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Confirming the efficacy of intravenous immunoglobulin in CIDP through minimum clinically important differences: shifting from statistical significance to clinical relevance
  1. I S J Merkies1,2,
  2. S I van Nes2,
  3. K Hanna3,
  4. R A C Hughes4,
  5. C Deng3
  1. 1Department of Neurology, Spaarne Hospital, Hoofddorp, The Netherlands
  2. 2Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands
  3. 3Department of Clinical Development, Talecris Biotherapeutics, Inc, Research Triangle Park, North Carolina, USA
  4. 4Department of Clinical Neuroscience, King's College London, London, UK
  1. Correspondence to Dr Ingemar Merkies, Spaarne Hospital Hoofddorp, Spaarnepoort 1 2134 TM Hoofddorp, The Netherlands; imerkies{at}spaarneziekenhuis.nl

Abstract

Background The ICE trial demonstrated the efficacy of immune globulin intravenous (IGIV-C) over placebo in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, improving the interpretability of the results by analysing the minimum clinically important difference (MCID) had not been considered.

Objectives To identify MCID thresholds of various outcome measures using different methods and to test treatment differences (IGIV-C vs placebo) using these thresholds.

Methods One anchor-based (Short Form-36 question 2) and three distribution-based (½ SD, 1 SE of measurement, and effect size) techniques were employed to identify MCID cut-offs for various impairments (electromyographic parameters, Medical Research Council (MRC) sum score, grip strength, inflammatory neuropathy cause and treatment (INCAT) sensory sum score), disability (INCAT scale score, Rotterdam handicap scale (RHS) score) and quality of life (SF-36). IGIV-C or placebo was administered every 3 weeks for up to 24 weeks to 117 CIDP patients. Patients who did not improve by ≥1 point on the INCAT scale received alternate treatment. The proportion of patients with results exceeding identified MCID thresholds was compared.

Results MCID cut-offs for outcomes were determined using each method. For the INCAT disability scale (primary ICE-trial outcome), all MCID methods identified significantly more responders with IGIV-C than placebo. Significant differences favouring IGIV-C were also demonstrated for various nerve conduction parameters, MRC sum score, grip strength, RHS score and SF-36 physical component summary score.

Conclusion In addition to being statistically significant, all MCID analyses showed that CIDP improvements with IGIV-C are clinically meaningful. Consideration of MCID is recommended in future therapeutic trials.

Trial Registration Number NCT00220740 (http://ClinicalTrials.gov)

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Footnotes

  • Funding Funding for the study was provided by Talecris Biotherapeutics, Center for Science and Education (Research Triangle Park, North Carolina, USA).

  • Competing interests RACH and ISJM received honoraria from Talecris Biotherapeutics. CD and KH are employees of Talecris Biotherapeutics.

  • Ethics approval Ethics approval was provided by all institutes involved as part of the ICE study.

  • Provenance and peer review Not commissioned; not externally peer reviewed.

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