Open Access Research article

Clinical baseline factors predict response to natalizumab: their usefulness in patient selection

Alice Laroni1, Ilaria Gandoglia1, Claudio Solaro2, Giuseppe Ribizzi3, Tiziana Tassinari4, Matteo Pizzorno5, Sergio Parodi6, Giovanna Baldassarre7, Maria Teresa Rilla8, Simonetta Venturi9, Elisabetta Capello1, Maria Pia Sormani10, Antonio Uccelli1 and Giovanni Luigi Mancardi1*

Author Affiliations

1 Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Largo Daneo 3, 16132 Genova, Italy

2 Neurology Unit, PA Micone Hospital Dip. Testa-Collo, ASL 3 Genovese, Genova, Italy

3 Multiple Sclerosis Center, San Martino Hospital, Genova, Italy

4 Multiple Sclerosis Center, Santa Corona Hospital, Pietra Ligure, Italy

5 Division of Neurology, San Paolo Hospital, Savona, Italy

6 Multiple Sclerosis Center, Sant’Andrea Hospital, La Spezia, Italy

7 Multiple Sclerosis Center, Giovanni Borea Hospital, Sanremo, Italy

8 Multiple Sclerosis Center, Imperia Hospital, Imperia, Italy

9 Multiple Sclerosis Center, Galliera Hospital, Genova, Italy

10 Department of Health Sciences, University of Genova, Genova, Italy

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BMC Neurology 2014, 14:103  doi:10.1186/1471-2377-14-103

Published: 12 May 2014

Abstract

Background

Optimal patient selection would improve the risk-benefit ratio of natalizumab treatment for relapsing-remitting multiple sclerosis (RR MS). Clinical features of subjects responding to natalizumab have not been univocally recognized.

Methods

Longitudinal data on RR MS patients treated with natalizumab in Liguria, Italy are reported. Predictors of relapse occurrence and disability improvement were analyzed with a logistic regression method in subjects treated for one year (N = 62). A new score, called “Better EDSS Trend (BET)”, was devised to describe the impact of the treatment on disability. Changes in annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) after one and two years and proportion of disease-free patients were evaluated.

Results

Previous EDSS worsening plus ARR ≥ 2 increased the risk of relapse during the treatment [Odds Ratio (OR) 4.12, P = 0.04], but this was not associated with an increase in disability at one year. EDSS 3.0-3.5 or high disease activity were associated with neurological improvement in the first year of treatment (respectively OR 5.78, P = 0.05 and OR 4.80, P = 0.05). Positive BET score, i.e. improvement in the disability trend, was observed in 40.3% of patients, and correlated with high ARR in the year before treatment (OR 1.69, P = 0.03).

Conclusion

Subjects with EDSS 3.0-3.5 and those with very active disease in the year before treatment are most likely to improve in neurological function under natalizumab. A relapse in the first year of treatment is associated to high pre-treatment disease activity; however, since the occurrence of a relapse did not have a negative impact on clinical improvement at one year, we suggest that it should not lead to treatment discontinuation. We propose BET as an additional endpoint of treatment response in MS.

Keywords:
Multiple sclerosis; Natalizumab; Neuropharmacology; Clinical neurology