A randomised, double-blind, placebo-controlled trial of lenalidomide in the treatment of moderately severe active Crohn's disease

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Alimentary Pharmacology & Therapeutics

OnlineAccepted Articles

To cite this article: J. C. MANSFIELD, M. PARKES, A. B. HAWTHORNE, A. FORBES, C. S. J. PROBERT, R. C. PEROWNE, A. COOPER, J. B. ZELDIS, D. C. MANNING, C. J. HAWKEY A randomised, double-blind, placebo-controlled trial of lenalidomide in the treatment of moderately severe active Crohn's disease Alimentary Pharmacology & Therapeutics (OnlineAccepted Articles). doi:10.1111/j.1365-2036.2007.03385.x

Abstract

A randomised, double-blind, placebo-controlled trial of lenalidomide in the treatment of moderately severe active Crohn's disease

J. C. MANSFIELD11Department of Gastroenterology, Royal Infirmary, Newcastle upon Tyne, NE1 4LP, UK, M. PARKES22Addenbrookes Hospital, Cambridge, CB2 2QQ, UK, A. B. HAWTHORNE33Department of Medicine, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK, A. FORBES44University College Hospital, 235 Euston Road, London, NW1 2BU, UK. (Previously at St Mark's Hospital, Harrow.), C. S. J. PROBERT55Department of Gastroenterology, Bristol Royal Infirmary, Bristol, BS2 8HW, UK, R. C. PEROWNE11Department of Gastroenterology, Royal Infirmary, Newcastle upon Tyne, NE1 4LP, UK, A. COOPER66Celgene Corporation, Summit, New Jersey 07901, USA, J. B. ZELDIS66Celgene Corporation, Summit, New Jersey 07901, USA, D. C. MANNING66Celgene Corporation, Summit, New Jersey 07901, USA & C. J. HAWKEY77Division of Gastroenterology, Queens Medical Centre, Nottingham, NG7 2UH, UK

1Department of Gastroenterology, Royal Infirmary, Newcastle upon Tyne, NE1 4LP, UK 2Addenbrookes Hospital, Cambridge, CB2 2QQ, UK 3Department of Medicine, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK 4University College Hospital, 235 Euston Road, London, NW1 2BU, UK. (Previously at St Mark's Hospital, Harrow.) 5Department of Gastroenterology, Bristol Royal Infirmary, Bristol, BS2 8HW, UK 6Celgene Corporation, Summit, New Jersey 07901, USA 7Division of Gastroenterology, Queens Medical Centre, Nottingham, NG7 2UH, UK

Address for Correspondence: Dr MansfieldConsultant Physician,Department of Gastroenterology,Royal Infirmary,Newcastle upon Tyne,NE1 4LP, UKTel 0191 2820135Fax 0191 2820523e.mail: john.mansfield@...

Summary

Background

Therapy targeted at TNFα has an established role in Crohn's disease. Lenalidomide, an analogue of thalidomide, is an oral immunomodulatory agent with powerful anti-TNFα properties. It is licensed for myeloma and myelodysplastic syndrome. Based upon reports of thalidomide efficacy, lenalidomide was evaluated in Crohn's disease.

Aim

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 randomised to lenalidomide 25mg daily, 5mg daily or placebo. Subjects were treated for 12 weeks. The primary endpoint was a 70 point reduction in CDAI.

Results

The overall clinical response rate was not significantly different between the 3 groups: lenalidomide 25 mg 26%, lenalidomide 5mg 48% and placebo 39%. Lenalidomide was generally well tolerated with only one serious adverse event, a deep vein thrombosis, being attributed to treatment.

Conclusion

Lenalidomide, an oral agent with anti TNFα 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 anti-TNFα action without apoptosis may be insufficient for activity in Crohn's disease.