Remarkable Rituximab Response on Tremor Related to Acute-Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy in an Antineurofascin155 Immunoglobulin G4-Seropositive Patient.
Ontology highlight
ABSTRACT:
SUBMITTER: Demichelis C
PROVIDER: S-EPMC6207116 | biostudies-literature | 2018 Sep-Oct
REPOSITORIES: biostudies-literature
Publications
Remarkable Rituximab Response on Tremor Related to Acute-Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy in an Antineurofascin155 Immunoglobulin G4-Seropositive Patient.
Demichelis Chiara C Franciotta Diego D Cortese Andrea A Callegari Ilaria I Serrati Carlo C Mancardi Gian Luigi GL Schenone Angelo A Leonardi Alessandro A Benedetti Luana L
Movement disorders clinical practice 20180824 5
Similar Datasets
Project description:Intravenous immunoglobulins are an efficacious treatment for chronic inflammatory demyelinating polyradiculoneuropathy. Biomarkers for disease activity are lacking, making the need for ongoing treatment difficult to assess, leading to potential overtreatment and high health-care costs. Our objective was to determine whether intravenous immunoglobulin withdrawal is non-inferior to continuing intravenous immunoglobulin treatment and to determine how often patients are overtreated. We performed a randomized, double-blind, intravenous immunoglobulin-controlled non-inferiority trial in seven centres in the Netherlands (Trial registration: ISRCTN 13637698; www.isrctn.com/ISRCTN13637698). Adults with clinically stable chronic inflammatory demyelinating polyradiculoneuropathy using intravenous immunoglobulin maintenance treatment for at least 6 months were included. Patients received either intravenous immunoglobulin withdrawal (placebo) as investigational treatment or continuation of intravenous immunoglobulin treatment (control). The primary outcome was the mean change in logit scores from baseline to 24-week follow-up on the patient-reported Inflammatory Rasch-Overall Disability Scale. The non-inferiority margin was predefined as between-group difference in mean change scores of -0.65. Patients who deteriorated could reach a relapse end point according to predefined criteria. Patients with a relapse end point after intravenous immunoglobulin withdrawal entered a restabilization phase. All patients from the withdrawal group who remained stable were included in an open-label extension phase of 52 weeks. We included 60 patients, of whom 29 were randomized to intravenous immunoglobulin withdrawal and 31 to continuation of treatment. The mean age was 58 years (SD 14.7) and 67% was male. The between-group difference in mean change Inflammatory Rasch-Overall Disability Scale scores was -0.47 (95% CI -1.24 to 0.31), indicating that non-inferiority of intravenous immunoglobulin withdrawal could not be established. In the intravenous immunoglobulin withdrawal group, 41% remained stable for 24 weeks, compared to 58% in the intravenous immunoglobulin continuation group (-17%; 95% CI -39 to 8). Of the intravenous immunoglobulin withdrawal group, 28% remained stable at the end of the extension phase. Of the patients in the restabilization phase, 94% restabilized within 12 weeks. In conclusion, it remains inconclusive whether intravenous immunoglobulin withdrawal is non-inferior compared to continuing treatment, partly due to larger than expected confidence intervals leading to an underpowered study. Despite these limitations, a considerable proportion of patients could stop treatment and almost all patients who relapsed were restabilized quickly. Unexpectedly, a high proportion of intravenous immunoglobulin-treated patients experienced a relapse end point, emphasizing the need for more objective measures for disease activity in future trials, as the patient-reported outcome measures might not have been able to identify true relapses reliably. Overall, this study suggests that withdrawal attempts are safe and should be performed regularly in clinically stable patients.
| S-EPMC9166547 | biostudies-literature
Project description:Background and purposeChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical and electrophysiological heterogeneous immune-mediated polyneuropathy. Intravenous immunoglobulin (IVIg), corticosteroids, and plasma exchange are proven effective treatments for CIDP. The clinical response to IVIg is variable between patients and currently unexplained. Finding biomarkers related to treatment response can help to understand the diversity of CIDP and personalise treatment choice.MethodsWe investigated whether genetic variation between patients may explain some of these differences in treatment response. Based on previous publications, we selected six candidate genes that might affect immune and axonal functions, IVIg metabolism, and treatment response in CIDP. Genetic variants were assessed in 172 CIDP patients treated with at least one course of IVIg (2 g/kg). A response to IVIg was defined by ≥1 grade improvement on the modified Rankin Scale. Blood samples were tested for variations in CNTN2, PRF1, FCGRT, FCGR2B, GJB1, and SH2D2A genes.ResultsIn univariate analysis, patients with the FCGR2B promoter variant 2B.4/2B.1 responded more often to IVIg than patients with the 2B.1/2B.1 variant (odds ratio [OR] = 6.9, 95% confidence interval [CI] = 1.6-30; p = 0.003). Patients with the p.(Ala91Val) variant of PRF1 were less often IVIg responsive (OR = 0.34, 95% CI = 0.13-0.91; p = 0.038). In multivariate analysis, both PRF1 and FCGR2B showed discriminative ability to predict the chance of IVIg response (area under the curve = 0.67).ConclusionsVariations in PRF1 and the promoter region of FCGR2B are associated with the response to IVIg in CIDP. These findings, which require validation, are a first step towards the understanding of the heterogeneity in the treatment response in CIDP.
| S-EPMC8247870 | biostudies-literature
Project description:Background and purposeHigh peak serum immunoglobulin G (IgG) levels may not be needed for maintenance intravenous immunoglobulin (IVIg) treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and such high levels may cause side effects. More frequent lower dosing may lead to more stable IgG levels and higher trough levels, which might improve efficacy. The aim of this trial is to investigate whether high frequent low dosage IVIg treatment is more effective than low frequent high dosage IVIg treatment.MethodsIn this randomized placebo-controlled crossover trial, we included patients with CIDP proven to be IVIg-dependent and receiving an individually established stable dose and interval of IVIg maintenance treatment. In the control arm, patients received their individual IVIg dose and interval followed by a placebo infusion at half the interval. In the intervention arm, patients received half their individual dose at half the interval. After a wash-out phase patients crossed over. The primary outcome measure was handgrip strength (assessed using a Martin Vigorimeter). Secondary outcome indicators were health-related quality of life (36-item Short-Form Health Survey), disability (Inflammatory Rasch-built Overall Disability Scale), fatigue (Rasch-built Fatigue Severity Scale) and side effects.ResultsTwenty-five patients were included and were treated at baseline with individually adjusted dosages of IVIg ranging from 20 to 80 g and intervals ranging from 14 to 35 days. Three participants did not complete the trial; the main analysis was therefore based on the 22 patients completing both treatment periods. There was no significant difference in handgrip strength change from baseline between the two treatment regimens (coefficient -2.71, 95% CI -5.4, 0.01). Furthermore, there were no significant differences in any of the secondary outcomes or side effects.ConclusionsMore frequent lower dosing does not further improve the efficacy of IVIg in stable IVIg-dependent CIDP and does not result in fewer side effects.
| S-EPMC7820989 | biostudies-literature
Project description:Background and aimsChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common chronic autoimmune neuropathy worldwide. A significant proportion of CIDP patients enter spontaneous or medication-related remission, remaining stable without immunotherapy. Overtreatment of CIDP has clinical and financial implications. We examined performance of IVIg cessation trials in our CIDP cohort and report safety and cost analysis outcomes.MethodsIn individuals with CIDP on maintenance IVIg treatment, a cessation trial was proposed in clinically stable patients with a static IVIg regimen over a 12-month period. We explored the proportion who were stable off treatment for 12 or more months and the time to recovery in those who declined and were re-treated. We examined cost implications of this approach.Results45/125 individuals met criteria for clinical stability, with median age 58 years, I-RODS 37/48, MRC-SS 69/70 and annual treatment costs £107 000/person. Nine individuals had cessation trials resulting in decline within 2 years prior and were not re-challenged, leaving 36 eligible individuals. 12 of 36 (33.3%) consented to cessation trial and eight of those (66.7%) remained stable off treatment for ≥ 12 months. The successful cessation trials resulted in a cost saving of £855 000/year, with a potential further saving of £1.7 million/year if all the eligible individuals had consented. All patients who deteriorated were rescued to previous baseline on retreatment.InterpretationIndividuals with CIDP should be counselled about the natural history of the disease and future scheduled, targeted cessation trials. A dedicated clinical infrastructure is vital to safely perform cessation trials.
| S-EPMC11836592 | biostudies-literature
Project description:ObjectiveTo determine the efficacy and safety of combined low-dose rituximab with conventional therapy for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) treatment.MethodsTotal 73 patients with CIDP were enrolled for the retrospective cohort study, and divided into conventional first-line therapy cohort (n = 40) and combined low-dose rituximab (100 mg per infusion) cohort (n = 33). The outcome measures include scores of I-RODS, mRS, INCAT, ONLS, TSS, and COMPASS 31 scale at baseline and regular four visits (4, 16, 28, and 52 weeks), as well as proportion of favorable response and outcome, corticosteroids dosage, and deterioration occurrence during follow-up.ResultsCompared to conventional therapy cohort, combined rituximab cohort presented better improvements and higher proportion of favorable response in scales assessments at each visit, as well as significantly reduced corticosteroids dosage and deterioration occurrence during the follow-up. Analyses of subgroups showed better improvements in both typical CIDP and CIDP variants in combined rituximab cohort than those in conventional therapy cohort, but had no differences between each other. Early initiating combined rituximab regimen (<10 weeks) showed better improvements than delayed initiation (≥10 weeks) at the first three visits within 28 weeks, while had no difference in favorable prognoses at the last visit of 52 weeks after once reinfusion. No rituximab correlated serious adverse events were reported in our patients.InterpretationOur simplified regimen of combined low-dose rituximab has been firstly demonstrated for the better efficacy and safety than conventional therapy in CIDP treatment.
| S-EPMC11752089 | biostudies-literature
Project description: Not available
| S-EPMC6481566 | biostudies-literature
Project description:IntroductionIntravenous immunoglobulin (IVIG) is recommended as first-line therapy for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), an immune-mediated neuropathy. The clinical profile of patients with CIDP newly initiating IVIG is poorly characterized. This claims-based cohort study describes characteristics of US patients with CIDP initiating IVIG treatment.MethodsAdult immunoglobulin (IG)-naïve patients with CIDP diagnosed between 2008 and 2018 and a subgroup of patients subsequently initiating IVIG were identified in the Merative MarketScan Research Databases. Demographics, clinical characteristics, and diagnostic procedures were described for patients initiating IVIG.ResultsOf 32,090 patients with CIDP identified, 3975 (mean age 57 years) subsequently initiated IVIG. In the 6 months prior to IVIG initiation, diagnoses of comorbidities including neuropathy (75%), hypertension (62%), and diabetes (33%) were frequent, as were CIDP features/symptoms/markers of functional status including chronic pain (80%), difficulty walking (30%), and weakness (30%). CIDP-related laboratory/diagnostic procedures were performed in approximately 20- > 40% of patients in the 3 months prior to IVIG initiation (63.7% underwent electrodiagnostic/nerve conduction testing in the 6 months prior to IVIG initiation). Patient characteristics by initial IVIG product differed only in IVIG initiation year, US geographic region, and insurance type. Comorbidities, CIDP severity or functional status markers, and other clinical variables were generally well balanced across initial IVIG product groups.ConclusionA heavy burden of symptoms, comorbidities, and diagnostic testing exists in patients with CIDP initiating IVIG. Characteristics of patients with CIDP initiating different IVIG products are well balanced, suggesting an absence of clinical or demographic determinants underlying IVIG selection.
| S-EPMC10310640 | biostudies-literature
Project description:ObjectiveTo discover whether Inflammatory Neuropathy Cause and Treatment Group (INCAT) electrophysiological criteria for demyelinating neuropathy predict response to immunotherapy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).MethodsThis was a retrospective case note study of patients who had attended Guy's Hospital Peripheral Nerve Clinic between January 2001 and March 2004, been diagnosed as having CIDP, and given treatment with corticosteroids, intravenous immunoglobulin (IVIg), or plasma exchange (PE). Patients' nerve conduction studies (NCS) were reviewed for evidence of demyelination and whether the abnormalities fulfilled modified INCAT electrophysiological criteria. Patients whose NCS fulfilled the criteria were assigned to the neurophysiologically definite CIDP group, while those that did not were labelled as neurophysiologically probable CIDP. Responses to any of the three immunotherapy agents were compared between the two groups.ResultsOut of 50 patients, 27 (54%) were classified as neurophysiologically definite and 23 (46%) as neurophysiologically probable CIDP patients. Twenty (74%) neurophysiologically definite and 17 (73.9%) neurophysiologically probable CIDP patients responded to treatment.ConclusionsINCAT electrophysiological criteria did not predict a higher rate of response to immunotherapy. Neurophysiologically probable CIDP patients should be given a trial of immunotherapy.
| S-EPMC2117406 | biostudies-literature
Project description:Background and purposeThe aim of this study was to determine the frequency of over- and underdiagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to identify related diagnostic pitfalls.MethodsWe conducted a retrospective study in Dutch patients referred to the Erasmus University Medical Centre Rotterdam between 2011 and 2017 with either a diagnosis of CIDP or another diagnosis that was revised to CIDP. We used the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 diagnostic criteria for CIDP to classify patients into three groups: overdiagnosis, underdiagnosis, or confirmed diagnosis of CIDP. Clinical and laboratory features and treatment history were compared between groups.ResultsA referral diagnosis of CIDP was revised in 32% of patients (31/96; overdiagnosis). Of 81 patients diagnosed with CIDP, 16 (20%) were referred with another diagnosis (underdiagnosis). In the overdiagnosed patients, 20% of muscle weakness was asymmetric, 48% lacked proximal muscle weakness, 29% only had distal muscle weakness, 65% did not fulfil the electrodiagnostic criteria for CIDP, 74% had an elevated cerebrospinal fluid (CSF) protein level, and 97% had another type of neuropathy. In the underdiagnosed patients, all had proximal muscle weakness, 50% had a clinically atypical CIDP, all fulfilled the electrodiagnostic criteria for CIDP, and 25% had an increased CSF protein level.ConclusionOver- and underdiagnosis of CIDP is common. Diagnostic pitfalls include lack of attention to proximal muscle weakness as a diagnostic hallmark of CIDP, insufficient recognition of clinical atypical phenotypes, overreliance on CSF protein levels, misinterpretation of nerve conduction studies and poor adherence to electrodiagnostic criteria, and failure to exclude other causes of polyneuropathy.
| S-EPMC8252611 | biostudies-literature
Project description:IntroductionChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare progressive or relapsing inflammatory disease. Intravenous immunoglobulin (IVIG) is recommended as a first-line therapy. The aim of this study was to describe real-world treatment patterns and outcomes of patients with CIDP in the Define initiating IVIG treatment.MethodsThis cohort study used health insurance claims data from the Merative MarketScan Research Databases (2008-2018). Adult patients (≥ 18 years old) with CIDP without prior immunoglobulin treatment were identified using International Statistical Classification of Diseases and Related Health Problems (ICD) codes, and patients subsequently initiating IVIG were included in the analysis. Real-world IVIG treatment patterns and treatment and safety outcomes (assessed via ICD codes) were described.ResultsIn total, 3975 patients (median age 58 years) with CIDP who initiated IVIG were identified. After the initial IVIG loading period, patients received IVIG at a median dosing interval of 21 days (quartile [Q]1, Q3: 7, 28), and continued treatment for a median of 129 days (Q1, Q3: 85, 271). After the 2-year follow-up period, 55% of patients had discontinued all IVIG treatment; more than one-half of these discontinuations occurred within 4 months. Diagnoses of impaired functional status were evident in more than 30% of patients at baseline, but at lower rates during follow-up. Rates of new-onset safety outcomes after IVIG treatment were low.ConclusionThis real-world analysis of IVIG treatment patterns and treatment and safety outcomes of patients with CIDP who initiated IVIG highlights the unmet need for improved long-term management. Further research is needed to evaluate the use of functional status measures as endpoints for immunoglobulin treatment effectiveness.
| S-EPMC10310601 | biostudies-literature