Contributions
Abstract: P942
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Introduction: The overall response score (ORS) is a composite of clinically relevant changes from baseline in Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), and 9-Hole Peg test (HPT). The ORS has been shown to reliably characterize disability worsening/improvement over time and differentiate known treatment differences with enhanced sensitivity in patients with relapsing forms of multiple sclerosis (MS). Clinical interpretation of the score, however, requires further elucidation. The difference between ORS and MSFC Z-score, and their respective relationship with patient-reported outcomes (PROs), are also key questions of interest.
Objectives: To evaluate the ORS for relevance to patients and clinical meaningfulness using the physical component summary (PCS) and mental component summary (MCS) from the 36-item Short Form survey (SF-36), a validated and widely used PRO questionnaire.
Methods: The relationship between the ORS of patients with relapsing-remitting MS in the AFFIRM study (natalizumab vs. placebo; total N=942) and change from baseline in SF-36 were assessed using Spearman correlation and linear regression models. Treatment groups were combined for the analyses and effects of baseline EDSS, T25FW, and 9HPT scores were also assessed.
Results: The ORS was correlated, with a linear relationship, with change from baseline in both the SF-36 PCS and MCS at both Year 1 (linear coefficient [LC] 1.66 for PCS and 1.10 for MCS; P< 0.001) and Year 2 (LC 1.63 for PCS and 1.49 for MCS; P< 0.001). The mean ORS over two years was also correlated with change from baseline in the SF-36 PCS and MCS at Year 2 (LC 2.23 for PCS and 2.11 for MCS; P< 0.001). An ORS score of 3 (improvement from baseline) at Year 2 was associated with a mean increase in the SF-36 PCS and MCS of 8.9 (SEM 1.8) and 9.1 (SEM 2.9), respectively. An ORS of -3 (worsening from baseline) at Year 2 was associated with a mean decrease in the SF-36 PCS and MCS of -4.7 (SEM, 1.4) and -2.3 (SEM, 1.7), respectively. No significant correlations between MSFC-z and SF-36 PCS and MCS were observed either at Year 1 or Year 2.
Conclusions: The significant correlations observed between ORS and an established PRO, the SF-36, support the direct relevance of treatment differences and MS population differences in disability worsening or improvement, as measured by ORS, to patients.
Disclosure: Supported by: Biogen (Cambridge, MA, USA). Writing and editorial support for the preparation of this abstract was provided by Excel Scientific Solutions (Southport, CT, USA): funding was provided by Biogen.
I. Chang, B. Zhu. S. Sheikh, R. Hyde, A. Deykin, and A. Sandrock are employees of and hold stock/stock options in Biogen.
G. Giovannoni is on advisory boards for AbbVie Biotherapeutics Inc., Almirall, Atara Biotherapeutics, Biogen, Merck, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva; speaker fees from AbbVie Biotherapeutics Inc., Biogen, Genzyme, Merck, Merck Serono, Sanofi-Genzyme, and Teva; is coeditor in chief of Multiple Sclerosis and Related Disorders; and has received research support unrelated to study from Biogen, Genzyme, and Novartis.
L. Kappos' Institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
P.A. Calabresi has received consulting fees from Biogen and Disarm Therapeutics; is associate editor of The Journal of Clinical Investigation; and has received research support/grants to his institution from Annexon Biosciences, Biogen, MedImmune, Novartis, and Sanofi.
Abstract: P942
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Introduction: The overall response score (ORS) is a composite of clinically relevant changes from baseline in Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), and 9-Hole Peg test (HPT). The ORS has been shown to reliably characterize disability worsening/improvement over time and differentiate known treatment differences with enhanced sensitivity in patients with relapsing forms of multiple sclerosis (MS). Clinical interpretation of the score, however, requires further elucidation. The difference between ORS and MSFC Z-score, and their respective relationship with patient-reported outcomes (PROs), are also key questions of interest.
Objectives: To evaluate the ORS for relevance to patients and clinical meaningfulness using the physical component summary (PCS) and mental component summary (MCS) from the 36-item Short Form survey (SF-36), a validated and widely used PRO questionnaire.
Methods: The relationship between the ORS of patients with relapsing-remitting MS in the AFFIRM study (natalizumab vs. placebo; total N=942) and change from baseline in SF-36 were assessed using Spearman correlation and linear regression models. Treatment groups were combined for the analyses and effects of baseline EDSS, T25FW, and 9HPT scores were also assessed.
Results: The ORS was correlated, with a linear relationship, with change from baseline in both the SF-36 PCS and MCS at both Year 1 (linear coefficient [LC] 1.66 for PCS and 1.10 for MCS; P< 0.001) and Year 2 (LC 1.63 for PCS and 1.49 for MCS; P< 0.001). The mean ORS over two years was also correlated with change from baseline in the SF-36 PCS and MCS at Year 2 (LC 2.23 for PCS and 2.11 for MCS; P< 0.001). An ORS score of 3 (improvement from baseline) at Year 2 was associated with a mean increase in the SF-36 PCS and MCS of 8.9 (SEM 1.8) and 9.1 (SEM 2.9), respectively. An ORS of -3 (worsening from baseline) at Year 2 was associated with a mean decrease in the SF-36 PCS and MCS of -4.7 (SEM, 1.4) and -2.3 (SEM, 1.7), respectively. No significant correlations between MSFC-z and SF-36 PCS and MCS were observed either at Year 1 or Year 2.
Conclusions: The significant correlations observed between ORS and an established PRO, the SF-36, support the direct relevance of treatment differences and MS population differences in disability worsening or improvement, as measured by ORS, to patients.
Disclosure: Supported by: Biogen (Cambridge, MA, USA). Writing and editorial support for the preparation of this abstract was provided by Excel Scientific Solutions (Southport, CT, USA): funding was provided by Biogen.
I. Chang, B. Zhu. S. Sheikh, R. Hyde, A. Deykin, and A. Sandrock are employees of and hold stock/stock options in Biogen.
G. Giovannoni is on advisory boards for AbbVie Biotherapeutics Inc., Almirall, Atara Biotherapeutics, Biogen, Merck, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva; speaker fees from AbbVie Biotherapeutics Inc., Biogen, Genzyme, Merck, Merck Serono, Sanofi-Genzyme, and Teva; is coeditor in chief of Multiple Sclerosis and Related Disorders; and has received research support unrelated to study from Biogen, Genzyme, and Novartis.
L. Kappos' Institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
P.A. Calabresi has received consulting fees from Biogen and Disarm Therapeutics; is associate editor of The Journal of Clinical Investigation; and has received research support/grants to his institution from Annexon Biosciences, Biogen, MedImmune, Novartis, and Sanofi.