title: Efficacy and Safety of Anti-Interleukin-20 Monoclonal Antibody in Patients With Rheumatoid Arthritis: A Randomized Phase IIa Trial.
abstract: OBJECTIVE
  Interleukin-20 (IL-20) is implicated in the pathogenesis of rheumatoid arthritis (RA). The efficacy, safety, and tolerability of NNC0109-0012, a selective anti-IL-20 recombinant human monoclonal antibody (mAb), were assessed in patients with active RA who had an inadequate response to methotrexate therapy.
  
  
  METHODS
  Sixty-seven patients with RA were enrolled and randomized (2:1) to receive NNC0109-0012 (3 mg/kg per week, subcutaneously) or placebo in a phase IIa, double-blind, 12-week trial with a 13-week followup. The primary end point was change in the Disease Activity Score in 28 joints based on C-reactive protein level (DAS28-CRP) from baseline to week 12.
  
  
  RESULTS
  In patients treated with NNC0109-0012, the primary end point, improvement in the DAS28-CRP at week 12, was achieved (estimated difference -0.88; P = 0.02), with significant improvement starting at week 1. A greater response was observed in seropositive patients (estimated difference -1.66; P < 0.001), which was sustained through 13 weeks of followup, whereas no improvement was noted in patients with seronegative RA. A significant proportion of patients with seropositive RA receiving NNC0109-0012, compared to those receiving placebo, achieved treatment responses according to the American College of Rheumatology 20% (ACR20) (59% versus 21%), ACR50 (48% versus 14%), and ACR70 (35% versus 0%) levels of improvement, and showed greater improvements in the Health Assessment Questionnaire disability index (P = 0.047). The most frequent adverse events reported with NNC0109-0012 were injection site reactions and infections (e.g., herpes, nasopharyngitis, respiratory, and urinary). No serious infections or discontinuations associated with NNC0109-0012 were observed.
  
  
  CONCLUSIONS
  In this phase IIa trial, treatment with NNC0109-0012 (anti-IL-20 mAb) was effective in patients with seropositive RA as early as week 1, with further improvements to week 12. No safety or tolerability concerns were identified with weekly NNC0109-0012 administration.
authors.affiliation: Institute of Rheumatology and 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Šenolt
authors.affiliation: Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Leszczynski
authors.affiliation: Medical Plus, s.r.o., Uherske Hradiste, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Dokoupilová
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Marie
authors.initials: M
authors.lastname: Göthberg
authors.affiliation: Novo Nordisk Inc., Princeton, New Jersey.
authors.forename: Xavier
authors.initials: X
authors.lastname: Valencia
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Brian Bekker
authors.initials: BB
authors.lastname: Hansen
authors.affiliation: Hospital Clinic de Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Cañete
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D000080908:Broadly Neutralizing Antibodies; D002097:C-Reactive Protein / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006561:Herpes Simplex / Q000139:chemically induced; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009304:Nasopharyngitis / Q000139:chemically induced; D010456:Peptides, Cyclic / Q000276:immunology; D012141:Respiratory Tract Infections / Q000139:chemically induced; D012217:Rheumatoid Factor / Q000276:immunology; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000139:chemically induced; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D018501:Antirheumatic Agents; D001323:Autoantibodies; D000080908:Broadly Neutralizing Antibodies; D007378:Interleukins; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; C000600094:Fletikumab; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; C422042:interleukin 20