25042199
BACKGROUND	Multicentric Castleman 's disease is a rare lymphoproliferative disorder driven by dysregulated production of interleukin 6 .
BACKGROUND	No randomised trials have been done to establish the best treatment for the disease .
BACKGROUND	We assessed the safety and efficacy of siltuximab-a chimeric monoclonal antibody against interleukin 6-in HIV-negative patients with multicentric Castleman 's disease .
METHODS	We did this randomised , double-blind , placebo-controlled study at 38 hospitals in 19 countries worldwide .
METHODS	We enrolled HIV-negative and human herpesvirus-8-seronegative patients with symptomatic multicentric Castleman 's disease .
METHODS	Treatment allocation was randomised with a computer-generated list , with block size six , and stratification by baseline corticosteroid use .
METHODS	Patients and investigators were masked to treatment allocation .
METHODS	Patients were randomly assigned ( 2:1 ) to siltuximab ( 11 mg/kg intravenous infusion every 3 weeks ) or placebo ; all patients also received best supportive care .
METHODS	Patients continued treatment until treatment failure .
METHODS	The primary endpoint was durable tumour and symptomatic response for at least 18 weeks for the intention-to-treat population .
METHODS	Enrolment has been completed .
METHODS	The study is registered with ClinicalTrials.gov , number NCT01024036 .
RESULTS	We screened 140 patients , 79 of whom were randomly assigned to siltuximab ( n = 53 ) or placebo ( n = 26 ) .
RESULTS	Durable tumour and symptomatic responses occurred in 18 ( 34 % ) of 53 patients in the siltuximab group and none of 26 in the placebo group ( difference 340 % , 95 % CI 111-548 , p = 00012 ) .
RESULTS	The incidence of grade 3 or more adverse events ( 25 [ 47 % ] vs 14 [ 54 % ] ) and serious adverse events ( 12 [ 23 % ] vs five [ 19 % ] ) was similar in each group despite longer median treatment duration with siltuximab than with placebo ( 375 days [ range 1-1031 ] vs 152 days [ 23-666 ] ) .
RESULTS	The most common grade 3 or higher were fatigue ( five vs one ) , night sweats ( four vs one ) , and anaemia ( one vs three ) .
RESULTS	Three ( 6 % ) of 53 patients had serious adverse events judged reasonably related to siltuximab ( lower respiratory tract infection , anaphylactic reaction , sepsis ) .
CONCLUSIONS	Siltuximab plus best supportive care was superior to best supportive care alone for patients with symptomatic multicentric Castleman 's disease and well tolerated with prolonged exposure .
CONCLUSIONS	Siltuximab is an important new treatment option for this disease .
BACKGROUND	Janssen Research & Development .

