13 research outputs found
Restabilization treatment after intravenous immunoglobulin withdrawal in chronic inflammatory demyelinating polyneuropathy: Results from the pre-randomization phase of the Polyneuropathy And Treatment with Hizentra study
© 2019 CSL Behring. Journal of the Peripheral Nervous System published by Wiley Periodicals, Inc. on behalf of Peripheral Nerve Society. In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), intravenous immunoglobulin (IVIG) is recommended to be periodically reduced to assess the need for ongoing therapy. However, little is known about the effectiveness of restabilization with IVIG in patients who worsen after IVIG withdrawal. In the Polyneuropathy And Treatment with Hizentra (PATH) study, the pre-randomization period included sudden stopping of IVIG followed by 12 weeks of observation. Those deteriorating were then restabilized with IVIG. Of 245 subjects who stopped IVIG, 28 did not show signs of clinical deterioration within 12 weeks. Two hundred and seven received IVIG restabilization with an induction dose of 2 g/kg bodyweight (bw) IgPro10 (Privigen, CSL Behring, King of Prussia, Pennsylvania) and maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks. Signs of clinical improvement were seen in almost all (n = 188; 91%) subjects. During IVIG restabilization, 35 subjects either did not show CIDP stability (n = 21, analyzed as n = 22 as an additional subject was randomized in error) or withdrew for other reasons (n = 14). Of the 22 subjects who did not achieve clinical stability, follow-up information in 16 subjects after an additional 4 weeks was obtained. Nine subjects were reported to have improved, leaving a maximum of 27 subjects (13%) who either showed no signs of clinical improvement during the restabilization phase and 4 weeks post-study or withdrew for other reasons. In conclusion, sudden IVIG withdrawal was effective in detecting ongoing immunoglobulin G dependency with a small risk for subjects not returning to their baseline 17 weeks after withdrawal
Restabilization treatment after intravenous immunoglobulin withdrawal in chronic inflammatory demyelinating polyneuropathy: Results from the pre-randomization phase of the Polyneuropathy And Treatment with Hizentra study
In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), intravenous immunoglobulin (IVIG) is recommended to be periodically reduced to assess the need for ongoing therapy. However, little is known about the effectiveness of restabilization with IVIG in patients who worsen after IVIG withdrawal. In the Polyneuropathy And Treatment with Hizentra (PATH) study, the pre-randomization period included sudden stopping of IVIG followed by 12 weeks of observation. Those deteriorating were then restabilized with IVIG. Of 245 subjects who stopped IVIG, 28 did not show signs of clinical deterioration within 12 weeks. Two hundred and seven received IVIG restabilization with an induction dose of 2 g/kg bodyweight (bw) IgPro10 (Privigen, CSL Behring, King of Prussia, Pennsylvania) and maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks. Signs of clinical improvement were seen in almost all (n = 188; 91%) subjects. During IVIG restabilization, 35 subjects either did not show CIDP stability (n = 21, analyzed as n = 22 as an additional subject was randomized in error) or withdrew for other reasons (n = 14). Of the 22 subjects who did not achieve clinical stability, follow-up information in 16 subjects after an additional 4 weeks was obtained. Nine subjects were reported to have improved, leaving a maximum of 27 subjects (13%) who either showed no signs of clinical improvement during the restabilization phase and 4 weeks post-study or withdrew for other reasons. In conclusion, sudden IVIG withdrawal was effective in detecting ongoing immunoglobulin G dependency with a small risk for subjects not returning to their baseline 17 weeks after withdrawal
Placebo effect in chronic inflammatory demyelinating polyneuropathy: The PATH study and a systematic review
© 2020 CSL Behring. Journal of the Peripheral Nervous System published by Wiley Periodicals LLC on behalf of Peripheral Nerve Society. The Polyneuropathy And Treatment with Hizentra (PATH) study required subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) to show dependency on immunoglobulin G (IgG) and then be restabilized on IgG before being randomized to placebo or one of two doses of subcutaneous immunoglobulin (SCIG). Nineteen of the 51 subjects (37%) randomized to placebo did not relapse over the next 24 weeks. This article explores the reasons for this effect. A post-hoc analysis of the PATH placebo group was undertaken. A literature search identified other placebo-controlled CIDP trials for review and comparison. In PATH, subjects randomized to placebo who did not relapse were significantly older, had more severe disease, and took longer to deteriorate in the IgG dependency period compared with those who relapsed. Published trials in CIDP, whose primary endpoint was stability or deterioration, had a mean non-deterioration (placebo effect) of 43%, while trials with a primary endpoint of improvement had a placebo response of only 11%. Placebo is an important variable in the design of CIDP trials. Trials designed to show clinical improvement will have a significantly lower effect of this phenomenon than those designed to show stability or deterioration
Restabilization treatment after intravenous immunoglobulin withdrawal in chronic inflammatory demyelinating polyneuropathy: Results from the pre-randomization phase of the Polyneuropathy And Treatment with Hizentra study
In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), intravenous immunoglobulin (IVIG) is recommended to be periodically reduced to assess the need for ongoing therapy. However, little is known about the effectiveness of restabilization with IVIG in patients who worsen after IVIG withdrawal. In the Polyneuropathy And Treatment with Hizentra (PATH) study, the pre-randomization period included sudden stopping of IVIG followed by 12 weeks of observation. Those deteriorating were then restabilized with IVIG. Of 245 subjects who stopped IVIG, 28 did not show signs of clinical deterioration within 12 weeks. Two hundred and seven received IVIG restabilization with an induction dose of 2 g/kg bodyweight (bw) IgPro10 (Privigen, CSL Behring, King of Prussia, Pennsylvania) and maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks. Signs of clinical improvement were seen in almost all (n = 188; 91%) subjects. During IVIG restabilization, 35 subjects either did not show CIDP stability (n = 21, analyzed as n = 22 as an additional subject was randomized in error) or withdrew for other reasons (n = 14). Of the 22 subjects who did not achieve clinical stability, follow-up information in 16 subjects after an additional 4 weeks was obtained. Nine subjects were reported to have improved, leaving a maximum of 27 subjects (13%) who either showed no signs of clinical improvement during the restabilization phase and 4 weeks post-study or withdrew for other reasons. In conclusion, sudden IVIG withdrawal was effective in detecting ongoing immunoglobulin G dependency with a small risk for subjects not returning to their baseline 17 weeks after withdrawal
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.]
How satisfied are cervical dystonia patients after 3 years of botulinum toxin type A treatment? Results from a prospective, long-term observational study
Background Patients with cervical dystonia (CD) typically require regular injections of botulinum toxin to maintain symptomatic control. We aimed to document long-term patient satisfaction with CD symptom control in a large cohort of patients treated in routine practice. Methods This was a prospective, international, observational study (NCT01753349) following the course of adult CD treated with botulinum neurotoxin type A (BoNT-A) over 3 years. A comprehensive clinical assessment status was performed at each injection visit and subjects reported satisfaction in two ways: satisfaction with symptom control at peak effect and at the end of treatment cycle. Results Subject satisfaction remained relatively stable from the first to the last injection visit. At 3 years, 89.9% of subjects reported satisfaction with symptom control at peak effect and 55.6% reported satisfaction with symptom control at end of treatment cycle. By contrast, objective ratings of CD severity showed an overall reduction over 3 years. Mean ± SD Toronto Western Spasmodic Rating Scale (TWSTRS) Total scores (clinician assessed at end of treatment cycle) decreased from 31.59 ± 13.04 at baseline to 24.49 ± 12.43 at 3 years (mean ± SD reduction from baseline of − 6.97 ± 11.56 points). Tsui scale scores also showed gradual improvement; the percent of subjects with a tremor component score of 4 reduced from 12.4% at baseline to 8.1% at 3 years. Conclusions Despite objective clinical improvements over 3 years, subject satisfaction with symptom control remained relatively constant, indicating that factors other than symptom control also play a role in patient satisfaction
Placebo effect in chronic inflammatory demyelinating polyneuropathy: The PATH study and a systematic review
none148siThe Polyneuropathy And Treatment with Hizentra (PATH) study required subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) to show dependency on immunoglobulin G (IgG) and then be restabilized on IgG before being randomized to placebo or one of two doses of subcutaneous immunoglobulin (SCIG). Nineteen of the 51 subjects (37%) randomized to placebo did not relapse over the next 24 weeks. This article explores the reasons for this effect. A post-hoc analysis of the PATH placebo group was undertaken. A literature search identified other placebo-controlled CIDP trials for review and comparison. In PATH, subjects randomized to placebo who did not relapse were significantly older, had more severe disease, and took longer to deteriorate in the IgG dependency period compared with those who relapsed. Published trials in CIDP, whose primary endpoint was stability or deterioration, had a mean non-deterioration (placebo effect) of 43%, while trials with a primary endpoint of improvement had a placebo response of only 11%. Placebo is an important variable in the design of CIDP trials. Trials designed to show clinical improvement will have a significantly lower effect of this phenomenon than those designed to show stability or deterioration.nonenoneLewis R.A.; Cornblath D.R.; Hartung H.-P.; Sobue G.; Lawo J.-P.; Mielke O.; Durn B.L.; Bril V.; Merkies I.S.J.; Bassett P.; Cleasby A.; van Schaik I.N.; Sabet A.; George K.; Roberts L.; Carne R.; Blum S.; Henderson R.; Van Damme P.; Demeestere J.; Larue S.; D'Amour C.; Kunc P.; Valis M.; Sussova J.; Kalous T.; Talab R.; Bednar M.; Toomsoo T.; Rubanovits I.; Gross-Paju K.; Sorro U.; Saarela M.; Auranen M.; Pouget J.; Attarian S.; Le Masson G.; Wielanek A.; Desnuelle C.; Delmon E.; Clavelou P.; Aufauvre D.; Schmidt J.; Zschuentzsch J.; Sommer C.; Kramer D.; Hoffmann O.; Goerlitz C.; Haas J.; Chatzopoulos M.; Yoon R.; Gold R.; Berlit P.; Jaspert-Grehl A.; Liebetanz D.; Kutschenko A.; Stangel M.; Trebst C.; Baum P.; Bergh F.; Klehmet J.; Meisel A.; Klostermann F.; Oechtering J.; Lehmann H.; Schroeter M.; Hagenacker T.; Mueller D.; Sperfeld A.; Bethke F.; Drory I.V.; Algom A.; Yarnitsky D.; Murinson B.; Di Muzio A.; Ciccocioppo F.; Sorbi S.; Mata S.; Schenone A.; Grandis M.; Lauria G.; Cazzato D.; Antonini G.; Morino S.; Cocito D.; Zibetti M.; Yokota T.; Ohkubo T.; Kanda T.; Kawai M.; Kaida K.; Onoue H.; Kuwabara S.; Mori M.; Iijima M.; Ohyama K.; Baba M.; Tomiyama M.; Nishiyama K.; Akutsu T.; Yokoyama K.; Kanai K.; van Schaik I.N.; Eftimov F.; Notermans N.C.; Visser N.; Faber C.; Hoeijmakers J.; Rejdak K.; Chyrchel-Paszkiewicz U.; Casanovas Pons C.; Antonia M.; Gamez J.; Salvado M.; Infante C.M.; Benitez S.; Lunn M.; Morrow J.; Gosal D.; Lavin T.; Melamed I.; Testori A.; Ajroud-Driss S.; Menichella D.; Simpson E.; Lai E.C.-H.; Dimachkie M.; Barohn R.J.; Beydoun S.; Johl H.; Lange D.; Shtilbans A.; Muley S.; Ladha S.; Freimer M.; Kissel J.; Latov N.; Chin R.; Ubogu E.; Mumfrey S.; Rao T.; MacDonald P.; Sharma K.; Gonzalez G.; Allen J.; Walk D.; Hobson-Webb L.; Gable K.Lewis, R. A.; Cornblath, D. R.; Hartung, H. -P.; Sobue, G.; Lawo, J. -P.; Mielke, O.; Durn, B. L.; Bril, V.; Merkies, I. S. J.; Bassett, P.; Cleasby, A.; van Schaik, I. N.; Sabet, A.; George, K.; Roberts, L.; Carne, R.; Blum, S.; Henderson, R.; Van Damme, P.; Demeestere, J.; Larue, S.; D'Amour, C.; Kunc, P.; Valis, M.; Sussova, J.; Kalous, T.; Talab, R.; Bednar, M.; Toomsoo, T.; Rubanovits, I.; Gross-Paju, K.; Sorro, U.; Saarela, M.; Auranen, M.; Pouget, J.; Attarian, S.; Le Masson, G.; Wielanek, A.; Desnuelle, C.; Delmon, E.; Clavelou, P.; Aufauvre, D.; Schmidt, J.; Zschuentzsch, J.; Sommer, C.; Kramer, D.; Hoffmann, O.; Goerlitz, C.; Haas, J.; Chatzopoulos, M.; Yoon, R.; Gold, R.; Berlit, P.; Jaspert-Grehl, A.; Liebetanz, D.; Kutschenko, A.; Stangel, M.; Trebst, C.; Baum, P.; Bergh, F.; Klehmet, J.; Meisel, A.; Klostermann, F.; Oechtering, J.; Lehmann, H.; Schroeter, M.; Hagenacker, T.; Mueller, D.; Sperfeld, A.; Bethke, F.; Drory, I. V.; Algom, A.; Yarnitsky, D.; Murinson, B.; Di Muzio, A.; Ciccocioppo, F.; Sorbi, S.; Mata, S.; Schenone, A.; Grandis, M.; Lauria, G.; Cazzato, D.; Antonini, G.; Morino, S.; Cocito, D.; Zibetti, M.; Yokota, T.; Ohkubo, T.; Kanda, T.; Kawai, M.; Kaida, K.; Onoue, H.; Kuwabara, S.; Mori, M.; Iijima, M.; Ohyama, K.; Baba, M.; Tomiyama, M.; Nishiyama, K.; Akutsu, T.; Yokoyama, K.; Kanai, K.; van Schaik, I. N.; Eftimov, F.; Notermans, N. C.; Visser, N.; Faber, C.; Hoeijmakers, J.; Rejdak, K.; Chyrchel-Paszkiewicz, U.; Casanovas Pons, C.; Antonia, M.; Gamez, J.; Salvado, M.; Infante, C. M.; Benitez, S.; Lunn, M.; Morrow, J.; Gosal, D.; Lavin, T.; Melamed, I.; Testori, A.; Ajroud-Driss, S.; Menichella, D.; Simpson, E.; Lai, E. C. -H.; Dimachkie, M.; Barohn, R. J.; Beydoun, S.; Johl, H.; Lange, D.; Shtilbans, A.; Muley, S.; Ladha, S.; Freimer, M.; Kissel, J.; Latov, N.; Chin, R.; Ubogu, E.; Mumfrey, S.; Rao, T.; Macdonald, P.; Sharma, K.; Gonzalez, G.; Allen, J.; Walk, D.; Hobson-Webb, L.; Gable, K
Restabilization treatment after intravenous immunoglobulin withdrawal in chronic inflammatory demyelinating polyneuropathy: Results from the pre-randomization phase of the Polyneuropathy And Treatment with Hizentra study
In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), intravenous immunoglobulin (IVIG) is recommended to be periodically reduced to assess the need for ongoing therapy. However, little is known about the effectiveness of restabilization with IVIG in patients who worsen after IVIG withdrawal. In the Polyneuropathy And Treatment with Hizentra (PATH) study, the pre-randomization period included sudden stopping of IVIG followed by 12 weeks of observation. Those deteriorating were then restabilized with IVIG. Of 245 subjects who stopped IVIG, 28 did not show signs of clinical deterioration within 12 weeks. Two hundred and seven received IVIG restabilization with an induction dose of 2 g/kg bodyweight (bw) IgPro10 (Privigen, CSL Behring, King of Prussia, Pennsylvania) and maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks. Signs of clinical improvement were seen in almost all (n = 188; 91%) subjects. During IVIG restabilization, 35 subjects either did not show CIDP stability (n = 21, analyzed as n = 22 as an additional subject was randomized in error) or withdrew for other reasons (n = 14). Of the 22 subjects who did not achieve clinical stability, follow-up information in 16 subjects after an additional 4 weeks was obtained. Nine subjects were reported to have improved, leaving a maximum of 27 subjects (13%) who either showed no signs of clinical improvement during the restabilization phase and 4 weeks post-study or withdrew for other reasons. In conclusion, sudden IVIG withdrawal was effective in detecting ongoing immunoglobulin G dependency with a small risk for subjects not returning to their baseline 17 weeks after withdrawal
Long-term safety and efficacy of subcutaneous immunoglobulin IgPro20 in CIDP PATH extension study
Objective To investigate the long-term safety and efficacy of weekly subcutaneous IgPro20 (Hizentra, CSL Behring) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods In a 48-week open-label prospective extension study to the PATH study, patients were initially started on 0.2 g/kg or on 0.4 g/kg weekly and-if clinically stable-switched to 0.2 g/kg weekly after 24 weeks. Upon CIDP relapse on the 0.2 g/kg dose, 0.4 g/kg was (re)initiated. CIDP relapse was defined as a deterioration by at least 1 point in the total adjusted Inflammatory Neuropathy Cause and Treatment score. Results Eighty-two patients were enrolled. Sixty-two patients initially received 0.4 g/kg, 20 patients 0.2 g/kg weekly. Seventy-two received both doses during the study. Sixty-six patients (81%) completed the 48-week study duration. Overall relapse rates were 10% in 0.4 g/kg-treated patients and 48% in 0.2 g/kg-treated patients. After dose reduction from 0.4 to 0.2 g/kg, 51% (27/53) of patients relapsed, of whom 92% (24 of 26) improved after reinitiation of the 0.4 g/kg dose. Two-thirds of patients (19/28) who completed the PATH study without relapse remained relapse-free on the 0.2 g/kg dose after dose reduction in the extension study. Sixty-two patients had adverse events (AEs) (76%), of which most were mild or moderate with no related serious AEs. Conclusions Subcutaneous treatment with IgPro20 provided long-term benefit at both 0.4 and 0.2 g/kg weekly doses with lower relapse rates on the higher dose. Long-term dosing should be individualized to find the most appropriate dose in a given patient. Classification of evidence This study provides Class IV evidence that for patients with CIDP, long-term treatment with SCIG beyond 24 weeks is safe and efficacious
Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial
Background 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. Methods 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\uc2\ub72 g/kg or 0\uc2\ub74 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. Findings 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\ue2\u80\u9374]) patients on placebo, 22 (39% [27\ue2\u80\u9352]) on low-dose SCIg, and 19 (33% [22\ue2\u80\u9346]) on high-dose SCIg had a relapse or were withdrawn from the study for other reasons (p=0\uc2\ub70007). Absolute risk reductions were 25% (95% CI 6\ue2\u80\u9341) for low-dose versus placebo (p=0\uc2\ub7007), 30% (12\ue2\u80\u9346) for high-dose versus placebo (p=0\uc2\ub7001), and 6% (\ue2\u88\u9211 to 23) for high-dose versus low-dose (p=0\uc2\ub732). 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. Interpretation 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. Funding CSL Behring