title: Safety and efficacy of ustekinumab or golimumab in patients with chronic sarcoidosis.
abstract: Sarcoidosis is characterised by non-caseating granulomas that secrete pro-inflammatory cytokines, including interleukin (IL)-12, IL-23, and tumour necrosis factor (TNF)-α. Ustekinumab and golimumab are monoclonal antibodies that specifically inhibit IL-12/IL-23 and TNF-α, respectively. Patients with chronic pulmonary sarcoidosis (lung group) and/or skin sarcoidosis (skin group) received either 180 mg ustekinumab at week 0 followed by 90 mg every 8 weeks, 200 mg golimumab at week 0 followed by 100 mg every 4 weeks, or placebo. Patients underwent corticosteroid tapering between weeks 16 and 28. The primary end-point was week 16 change in percentage predicted forced vital capacity (ΔFVC % pred) in the lung group. Major secondary end-points were: week 28 for ΔFVC % pred, 6-min walking distance, St George's Respiratory Questionnaire (lung group), and Skin Physician Global Assessment response (skin group). At week 16, no significant differences were observed in ΔFVC % pred with ustekinumab (-0.15, p = 0.13) or golimumab (1.15, p = 0.54) compared with placebo (2.02). At week 28, there were no significant improvements in the major secondary end-points, although a nonsignificant numerically greater Skin Physician Global Assessment response was observed following golimumab treatment (53%) when compared with the placebo (30%). Serious adverse events were similar in all treatment groups. Although treatment was well tolerated, neither ustekinumab nor golimumab demonstrated efficacy in pulmonary sarcoidosis. However, trends towards improvement were observed with golimumab in some dermatological end-points.
authors.affiliation: Dept of Medicine, Albany Medical College, Albany, NY, USA judsonm@mail.amc.edu.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Judson
authors.affiliation: Dept of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Baughman
authors.affiliation: Ruhrlandklinik and University of Duisburg-Essen, Essen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
authors.affiliation: Dept of Interstitial Lung Diseases, Gelderse Vallei Hospital, Ede, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Drent
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Gibson
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raghu
authors.affiliation: University of Southern California, Los Angeles, CA, USA Division of Pulmonary and Critical Care Medicine, University of Nevada School of Medicine, Las Vegas, NV, USA.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Shigemitsu
authors.affiliation: Pulmonary and Critical Care Medicine, University of Alabama, Birmingham, AL, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Barney
authors.affiliation: Pulmonary, Allergy and Critical Care Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Culver
authors.affiliation: Dept of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Nabeel Y
authors.initials: NY
authors.lastname: Hamzeh
authors.affiliation: Dept of Pulmonary Disease, Erasmus MC, University Hospital Rotterdam, Rotterdam, The Netherlands.
authors.forename: Marlies S
authors.initials: MS
authors.lastname: Wijsenbeek
authors.affiliation: Dept of Pulmonary Medicine, Erasmus Medical Centre, University Hospital Rotterdam, Rotterdam, The Netherlands.
authors.forename: Carlo
authors.initials: C
authors.lastname: Albera
authors.affiliation: Dept of Medicine, Texas Tech University Health Science Center, Lubbock, TX, USA.
authors.forename: Isham
authors.initials: I
authors.lastname: Huizar
authors.affiliation: Biostatistics, Janssen Research and Development, LLC, Spring House, PA, USA.
authors.forename: Prasheen
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Immunology Biomarkers, Janssen Research and Development, LLC, Spring House, PA, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Brodmerkel
authors.affiliation: Immunology, Janssen Research and Development, LLC, Spring House, PA, USA.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Watt
authors.affiliation: Immunology, Janssen Research and Development, LLC, Spring House, PA, USA.
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Barnathan
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000037:antagonists & inhibitors; D053759:Interleukin-23 / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D012507:Sarcoidosis / Q000188:drug therapy* / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000069549:Ustekinumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D053759:Interleukin-23; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C529000:golimumab; D000069549:Ustekinumab