Long-term safety and tolerability of bimagrumab (BYM338) in sporadic inclusion body myositis.

Autor:	Sivakumar K; From the Neuromuscular Research Center (K.S.), Phoenix, AZ; Department of Neurology (T.I.C., A.A.A), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Novartis Institutes for BioMedical Research (B.S., D.L.), Basel, Switzerland; Novartis Healthcare Pvt Ltd (H.A.), Hyderabad, India; Novartis Pharma AG (L.B.T), Basel, Switzerland. Dr. Cochrane is now at Biogen Inc, Cambridge, MA. Dr. Sloth is now at Novo Nordisk, Copenhagen, Denmark. ksiva@nrcaz.com., Cochrane TI; From the Neuromuscular Research Center (K.S.), Phoenix, AZ; Department of Neurology (T.I.C., A.A.A), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Novartis Institutes for BioMedical Research (B.S., D.L.), Basel, Switzerland; Novartis Healthcare Pvt Ltd (H.A.), Hyderabad, India; Novartis Pharma AG (L.B.T), Basel, Switzerland. Dr. Cochrane is now at Biogen Inc, Cambridge, MA. Dr. Sloth is now at Novo Nordisk, Copenhagen, Denmark., Sloth B; From the Neuromuscular Research Center (K.S.), Phoenix, AZ; Department of Neurology (T.I.C., A.A.A), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Novartis Institutes for BioMedical Research (B.S., D.L.), Basel, Switzerland; Novartis Healthcare Pvt Ltd (H.A.), Hyderabad, India; Novartis Pharma AG (L.B.T), Basel, Switzerland. Dr. Cochrane is now at Biogen Inc, Cambridge, MA. Dr. Sloth is now at Novo Nordisk, Copenhagen, Denmark., Ashar H; From the Neuromuscular Research Center (K.S.), Phoenix, AZ; Department of Neurology (T.I.C., A.A.A), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Novartis Institutes for BioMedical Research (B.S., D.L.), Basel, Switzerland; Novartis Healthcare Pvt Ltd (H.A.), Hyderabad, India; Novartis Pharma AG (L.B.T), Basel, Switzerland. Dr. Cochrane is now at Biogen Inc, Cambridge, MA. Dr. Sloth is now at Novo Nordisk, Copenhagen, Denmark., Laurent D; From the Neuromuscular Research Center (K.S.), Phoenix, AZ; Department of Neurology (T.I.C., A.A.A), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Novartis Institutes for BioMedical Research (B.S., D.L.), Basel, Switzerland; Novartis Healthcare Pvt Ltd (H.A.), Hyderabad, India; Novartis Pharma AG (L.B.T), Basel, Switzerland. Dr. Cochrane is now at Biogen Inc, Cambridge, MA. Dr. Sloth is now at Novo Nordisk, Copenhagen, Denmark., Tankó LB; From the Neuromuscular Research Center (K.S.), Phoenix, AZ; Department of Neurology (T.I.C., A.A.A), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Novartis Institutes for BioMedical Research (B.S., D.L.), Basel, Switzerland; Novartis Healthcare Pvt Ltd (H.A.), Hyderabad, India; Novartis Pharma AG (L.B.T), Basel, Switzerland. Dr. Cochrane is now at Biogen Inc, Cambridge, MA. Dr. Sloth is now at Novo Nordisk, Copenhagen, Denmark., Amato AA; From the Neuromuscular Research Center (K.S.), Phoenix, AZ; Department of Neurology (T.I.C., A.A.A), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Novartis Institutes for BioMedical Research (B.S., D.L.), Basel, Switzerland; Novartis Healthcare Pvt Ltd (H.A.), Hyderabad, India; Novartis Pharma AG (L.B.T), Basel, Switzerland. Dr. Cochrane is now at Biogen Inc, Cambridge, MA. Dr. Sloth is now at Novo Nordisk, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2020 Oct 06; Vol. 95 (14), pp. e1971-e1978. Date of Electronic Publication: 2020 Jul 20.
DOI:	10.1212/WNL.0000000000010417
Abstrakt:	Objective: To assess the long-term safety and tolerability and to monitor benefits of extended use of bimagrumab in individuals with sporadic inclusion body myositis (sIBM) who completed a single-dose core study. Methods: In this multicenter, open-label extension study, 10 adults received bimagrumab 10 mg/kg IV every 4 weeks up to 2 years (104 weeks). Safety (primary endpoint) was assessed by recording adverse events (AEs). Clinical benefits were assessed by changes from baseline in thigh muscle volume (TMV), lean body mass (LBM), 6-minute walk distance (6MWD), handgrip, and quadriceps strength. Results: Participants had a mean age of 70.1 (SD 10.4) years. All participants (n = 10) discontinued the treatment due to early termination of the study (n = 7) or AEs (n = 3; myocardial infarction, esophageal carcinoma, and dementia, none of which were treatment related). The most common AEs were muscle spasms and falls (both 9 of 10, 90%), followed by diarrhea (6 of 10, 60%) and acne and skin eruption (both 5 of 10, 50%). At weeks 8 and 16, mean TMV increased from baseline by 4.1% (SD 4.3%) and 4.5% (SD 6.3%). Mean LBM increased from baseline and was sustained at 6.9% (SD 3.9%) at week 76. Means of 6MWD showed a progressive decline from baseline to week 76, during which there was a modest numerical increase in handgrip strength and no significant changes in quadriceps strength. Conclusions: Long-term treatment up to 2 years with bimagrumab had a good safety profile and was well tolerated in individuals with sIBM. An increase in muscle mass was noted on a group level; however, there was no evidence of clinical improvement. Clinicaltrialsgov Identifier: NCT02250443. Classification of Evidence: This study provides Class IV evidence that for patients with sIBM, long-term bimagrumab treatment was safe and well tolerated and did not lead to functional improvement. (© 2020 American Academy of Neurology.)
Databáze:	MEDLINE
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