Search

Supplemental material, sj-pdf-3-mso-10.1177_2055217321990852 for Early MRI outcomes in participants with a first clinical demyelinating event at risk of multiple sclerosis in the ORACLE-MS study by Mark S Freedman Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada, Patricia K Coyle Department of Neurology, Stony Brook University, Stony Brook, NY, USA, Giancarlo Comi Institute of Experimental Neurology, IRCCS Ospedale San Raffaele, Milan, Italy, Susan L Scarberry Sanford Health Multiple Sclerosis Center, Fargo, ND, USA, Doris Damian EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany, Yann Hyvert Merck KGaA, Darmstadt, Germany, Fernando Dangond EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany,Andrew Galazka, Dominic JackMerck KGaA, Darmstadt, Germany, Lori A Lebson EMD Serono, Inc, Rockland, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany, Thomas P Leist Comprehensive Multiple Sclerosis Center, Jefferson University Hospital, Philadelphia, PA, USA in Multiple Sclerosis Journal – Experimental, Translational and Clinical

Supplemental material, sj-pdf-4-mso-10.1177_2055217321990852 for Early MRI outcomes in participants with a first clinical demyelinating event at risk of multiple sclerosis in the ORACLE-MS study by Mark S Freedman Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada, Patricia K Coyle Department of Neurology, Stony Brook University, Stony Brook, NY, USA, Giancarlo Comi Institute of Experimental Neurology, IRCCS Ospedale San Raffaele, Milan, Italy, Susan L Scarberry Sanford Health Multiple Sclerosis Center, Fargo, ND, USA, Doris Damian EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany, Yann Hyvert Merck KGaA, Darmstadt, Germany, Fernando Dangond EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany,Andrew Galazka, Dominic JackMerck KGaA, Darmstadt, Germany, Lori A Lebson EMD Serono, Inc, Rockland, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany, Thomas P Leist Comprehensive Multiple Sclerosis Center, Jefferson University Hospital, Philadelphia, PA, USA in Multiple Sclerosis Journal – Experimental, Translational and Clinical

Supplemental material, sj-pdf-3-mso-10.1177_2055217321990852 for Early MRI outcomes in participants with a first clinical demyelinating event at risk of multiple sclerosis in the ORACLE-MS study by Mark S Freedman Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada, Patricia K Coyle Department of Neurology, Stony Brook University, Stony Brook, NY, USA, Giancarlo Comi Institute of Experimental Neurology, IRCCS Ospedale San Raffaele, Milan, Italy, Susan L Scarberry Sanford Health Multiple Sclerosis Center, Fargo, ND, USA, Doris Damian EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany, Yann Hyvert Merck KGaA, Darmstadt, Germany, Fernando Dangond EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany,Andrew Galazka, Dominic JackMerck KGaA, Darmstadt, Germany, Lori A Lebson EMD Serono, Inc, Rockland, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany, Thomas P Leist Comprehensive Multiple Sclerosis Center, Jefferson University Hospital, Philadelphia, PA, USA in Multiple Sclerosis Journal – Experimental, Translational and Clinical

Supplemental material, sj-pdf-1-msj-10.1177_13524585211010294 for Analysis of frequency and severity of relapses in multiple sclerosis patients treated with cladribine tablets or placebo: The CLARITY and CLARITY Extension studies by Nicola De Stefano, Maria Pia Sormani, Gavin Giovannoni, Kottil Rammohan, Thomas Leist, Patricia K Coyle, Fernando Dangond, Birgit Keller, Nektaria Alexandri and Andrew Galazka in Multiple Sclerosis Journal

Supplemental material, sj-pdf-1-mso-10.1177_20552173211024298 for Treatment-emergent adverse events occurring early in the treatment course of cladribine tablets in two phase 3 trials in multiple sclerosis by Jiwon Oh, Bryan Walker, Gavin Giovannoni, Dominic Jack, Fernando Dangond, Axel Nolting, Julie Aldridge, Lori A Lebson and Thomas P Leist in Multiple Sclerosis Journal—Experimental, Translational and Clinical

Supplemental material, sj-pdf-1-msj-10.1177_13524585211010294 for Analysis of frequency and severity of relapses in multiple sclerosis patients treated with cladribine tablets or placebo: The CLARITY and CLARITY Extension studies by Nicola De Stefano, Maria Pia Sormani, Gavin Giovannoni, Kottil Rammohan, Thomas Leist, Patricia K Coyle, Fernando Dangond, Birgit Keller, Nektaria Alexandri and Andrew Galazka in Multiple Sclerosis Journal

Supplemental material, sj-pdf-1-mso-10.1177_20552173211024298 for Treatment-emergent adverse events occurring early in the treatment course of cladribine tablets in two phase 3 trials in multiple sclerosis by Jiwon Oh, Bryan Walker, Gavin Giovannoni, Dominic Jack, Fernando Dangond, Axel Nolting, Julie Aldridge, Lori A Lebson and Thomas P Leist in Multiple Sclerosis Journal—Experimental, Translational and Clinical

Supplemental material, sj-pdf-3-mso-10.1177_2055217321990852 for Early MRI outcomes in participants with a first clinical demyelinating event at risk of multiple sclerosis in the ORACLE-MS study by Mark S Freedman Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada, Patricia K Coyle Department of Neurology, Stony Brook University, Stony Brook, NY, USA, Giancarlo Comi Institute of Experimental Neurology, IRCCS Ospedale San Raffaele, Milan, Italy, Susan L Scarberry Sanford Health Multiple Sclerosis Center, Fargo, ND, USA, Doris Damian EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany, Yann Hyvert Merck KGaA, Darmstadt, Germany, Fernando Dangond EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany,Andrew Galazka, Dominic JackMerck KGaA, Darmstadt, Germany, Lori A Lebson EMD Serono, Inc, Rockland, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany, Thomas P Leist Comprehensive Multiple Sclerosis Center, Jefferson University Hospital, Philadelphia, PA, USA in Multiple Sclerosis Journal – Experimental, Translational and Clinical

Supplemental material, Supplementary_Materials for Effects of cladribine tablets on lymphocyte subsets in patients with multiple sclerosis: an extended analysis of surface markers by Olaf Stuve, Per Soelberg Soerensen, Thomas Leist, Gavin Giovannoni, Yann Hyvert, Doris Damian, Fernando Dangond and Ursula Boschert in Therapeutic Advances in Neurological Disorders

Figure S5. Proportion progressed at each year by ≥2 versus 0–1 active T2 lesions at 12 months. (a) Placebo/delayed treatment, ≥2 versus 0–1 T2 lesions at 12 months; (b) IFN β-1a 22 μg SC tiw, ≥2 versus 0–1 T2 lesions at 12 months; (c) IFN β-1a 44 μg SC tiw, ≥2 versus 0–1 T2 lesions at 12 months. (PDF 183 kb)

Table S1. Baseline characteristics of patients in the PRISMS-2 study (adapted from PRISMS Study Group. Lancet. 1998;352:1498â 504). (DOCX 15 kb)

Supplementary Material, MSJ771875_supplementary_material for Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study by Gavin Giovannoni, Per Soelberg Sorensen, Stuart Cook, Kottil W Rammohan, Peter Rieckmann, Giancarlo Comi, Fernando Dangond, Christine Hicking and Patrick Vermersch in Multiple Sclerosis Journal

Figure S2. Proportion with EDSS progression at each year in the placebo/delayed treatment and IFN β-1a 44 μg SC tiw groups by ≥4 versus 0 active T2 lesions at 6 months. (PDF 189 kb)

Figure S2. Post hoc analysis of MRI endpoints. (PDF 170 kb)

Table S1. (a) Performance of T2 lesions on predicting EDSS progression at Year 2 and Year 4. (b) Performance of T2 lesions on predicting relapse at Year 2 and Year 4. (DOCX 15Â kb)

Figure S1. Incremental quarterly relapse count over 1Â year. (PDF 145 kb)

Figure S1. Proportion with EDSS progression at each year by ≥2 versus 0–1 active T2 lesions at 6 months. (a) Placebo/delayed treatment group; (b) IFN β-1a 22 μg SC tiw group; (c) IFN β-1a 44 μg SC tiw group. (PDF 258 kb)

The pharmacometric analysis of the double-blind, randomized, phase II study (NCT02975349) investigating the safety and efficacy of evobrutinib, explored exposure-response relationships and suitable dosing regimens of evobrutinib for relapsing multiple sclerosis. Population pharmacokinetic (PK)/pharmacodynamic modeling was applied to data collected in fasted patients treated with placebo or evobrutinib (25 mg once-daily [q.d.], 75 mg q.d., or 75 mg twice-daily [b.i.d.]) for 24 weeks, followed by a 24-week blinded extension (placebo patients switched to 25 mg q.d.). Model-based exposures for PK and Bruton's tyrosine kinase occupancy (BTKO) were used for exposure-response analyses (maximum 207 patients). PK, BTKO profiles, and annualized relapse rate (ARR) after 48 weeks of treatment under alternative dosing regimens were simulated. Exposure-response modeling identified a relationship between evobrutinib exposure and clinical response for a total number of T1 Gd+ and new/enlarging T2 lesions at weeks 12-24, and ARR at week 48. Area under the concentration-time curve over 24 h at steady-state (AUC(0-24,SS)) of 468 and >= 400 ng/ml h was associated with T1 Gd+/T2 lesion reduction and ARR improvement, respectively. These exposures were associated with steady-state (SS) predose BTKO >= 95%. Based on PK and BTKO profile simulations, evobrutinib 75 mg b.i.d. while fasted is predicted to maintain SS predose BTKO >95% in 92% of patients. Evobrutinib 45 mg b.i.d. with food is predicted to achieve similar exposure as 75 mg b.i.d. while fasted (predose BTKO >95% in 93% of patients). Evobrutinib 45 mg b.i.d. with food is predicted to have comparable exposure and BTKO to 75 mg b.i.d. without food (phase II) and will be pharmacologically effective and appropriate for clinical use in phase III multiple sclerosis studies.

Figure S6. Proportion relapsed at each year by ≥2 versus 0–1 active T2 lesions at 12 months. (a) Placebo/delayed treatment group; (b) IFN β-1a 22 μg SC tiw group; (c) IFN β-1a 44 μg SC tiw group. (PDF 273 kb)

Figure S1. Proportion with EDSS progression at each year by ≥2 versus 0–1 active T2 lesions at 6 months. (a) Placebo/delayed treatment group; (b) IFN β-1a 22 μg SC tiw group; (c) IFN β-1a 44 μg SC tiw group. (PDF 258 kb)

Figure S1. Incremental quarterly relapse count over 1Â year. (PDF 145 kb)

Figure S6. Proportion relapsed at each year by ≥2 versus 0–1 active T2 lesions at 12 months. (a) Placebo/delayed treatment group; (b) IFN β-1a 22 μg SC tiw group; (c) IFN β-1a 44 μg SC tiw group. (PDF 273 kb)

Figure S4. Proportion relapsed at each year by ≥2 versus 0–1 active T2 lesions at 6 months. (a) Placebo/delayed treatment group; (b) IFN β-1a 22 μg SC tiw group; (c) IFN β-1a 44 μg SC tiw group. (PDF 269 kb)

Figure S3. Time to sustained EDSS progression by ≥2 versus 0–1 active T2 lesions at 6 months. (a) Placebo/delayed treatment group; (b) IFN β-1a 22 μg SC tiw group; (c) IFN β-1a 44 μg SC tiw group. (PDF 229 kb)

Figure S4. Proportion relapsed at each year by ≥2 versus 0–1 active T2 lesions at 6 months. (a) Placebo/delayed treatment group; (b) IFN β-1a 22 μg SC tiw group; (c) IFN β-1a 44 μg SC tiw group. (PDF 269 kb)

Figure S3. Time to sustained EDSS progression by ≥2 versus 0–1 active T2 lesions at 6 months. (a) Placebo/delayed treatment group; (b) IFN β-1a 22 μg SC tiw group; (c) IFN β-1a 44 μg SC tiw group. (PDF 229 kb)