Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


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

Pathan1,  E., Abraham1,  S.M, Van-Rossen2,  L., Withrington3,  Robin, Keat4,  AC, Charles5,  Peter J., Paterson5,  E.

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

Background/Purpose:

Apremilast (APR) is a novel, orally available small molecule that specifically inhibits phosphodiesterase-4, increasing intracellular cAMP and thus modulates multiple pro- and anti-inflammatory mediators. APR has been shown to significantly improve PASI-75 and ACR 20 in subjects with psoriasis and psoriatic arthritis, respectively.

Objectives:

To evaluate the efficacy and safety of APR by monitoring changes in signs and symptoms in a pilot study of patients with ankylosing spondylitis (AS) and to investigate the effect of APR on blood levels of sclerostin, Receptor Activator of NFkB Ligand (RANKL) and Osteoprotegrin (OPG) as biomarkers of bone biology in this cohort.

Methods:

This was a double-blind, Placebo (PBO)-controlled Phase II unpowered pilot study in AS patients, symptomatic for >=2 years, uncontrolled on conventional non-steroidal anti-inflammatory drugs and with daily spinal pain and stiffness for >=2 weeks before being randomised equally to oral APR 30 mg BID, titrated over 5 days, or PBO. Treatment was assessed using Bath indices over 12 weeks, followed by a 4-week observation phase. Results were compared at each time point using analysis of co-variance (ANCOVA).

Plasma levels of sclerostin and serum levels of RANKL and OPG were measured by ELISA at baseline and after 12 weeks of therapy. Differences in the 2 treatment groups were expressed as percentage change from baseline and compared using the Mann Whitney U test.

Results:

38 subjects were randomised (safety population) and 36 subjects had >=1 post-baseline assessment (intent-to-treat population) and completed the study. At week 12, APR was associated with a trend to greater mean improvement from baseline for all clinical assessments compared with PBO (Table). There was a significant mean percentage change from baseline in levels of Sclerostin and RANKL, but not of OPG levels, in the APR group vs PBO.

Clinical ParameterMean change from baseline (SD)p value (ANCOVA)
 Apremilast (n = 17)Placebo (n = 19) 
BASDAI-1.59 (1.48)-0.77 (1.47)0.139
BASFI-1.74 (1.91)-0.28 (1.61)0.108 (non-parametric)
BASMI-1.36 (2.35)-0.17 (2.83)0.166
BASG-0.51 (1.02)-0.21 (0.67)0.617
Laboratory markerMean percentage change from baseline (SD) [No change = 100%]p value (Mann Whitney U test)
RANKL73.2 (30.9)108.2 (32.01)0.016
OPG97.8 (18.3)92.8 (18.8)0.41
RANKL:OPG78.3 (33.8)108.5 (34.6)0.08
Sclerostin84.8 (23.03)110.1 (32.68)0.011

More APR-treated vs PBO subjects reported loose stools (26.3% vs 10.5%) and headache (42.1% vs 26.3%), but there was no relevant difference in the incidence of diarrhoea, nausea and upper respiratory tract infections: 10.5%, 15.8% and 31.6%, respectively. There were no serious AEs reported.

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.

To cite this abstract, please use the following information:
Pathan, E., Abraham, S.M, Van-Rossen, L., Withrington, Robin, Keat, AC, Charles, Peter J., et al; Efficacy and Safety of Apremilast, An Oral Phosphodiesterase Inhibitor, in Ankylosing Spondylitis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1652
DOI:

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