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

Self Cite

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.].

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Merkies

Schaik

Léger

et al. 2019

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“…Consequently, other therapeutic options are being investigated. Subcutaneous immunoglobulin has been tested in small studies in MMN; although maintenance was not obtained in all subjects, this option could be more convenient for some patients, as for chronic inflammatory demyelinating polyneuropathy . The addition of eculizumab, which neutralises human complement C5, to IVIg in one small‐controlled trial showed a trend towards improvement which needs to be confirmed in larger studies.…”

Section: Discussionmentioning

confidence: 99%

IqYmune® is an effective maintenance treatment for multifocal motor neuropathy: A randomised, double‐blind, multi‐center cross‐over non‐inferiority study vs Kiovig®—The LIME Study

Léger

Cissé

Cocito

et al. 2018

Intravenous immunoglobulin (IVIg) is the gold‐standard for maintenance treatment of multifocal motor neuropathy (MMN). This phase III, randomised, double‐blind, multi‐centre, active‐control, crossover study, aimed to evaluate the non‐inferiority of IqYmune® relative to Kiovig®, primarily based on efficacy criteria. Twenty‐two adult MMN patients, treated with any brand of IVIg (except Kiovig® or IqYmune®) at a stable maintenance dose within the range of 1 to 2 g/kg every 4 to 8 weeks, were randomised to receive either Kiovig® followed by IqYmune®, or IqYmune® followed by Kiovig®. Each product was administered for 24 weeks. The primary endpoint was the difference between IqYmune® and Kiovig® in mean assessments of modified Medical Research Council (MMRC) 10 sum score (strength of 5 upper‐limb and 5 lower‐limb muscle groups, on both sides, giving a score from 0 to 100) during the evaluation period (non‐inferiority margin of Δ = 2). A linear mixed model analysis demonstrated the non‐inferiority of IqYmune® relative to Kiovig®, independently of the covariates (value at baseline, treatment period, and treatment sequence). The estimated “IqYmune® − Kiovig®” difference was −0.01, with a 95% confidence interval (CI) −0.51 to 0.48. The number of adverse reactions (ARs) and the percentage of patients affected were similar for the two products: 39 ARs in 10 patients with IqYmune® vs 32 ARs in 11 patients with Kiovig®. No thromboembolic events nor haemolysis nor renal impairment were observed. In this first clinical trial comparing two IVIg brands for maintenance treatment of MMN, efficacy and tolerability of both brands were similar.

“…For IVIG in CIDP, current guidelines recommend using the lowest effective maintenance dose and suggest that stable patients undergo periodic dose reduction or interval lengthening trials to establish the need for ongoing therapy (Joint Task Force of the EFNS and the PNS, ) . The observation that in one clinical trial 44% of patients treated with placebo in addition to previous medications were able to reduce mean weekly doses of CS or IVIG by greater than 20% (RMC Trial Group, ) and in another trial 40% of placebo‐treated patients did not relapse even though an IVIG dependency test was required prior to randomization (van Schaik et al, ) indicates that overtreatment is common and not well addressed in clinical practice. The importance of treatment individualization as highlighted in current guidelines and supported by the findings in prior clinical trials is indisputable.…”

Section: Introductionmentioning

confidence: 99%

Individualized immunoglobulin therapy in chronic immune‐mediated peripheral neuropathies*

Allen

Berger

Querol

et al. 2018

Despite the well‐recognized importance of immunoglobulin therapy individualization during the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP), the pathway to best achieve optimization is unknown. There are many pharmacokinetic and immunobiologic variables that can potentially influence the appropriateness of any individual therapy. Although identification of specific autoantibodies and their targets has only been accomplished in a minority of patients with CIDP, already the diagnostic and treatment implications of specific autoantibody detection are being realized. Individual variability in IgG pharmacokinetic properties including IgG catabolic rates and distribution, as well as the IgG level necessary for disease control also require consideration during the optimization process. For optimization to be successful there must be a measure of treatment response that has a clinically meaningful interpretation. There are currently available well‐defined and validated clinical assessment tools and outcome measures that are well suited for this purpose. While there remains much to learn on how best to manipulate immunopathology and immunoglobulin pharmacokinetics in the most favorable way, there currently exists an understanding of these principles to a degree sufficient to begin to develop rational and evidence‐based treatment optimization strategies.