Assessing deterioration using impairment and functional outcome measures in chronic inflammatory demyelinating polyneuropathy: A post-hoc analysis of the immunoglobulin overtreatment in CIDP trial

Abstract

It is unclear whether frequently used cutoff values for outcome measures defining minimal clinically important differences (MCIDs) can accurately identify meaningful deterioration in chronic inflammatory demyelinating polyneuropathy (CIDP). We used data from the immunoglobulin overtreatment in CIDP (IOC) trial, in which 60 clinically stable patients with CIDP were randomized to intravenous immunoglobulin (IVIg) withdrawal or continuation. We calculated change scores of the Inflammatory Rasch-Built Overall Disability Scale (I-RODS), grip strength, and Medical Research Council-sum score (MRC-SS) and classified visits based on a treatment anchor (ie, decision to restart/increase treatment after reaching a predefined early endpoint of deterioration). The variability of scores in patients without deterioration was calculated using the limits of agreement. We defined optimized MCIDs for deterioration and specific combinations of MCIDs from different outcome measures, and subsequently calculated the accuracies of the (combined) MCIDs. Substantial variability was found in scores of the I-RODS, grip strength and MRC-SS in patients without deterioration over time, and most MCIDs were within the limits of the variability observed in patients without deterioration. Some MCID cut-offs were insensitive but highly specific for detecting deterioration, for example, the MCID-SE of −1.96 of the I-RODS and −2 point on the MRC-SS. Others were sensitive, but less specific, for example, −4 centiles of the I-RODS. Some combined MCIDs resulted in high specificities and moderate sensitivities. Our results suggest that clinically important deterioration cannot be distinguished from variability over time with currently used MCIDs on the individual level. Combinations of MCIDs might improve the accuracy of determining deterioration, but this needs validation.