When should we consider that CIDP patient is non-responder to IVIg?

Authors: R. Ouaja1, R. Bonek2, D. Cocito3, A. Schenone4, S. Pujol1, F. Kasiborski1 and E. Nobile-Orazio5 on behalf on the PRISM study investigators

1 LFB, Les Ulis, France

2 Department of Neurology, Bydgoszcz, Poland

3 Department of Neurosciences, Molinette Hospital, Universita degli Studi di Torino, Torino, Italy

4 Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, RCCS Policlinico San Martino, University of Genova, Genoa, Italy

5 Neuromuscular and neuroimmunology service, Humanitas clinical and research center, Milan University, Milan, Italy

Abstract: For CIDP, IVIg treatment is often the first choice as improvement can be fast [1]. However, there is no consensus on when considering alternative therapy (corticosteroids or plasma exchange) for non-responder patients. In PRISM study (efficacy and safety of Iqymune® in CIDP), time to response was analyzed as secondary endpoint.

In this study, 42 patients with CIDP were treated with Iqymune® (8 courses at 3-week intervals) and included in the efficacy set. Among them, 23 were never previously treated with IgG (IgG-naïve patients) and 19 were already treated with IgG but in clinical relapse following IgG therapy discontinuation (IgG-pretreated patients).

Although no statistical comparison were performed between subgroups, we observed that responder rate at the end of study (24 weeks) was numerically higher in IgG-pretreated patients than in IgG-naïve patients but confidence intervals (CIs) of these subgroups were largely overlapping (84.2% with 95% CI of [60.4-96.6%] versus 69.6% [47.1-86.8%]). We also observed that the response occurred earlier in IgG-pretreated patients than in IgG-naïve patients (median of 7.9 weeks with 95% CI of [3.4-12.1%] versus 19.1 weeks [12.1-24.1%] estimated by Kaplan-Meier method taking into account non-responder patients). Before the 5th course of Iqymune®, 13/16 responders in IgG-pretreated subgroup versus 7/16 responders in IgG-naïve subgroup had achieved a response. In other words, 12/32 responders showed a “late” response (after 5 to 8 courses).

These efficacy results are in line with the results from previous clinical study [2]. Both results may suggest that CIDP patients, IgG-pretreated and mainly IgG-naïve, should be maintained under IVIg for longer time (6 months) before considering other alternative therapy as indicated by EMA guideline [3].

Ref: [1] European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society–First Revision.

Joint Task Force of the EFNS and the PNS. J Peripher Nerv Syst. 2010 Mar;15(1)

[2] Efficacy and safety of Privigen® in patients with chronic inflammatory demyelinating polyneuropathy: results of a prospective, single-arm, open-label Phase III study (the PRIMA study)

Jean-Marc Léger. Journal of the Peripheral Nervous System 18:130–140 (2013)

[3]Guideline on core SmPC for human normal immunoglobulin for intravenous administration (IVIg). EMA/CHMP/BPWP/94038/2007 Rev. 5. 28 June 2018.