Contributions
Abstract: EP1544
Type: ePoster
Abstract Category: Therapy - disease modifying - Others
Background: Disability reduction can be observed in 20-30% of relapsing-remitting multiple sclerosis (RRMS) patients treated with monoclonal antibodies (MABs), namely natalizumab and alemtuzumab. This suggests that the robust anti-inflammatory effect driven by MABs may promote endogenous restorative mechanisms, leading to partial functional recovery in some patients. Therefore, the identification of baseline predictors for disability reduction deserves further investigation.
Objective: To explore which baseline variables are associated with disability reduction after natalizumab start.
Methods: We prospectively collected data of RRMS patients starting natalizumab and followed up to 24 months according to an intention-to-treat approach. Changes in Expanded Disability Status Scale (EDSS) score were calculated at the end of the follow-up versus baseline and categorized as follows: disability reduction (≥1-step EDSS decrease), stable disability (no change or ±0.5-point EDSS change); disability worsening (≥1-step EDSS decrease). The probability of disability reduction was plotted across each pre-treatment EDSS step. A classification and regression tree analysis (CART) was carried out to best discriminate patients with disability reduction from those ones with stable disability and disability worsening over all potential baseline predictors.
Results: We collected data of 496 (346 women, 156 men) with a mean age of 36.2+/-9.5 years, mean time since first symptom of 8.6+/-6.0 years, and median EDSS score of 3.0 (range 1.0-8.5). At follow-up, disability reduction was observed in 96 (19.4%), stable disability in 336 (67.7%), and disability worsening in 64 (12.9%) patients. The probability of disability reduction showed an inverted U-shaped distribution, being higher at intermediate EDSS steps (EDSS 3.0-4.0). The CART analysis revealed distinct baseline predictors for disability reduction according to the pre-treatment EDSS score, i.e. a lower number of pre-treatment relapses in patients scoring below 3.0 (adjusted-p=0.04) and a younger age in those ones scoring 3.0 or more (adjusted-p=0.002). We found consisent findings even after removing from the CART patients experiencing disability worsening.
Discussion: The detection of functional recovery may be challenging at lowest disability levels, likely due to the floor effect of EDSS. Starting natalizumab after multiple relapses and age-related processes may independently preclude the potential of functional recovery.
Disclosure:
FF: nothing to disclose.
SR: nothing to disclose.
LP: consulting fees from Biogen and Novartis; speaker honoriaria from Biogen, Genzyme, Novartis, Teva; research grants from Genzyme.
CP: consulting fees and/or speaker honoraria from Almirall, Biogen, Genzyme, Merck Serono, Novartis, Roche, Teva; research grants from Merck Serono and Novartis.
RC: consulting fees from Biogen and Novartis, and lecture fees and/or travel grants from Novartis, Biogen, Genzyme and Sanofi-Aventis.
Abstract: EP1544
Type: ePoster
Abstract Category: Therapy - disease modifying - Others
Background: Disability reduction can be observed in 20-30% of relapsing-remitting multiple sclerosis (RRMS) patients treated with monoclonal antibodies (MABs), namely natalizumab and alemtuzumab. This suggests that the robust anti-inflammatory effect driven by MABs may promote endogenous restorative mechanisms, leading to partial functional recovery in some patients. Therefore, the identification of baseline predictors for disability reduction deserves further investigation.
Objective: To explore which baseline variables are associated with disability reduction after natalizumab start.
Methods: We prospectively collected data of RRMS patients starting natalizumab and followed up to 24 months according to an intention-to-treat approach. Changes in Expanded Disability Status Scale (EDSS) score were calculated at the end of the follow-up versus baseline and categorized as follows: disability reduction (≥1-step EDSS decrease), stable disability (no change or ±0.5-point EDSS change); disability worsening (≥1-step EDSS decrease). The probability of disability reduction was plotted across each pre-treatment EDSS step. A classification and regression tree analysis (CART) was carried out to best discriminate patients with disability reduction from those ones with stable disability and disability worsening over all potential baseline predictors.
Results: We collected data of 496 (346 women, 156 men) with a mean age of 36.2+/-9.5 years, mean time since first symptom of 8.6+/-6.0 years, and median EDSS score of 3.0 (range 1.0-8.5). At follow-up, disability reduction was observed in 96 (19.4%), stable disability in 336 (67.7%), and disability worsening in 64 (12.9%) patients. The probability of disability reduction showed an inverted U-shaped distribution, being higher at intermediate EDSS steps (EDSS 3.0-4.0). The CART analysis revealed distinct baseline predictors for disability reduction according to the pre-treatment EDSS score, i.e. a lower number of pre-treatment relapses in patients scoring below 3.0 (adjusted-p=0.04) and a younger age in those ones scoring 3.0 or more (adjusted-p=0.002). We found consisent findings even after removing from the CART patients experiencing disability worsening.
Discussion: The detection of functional recovery may be challenging at lowest disability levels, likely due to the floor effect of EDSS. Starting natalizumab after multiple relapses and age-related processes may independently preclude the potential of functional recovery.
Disclosure:
FF: nothing to disclose.
SR: nothing to disclose.
LP: consulting fees from Biogen and Novartis; speaker honoriaria from Biogen, Genzyme, Novartis, Teva; research grants from Genzyme.
CP: consulting fees and/or speaker honoraria from Almirall, Biogen, Genzyme, Merck Serono, Novartis, Roche, Teva; research grants from Merck Serono and Novartis.
RC: consulting fees from Biogen and Novartis, and lecture fees and/or travel grants from Novartis, Biogen, Genzyme and Sanofi-Aventis.