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Background: Alemtuzumab is a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS), and immune thrombocytopenia (ITP) has been identified as a risk. Objective: To examine ITP incidence, treatment, and outcomes during the clinical development of alemtuzumab for RRMS and discuss postmarketing experience outside clinical trials. Methods: CAMMS223 and Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) I and II investigated two annual courses of alemtuzumab 12 mg (or 24 mg in CAMMS223/CARE-MS II) versus subcutaneous interferon beta-1a three times per week. Patients completing core studies could enroll in an extension. Monthly monitoring for ITP continued until 48 months after the last alemtuzumab infusion. Results: Of 1485 alemtuzumab-treated MS patients in the clinical development program, 33 (2.2%) developed ITP (alemtuzumab 12 mg, 24 [2.0%]; alemtuzumab 24 mg, 9 [3.3%]) over median 6.1 years of follow-up after the first infusion; most had a sustained response to first-line ITP therapy with corticosteroids, platelets, and/or intravenous immunoglobulin. All cases occurred within 48 months of the last alemtuzumab infusion. Postmarketing surveillance data suggest that the ITP incidence is not higher in clinical practice than in clinical trials. Conclusion: Alemtuzumab-associated ITP occurs in approximately 2% of patients and is responsive to therapy. Careful monitoring is key for detection and favorable outcomes. [ABSTRACT FROM AUTHOR]

Background: Diroximel fumarate (DRF) is approved for adults with relapsing-remitting multiple sclerosis (RRMS) in Europe and for relapsing forms of MS in the United States. DRF and dimethyl fumarate (DMF) yield bioequivalent exposure of the active metabolite monomethyl fumarate. Prior studies indicated fewer gastrointestinal (GI)-related adverse events (AEs) with DRF compared with DMF., Objective: To report final outcomes from EVOLVE-MS-1., Methods: EVOLVE-MS-1 was an open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in patients with RRMS. The primary endpoint was safety and tolerability; efficacy endpoints were exploratory., Results: Overall, 75.7% (800/1057) of patients completed the study; median exposure was 1.8 (range: 0.0-2.0) years. AEs occurred in 938 (88.7%) patients, mostly of mild (28.9%) or moderate (50.3%) severity. DRF was discontinued due to AEs in 85 (8.0%) patients, with < 2% discontinuing due to GI or flushing/flushing-related AEs. At Week 96, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (72.7%; p < 0.0001); adjusted annualized relapse rate was 0.13 (95% confidence interval: 0.11-0.15)., Conclusion: DRF was generally well tolerated over 2 years, with few discontinuations due to AEs; radiological measures indicated decreased disease activity from baseline. These outcomes support DRF as a treatment option in patients with RRMS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BAS: research grant support from AbbVie, Biogen, Bristol Myers Squibb, Greenwich Biosciences, Novartis, and Sanofi and consulting and/or speaking fees from Alexion, Biogen, Bristol Myers Squibb, Cigna, Cycle, EMD Serono, Genentech, Horizon, Janssen, Novartis, Octave Bioscience, Roche, Sanofi, and TG Therapeutics.DLA: consulting fees from Albert Charitable Trust, Alexion Pharma, Biogen, Celgene, Frequency Therapeutics, Genentech, Med-Ex Learning, Merck, Novartis, Population Council, Receptos, Roche, and Sanofi-Aventis; grants from Biogen, Immunotec, and Novartis; and equity interest in NeuroRx.JD: advisory boards for Amicus, Biogen, Janssen, Medis, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva; speaker bureaus for Biogen, Bayer, Hemofarm, Janssen, Medis, Medtronic, Merck, Novartis, Roche, Sanofi-Genzyme, Teva, and Zentiva; and research grant from Roche.MSF: research/educational grants from Sanofi-Genzyme; honoraria/consultation fees from Alexion/AstraZeneca, BMS (Celgene), EMD Serono, Hoffman La-Roche, Actelion/Janssen (J&J), Novartis, Quanterix, Sanofi-Genzyme, and Teva Canada Innovation; advisory boards/boards of directors for Alexion/AstraZeneca, Atara Biotherapeutics, Bayer Healthcare, Celestra Health, Hoffman La-Roche, Actelion/Janssen (J&J), EMD Serono/Merck Serono, Novartis, and Sanofi-Genzyme; and participated in speakers bureau for Sanofi-Genzyme and EMD Serono.RG: research support and speaker’s honoraria from Bayer-Schering, Biogen Idec, BMS, Chugai, Eisai, Genesis, Janssen, Merck Serono, Nikkiso Pharma, Novartis, Roche, Sanofi-Genzyme, Sandoz, and Teva; consulting honoraria from ZLB Behring, Baxter, Roche, and Talecris; and personal stock options in Bayer, Merck, and Roche.MG: consulting fees from Biogen, EMD Serono, Novartis, and Sanofi-Genzyme; research support from Alkermes; and speaker bureaus for Biogen, EMD Serono, Genentech-Roche, and Sanofi-Genzyme.EJ: advisory boards for Biogen and speaker fees from Biogen, Novartis, Roche, and Sanofi.CLG: consultant/advisory boards/speaker bureaus for Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Janssen, Novartis, Sanofi-Genzyme, and TG Therapeutics.RTN: consultant for Abata Therapeutics, Banner Life Sciences, BeiGene, Biogen, Bristol Myers Squibb, Genentech, Genzyme, GW Therapeutics, Janssen, Horizon Therapeutics, Lundbeck, NervGen, and TG Therapeutics.DN: research support from and consultant/advisory boards/speaker bureaus for Adamas, Alkermes, Alexion, Bayer, Biogen, Celgene/BMS, EMD Serono, Janssen, Novartis, Roche-Genentech, and Sanofi-Genzyme.JO: research support from Biogen Idec, EMD Serono, and Roche and personal compensation for consulting/speaking from Biogen Idec, BMS, EMD Serono, Eli Lilly, Roche, Sanofi-Genzyme, and Novartis.MAHP: consultant/advisory boards/speaker bureaus for Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Janssen, Novartis, Sanofi-Genzyme, and TG Therapeutics.KS: research support from Merck; advisory boards for Biogen, Celgene/BMS, Merck, Novartis, Roche, Sanofi, and TG Therapeutics.FTB: research support and travel grants, through his institution, from the German Science Fund (DFG), German Federal Ministry of Education and Science (BMBF), Bayer-Schering, Merck, Novartis, Pfizer, Roche, Sanofi, and Teva and speaker fees from and advisory boards for Actelion, Alexion, Bayer, Biogen, CSL Behring, Fresenius, Horizon, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva.AW: adviser fees from AbbVie and research support from AbbVie, Alkermes, and Biogen.TZ: personal compensation for consulting services and speaker honoraria from Bayer, Biogen Idec, Novartis, Sanofi, Synthon, and Teva and financial support for research activities from Bayer, Biogen Idec, Novartis, Sanofi-Aventis, and Teva.WC-B, HC, SL, MS, SLS, and TW: employees of and hold stock/stock options in Biogen.SW: consulting fees from and advisory boards for Biogen, Celgene, and EMD Serono; speaker bureaus for Biogen, Celgene, EMD Serono, Roche-Genentech, and Sanofi-Genzyme; and research support from Biogen, Celgene, EMD Serono, Novartis, Receptos, Roche-Genentech, Sanofi-Genzyme, and TG.

Background: Alemtuzumab is a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS), and immune thrombocytopenia (ITP) has been identified as a risk., Objective: To examine ITP incidence, treatment, and outcomes during the clinical development of alemtuzumab for RRMS and discuss postmarketing experience outside clinical trials., Methods: CAMMS223 and Comparison of Alemtuzumab and Rebif ® Efficacy in Multiple Sclerosis (CARE-MS) I and II investigated two annual courses of alemtuzumab 12 mg (or 24 mg in CAMMS223/CARE-MS II) versus subcutaneous interferon beta-1a three times per week. Patients completing core studies could enroll in an extension. Monthly monitoring for ITP continued until 48 months after the last alemtuzumab infusion., Results: Of 1485 alemtuzumab-treated MS patients in the clinical development program, 33 (2.2%) developed ITP (alemtuzumab 12 mg, 24 [2.0%]; alemtuzumab 24 mg, 9 [3.3%]) over median 6.1 years of follow-up after the first infusion; most had a sustained response to first-line ITP therapy with corticosteroids, platelets, and/or intravenous immunoglobulin. All cases occurred within 48 months of the last alemtuzumab infusion. Postmarketing surveillance data suggest that the ITP incidence is not higher in clinical practice than in clinical trials., Conclusion: Alemtuzumab-associated ITP occurs in approximately 2% of patients and is responsive to therapy. Careful monitoring is key for detection and favorable outcomes.