title: Long-Term Safety and Efficacy of Fulranumab in Patients With Moderate-to-Severe Osteoarthritis Pain: A Phase II Randomized, Double-Blind, Placebo-Controlled Extension Study.
abstract: To evaluate the long-term safety and efficacy of fulranumab in patients with knee or hip pain caused by moderate-to-severe chronic osteoarthritis (OA).
  
  
  
  In this phase II double-blind, placebo-controlled extension study, patients who were randomized in equal proportions to receive subcutaneous doses of either placebo or fulranumab (1 mg every 4 weeks, 3 mg every 8 weeks, 3 mg every 4 weeks, 6 mg every 8 weeks, or 10 mg every 8 weeks) in the 12-week double-blind efficacy phase and who completed this double-blind efficacy phase were eligible to continue the dosage throughout a 92-week double-blind extension phase, followed by a 24-week posttreatment follow-up period. Safety assessments included evaluation of treatment-emergent adverse events (TEAEs), pre-identified AEs of interest, and joint replacements. Efficacy assessments included changes from baseline to the end of the double-blind extension phase in scores on the patient's global assessment and the pain and physical function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index.
  
  
  
  Overall, 401 of the 423 patients who completed the 12-week double-blind efficacy phase entered the extension study. Long-term sustained improvements were observed in all efficacy parameters following fulranumab treatment (1 mg every 4 weeks, 3 mg every 4 weeks, and 10 mg every 8 weeks) as compared with placebo. Similar percentages of patients in both groups experienced TEAEs (88% taking placebo and 91% taking fulranumab; all phases). Across all fulranumab groups, arthralgia (21%) and OA (18%) (e.g., exacerbation of OA pain) were the most common TEAEs. The most common serious TEAEs were the requirement for knee (10%) and hip (7%) arthroplasty, with 80% occurring during the posttreatment follow-up period. Neurologic-related TEAEs (28%; all phases) were generally mild-to-moderate. Overall, 81 joint replacements were performed in 71 patients (8 [11%] receiving placebo and 63 [89%] receiving fulranumab); 15 patients (21%) had rapid progression of OA (RPOA). All cases of RPOA occurred in fulranumab-treated patients who were concurrently receiving nonsteroidal antiinflammatory drugs and occurred in joints with preexisting OA.
  
  
  
  Long-term treatment with fulranumab was generally well-tolerated and efficacious. RPOA was observed as a safety signal. Future studies are warranted to demonstrate whether the risk of RPOA can be reduced in patients taking fulranumab.
authors.affiliation: Janssen Research & Development, Titusville, New Jersey.
authors.forename: Panna
authors.initials: P
authors.lastname: Sanga
authors.affiliation: Analgesic Solutions, Natick, Massachusetts, and Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Katz
authors.affiliation: Janssen Research & Development, Titusville, New Jersey.
authors.forename: Elena
authors.initials: E
authors.lastname: Polverejan
authors.affiliation: Janssen Research & Development, Titusville, New Jersey.
authors.forename: Steven
authors.initials: S
authors.lastname: Wang
authors.affiliation: Janssen Research & Development, Titusville, New Jersey.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Kelly
authors.affiliation: Janssen Research & Development, Titusville, New Jersey.
authors.forename: Juergen
authors.initials: J
authors.lastname: Haeussler
authors.affiliation: Janssen Research & Development, Titusville, New Jersey.
authors.forename: John
authors.initials: J
authors.lastname: Thipphawong
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000150:complications / Q000188:drug therapy*; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C000592179:fulranumab