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: Marc A Judson, Robert P Baughman, Ulrich Costabel, Marjolein Drent, Kevin F Gibson, Ganesh Raghu, Hidenobu Shigemitsu, Joseph B Barney, Daniel A Culver, Nabeel Y Hamzeh, Marlies S Wijsenbeek, Carlo Albera, Isham Huizar, Prasheen Agarwal, Carrie Brodmerkel, Rosemary Watt, Elliot S Barnathan
• Journal: The European respiratory journal (Eur Respir J) Vol. 44 Issue 5 Pg. 1296-307 (Nov 2014) ISSN: 1399-3003 [Electronic] England
• PMID: 25034562 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: ©ERS 2014.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Interleukin-23
• Tumor Necrosis Factor-alpha
• Interleukin-12
• golimumab
• Ustekinumab

Topics

• Adult
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antirheumatic Agents (therapeutic use)
• Chronic Disease
• Double-Blind Method
• Female
• Humans
• Interleukin-12 (antagonists & inhibitors)
• Interleukin-23 (antagonists & inhibitors)
• Male
• Middle Aged
• Sarcoidosis (drug therapy, physiopathology)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)
• Ustekinumab