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. 2015 Mar 24;2015(3):CD005376.
doi: 10.1002/14651858.CD005376.pub3.

Treatment for IgG and IgA paraproteinaemic neuropathy

Abraham C J Stork  1 , Michael P T Lunn, Eduardo Nobile-Orazio, Nicolette C Notermans
Affiliations

Treatment for IgG and IgA paraproteinaemic neuropathy

Abraham C J Stork et al. Cochrane Database Syst Rev. .

Abstract

Background: Paraproteinaemic neuropathy refers to those neuropathies associated with a monoclonal gammopathy or paraprotein. The most common of these present with a chronic, predominantly sensory, symmetrical neuropathy, similar to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but with relatively more sensory involvement, both clinically and neurophysiologically. The optimal treatment for neuropathies associated with IgG and IgA monoclonal gammopathy of uncertain significance is not known. This is an update of a review first published in 2007.

Objectives: To assess the effects of any treatment for IgG or IgA paraproteinaemic peripheral neuropathy.

Search methods: On 18 January 2014 we searched the Cochrane Neuromuscular Disease Group Trials Specialized Register, CENTRAL, MEDLINE and EMBASE. We also checked bibliographies for controlled trials of treatments for IgG or IgA paraproteinaemic peripheral neuropathy. We checked clinical trials registries for ongoing studies in November 2014.

Selection criteria: We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs using any treatment for IgG or IgA paraproteinaemic peripheral neuropathy. We excluded people with IgM paraproteins. We excluded people where the monoclonal gammopathy was considered secondary to an underlying disorder. We included participants of any age with a diagnosis of monoclonal gammopathy of uncertain significance with a paraprotein of the IgG or IgA class and a neuropathy. Included participants were not required to fulfil specific electrophysiological diagnostic criteria.

Data collection and analysis: We used standard Cochrane methodology to select studies, extract data and analyse results. One trial author provided additional data and clarification.

Main results: We identified one RCT, with 18 participants, that fulfilled the predetermined inclusion criteria. The trial compared plasma exchange to sham plasma exchange in participants with IgG or IgA paraproteinaemic neuropathy over a three-week follow-up period. We identified four other studies but these were not RCTs or quasi-RCTs. The included RCT did not report our predefined primary outcome measure, change in disability six months after randomisation. The trial revealed a modest benefit of plasma exchange in the weakness component of the Neuropathy Disability Score (NDS, now the Neuropathy Impairment Score); the mean improvement with plasma exchange was 17 points (95% confidence interval (CI) 5.2 to 28.8 points) versus 1 point (95% CI -7.7 to 9.7 points) in the sham exchange group at three weeks' follow-up (mean difference (MD) 16.00; 95% CI 1.37 to 30.63, low quality evidence). There was no statistically significant difference in the overall NDS (MD 18.00; 95% CI -2.03 to 38.03, low quality evidence), vibration thresholds or neurophysiological indices. Adverse events were not reported. The trial was at low risk of bias overall, although limitations of trial size and duration reduce the quality of the evidence in support of its conclusions.

Authors' conclusions: The evidence from RCTs for the treatment of IgG or IgA paraproteinaemic neuropathy is currently inadequate. More RCTs of treatments are required. These should have adequate follow-up periods and contain larger numbers of participants, perhaps through multicentre collaboration, considering the relative infrequency of this condition. Observational or open trial data provide limited support for the use of treatments such as plasma exchange, cyclophosphamide combined with prednisolone, intravenous immunoglobulin, and corticosteroids. These interventions show potential therapeutic promise but the potential benefits must be weighed against adverse effects. Their optimal use and the long-term benefits need to be considered and validated with well-designed RCTs.

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Conflict of interest statement

ACJS: no disclosures.

MPTL has received honoraria for consultation from Baxter Pharmaceuticals, CSL Behring and LfB and a travel support grant from Grifols, all manufacturers of IVIG. He was a blinded investigator in the study of Comi et al 2002.

EN‐O reports personal compensation for serving in the Steering or Advisory Board of Baxter, Italy, CSL Behring, Italy, Kedrion, Italy, and Novartis, Switzerland. He received honoraria for lecturing from Baxter, Italy, CSL Behring, Italy, Grifols, Spain, and Kedrion, Italy and travel support for scientific meetings from Baxter, CSL and Kedrion. He was the principal investigator of a RCT comparing the efficacy of IVIg and intravenous methylprednisolone in a related condition, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), for which financial support was provided by Kedrion, Italy.

NCN: no disclosures.

This review is not compliant with the Cochrane Commercial Sponsorship policy. Future updates will have the majority of review authors and the lead author free of conflicts.

Figures

1
1
Risk of bias summary: review authors' judgements about each 'Risk of bias' item for each included study. Green (+) = low risk of bias; yellow (?) = unclear risk of bias; red (‐) = high risk of bias (not shown).
1.1
1.1. Analysis
Comparison 1 Plasma exchange (PE) versus control, Outcome 1 Change in Neuropathy Disability Score.
1.2
1.2. Analysis
Comparison 1 Plasma exchange (PE) versus control, Outcome 2 Change in Neuropathy Disability Score (weakness).
1.3
1.3. Analysis
Comparison 1 Plasma exchange (PE) versus control, Outcome 3 Change in vibration detection threshold.
1.4
1.4. Analysis
Comparison 1 Plasma exchange (PE) versus control, Outcome 4 Change in summed compound muscle action potential (CMAP) (mV).
1.5
1.5. Analysis
Comparison 1 Plasma exchange (PE) versus control, Outcome 5 Change in summed motor nerve conduction velocity (m/s).
See this image and copyright information in PMC

Update of

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References to other published versions of this review

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