B-cell and T-cell receptor repertoire in chronic inflammatory demyelinating polyneuropathy, a prospective cohort study.

The immunopathophysiological mechanisms underlying chronic inflammatory demyelinating polyneuropathy (CIDP) in an individual patient are largely unknown. Better understanding of these mechanisms may aid development of biomarkers and targeted therapies. Both B- and T-cell dominant mechanisms have been implicated. We therefore investigated whether B-cell and T-cell receptor (BCR/TCR) repertoires might function as immunological biomarkers in CIDP. In this prospective cohort study, we longitudinally sampled peripheral blood of CIDP patients in three different phases of CIDP: starting induction treatment (IT), starting withdrawal from IVIg maintenance treatment (MT), and patients in remission (R). BCR and TCR repertoires were analyzed using RNA based high throughput sequencing. In baseline samples, the number of total clones, the number of dominant BCR and TCR clones and their impact on the repertoire was similar for patients in the IT, MT, and remission groups compared with healthy controls. Baseline samples in the IT or MT did not predict treatment response or potential relapse at follow-up. Treatment responders in the IT group showed a potential IVIg-induced increase in the number of dominant BCR clones and their impact at follow-up (baseline1.0 [IQR 1.0-2.8] vs. 6 m 3.5 [0.3-6.8]; P < .05, Wilcoxon test). Although the BCR repertoire changed over time, the TCR repertoire remained robustly stable. We conclude that TCR and BCR repertoire distributions do not predict disease activity, treatment response or response to treatment withdrawal.

The effect of tremor on disability assessment in chronic inflammatory demyelinating polyradiculoneuropathy.

Tremor in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is common, often unresponsive to treatment, and may contribute to disability. We aim to investigate whether tremor is associated with disability as measured in daily practice and clinical trials, independent of other impairments. We included 76 CIDP patients in this cross-sectional study. We assessed tremor with the Tremor Research Group essential tremor rating assessment scale (TETRAS) and the Fahn-Tolosa-Marin clinical rating scale (FTM). Disability was measured with the inflammatory Rasch-built overall disability scale (I-RODS) and the adjusted Inflammatory Neuropathy Cause and Treatment disability scale (INCAT-DS, categorized separately in arm score, or total score). Impairments including strength, sensory impairment, and fatigue were measured using specific impairment scales. We tested whether "the presence of a clinically relevant tremor" (based on TETRAS and FTM) or "tremor severity" (FTM part B sum score) was associated with disability scores (I-RODS, INCAT-DS total score, and INCAT-DS arm score), independent of the impairment scores, using multivariate regression. Both "the presence of a clinically relevant tremor" and "tremor severity" were significantly associated with disability measured by the INCAT-DS (arm score and total score), but not the I-RODS, independent of strength, sensory impairment, and fatigue. The explained variances were low. Clinically relevant tremor can (partly) explain disability in CIDP, as measured with the INCAT-DS, independent of muscle strength, sensory deficits, and fatigue. To assess disease activity in CIDP patients with tremor, both impairment and disability outcomes should be assessed, as disability is caused partly by tremor while the effect of immunotherapy on tremor seems limited.

Clinical outcome of CIDP one year after start of treatment: a prospective cohort study.

OBJECTIVE: To assess clinical outcome in treatment-naive patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: We included adult treatment-naive patients participating in the prospective International CIDP Outcome Study (ICOS) that fulfilled the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria for CIDP. Patients were grouped based on initial treatment with (1) intravenous immunoglobulin (IVIg), (2) corticosteroid monotherapy or (3) IVIg and corticosteroids (combination treatment). Outcome measures included the inflammatory Rasch-built overall disability scale (I-RODS), grip strength, and Medical Research Council (MRC) sum score. Treatment response, treatment status, remissions (improved and untreated), treatment changes, and residual symptoms or deficits were assessed at 1 year. RESULTS: Forty patients were included of whom 18 (45%) initially received IVIg, 6 (15%) corticosteroids, and 16 (40%) combination treatment. Improvement on ≥ 1 of the outcome measures was seen in 31 (78%) patients. At 1 year, 19 (48%) patients were still treated and fourteen (36%) patients were in remission. Improvement was seen most frequently in patients started on IVIg (94%) and remission in those started on combination treatment (44%). Differences between groups did not reach statistical significance. Residual symptoms or deficits ranged from 25% for neuropathic pain to 96% for any sensory deficit. CONCLUSIONS: Improvement was seen in most patients. One year after the start of treatment, more than half of the patients were untreated and around one-third in remission. Residual symptoms and deficits were common regardless of treatment.

Virus discovery in chronic inflammatory demyelinating polyneuropathy.

The events triggering and/or sustaining the auto-immune response underlying chronic inflammatory demyelinating polyneuropathy (CIDP) are unknown. Similar to Guillain-Barré syndrome (GBS), a viral infection might play a role in CIDP. In this study, an virus detection method (VIDISCA-next generation sequencing) capable of detecting known and unknown viruses, was used to analyze the virome in serum of 47 CIDP patients at different time points of the disease and, when available, in cerebrospinal fluid (CSF) samples (N: 17). Serum samples of GBS patients (N:24) and healthy controls (N:114) were used for comparisons. In 5/47 (10.6%; 95% CI: 4-23) CIDP samples, 10/24 (42%; 95% CI: 22-63) GBS samples and 32/114 (28.1%; 95% CI: 20-37) healthy controls samples, anelloviruses were detected, generally regarded as a non-pathogenic species. Parvovirus B19 and GB virus C were found in two CIDP samples (4%). Parvovirus B19, HIV-1 and GB virus C were found in three GBS samples (13%). In 2/17 CIDP CSF samples, an anellovirus and polyomavirus were detected, probably due to contamination during lumbar puncture. No sequences of other viruses were detected in serum or CSF. A (persistent) viral infection sustaining the auto-immune response in CIDP seems therefore unlikely.

Intravenous immunoglobulin and intravenous methylprednisolone as optimal induction treatment in chronic inflammatory demyelinating polyradiculoneuropathy: protocol of an international, randomised, double-blind, placebo-controlled trial (OPTIC).

BACKGROUND: International guidelines recommend either intravenous immunoglobulin (IVIg) or corticosteroids as first-line treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). IVIg treatment usually leads to rapid improvement and is generally safe, but does not seem to lead to long-term remissions. Corticosteroids act more slowly and are associated with more side effects, but may induce long-term remissions. The hypothesis of this study is that combined IVIg and corticosteroid induction treatment will lead to more frequent long-term remissions than IVIg treatment alone. METHODS: An international, randomised, double-blind, placebo-controlled trial, in adults with 'probable' or 'definite' CIDP according to the EFNS/PNS 2010 criteria. Three groups of patients are included: (1) treatment naïve, (2) known CIDP patients with a relapse after > 1 year without treatment, and (3) patients with CIDP who improved within 3 months after a single course of IVIg, who subsequently deteriorate at any interval without having received additional treatment. Patients are randomised to receive 7 courses of IVIg and 1000 mg intravenous methylprednisolone (IVMP) (in sodium chloride 0.9%) or IVIg and placebo (sodium chloride 0.9%), every 3 weeks for 18 weeks. IVIg treatment consists of a loading dose of 2 g/kg (over 3-5 days) followed by 6 courses of IVIg 1/g/kg (over 1-2 days). The primary outcome is remission at 1 year, defined as improvement in disability from baseline, sustained between week 18 and week 52 without further treatment. Secondary outcomes include changes in disability, impairment, pain, fatigue, quality of life, care use and costs and (long-term) safety. DISCUSSION: In case of superiority of the combined treatment, patients will experience the advantages of two proven efficacious treatments, namely rapid improvement due to IVIg and long-term remission due to corticosteroids. Long-term remission would reduce the need for maintenance IVIg treatment and may decrease health care costs. Additionally, we expect that the combined treatment leads to a higher proportion of patients with improvement as some patients who do not respond to IVIg will respond to corticosteroids. Risks of short and long-term additional adverse events of the combined treatment need to be assessed. TRIAL REGISTRATION: ISRCTN registry ISRCTN15893334 . Prospectively registered on 12 February 2018.

Patient-reported outcomes with subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy: the PATH study.

BACKGROUND AND PURPOSE: Chronic inflammatory demyelinating polyneuropathy (CIDP) causes weakness which adversely impacts function and quality of life (QOL). CIDP often requires long-term management with intravenous or subcutaneous immunoglobulin. The Polyneuropathy and Treatment with Hizentra® (PATH) study showed that subcutaneous immunoglobulin (SCIG) was efficacious in CIDP maintenance. Here, patient-reported outcomes in patients on SCIG are assessed. METHODS: Subjects stabilized on intravenous immunoglobulin were randomly allocated to receive weekly 0.2 or 0.4 g/kg bodyweight of 20% SCIG (IgPro20) or placebo. Overall QOL/health status was assessed using the EuroQoL 5-Dimension (EQ-5D) health profile and visual analog scale, treatment satisfaction was assessed with the Treatment Satisfaction Questionnaire for Medicine (TSQM) and work-related impact was assessed with the Work Productivity and Activity Impairment Questionnaire for General Health (WPAI-GH). The EQ-5D health profile was assessed in terms of the percentage of subjects maintained or improved at week 25 of SCIG therapy on each of the EQ-5D domains versus baseline after intravenous immunoglobulin stabilization. TSQM and WPAI-GH were assessed by median score changes from baseline to week 25. RESULTS: In total, 172 subjects were randomized to placebo (n = 57), 0.2 g/kg IgPro20 (n = 57) and 0.4 g/kg IgPro20 (n = 58). Significantly higher proportions of IgPro20-treated subjects improved/maintained their health status on the EQ-5D usual activities dimension, and in additional dimensions (mobility and pain/discomfort) in sensitivity analyses. TSQM and WPAI-GH scores were more stable with IgPro20 treatment compared with placebo. CONCLUSIONS: IgPro20 maintained or improved QOL in most subjects with CIDP, consistent with the PATH study findings that both IgPro20 doses were efficacious in maintaining CIDP.

Combined intravenous immunoglobulin and methylprednisolone as induction treatment in chronic inflammatory demyelinating polyneuropathy (OPTIC protocol): a prospective pilot study.

BACKGROUND AND PURPOSE: We hypothesized that combining intravenous immunoglobulin (IVIg) and intravenous methylprednisolone (IVMP) leads to more frequent remission compared with IVIg alone while maintaining the fast efficacy of IVIg. In this uncontrolled pilot study, we evaluated remission, rate of improvement and safety in patients with chronic inflammatory demyelinating polyradiculoneuropathy receiving induction treatment with combined IVIg and IVMP. METHODS: Consecutive treatment-naive patients with chronic inflammatory demyelinating polyradiculoneuropathy were treated with IVIg infusions, consisting of a 2 g/kg loading dose and 1 g/kg maintenance treatment every 3 weeks, combined with 3-weekly 1-g IVMP infusions, for a total of 18 weeks. The cumulative steroid dose was 7 g. Primary outcome was remission at 1 year in patients who completed the treatment schedule. Remission was defined as improvement at 18 weeks without the need for further immune treatment between end of the treatment schedule and 1-year follow-up. Improvement was defined as a minimal clinically important difference on the Inflammatory Rasch-Built Overall Disability Scale and/or an increase of ≥8 kPa in grip strength between baseline and week 18. RESULTS: A total of 20 patients were included; 17 completed the treatment schedule. A total of 13 (76%) of these patients improved at 18 weeks after start of treatment and 10 (59%) patients were in remission at 1 year. Serious adverse events were found in four patients. CONCLUSIONS: Short-term combined induction treatment with IVIg and IVMP induced remission in almost 60% of patients who completed the treatment schedule. Combined induction therapy was generally well tolerated. A randomized controlled trial is currently running to confirm efficacy and safety of IVMP as add-on treatment to IVIg.

Corticosteroids in chronic inflammatory demyelinating polyneuropathy : A retrospective, multicentre study, comparing efficacy and safety of daily prednisolone, pulsed dexamethasone, and pulsed intravenous methylprednisolone.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) can be treated with corticosteroids or intravenous immunoglobulins. Various corticosteroid regimens are currently used in CIDP, but it is unknown whether they are equally efficacious. In this retrospective study, we compared efficacy and safety of three corticosteroid regimens in CIDP patients. METHODS: We included treatment naïve patients that fulfilled the EFNS/PNS criteria for CIDP. Patients were treated with corticosteroids according to the local protocol of three CIDP expertise centres. Corticosteroid regimens consisted of daily oral prednisolone, pulsed oral dexamethasone, or pulsed intravenous methylprednisolone. Outcomes were number of responders to treatment, remission rate of treatment responders, overall probability of 5-year remission, and the occurrence of adverse events. RESULTS: A total of 125 patients were included. Sixty-seven (54%) patients received daily prednisone or prednisolone, 37 (30%) pulsed dexamethasone, and 21 (17%) pulsed intravenous methylprednisolone. Overall, 60% (95% CI 51-69%) responded to corticosteroids, with no significant difference between the three treatment regimens (p = 0.56). From the 75 responders, 61% (95% CI 50-73%) remained in remission, during a median follow-up of 55 months (range 1-197 months). The probability of responders reaching 5-year remission was 55% (95% Cl 44-70%), with no difference between the three groups. Adverse events leading to a change in treatment occurred in ten patients (8%). Two patients had a serious adverse event. CONCLUSION: Corticosteroids lead to improvement in 60% of patients and to remission in 61% of treatment responders. There were no differences between treatment modalities in terms of efficacy and safety.

Pain management strategies for neuropathic pain in Fabry disease--a systematic review.

BACKGROUND: Neuropathic pain is one of the key features of (classical) Fabry disease (FD). No randomized clinical trials comparing effectiveness of different pain management strategies have been performed. This review aims to give an overview of existing pain management strategies. METHODS: PubMed and Embase were searched up to September 2014 for relevant articles on treatment of neuropathic pain in FD. RESULTS: Seven-hundred-thirty-one articles were identified of which 26 were included in the analysis. Studies reported on 55 individuals in total, with group-sizes ranging from 1 to 8. Carbamazepine appeared most beneficial: complete pain relief in 5/25, partial relief in 17/25, and no benefit in 3/25 patients. Phenytoin resulted in complete relief in 1/27, partial relief in 12/27 and no benefit in 6/27 patients. In 8 patients a significant reduction in the frequency of pain attacks was described. Gabapentin caused partial relief in 6/7 and no relief in 1/7 patients. Little evidence was reported for SSNRI's or treatment combinations. Adverse-effects were reported in all treatment strategies. CONCLUSIONS: Only for carbamazepine, phenytoin and gabapentin there is evidence of effectiveness in neuropathic pain due to FD, but comparison of effectiveness between these drugs is lacking. In routine clinical practice adverse-effects may discourage use of carbamazepine and phenytoin in favor of second-generation antiepileptic drugs, but this is currently not supported by clinical evidence. This review suffers greatly from incomplete outcome reports and a predominance of case reports, which emphasizes the need for robust clinical trials and observational cohort studies.

Effects of early and late diabetic neuropathy on sciatic nerve block duration and neurotoxicity in Zucker diabetic fatty rats.

BACKGROUND: The neuropathy of type II diabetes mellitus (DM) is increasing in prevalence worldwide. We aimed to test the hypothesis that in a rodent model of type II DM, neuropathy would lead to increased neurotoxicity and block duration after lidocaine-induced sciatic nerve block when compared with control animals. METHODS: Experiments were carried out in Zucker diabetic fatty rats aged 10 weeks (early diabetic) or 18 weeks (late diabetic, with or without insulin 3 units per day), and age-matched healthy controls. Left sciatic nerve block was performed using 0.2 ml lidocaine 2%. Nerve conduction velocity (NCV) and F-wave latency were used to quantify nerve function before, and 1 week after nerve block, after which sciatic nerves were used for neurohistopathology. RESULTS: Early diabetic animals did not show increased signs of nerve dysfunction after nerve block. In late diabetic animals without insulin vs control animals, NCV was 34.8 (5.0) vs 41.1 (4.1) ms s(-1) (P<0.01), and F-wave latency was 7.7 (0.5) vs 7.0 (0.2) ms (P<0.01), respectively. Motor nerve block duration was prolonged in late diabetic animals, but neurotoxicity was not. Late diabetic animals receiving insulin showed intermediate results. CONCLUSIONS: In a rodent type II DM model, nerves have increased sensitivity for short-acting local anaesthetics without adjuvants in vivo, as evidenced by prolonged block duration. This sensitivity appears to increase with the progression of neuropathy. Our results do not support the hypothesis that neuropathy due to type II DM increases the risk of nerve injury after nerve block.

Autonomic dysfunction in ICU-acquired weakness: a prospective observational pilot study.

PURPOSE: Intensive care unit-acquired weakness (ICU-AW) is a frequent complication of critical illness. It is unknown if patients with ICU-AW also have autonomic dysfunction, another frequent neurological complication of critical illness. We hypothesized that patients who develop ICU-AW also develop autonomic dysfunction. Furthermore, we hypothesized that patients with ICU-AW are more prone to develop autonomic dysfunction compared to patients without ICU-AW. METHODS: This was an observational cohort study of patients newly admitted to the ICU. Autonomic dysfunction was measured daily using heart rate variability (HRV) to a maximum of 15 days after admission. ICU-AW was diagnosed using the Medical Research Council score. Abnormal HRV was defined using age-matched reference values. The association between ICU-AW and HRV was analyzed using linear mixed effects models. RESULTS: We included 83 patients, 15 (18 %) of whom were diagnosed with ICU-AW. Of 279 HRV measurements, 204 could be analyzed. Abnormal HRV was found in all critically ill patients irrespective of the presence of ICU-AW (ICU-AW 100 % (IQR 71-100) vs. no ICU-AW 100 % (IQR 40-100); p = 0.40). Mechanical ventilation, sedation, norepinephrine, heart rate, and HRV artifacts were identified as confounders for HRV. ICU-AW was not associated with HRV. CONCLUSION: Abnormal HRV is frequent in critically ill patients, both with and without ICU-AW. It is unlikely that patients with ICU-AW are more prone to develop abnormal HRV. However, we found that abnormal HRV may not be an accurate indicator of autonomic dysfunction because of confounders.

Examination of cardiovascular and peripheral autonomic function in the ICU: a pilot study.

UNLABELLED: Critical illness may affect the autonomic nervous system. Decreased cardiovascular autonomic function measured by heart rate variability (HRV) has been reported in critically ill patients but limited information exists about other autonomic functions. The cold face test (CFT) and skin wrinkle test (SWT) have never been investigated in critically ill patients. Feasibility and safety of the CFT and SWT were investigated in critically ill patients. EXCLUSION CRITERIA: polyneuropathy, autonomic neuropathy, admission after stroke, spinal cord injury or cardiac arrest. For the CFT, a cold pack was applied to the forehead to measure the maximal increase in RR interval. The simulated SWT was used and wrinkling was assessed on a five-point scale. HRV was investigated using power spectral analysis of continuous 5-min ECG recordings. Twelve critically ill patients were included (mean age 54). No adverse effects for the CFT and SWT were noted. The CFT could be performed in 10 patients and showed an abnormal response in 9. The SWT could be performed in 11 patients; results were abnormal in 6. HRV analysis showed decreased HRV in all patients. CFT and HRV responses were correlated with each other, no correlation was found between SWT and CFT or HRV results. The CFT and SWT are feasible and safe in critically ill patients. Cardiovascular dysfunction may be more prevalent in critical illness than peripheral sympathetic dysfunction. Influence of confounders and further validation of these tests needs to be investigated.

The long-term follow-up of treatment with corticosteroid injections in patients with carpal tunnel syndrome. When are multiple injections indicated?

The objective of this prospective study was to investigate the long-term effect of one or more local corticosteroid injections in patients with carpal tunnel syndrome and whether a good response can be predicted. Follow-up visits took place at 3 weeks, 6 months, and 1 year after the first corticosteroid injection. Thirty of the 120 patients (25%) had a good outcome with a single injection, 11 additional patients (9%) needed a second injection, and five patients (4%) needed a third injection to reach a good outcome after 1 year. Of patients with an initial good treatment response, 28 (52%) had a good outcome after 1 year compared with 18 (27 %) who had an initially moderate or no response to treatment. One-third of patients with carpal tunnel syndrome had a long-term beneficial effect from corticosteroid injection, especially when they had a good initial response.

Botulinum toxin as treatment for focal dystonia: a systematic review of the pharmaco-therapeutic and pharmaco-economic value.

Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the pharmaco-therapeutic and pharmaco-economic value of botulinum toxin as treatment for focal dystonia, which yielded the following results. Botulinum toxin is the most effective treatment for reducing dystonic symptoms measured with dystonia-specific and general questionnaires, and pain in patients with focal dystonia. Seventy-one percent of patients with cervical dystonia had a reduction in neck pain compared to 12 % in placebo groups. Adverse events occur in 58 % of patients during treatment with botulinum toxin compared to 46 % treated with placebo. Especially dry mouth, neck weakness, dysphagia, and voice changes are common. Adverse events are usually mild and self-limiting. Health-related quality of life, measured with the SF-36 is 20-50 points lower in patients with focal dystonia compared to controls and the effect of botulinum toxin on health-related quality of life is unclear. Botulinum toxin treatment is expensive because the drug itself is expensive. Yearly costs for treating a patient with focal dystonia with botulinum toxin range from EUR 347 to EUR 3,633 and the gain in QALYs with BTX treatment is small. Focal dystonia impairs the productivity and the ability to work. At start of botulinum toxin treatment only 47-50 % was working. Botulinum toxin partly improves this. Overall, we conclude that botulinum toxin is an expensive drug with good effects. From a societal perspective, the costs may well weigh up to the regained quality of life. However, the available literature concerning costs, health-related quality of life and labor participation is very limited. An extensive cost-effectiveness study should be performed incorporating all these aspects.

Long-term remission of CIDP after pulsed dexamethasone or short-term prednisolone treatment.

OBJECTIVE: Achieving long-term remission after a limited more intense treatment period would prevent prolonged use of corticosteroids or IV immunoglobulin (IVIg) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this prospective cohort study we present long-term follow-up data on patients included in a multicenter randomized controlled trial comparing 6 monthly pulses of dexamethasone with 8 months of daily prednisolone. METHODS: Treatment effect was assessed with the Inflammatory Neuropathy Cause and Treatment disability scale and the Rivermead Mobility Index and was categorized using the CIDP Disease Activity Status (CDAS) scale. RESULTS: By March 2011, 39 out of 40 patients were included with a median follow-up of 4.5 years. Cure (>5 years off treatment) or remission according to the CDAS criteria after 1 or 2 courses of pulsed dexamethasone or daily prednisolone was achieved in 10 out of 39 patients (26%). Half of the patients who were in remission after initial treatment experienced a relapse (median treatment-free interval: 17.5 months for dexamethasone, 11 months for prednisolone). Alternative diagnosis was made in 7 out of 12 (58%) who did not respond to any therapy and in none of the treatment-responsive patients. CONCLUSIONS: Cure or long-term remission can be achieved in about one-quarter of patients with CIDP after 1 or 2 courses of pulsed dexamethasone or 8-month daily prednisolone. In treatment-nonresponsive patients, the diagnosis CIDP should be reconsidered. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that pulsed dexamethasone or 8-month daily prednisolone can lead to long-term remission in CIDP.

A monozygotic twin pair with highly discordant Gaucher phenotypes.

We describe monozygotic twin sisters, born to consanguineous Moroccan parents, who are highly discordant for the manifestations of Gaucher disease. Both carry Gaucher genotype N188S/N188S. One has severe visceral involvement, epilepsy, and a cerebellar syndrome. Her twin does not manifest any symptoms or signs of Gaucher disease but suffers from type 1 diabetes mellitus. The concurrence of a mild Gaucher mutation with a severe phenotype, as well as the occurrence of highly discordant phenotypes in a pair of monozygotic twins, is discussed.

Randomised controlled trial comparing two different intravenous immunoglobulins in chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Different preparations of intravenous immunoglobulin (IVIg) are considered to have comparable clinical efficacy but this has never been formally investigated. Some patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) report that some IVIg brands are more effective than others. A liquid IVIg preparation is more user friendly and potentially can be infused at a faster rate. OBJECTIVES: The primary objective was to compare the efficacy of two different IVIg brands in CIDP. The secondary objective was to compare their safety. METHODS: This was an investigator-initiated multi-centre randomised controlled double-blind trial. Twenty-seven patients with active but stable CIDP treated with their individual stable IVIg (Gammagard S/D) maintenance dose and interval were randomised to receive four infusions of freeze-dried 5% IVIg (Gammagard S/D) or the new liquid 10% IVIg (Kiovig). The overall disability sum score (ODSS) was used as the primary outcome scale. The equivalence margin was defined as a difference of ≤1 point in mean ΔODSS between treatment groups. Main secondary outcome scales were the MRC sum score and the Vigorimeter. RESULTS: Repeated measurements analysis of variance, adjusted for baseline ODSS, showed a clinically insignificant treatment difference of 0.004 (95% CI -0.4 to 0.4). We also found no significant differences in any of the other outcome measures. Besides a lower occurrence of cold shivers in patients randomised to Kiovig (p=0.03), no significant differences were found in the occurrence of adverse events. CONCLUSIONS: This trial demonstrated equal clinical efficacy between a freeze-dried and a liquid IVIg preparation for maintenance treatment of CIDP.