Contributions
Abstract: 156
Type: Scientific Session
Abstract Category: Therapy - Tools for detecting therapeutic response
Background: Studies on natural history of multiple sclerosis (MS) suggest that demographic and clinical factors at onset predict disability progression. Disease-modifying drugs (DMDs) may influence MS natural history. Current scoring systems for treatment response are mainly based on clinical and magnetic resonance activity measures collected one year after DMD start. These scoring systems do not take into account baseline demographic and clinical factors (treatment effect modifiers) that can affect longer-term outcome. To date no study has evaluated the effect on long-term disability progression by a scoring system in which parameters of treatment response and clinical baseline factors are considered together.
Objective: (1) To develop a scoring system computing baseline factors and one-year variables of treatment response into a single numeric score; and (2) to evaluate if this score is able to predict the 10-year risk of ambulatory disability in patients starting an injectable DMD.
Methods: We collected data of patients who started Interferon Beta or Glatiramer Acetate, had an EDSS≤3.5 at DMD start and were followed for 10 years.
The whole dataset was randomly split in near 1:1 ratio to obtain a training set and a validation set. The training set served as framework to create the so-called RoAD score (Risk of Ambulatory Disability) as follows: (i) a multivariable Cox analysis was run to identify baseline and one-year factors associated with the risk of reaching EDSS≥6.0; (ii) each identified risk factor was scored by rounding the derived Beta coefficient to the nearest integer. Performance of RoAD score was then tested by receiver operating characteristic (ROC) and area under the curve (AUC) analyses.
Results: We analyzed 1,224 patients (70% women) with a mean age of 34 years and median EDSS of 1.5. At 10-year follow-up, 162 (13%) reached an EDSS≥6.0. The RoAD score, derived from the training set (n=606), was based on sex, age, disease duration, EDSS score (at baseline) and no. of relapses and new T2 lesions (after the first treatment year). When applied to the validation set (n=618), a risk score based only on one-year disease activity showed a sensitivity of 58% and specificity of 81% (AUC=0.67). The RoAD score, based on a combination of baseline factors and one-year variables, yielded to an increased sensitivity of 72% and specificity of 82% (AUC=0.83; p< 0.001).
Conclusion: We propose the RoAD score as an useful tool to orient treatment strategy in MS.
Disclosure: CG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis, Genzyme.
LP: consulting fees from Biogen, Novartis and Roche; speaker honoraria from Almirall, Biogen, Genzyme, Merck Serono, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme.
CT: honoraria for speaking and travel grant from Biogen, Sanofi-Aventis, Merck Serono, Bayer-Schering, Teva, Genzyme, Almirall and Novartis.
SH: consulting fees, speaker honoraria and travel grants from Biogen, Genzyme, Teva, CSL Behrig, Zambon and research grants from Italian Minister of Foreign Affairs.
SR: speaking honoraria from Merck Serono and Teva.
CRM: nothing to disclose.
SG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Almirall, Sanofi-Aventis, Novartis, Genzyme.
RC: lecture fees and/or travel grants from Novartis, Biogen, Celgene, Novartis, Teva, Genzyme and Sanofi-Aventis.
CP: scientific advisory boards for Actelion, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck Serono, Novartis, Sanofi, Teva; consulting and/or speaking fees, research support and travel grants from Allergan, Almirall, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck Serono, Novartis, Sanofi and Teva.
Abstract: 156
Type: Scientific Session
Abstract Category: Therapy - Tools for detecting therapeutic response
Background: Studies on natural history of multiple sclerosis (MS) suggest that demographic and clinical factors at onset predict disability progression. Disease-modifying drugs (DMDs) may influence MS natural history. Current scoring systems for treatment response are mainly based on clinical and magnetic resonance activity measures collected one year after DMD start. These scoring systems do not take into account baseline demographic and clinical factors (treatment effect modifiers) that can affect longer-term outcome. To date no study has evaluated the effect on long-term disability progression by a scoring system in which parameters of treatment response and clinical baseline factors are considered together.
Objective: (1) To develop a scoring system computing baseline factors and one-year variables of treatment response into a single numeric score; and (2) to evaluate if this score is able to predict the 10-year risk of ambulatory disability in patients starting an injectable DMD.
Methods: We collected data of patients who started Interferon Beta or Glatiramer Acetate, had an EDSS≤3.5 at DMD start and were followed for 10 years.
The whole dataset was randomly split in near 1:1 ratio to obtain a training set and a validation set. The training set served as framework to create the so-called RoAD score (Risk of Ambulatory Disability) as follows: (i) a multivariable Cox analysis was run to identify baseline and one-year factors associated with the risk of reaching EDSS≥6.0; (ii) each identified risk factor was scored by rounding the derived Beta coefficient to the nearest integer. Performance of RoAD score was then tested by receiver operating characteristic (ROC) and area under the curve (AUC) analyses.
Results: We analyzed 1,224 patients (70% women) with a mean age of 34 years and median EDSS of 1.5. At 10-year follow-up, 162 (13%) reached an EDSS≥6.0. The RoAD score, derived from the training set (n=606), was based on sex, age, disease duration, EDSS score (at baseline) and no. of relapses and new T2 lesions (after the first treatment year). When applied to the validation set (n=618), a risk score based only on one-year disease activity showed a sensitivity of 58% and specificity of 81% (AUC=0.67). The RoAD score, based on a combination of baseline factors and one-year variables, yielded to an increased sensitivity of 72% and specificity of 82% (AUC=0.83; p< 0.001).
Conclusion: We propose the RoAD score as an useful tool to orient treatment strategy in MS.
Disclosure: CG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis, Genzyme.
LP: consulting fees from Biogen, Novartis and Roche; speaker honoraria from Almirall, Biogen, Genzyme, Merck Serono, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme.
CT: honoraria for speaking and travel grant from Biogen, Sanofi-Aventis, Merck Serono, Bayer-Schering, Teva, Genzyme, Almirall and Novartis.
SH: consulting fees, speaker honoraria and travel grants from Biogen, Genzyme, Teva, CSL Behrig, Zambon and research grants from Italian Minister of Foreign Affairs.
SR: speaking honoraria from Merck Serono and Teva.
CRM: nothing to disclose.
SG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Almirall, Sanofi-Aventis, Novartis, Genzyme.
RC: lecture fees and/or travel grants from Novartis, Biogen, Celgene, Novartis, Teva, Genzyme and Sanofi-Aventis.
CP: scientific advisory boards for Actelion, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck Serono, Novartis, Sanofi, Teva; consulting and/or speaking fees, research support and travel grants from Allergan, Almirall, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck Serono, Novartis, Sanofi and Teva.