title: The effects of the spleen tyrosine kinase inhibitor fostamatinib on ambulatory blood pressure in patients with active rheumatoid arthritis: results of the OSKIRA-ABPM (ambulatory blood pressure monitoring) randomized trial.
abstract: Clinical trials of fostamatinib in patients with rheumatoid arthritis showed blood pressure (BP) elevation using clinic measurements. The OSKIRA-ambulatory BP monitoring trial assessed the effect of fostamatinib on 24-hour ambulatory systolic BP (SBP) in patients with active rheumatoid arthritis. One hundred thirty-five patients were randomized to fostamatinib 100 mg twice daily (bid; n = 68) or placebo bid (n = 67) for 28 days. Ambulatory, clinic, and home BPs were measured at baseline and after 28 days of therapy. Primary end point was change from baseline in 24-hour mean SBP. Fostamatinib increased 24-hour mean SBP by 2.9 mm Hg (P = .023) and diastolic BP (DBP) by 3.5 mm Hg (P < .001) versus placebo. Clinic/home-measured BPs were similar to those observed with ambulatory BP monitoring. After treatment discontinuation (1 week), clinic BP values returned to baseline levels. Fostamatinib induced elevations in 24-hour mean ambulatory SBP and DBP. BP elevations resolved with fostamatinib discontinuation.
authors.affiliation: The Dudley Group NHS Foundation Trust, Dudley, UK; Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, UK. Electronic address: gd.kitas@dgoh.nhs.uk.
authors.forename: George D
authors.initials: GD
authors.lastname: Kitas
authors.affiliation: AstraZeneca Research and Development, Mölndal, Sweden.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Abreu
authors.affiliation: Przychodnia Neuromedyka, Żyrardów, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Jedrychowicz-Rosiak
authors.affiliation: SW Florida Clinical Research Center, Tampa, FL, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Miller
authors.affiliation: Former AstraZeneca Research and Development, Mölndal, Sweden.
authors.forename: Roumen
authors.initials: R
authors.lastname: Nakov
authors.affiliation: AstraZeneca Research and Development, Mölndal, Sweden.
authors.forename: Seva
authors.initials: S
authors.lastname: Panfilov
authors.affiliation: Institute of Rheumatology, Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Vencovsky
authors.affiliation: AstraZeneca Research and Development, Macclesfield, Cheshire East, UK.
authors.forename: Millie
authors.initials: M
authors.lastname: Wang
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.affiliation: Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: White
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000631:Aminopyridines; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D018660:Blood Pressure Monitoring, Ambulatory; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009025:Morpholines; D015999:Multivariate Analysis; D010078:Oxazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use*; D011743:Pyrimidines; D012016:Reference Values; D018570:Risk Assessment; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D000631:Aminopyridines; D018501:Antirheumatic Agents; D009025:Morpholines; D010078:Oxazines; D011725:Pyridines; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; C523665:fostamatinib
keywords: Hypertension; spleen tyrosine kinase inhibitor; systolic blood pressure