title: Efficacy, safety, and tolerability of fulranumab, an anti-nerve growth factor antibody, in the treatment of patients with moderate to severe osteoarthritis pain.
abstract: Nerve growth factor (NGF) is increased in chronic pain conditions. This study examined analgesic efficacy and safety of fulranumab, a fully human monoclonal anti-NGF antibody, in adults with chronic osteoarthritis pain. Patients (n=466, intent-to-treat) were randomized to receive, in addition to their current pain therapy, subcutaneous injections in 1 of 6 parallel treatment groups: placebo (n=78), fulranumab 1 mg (n=77) or 3 mg (n=79) every 4 weeks (Q4wk), 3 mg (n=76), 6 mg (n=78), or 10 mg (n=78) every 8 weeks (Q8wk). Primary efficacy results showed that fulranumab significantly reduced the average pain intensity score (P < or = 0.030) from baseline to week 12 compared with placebo in the 3mgQ4wk, 6mgQ8wk, and 10mgQ8wk groups. Secondary efficacy outcomes indicated that significant improvement occurred compared with placebo at week 12 on the Western Ontario and McMaster Universities Osteoarthritis Index subscales of pain, stiffness, and physical function (P < 0.040) across all fulranumab groups except 1mgQ4wk, on the Brief Pain Inventory-Short Form subscales of pain intensity (P < or = 0.016) and pain interference (P < or = 0.030) in the 3mgQ4wk and 10mgQ8wk groups, and on the Patient Global Assessment score (P < or = 0.040) in the 3mgQ4wk, 6mgQ8wk, and 10mgQ8wk groups. The most common (> or = 5% of patients) treatment-emergent adverse events in overall fulranumab groups during the first 12weeks included paresthesia (7%), headache (5%), and nasopharyngitis (5%). Most neurologic-related treatment-emergent adverse events were mild or moderate and resolved at the end of week 12. Serious adverse events occurred in 3 patients, but they were not neurologically related and resolved before study completion. Fulranumab treatment resulted in statistically significant efficacy in pain measures and physical function versus placebo and was generally well tolerated.
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA Analgesic Solutions, Natick, MA, USA Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Panna
authors.initials: P
authors.lastname: Sanga
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Katz
authors.forename: Elena
authors.initials: E
authors.lastname: Polverejan
authors.forename: Steven
authors.initials: S
authors.lastname: Wang
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Kelly
authors.forename: Juergen
authors.initials: J
authors.lastname: Haeussler
authors.forename: John
authors.initials: J
authors.lastname: Thipphawong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement / Q000379:methods; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D020932:Nerve Growth Factor
keywords: Efficacy; Fulranumab; Nerve growth factor; Osteoarthritis pain; Safety