Monday, January 23, 2012

Efficacy and Safety of Apremilast, An Oral Phosphodiesterase Inhibitor, in Ankylosing Spondylitis

We recently talked about an oral phosphodiesterase inhibitor on the net, though we talked about an off label use of an old drug. This weekend I attended the TNF alpha Forum at Munich and someone mentioned an abstract from the 2011 ACR meeting at Chicago, which I had overlooked. But here it is.

E. Pathan and colleagues investigated apremilast in patients suffering from ankylosing spondylitis. Apremilast inhibits phosphodiesterase-4, increasing intracellular cAMP and consecutively modulates multiple pro- and anti-inflammatory mediators. “Treatment was assessed using Bath indices over 12 weeks, followed by a 4-week observation phase.” “Plasma levels of sclerostin and serum levels of RANKL and OPG were measured by ELISA at baseline and after 12 weeks of therapy.” The authors observed a trend in BASDAI, BASFI, BASMI, BASG, but couldn’t show significant chances, which might be due to the some number of patients (verum: N=17, placebo: N=19). However, they showed a significant change from baseline in levels of sclerostin and RANKL. The authors concluded, that this small pilot study shows encouraging data, which warrant further research of apremilast in axial inflammation.

Apremilast has a long way to go, however. As low sclerostin is associated with the formation of spondylophytes, one will have to look very careful in long term outcomes.


Efficacy and Safety of Apremilast, An Oral Phosphodiesterase Inhibitor, in Ankylosing Spondylitis.

E. Pathan1, S.M Abraham1, L. Van-Rossen2, Robin Withrington3, AC Keat4, Peter J. Charles5, E. Paterson5, Muslima Chowdhury6, L. Hastings1, A. Fox1, C. McClinton1 and Peter Taylor7.

1Kennedy Institute of Rheumatology, London W6 8RF, United Kingdom, 2Kent and Canterbury Hospital, Canterbury, Kent CT1 3NG, United Kingdom, 3Kent & Canterbury Hosp, Canterbury, United Kingdom, 4Northwick Park Hospital, Harrow, United Kingdom, 5Kennedy Institute of Rheumatology, Imperial College, London, United Kingdom, London, England, 6Imperial College London, London, United Kingdom, 7Kennedy Institute of Rheumatology, London, United Kingdom

Conclusion: Although a small pilot study, these results show that APR may be effective and well tolerated in AS and modulates biomarkers of bone biology. Given the current lack of oral DMARDs for AS, these encouraging pilot data support further research of APR in axial inflammation.

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