Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement.
BACKGROUND
Evidence suggests that tumor necrosis factor (TNF)-alpha plays an important role in the pathophysiology of sarcoidosis.


OBJECTIVE
To assess the efficacy of infliximab in sarcoidosis.


METHODS
A phase 2, multicenter, randomized, double-blind, placebo-controlled study was conducted in 138 patients with chronic pulmonary sarcoidosis. Patients were randomized to receive intravenous infusions of infliximab (3 or 5 mg/kg) or placebo at Weeks 0, 2, 6, 12, 18, and 24 and were followed through Week 52.


RESULTS
The primary endpoint was the change from baseline to Week 24 in percent of predicted FVC. Major secondary efficacy parameters included Saint George's Respiratory Questionnaire, 6-min walk distance, Borg's CR10 dyspnea score, and the proportion of Lupus Pernio Physician's Global Assessment responders for patients with facial skin involvement. Patients in the combined infliximab groups (3 and 5 mg/kg) had a mean increase of 2.5% from baseline to Week 24 in the percent of predicted FVC, compared with no change in placebo-treated patients (p = 0.038). No significant differences between the treatment groups were observed for any of the major secondary endpoints at Week 24. Results of post hoc exploratory analyses suggested that patients with more severe disease tended to benefit more from infliximab treatment.


CONCLUSIONS
Infliximab therapy resulted in a statistically significant improvement in % predicted FVC at Week 24. The clinical importance of this finding is not clear. The results of this Phase 2 clinical study support further evaluation of anti-TNF-alpha therapy in severe, chronic, symptomatic sarcoidosis.
Baughman
Robert P
RP
University of Cincinnati Medical Center, Cincinnati, OH 45267, USA. bob.baughman@uc.edu
Drent
Marjolein
M
Kavuru
Mani
M
Judson
Marc A
MA
Costabel
Ulrich
U
du Bois
Roland
R
Albera
Carlo
C
Brutsche
Martin
M
Davis
Gerald
G
Donohue
James F
JF
Müller-Quernheim
Joachim
J
Schlenker-Herceg
Rozsa
R
Flavin
Susan
S
Lo
Kim Hung
KH
Oemar
Barry
B
Barnathan
Elliot S
ES
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D017565:Sarcoidosis, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014797:Vital Capacity / Q000187:drug effects
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D007703:Peptidyl-Dipeptidase A