A randomized, double-blind, placebo-controlled trial of lenalidomide in the treatment of moderately severe active Crohn's disease.
BACKGROUND
Therapy targeted at tumour necrosis factor-alpha has an established role in Crohn's disease. Lenalidomide, an analogue of thalidomide, is an oral immunomodulatory agent with powerful antitumour necrosis factor-alpha properties. It is licensed for myeloma and myelodysplastic syndrome. Based upon reports of thalidomide efficacy, lenalidomide was evaluated in Crohn's disease.


OBJECTIVE
To evaluate the efficacy and safety of lenalidomide in subjects with moderately severe active Crohn's disease.


METHODS
In a multicentre, double-blind, placebo-controlled parallel group study 89 subjects were randomized to lenalidomide 25 mg daily, 5 mg daily or placebo. Subjects were treated for 12 weeks. The primary end point was a 70-point reduction in Crohn's Disease Activity Index.


RESULTS
The overall clinical response rate was not significantly different between the three groups: lenalidomide 25 mg 26%, lenalidomide 5 mg 48% and placebo 39%. Lenalidomide was generally well tolerated with only one serious adverse event, a deep vein thrombosis, being attributed to treatment.


CONCLUSIONS
Lenalidomide, an oral agent with antitumour necrosis factor-alpha properties, was not effective in active Crohn's disease in contrast to reports of benefit from thalidomide. The reasons for this lack of efficacy are speculative, other physiological activities may offset its action on inflammatory cytokines, or its antitumour necrosis factor-alpha action without apoptosis may be insufficient for activity in Crohn's disease.
Mansfield
J C
JC
Department of Gastroenterology, Royal Victoria Infirmary, Newcastle upon Tyne, UK. john.mansfield@nuth.northy.nhs.uk
Parkes
M
M
Hawthorne
A B
AB
Forbes
A
A
Probert
C S J
CS
Perowne
R C
RC
Cooper
A
A
Zeldis
J B
JB
Manning
D C
DC
Hawkey
C J
CJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012720:Severity of Illness Index; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000139:chemically induced
D007166:Immunosuppressive Agents; D010919:Placebos; D013792:Thalidomide; D000077269:Lenalidomide