title: A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study.
abstract: BACKGROUND
  CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®). The aim of this study was to compare the 54-week efficacy, immunogenicity, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of CT-P13 and RP in patients with active rheumatoid arthritis (RA).
  
  
  METHODS
  In this multinational phase III double-blind study, patients with active RA and an inadequate response to methotrexate (MTX) were randomized (1:1) to receive CT-P13 (3 mg/kg) or RP (3 mg/kg) at weeks 0, 2, 6 and then every 8 weeks to week 54 in combination with MTX (12.5-25 mg/week). Efficacy endpoints included American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates, Disease Activity Score in 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), European League Against Rheumatism (EULAR) response rates, patient-reported outcomes and joint damage progression. Immunogenicity, safety and PK/PD outcomes were also assessed.
  
  
  RESULTS
  Of 606 randomized patients, 455 (CT-P13 233, RP 222) were treated up to week 54. At week 54, ACR20 response rate was highly similar between groups (CT-P13 74.7 %, RP 71.3 %). ACR50 and ACR70 response rates were also comparable between groups (CT-P13 43.6 % and 21.3 %, respectively; RP 43.1 % and 19.9 %, respectively). DAS28, SDAI and CDAI decreased from baseline to week 54 to a similar extent with CT-P13 and RP. Radiographic progression measured by Sharp scores as modified by van der Heijde was also comparable. With both treatments, patient assessments of pain, disease activity and physical ability, as well as mean scores on the Medical Outcomes Study Short Form Health Survey (SF-36), improved markedly at week 14 and remained stable thereafter up to week 54. The proportion of patients positive for antidrug antibodies at week 54 was similar between the two groups: 41.1 % and 36.0 % with CT-P13 and RP, respectively. CT-P13 was well tolerated and had a similar safety profile to RP. PK/PD results were also comparable between CT-P13 and RP.
  
  
  CONCLUSIONS
  CT-P13 and RP were comparable in terms of efficacy (including radiographic progression), immunogenicity and PK/PD up to week 54. The safety profile of CT-P13 was also similar to that of RP.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01217086 . Registered 4 Oct 2010.
authors.affiliation: Hanyang University Hospital, Seoul, Republic of Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Yoo
authors.affiliation: NZOZ Osteo-Medic, Bialystok, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Racewicz
authors.affiliation: Wojewodzki Szpital Zespolony, Elblag, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Brzezicki
authors.affiliation: Ivano-Frankivsk Regional Clinical Hospital, Ivano-Frankivsk, Ukraine.
authors.forename: Roman
authors.initials: R
authors.lastname: Yatsyshyn
authors.affiliation: Hospital Militar Central, Bogota, Colombia.
authors.forename: Edgardo Tobias
authors.initials: ET
authors.lastname: Arteaga
authors.affiliation: Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Asta
authors.initials: A
authors.lastname: Baranauskaite
authors.affiliation: Hospital Central Dr. Ignacio Morones Prieto, San Luis Potosi, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Abud-Mendoza
authors.affiliation: St. Luke's Medical Center, Quezon City, Philippines.
authors.forename: Sandra
authors.initials: S
authors.lastname: Navarra
authors.affiliation: University Hospital St. Marina, Varna, Bulgaria.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kadinov
authors.affiliation: Prosalud y Cia Ltda, Santiago, Chile.
authors.forename: Irmgadt Goecke
authors.initials: IG
authors.lastname: Sariego
authors.affiliation: CELLTRION, Incheon, Republic of Korea.
authors.forename: Seung Suh
authors.initials: SS
authors.lastname: Hong
authors.affiliation: CELLTRION, Incheon, Republic of Korea.
authors.forename: Sung Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Inha University Hospital, Incheon, Republic of Korea. parkwon@inha.ac.kr.
authors.forename: Won
authors.initials: W
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C000591237:CT-P13; D000069285:Infliximab
keywords: ACR20; Biosimilar; CT-P13; Efficacy; Immunogenicity; Infliximab; Pharmacokinetics; Rheumatoid arthritis; Safety; Sharp score