, multiple inter-related diagnostic and management challenges remain for chronic inflammatory demyelinating polyneuropathy (CIDP). Areas Covered A literature review was performed on diagnosis and treatment in CIDP. The clinical features and disease course were evaluated. Investigative techniques, including electrophysiology, cerebrospinal fluid examination, neuropathology, imaging, and neuroimmunology, were considered in relation to technical aspects, sensitivity, specificity, availability, and cost. Available evidenced-based treatments and those with possible efficacy despite lack of evidence, were considered, as well as current methods for evaluation of treatment effects. Expert Opinion CIDP remains a clinical diagnosis, supported first and foremost by electrophysiology. Other investigative techniques have limited impact. Most patients with CIDP respond to available first-line treatments and immunosuppression may be efficacious in those who do not. Consideration of the natural history and of the high reported remission rate, of under-recognized associated disabling features, of treatment administration modalities and assessment methods, require enhanced attention.

P 46. Assessment of individualized treatment decisions for intravenous immunoglobulin therapy in patients with chronic immune-mediated neuropathies: observational study design and progress

Introduction. Chronic immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are associated with immune mediated peripheral nerve damage and neurological deficits. Randomized, controlled clinical trials have demonstrated the effectiveness of human intravenous immunoglobulin (IVIG) for these conditions. IVIG is considered a treatment of choice for both disorders. German and EFNS/PNS guidelines recommend individualization of IVIG therapy during treatment for CIDP and MMN. However, there is a lack of documentation of individualized dosing in real-world practice. Objective. This study is designed to determine the patterns of use of 10% IVIG in real-world clinical practice and identify the factors driving treatment decisions for patients with CIDP or MMN. Methods. The study is non-interventional, longitudinal, multicenter design. Primary data collected will be physicians“ practice patterns, demographics, treatment regimens and tolerability of 10% IVIG. Adult patients (n=150) diagnosed with CIDP or MMN and with current or prospective therapy with 10% IVIG will be eligible for the study. Approximately 40 sites in Germany will participate in the study. The planned recruitment period for the study is 18 months starting in first half of 2021. Results. According to the study protocol, patient demographics, medical and disease history and concomitant medication are to be assessed at baseline. Data will be collected at the baseline visit and at each infusion visit (approximately every 3 weeks as scheduled for routine care) for up to 18 months . In addition, the study will include an initial , cross-sectional, quantitative survey for participating physicians on their current practice patterns for CIDP and MMN. The survey will include assessment of initial therapy choices, IVIG dosing, outcome measures, dosing reductions and treatment schemes for relapses. The criteria used for decisions about initiation, continuation and individualization of IVIG treatment (dosing, intervals, co-medication) will be recorded at each visit. Physicians are also requested to provide the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score at baseline and other study visits, if these scores are routinely determined. The physician-assessed Clinical Global Impression of Improvement (CGI-I) is to be performed at all visits. The potential impact of the COVID-19 pandemic on an individual subject“s treatment algorithm will also be captured in the electronic data capture system . To assess safety, serious adverse events and adverse drug reactions will be evaluated at each visit. Conclusions. Results from this clinical trial will allow identification of the factors driving treatment decisions by physicians utilizing 10% IVIG to treat patients with CIDP or MMN as part of their clinical routine and allow assessment of the influence of patient-reported outcomes and objective clinical measures.

A Global Survey of Disease Burden in Patients Who Carry a Diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy.

IntroductionThe extent to which work productivity, emotional well-being, social interactions, and family life are impacted in patients who self-identify as having chronic inflammatory demyelinating polyneuropathy (CIDP) is not well characterized.MethodsData from an online survey of 595 individuals with self-reported CIDP, recruited by the Guillain–Barré syndrome (GBS)/CIDP Foundation, were used to assess disease and treatment burden. A total of 37% of patients were classified as “likely”, 34% as “somewhat likely”, and 28% as “unlikely” CIDP.ResultsOf ten symptoms that patients with CIDP may experience, each symptom was experienced by 77–94% of “likely”, 79–96% of “somewhat likely”, and 66–91% of “unlikely” patients. In “likely” CIDP patients 44% stopped working because of their symptoms and 24% moved to a new home. The most common treatments were intravenous immunoglobulin (IVIg) infusion and corticosteroids. IVIg was associated with venous access issues and work/school absenteeism.ConclusionsCIDP diagnostic confirmation was not performed in any of the survey respondents. Our results do not add any knowledge on the diagnosis or treatment of CIDP. Our findings do provide insight into the symptoms that patients that think they have CIDP or have been told they have CIDP experience, explores how patients that are labeled as having CIDP view treatment expectations, and highlights how these symptoms affect home and work life. We hope that the findings are constructively used to get patients the services they need to improve quality of life, maintain employment, and ensure a safe home environment regardless of diagnostic accuracy.

Longer-term effects of intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: Who benefits?

Intravenous immunoglobulins (IVIg) represent an established cornerstone for the immunotherapy of chronic inflammatory demyelinating polyneuropathy (CIDP). Efficacy of IVIg for CIDP was proven in a large phase III trial. Yet, data on longer-term efficacy and effects in distinct subgroups are scarce. Our trial investigates the long-term efficacy of IVIg treatment in CIDP patients.In this observational real-world study, we retrospectively analyzed 49 CIDP patients receiving continuous IVIg treatment with a mean initial dosage of 87 g (1 g/kg body weight) every 4 weeks over a mean time of 45 months between 2010 and 2018. INCAT-Scores before the start of treatment and at the end of the observation period were compared.Over the observation period, IVIg treatment led to a median improvement of one INCAT score point. Subgroup analyses revealed a more pronounced improvement of INCAT scores in female CIDP patients, individuals with relapsing disease courses, patients with more pronounced motor impairment (higher initial INCAT scores) and in the cohort without need for concomitant other immunotherapies.These data argue for sustained beneficial effects of longer-term immunotherapy with IVIg in CIDP, particularly in females and relapsing disease forms with higher disease activity.

Pathophysiology of Chronic Inflammatory Demyelinating Polyneuropathy: Insights into Classification and Therapeutic Strategy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is classically defined as polyneuropathy with symmetric involvement of the proximal and distal portions of the limbs. In addition to this “typical CIDP”, the currently prevailing diagnostic criteria proposed by the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) define “atypical CIDP” as encompassing the multifocal acquired demyelinating sensory and motor (MADSAM), distal acquired demyelinating symmetric (DADS), pure sensory, pure motor, and focal subtypes. Although macrophage-induced demyelination is considered pivotal to the pathogenesis of CIDP, recent studies have indicated the presence of distinctive mechanisms initiated by autoantibodies against paranodal junction proteins, such as neurofascin 155 and contactin 1. These findings led to the emergence of the concept of nodopathy or paranodopathy. Patients with these antibodies tend to show clinical features compatible with typical CIDP or DADS, particularly the latter. In contrast, classical macrophage-induced demyelination is commonly found in some patients in each major subtype, including the typical CIDP, DADS, MADSAM, and pure sensory subtypes. Differences in the distribution of lesions and the repair processes underlying demyelination by Schwann cells may determine the differences among subtypes. In particular, the preferential involvement of proximal and distal nerve segments has been suggested to occur in typical CIDP, whereas the involvement of the middle nerve segments is conspicuous in MADSAM. These findings suggest that humoral rather than cellular immunity predominates in the former because nerve roots and neuromuscular junctions lack blood–nerve barriers. Treatment for CIDP consists of intravenous immunoglobulin (IVIg) therapy, steroids, and plasma exchange, either alone or in combination. However, patients with anti-neurofascin 155 and contactin 1 antibodies are refractory to IVIg. It has been suggested that rituximab, a monoclonal antibody to CD20, could have efficacy in these patients. Further studies are needed to validate the CIDP subtypes defined by the EFNS/PNS from the viewpoint of pathogenesis and establish therapeutic strategies based on the pathophysiologies specific to each subtype.

Immunoglobulin administration for the treatment of CIDP: IVIG or SCIG?

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired neurological disorder characterized clinically by weakness and impaired sensory function evolving over 2 months or more, loss or significant decrease in deep tendon reflexes, and by electrophysiological evidence of peripheral nerve demyelination. Expeditious diagnosis and treatment of CIDP early in the disease course is critical such that irreversible disability can be avoided. Intravenous immunoglobulin (IVIG) is one first-line and maintenance therapy option for CIDP. The US Food & Drug Administration's (FDA's) approval of subcutaneous immunoglobulin (SCIG) in 2018 provides patients with CIDP more treatment options for maintenance therapy. The different options for administration of IG treatment create the need for information to assist clinicians and patients in choosing the optimal therapeutic approach. Considerations for pharmacokinetics, administration procedures, adverse events, patient variables, and cost will all be discussed in this article.

Outcome measures for chronic inflammatory demyelinating polyneuropathy in research: relevance and applicability to clinical practice.

Outcome measures are recommended in the management of chronic inflammatory demyelinating polyneuropathy (CIDP). Various scales have been proposed in recent years, some now commonly utilized in daily clinical practice. The available evidence base relies itself on randomized controlled trial data obtained over the past 30 years, with several studies using different primary and secondary outcomes. We here review the different outcome measures used in CIDP research in relation to those currently recommended for clinical management. We consider the evidence base for CIDP treatment from the primary and secondary outcomes used in these studies and attempt to assess how this may relate to current clinical practice of routine evaluation of treatment effects and long-term monitoring.

AN UPDATE DATA ON THE TREATMENT OF CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY (review of literature)

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.

Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies.

Intravenous immunoglobulin (IVIG) is a potential therapy for chronic inflammatory demyelinating polyneuropathy (CIDP). To investigate the efficacy and safety of the IVIG IgPro10 (Privigen) for treatment of CIDP, results from Privigen Impact on Mobility and Autonomy (PRIMA), a prospective, open‐label, single‐arm study of IVIG in immunoglobulin (Ig)‐naïve or IVIG pre‐treated subjects (NCT01184846, n = 28) and Polyneuropathy And Treatment with Hizentra (PATH), a double‐blind, randomized study including an open‐label, single‐arm IVIG phase in IVIG pre‐treated subjects (NCT01545076, IVIG restabilization phase n = 207) were analyzed separately and together (n = 235). Efficacy assessments included change in adjusted inflammatory neuropathy cause and treatment (INCAT) score, grip strength and Medical Research Council (MRC) sum score. Adverse drug reactions (ADRs) and ADRs/infusion were recorded. Adjusted INCAT response rate was 60.7% in all PRIMA subjects at Week 25 (76.9% in IVIG pre‐treated subjects) and 72.9% in PATH. In the pooled cohort (n = 235), INCAT response rate was 71.5%; median time to INCAT improvement was 4.3 weeks. No clear demographic differences were noticed between early (responding before Week 7, n = 148) and late responders (n = 21). In the pooled cohort, median change from baseline to last observation was −1.0 (interquartile range −2.0; 0.0) point for INCAT score; +8.0 (0.0; 20.0) kPa for maximum grip strength; +3.0 (1.0; 7.0) points for MRC sum score. In the pooled cohort, 271 ADRs were reported in 105 subjects (44.7%), a rate of 0.144 ADRs per infusion. This analysis confirms the efficacy and safety of IgPro10, a recently FDA‐approved IVIG for CIDP, in a population of mainly pre‐treated subjects with CIDP [Correction added on 14 March 2019 after first online publication: the INCAT response rate has been corrected.].

Existing and Emerging Approaches to Treating Chronic Inflammatory Demyelinating Polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare disabling disease with an incompletely understood autoimmune etiology. Differentiating the condition from other neurological diseases can be challenging and appropriate treatment is often delayed. Intravenous immunoglobulin (IVIg), plasmapheresis, corticosteroids and subcutaneous immunoglobulin (SCIg) have all been demonstrated to be beneficial in placebo-controlled, randomized clinical trials. Corticosteroids, including methylprednisolone and dexamethasone are effective and frequently used in CIDP but their long-term use is limited by side effects. One of the most commonly prescribed treatments for CIDP is IVIg which diminishes inflammatory processes and prevents disease progression. Treatment with IVIg has proven effective in randomized, double blind, placebo controlled, clinical trials and the results support its use in CIDP. For some patients, the benefit of IVIg, is limited by the frequency of infusions and systemic side effects such as flu-like symptoms, headache, and nausea. Other effective treatments for CIDP include corticosteroids that are associated with serious side effects in long-term use and plasmapheresis which requires specialized facilities. More recently, SCIg has been demonstrated in double blind, placebo-controlled studies to be effective for maintenance use in CIDP in patients whose disease has been controlled by IVIg. In a large clinical trial, 0.2 g/kg and 0.4 g/kg body weight doses of 20% SCIg equivalent to 1 mL/kg or 2 mL/kg, respectively, administered weekly, demonstrated efficacy in CIDP and were well tolerated. Immunomodulating treatments such as cyclophosphamide, mycophenolate mofetil and rituximab have also shown efficacy in select populations with CIDP.

Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial

Approximately two-thirds of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) need long-term intravenous immunoglobulin. Subcutaneous immunoglobulin (SCIg) is an alternative option for immunoglobulin delivery, but has not previously been investigated in a large trial of CIDP. The PATH study compared relapse rates in patients given SCIg versus placebo. Between March 12, 2012, and Sept 20, 2016, we studied patients from 69 neuromuscular centres in North America, Europe, Israel, Australia, and Japan. Adults with definite or probable CIDP who responded to intravenous immunoglobulin treatment were eligible. We randomly allocated participants to 0·2 g/kg or 0·4 g/kg of a 20% SCIg solution (IgPro20) weekly versus placebo (2% human albumin solution) for maintenance treatment for 24 weeks. We did randomisation in a 1:1:1 ratio with an interactive voice and web response system with a block size of six, stratified by region (Japan or non-Japan). The primary outcome was the proportion of patients with a CIDP relapse or who were withdrawn for any other reason during 24 weeks of treatment. Patients, caregivers, and study personnel, including those assessing outcomes, were masked to treatment assignment. Analyses were done in the intention-to-treat and per-protocol sets. This trial is registered with ClinicalTrials.gov, number NCT01545076. In this randomised, double-blind, placebo-controlled trial, we randomly allocated 172 patients: 57 (33%) to the placebo group, 57 (33%) to the low-dose group, and 58 (34%) to the high-dose group. In the intention-to-treat set, 36 (63% [95% CI 50-74]) patients on placebo, 22 (39% [27-52]) on low-dose SCIg, and 19 (33% [22-46]) on high-dose SCIg had a relapse or were withdrawn from the study for other reasons (p=0·0007). Absolute risk reductions were 25% (95% CI 6-41) for low-dose versus placebo (p=0·007), 30% (12-46) for high-dose versus placebo (p=0·001), and 6% (-11 to 23) for high-dose versus low-dose (p=0·32). Causally related adverse events occurred in 47 (27%) patients (ten [18%] in the placebo group, 17 [30%] in the low-dose group, and 20 [34%] in the high-dose group). Six (3%) patients had 11 serious adverse events: one (2%) patient in the placebo group, three (5%) in the low-dose group, and two (3%) in the high-dose group; only one (an acute allergic skin reaction in the low-dose group) was assessed to be causally related. This study, which is to our knowledge, the largest trial of CIDP to date and the first to study two administrations of immunoglobulins and two doses, showed that both doses of SCIg IgPro20 were efficacious and well tolerated, suggesting that SCIg can be used as a maintenance treatment for CIDP. CSL Behring.

Unconventional treatments for chronic inflammatory demyelinating polyneuropathy.

This article focuses on the unconventional treatments used in chronic inflammatory demyelinating polyneuropathy (CIDP). First line, evidence-based treatments for CIDP include corticosteroids, immunoglobulins and plasma exchanges. Several unproven treatments are however given in treatment-refractory disease or to reduce requirements in validated therapies for reasons of side effects/practical delivery/cost. Despite methodological issues, IFN-α, azathioprine and methotrexate have not been shown to be useful in randomized controlled trials. Cyclophosphamide, rituximab and, as final resort in highly selected cases, hematopoietic stem cell transplant may be options considered in severely disabled refractory patients. Debatably, azathioprine, methotrexate, cyclosporine and mycophenolate mofetil are still occasionally used, among others, in milder disease. Physical therapy may be of benefit in CIDP but is not systematically considered as an integral part of management strategies. Current literature relating to unconventional therapies in CIDP is reviewed here and the possible avenues that require consideration in severe refractory disease and less disabling forms are discussed.

Abstracts from Muscle Study Group Annual Scientific Meeting: Neuromuscular Therapeutics: Bench to Bedside and Beyond, Snowbird Ski & Summer Resort, Snowbird, UT, September 23-25, 2017.

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) often require long-term intravenous immunoglobulin (IVIG) maintenance therapy. Subcutaneous immunoglobulin (SCIG) offers an alternative administration option with anticipated improvements in patient quality of life, convenience, and flexibility. To evaluate IgPro20 (SCIG) as a maintenance treatment in CIDP. A randomized, double-blind trial in CIDP patients (n=172) investigated 0.2 and 0.4 g/kg weekly doses of IgPro20 versus placebo. The primary outcome was percentage of patients with CIDP relapse/withdrawal during 24-weeks of treatment determined by Inflammatory Neuropathy Cause and Treatment score. Secondary endpoints included grip strength and patient satisfaction. Both IgPro20 doses significantly reduced rate of CIDP relapse/withdrawal versus placebo. Grip strength remained stable with Hizentra®, but deteriorated with placebo. Most subjects preferred SCIG over IVIG. Local reactions, reported in 33% of IgPro20-treated patients, were mild or moderate in intensity. IgPro20 is efficacious and well-tolerated as maintenance treatment in CIDP. This article is protected by copyright. All rights reserved

Chronic inflammatory demyelinating polyneuropathy in adults: diagnostic approaches and first line therapy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is among the key reasons of chronic polyneuropathies in adults. Diagnostic algorithm of CIDP in adults is presented. Diagnosis of CIDP is based on clinical and electrodiagnostic criteria of European Federation of Neurological Societies/Peripheral Nervous System in 2010. Principles of CIDP treatment are discussed, including modern trends of standard and 10 % IVIG solutions.