Contributions
Abstract: P1279
Type: Poster
Abstract Category: Therapy - disease modifying - Treatment of progressive MS
Background: Patient-reported outcomes (PROs) comprise a diverse range of measures that assess the impact of disease and therapeutic efficacy from the patient"s perspective. ORATORIO was a randomised, double-blind, placebo-controlled Phase III study that evaluated the efficacy and safety of ocrelizumab (OCR), a humanised monoclonal antibody that selectively targets CD20+ B cells, in primary progressive multiple sclerosis (PPMS).
Objective: To evaluate the effect of OCR on two PROs, the Short Form-36 (SF-36) and Modified Fatigue Impact Scale (MFIS), in patients with PPMS.
Methods: The SF-36 assesses patients" perception of functional health across 8 concepts that can be reported individually or combined to provide a Physical Component Summary (PCS) and a Mental Component Summary (MCS). The MFIS assesses the effects of fatigue on physical, cognitive and psychosocial functioning. In ORATORIO, patients were randomised (2:1) to receive OCR 600 mg or placebo intravenously as two 300 mg infusions 14 days apart, every 24 weeks for ≥120 weeks until a prespecified number of 12-week confirmed disability progression events occurred. The SF-36 and MFIS were administered at baseline, Week 48 and Week 120. Change in SF-36 PCS and changes in SF-36 MCS and MFIS total score from baseline to Week 120 were assessed secondary and exploratory endpoints, respectively. T scores for SF-36 were calculated using the 2009 US Normative data; a mean (SD) score of 50 (10) corresponds to that of the general US population.
Results: There was no statistically significant difference in the decline in SF-36 PCS in the OCR group vs the placebo group (adjusted mean -0.688 with OCR vs -1.086 with placebo [p=0.5576]). However, OCR significantly improved SF-36 MCS compared with placebo (adjusted mean 1.577 with OCR vs -1.483 with placebo [p=0.0006]) from baseline to Week 120. Further, OCR significantly improved the MFIS total score compared with placebo (adjusted mean -0.462 with OCR vs 2.994 with placebo [p=0.0091]) and performed better than placebo for all three MFIS subscale components from baseline to Week 120.
Conclusions: In patients with PPMS, ocrelizumab reduced physical, cognitive and psychosocial aspects of fatigue and improved the mental well-being component of health-related quality of life compared with placebo, as measured from the patients" perspective. There was no difference observed between ocrelizumab and placebo groups in the SF-36 PCS.
Sponsored by F. Hoffmann-La Roche Ltd.
Disclosure: Jérôme de Seze has received consultancy fees and served as an expert for advisory boards for Alexion, Allergan, Almiral, Bayer, Biogen, Chugai, CSL Behring, F. Hoffmann-La Roche Ltd., Genzyme, LFB, Merck, Novartis, and Teva.
Xavier Montalban has received speaking honoraria and travel expense reimbursement for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Almirall, Bayer, Biogen, Genzyme, Merck, Novartis, Octapharma, Receptos, F. Hoffmann-La Roche Ltd., Sanofi, Teva and Trophos.
Fiona McDougall is an employee of F. Hoffmann-La Roche Ltd.
Annette Sauter is an employee and shareholder of F. Hoffmann-La Roche Ltd. Gurpreet Deol-Bhullar is an employee of F. Hoffmann-La Roche Ltd.
Jerry Wolinsky in the last 3 years has received compensation for service on steering committees or data monitoring boards for F. Hoffmann-La Roche Ltd., Medday Pharmaceuticals, Novartis, Sanofi Genzyme and Teva Pharmaceuticals; consultant fees from AbbVie, Actelion, Alkermes, EMD Serono, Forward Pharma, Genentech, Inc., F. Hoffmann-La Roche Ltd., Novartis, Sanofi Genzyme, Takeda, Teva, and XenoPort; research support from, Sanofi Genzyme, the NIH and the NMSS through the University of Texas Health Science Center at Houston (UTHSCH) and royalties for monoclonal antibodies out-licensed to Chemicon International through UTHSCH.
Abstract: P1279
Type: Poster
Abstract Category: Therapy - disease modifying - Treatment of progressive MS
Background: Patient-reported outcomes (PROs) comprise a diverse range of measures that assess the impact of disease and therapeutic efficacy from the patient"s perspective. ORATORIO was a randomised, double-blind, placebo-controlled Phase III study that evaluated the efficacy and safety of ocrelizumab (OCR), a humanised monoclonal antibody that selectively targets CD20+ B cells, in primary progressive multiple sclerosis (PPMS).
Objective: To evaluate the effect of OCR on two PROs, the Short Form-36 (SF-36) and Modified Fatigue Impact Scale (MFIS), in patients with PPMS.
Methods: The SF-36 assesses patients" perception of functional health across 8 concepts that can be reported individually or combined to provide a Physical Component Summary (PCS) and a Mental Component Summary (MCS). The MFIS assesses the effects of fatigue on physical, cognitive and psychosocial functioning. In ORATORIO, patients were randomised (2:1) to receive OCR 600 mg or placebo intravenously as two 300 mg infusions 14 days apart, every 24 weeks for ≥120 weeks until a prespecified number of 12-week confirmed disability progression events occurred. The SF-36 and MFIS were administered at baseline, Week 48 and Week 120. Change in SF-36 PCS and changes in SF-36 MCS and MFIS total score from baseline to Week 120 were assessed secondary and exploratory endpoints, respectively. T scores for SF-36 were calculated using the 2009 US Normative data; a mean (SD) score of 50 (10) corresponds to that of the general US population.
Results: There was no statistically significant difference in the decline in SF-36 PCS in the OCR group vs the placebo group (adjusted mean -0.688 with OCR vs -1.086 with placebo [p=0.5576]). However, OCR significantly improved SF-36 MCS compared with placebo (adjusted mean 1.577 with OCR vs -1.483 with placebo [p=0.0006]) from baseline to Week 120. Further, OCR significantly improved the MFIS total score compared with placebo (adjusted mean -0.462 with OCR vs 2.994 with placebo [p=0.0091]) and performed better than placebo for all three MFIS subscale components from baseline to Week 120.
Conclusions: In patients with PPMS, ocrelizumab reduced physical, cognitive and psychosocial aspects of fatigue and improved the mental well-being component of health-related quality of life compared with placebo, as measured from the patients" perspective. There was no difference observed between ocrelizumab and placebo groups in the SF-36 PCS.
Sponsored by F. Hoffmann-La Roche Ltd.
Disclosure: Jérôme de Seze has received consultancy fees and served as an expert for advisory boards for Alexion, Allergan, Almiral, Bayer, Biogen, Chugai, CSL Behring, F. Hoffmann-La Roche Ltd., Genzyme, LFB, Merck, Novartis, and Teva.
Xavier Montalban has received speaking honoraria and travel expense reimbursement for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Almirall, Bayer, Biogen, Genzyme, Merck, Novartis, Octapharma, Receptos, F. Hoffmann-La Roche Ltd., Sanofi, Teva and Trophos.
Fiona McDougall is an employee of F. Hoffmann-La Roche Ltd.
Annette Sauter is an employee and shareholder of F. Hoffmann-La Roche Ltd. Gurpreet Deol-Bhullar is an employee of F. Hoffmann-La Roche Ltd.
Jerry Wolinsky in the last 3 years has received compensation for service on steering committees or data monitoring boards for F. Hoffmann-La Roche Ltd., Medday Pharmaceuticals, Novartis, Sanofi Genzyme and Teva Pharmaceuticals; consultant fees from AbbVie, Actelion, Alkermes, EMD Serono, Forward Pharma, Genentech, Inc., F. Hoffmann-La Roche Ltd., Novartis, Sanofi Genzyme, Takeda, Teva, and XenoPort; research support from, Sanofi Genzyme, the NIH and the NMSS through the University of Texas Health Science Center at Houston (UTHSCH) and royalties for monoclonal antibodies out-licensed to Chemicon International through UTHSCH.