Research Article: A Predictive Model for Corticosteroid Response in Individual Patients with MS Relapses

Date Published: March 18, 2015

Publisher: Public Library of Science

Author(s): Martin Rakusa, Stefan J. Cano, Bernadette Porter, Afsane Riazi, Alan J. Thompson, Jeremy Chataway, Todd A. Hardy, Orhan Aktas.

http://doi.org/10.1371/journal.pone.0120829

Abstract

To derive a simple predictive model to guide the use of corticosteroids in patients with relapsing remitting MS suffering an acute relapse.

We analysed individual patient randomised controlled trial data (n=98) using a binary logistic regression model based on age, gender, baseline disability scores [physician-observed: expanded disability status scale (EDSS) and patient reported: multiple sclerosis impact scale 29 (MSIS-29)], and the time intervals between symptom onset or referral and treatment.

Based on two a priori selected cut-off points (improvement in EDSS ≥ 0.5 and ≥ 1.0), we found that variables which predicted better response to corticosteroids after 6 weeks were younger age and lower MSIS-29 physical score at the time of relapse (model fit 71.2% – 73.1%).

This pilot study suggests two clinical variables which may predict the majority of the response to corticosteroid treatment in patients undergoing an MS relapse. The study is limited in being able to clearly distinguish factors associated with treatment response or spontaneous recovery and needs to be replicated in a larger prospective study.

Partial Text

Relapsing-remitting multiple sclerosis (RRMS) is characterised by recurrent attacks of neurological symptoms reflecting underlying central inflammatory demyelination [1]. MS relapses vary in terms of their frequency, location, severity and outcome.

The patient characteristics are displayed in Table 1. 98 of 113 patients with RRMS from the original study had a complete data set and were included in this study. 75 were female and the mean age was 39 years (see Table 1). The average time from relapse onset to treatment was 17 days (SD ± 7) and from referral to treatment was 5 days (SD ± 3). The mean baseline EDSS score following an attack was 4.9 which improved on average by 1.1 when re-measured at 6 weeks (Table 1, Fig. 1). Baseline EDSS and MSIS-29 physical correlated well (rho 0.5, p < 0.01) as well as baseline MSIS-29 physical and MSIS-29 psychological (rho 0.6, p < 0.01). There was also a positive correlation between the difference in EDSS and MSIS-29 physical measured at 6 weeks (rho 0.39, p < 0.01). In this study improvement in EDSS was used as a monitor of response to corticosteroids. While the EDSS has well-described limitations [15], it has the distinct advantage of being widely used and accepted [15], and setting the boundaries at ≥0.5 and ≥1.0 is a pragmatic way of allowing us to compute an anticipated response to treatment for relevant variables. From our modelling, the most important factor appeared to be age, with younger patients responding more favourably to treatment. Attack severity is also important with patients suffering from less severe attacks (i.e. lower MSIS-29 physical score) likely to benefit the most from treatment (Fig. 2). The study is novel in including a Patient Reported Outcome (PRO) tool, in addition to EDSS, as an outcome predictor of relapse disability and it may be that such a tool is a more sensitive mechanism for detecting the impact of relapses and their response to treatment than EDSS alone.   Source: http://doi.org/10.1371/journal.pone.0120829