Understanding the consequences of chronic inflammatory demyelinating polyradiculoneuropathy from impairments to activity and participation restrictions and reduced quality of life: the ICE study.

A randomized trial (ICE trial) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) demonstrated significantly more improvement with intravenous immunoglobulin (Gamunex(®), Talecris Biotherapeutics, Inc., Research Triangle Park, NC) than placebo. To understand the relationship between CIDP impairments, activity and participation restrictions, and quality of life (QoL) in this trial, we investigated the association between scales representing these outcome levels. Gamunex or placebo was given every 3 weeks for up to 24 weeks to 117 patients in an initial treatment period after which treatment failures were crossed over (alternative treatment). We assessed impairments, activity and participation, and SF-36 component mental (MCS) and physical summaries (PCS). Regression analyses of baseline data were performed (all subjects) and change from baseline to endpoint (Gamunex-treated group only) to determine correlations between outcomes. Grip strength, medical research council (MRC) sum score, and inflammatory neuropathy cause and treatment (INCAT) sensory sum score were the strongest explanatory variables of disability (at baseline: r(2) = 0.46; change from baseline: r(2) = 0.66). Only up to half of the variance in QoL scores (PCS at baseline: r(2) = 0.30; change from baseline: r(2) = 0.41; MCS: at baseline: r(2) = 0.10; change from baseline: r(2) = 0.24) was explained by impairment and activity and participation measures. Future studies are required to elucidate the impact of CIDP on disability and QoL changes, because the obtained correlations provide only partial explanation

Timing and course of clinical response to intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy.

none59Abstract OBJECTIVE: To investigate the timing, course, and clinical characteristics of the response to intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). DESIGN: Data were extracted from the ICE trial, a randomized, double-blind, placebo-controlled trial of immune globulin intravenous, 10% caprylate/chromatography purified (IGIV-C). SETTING: Multiple international centers. PARTICIPANTS: One hundred seventeen individuals with CIDP. Intervention Treatment with IGIV-C (Gamunex, n = 59) or placebo (n = 58), with IGIV-C administered as a 2-g/kg loading dose followed by a 1-g/kg maintenance dose every 3 weeks, for up to 24 weeks. MAIN OUTCOME MEASURES: The primary efficacy parameter was an improvement of 1 or more points in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Participants treated with IGIV-C were divided into subgroups based on meeting responder vs nonresponder definitions and by time to first improvement. RESULTS: Among 30 responders to IGIV-C, 14 (47%) patients had improved adjusted INCAT scores by week 3, and 16 (53%) patients improved at week 6 after a second infusion. Participants who improved by week 3 were more severely disabled at baseline than those who improved at 6 weeks. In patients who improved, the number of individuals reaching maximal improvement continued to increase during maintenance therapy for up to 24 weeks. For patients with first improvement by week 3, the change in dominant-hand grip strength over time tended to parallel the INCAT score. In patients with first improvement by week 6, however, the improvement in dominant-hand grip strength preceded initial improvement in INCAT score. CONCLUSIONS: Data suggest that treatment with 2 courses of IGIV-C administered 3 weeks apart may be required for initial improvement, and continued maintenance therapy may be necessary to achieve a maximal therapeutic response. Trial Registration clinicaltrials.gov Identifier: NCT00220740Latov, N; Deng, C; Dalakas, Mc; Bril, V; Donofrio, P; Hanna, K; Hartung, Hp; Hughes, Ra; Merkies, Is; van Doorn, Pa; Ice, Sg; Apostolski, S; Banach, M; Barroso, F; Bartosik-Psujek, H; Basta, I; Bednarik, J; Belniak, E; Benedetti, L; Buchman, A; Caress, J; Chapman, K; Chyrchel, U; del Carro, U; Drory, V; Dubrovsky, A; Ehler, E; Fryze, W; Fulgenzi, E; Gibson, G; Gonzalez-Cornejo, S; Gonzalez-Jaime, Jd; Grandis, M; Haas, J; Kaminski, M; Marchesoni, C; Munch, C; Narciso, E; Nations, S; Nogues, M; Patwa, H; Pavlovic, S; Pizzorno, M; Reisin, R; Romero-Vargas, S; Ruiz-Sandoval, Jl; Ruiz-Sandoval, Md; Schenone, A; Selmaj, K; Stelmasiak, Z; Szczudlik, A; Thomas, Fp; Tsao, B; Trivedi, J; Uncini, A; Villa, A; Vohanka, S; Wolfe, G; Zapletalova, O.Latov, N; Deng, C; Dalakas, Mc; Bril, V; Donofrio, P; Hanna, K; Hartung, Hp; Hughes, Ra; Merkies, Is; van Doorn, Pa; Ice, Sg; Apostolski, S; Banach, M; Barroso, F; Bartosik Psujek, H; Basta, I; Bednarik, J; Belniak, E; Benedetti, L; Buchman, A; Caress, J; Chapman, K; Chyrchel, U; del Carro, U; Drory, V; Dubrovsky, A; Ehler, E; Fryze, W; Fulgenzi, E; Gibson, G; Gonzalez Cornejo, S; Gonzalez Jaime, Jd; Grandis, Marina; Haas, J; Kaminski, M; Marchesoni, C; Munch, C; Narciso, E; Nations, S; Nogues, M; Patwa, H; Pavlovic, S; Pizzorno, M; Reisin, R; Romero Vargas, S; Ruiz Sandoval, Jl; Ruiz Sandoval, Md; Schenone, Angelo; Selmaj, K; Stelmasiak, Z; Szczudlik, A; Thomas, Fp; Tsao, B; Trivedi, J; Uncini, A; Villa, A; Vohanka, S; Wolfe, G; Zapletalova, O

Electrophysiologic correlations with clinical outcomes in CIDP.

Data are lacking on correlations between changes in nerve conduction (NC) studies and treatment response in chronic inflammatory demyelinating polyneuropathy (CIDP). This report examined data from a randomized, double-blind trial of immune globulin intravenous, 10% caprylate/chromatography purified (IGIV-C [Gamunex]; n = 59) versus placebo (n = 58) every 3 weeks for up to 24 weeks in CIDP. Motor NC results and clinical measures were assessed at baseline and endpoint/week 24. Improvement from baseline in adjusted inflammatory neuropathy cause and treatment score correlated with improvement in proximally evoked compound muscle action potential (CMAP) amplitudes (r = -0.53; P < 0.001) of all nerves tested and with improvement in CMAP amplitude of the most severely affected motor nerve (r = -0.36; P < 0.001). Correlations were observed between improvement in averaged CMAP amplitudes and dominant-hand grip strength (r = 0.44; P < 0.001) and Medical Research Council sum score (r = 0.38; P < 0.001). Overall, the change in electrophysiologic measures of NC in CIDP correlated with clinical response to treatment

Safety and tolerability of immune globulin intravenous in chronic inflammatory demyelinating polyradiculoneuropathy.

Abstract BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a common inflammatory neuropathy that can be progressive, stepwise progressive, or relapsing and remitting. OBJECTIVES: To further evaluate the long-term safety and tolerability of immune globulin intravenous, 10% caprylate-chromatography purified immune globulin intravenous in CIDP. DESIGN: Randomized multicenter trial. SETTING: Hospitals and outpatient clinics. Patients: Adults with CIDP (n = 117) [corrected]. INTERVENTIONS: Immune globulin intravenous, 10% caprylate-chromatography purified (2 g/kg of body weight) or placebo was infused as a baseline loading dose, followed by a maintenance dose (1 g/kg) every 3 weeks for up to 24 weeks. Patients who responded were rerandomized into a double-blind extension phase of immune globulin intravenous, 10% caprylate-chromatography purified (1 g/kg) or placebo every 3 weeks for up to 24 weeks. Patients who relapsed during the extension phase were withdrawn from the study. MAIN OUTCOME MEASURES: Additional analyses of safety and tolerability. RESULTS: Overall, 113 patients and 95 patients were exposed to immune globulin intravenous, 10% caprylate-chromatography purified and placebo, respectively. Exposure to immune globulin intravenous, 10% caprylate-chromatography purified was approximately twice that of placebo (1096 vs 575 infusions). Most maintenance dose courses were administered over 1 day in the immune globulin intravenous, 10% caprylate-chromatography purified (89.1% of 783 dose courses) and placebo (91.1% of 359 dose courses) groups. The most common drug-related adverse events (AEs) with immune globulin intravenous, 10% caprylate-chromatography purified were headache (4.0 per 100 infusions) and pyrexia (2.4 per 100 infusions). Five drug-related serious AEs (pulmonary embolism, pyrexia, vomiting, and 2 headache events) were reported in 3 patients (2.7%) exposed to immune globulin intravenous, 10% caprylate-chromatography purified. The incidence of drug-related serious AEs was higher after loading dose infusions than after maintenance dose infusions (4 AEs vs 1 AE). Age, weight, CIDP severity, and previous immune globulin intravenous exposure had no substantial effect on the percentage of patients with AEs, including serious AEs. CONCLUSION: Data support a favorable safety and tolerability profile for administration of immune globulin intravenous, 10% caprylate-chromatography purified as CIDP maintenance therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00220740

Electrophysiology in chronic inflammatory demyelinating polyneuropathy with IGIV.

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) received immune globulin intravenous, 10% caprylate/chromatography purified (IGIV-C, Gamunex; n=59) or placebo (n=58) every 3 weeks for up to 24 weeks (first period) in a randomized, double-blind, parallel-group, response-conditional, crossover study. Motor and sensory nerves were assessed at baseline and endpoint/week 24. A nonsignificant trend toward improvement in the proximal amplitude of the most severely affected motor nerve was observed with IGIV-C (0.69+/-1.86 mV) versus placebo (0.47+/-2.29 mV), and a greater improvement of 1.08+/-2.15 mV with IGIV-C versus 0.46+/-2.03 mV with placebo (P=0.089) was observed with exclusion of data from Erb's point stimulation. Greater improvements from baseline favoring IGIV-C were observed for 127/142 electrophysiologic parameters. The averaged motor amplitudes from all motor nerves significantly improved with IGIV-C versus placebo [treatment difference, 0.62 mV; 95% confidence interval (CI), 0.05, 1.20; P=0.035], and conduction block decreased significantly (treatment difference, -5.54%; 95% CI, -10.43, -0.64; P=0.027), particularly in the lower limbs. Overall, the data suggest that IGIV-C improves electrophysiologic parameters in CIDP