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OBJECTIVES: To evaluate the efficacy and safety of an oral phosphodiesterase 4 inhibitor, apremilast, in treatment of ankylosing spondylitis (AS) by monitoring symptoms and signs in a pilot study including exploratory investigation of effects of PDE4 inhibition on blood biomarkers of bone biology. METHODS: In this double-blind, placebo-controlled, single-centre, Phase II study, patients with symptomatic AS with active disease on MRI were randomised to apremilast 30 mg BID or placebo over 12 weeks. Bath Indices were monitored serially. Patients were followed for 4 weeks after stopping medication. Bone biomarkers were assessed at baseline and day 85. RESULTS: 38 subjects were randomised and 36 subjects completed the study. Although the primary end-point (change in BASDAI at week 12) was not met, apremilast was associated with numerically greater improvement from baseline for all clinical assessments compared with placebo with mean change in BASDAI (-1.59±1.48 vs -0.77±1.47), BASFI (-1.74±1.91 vs -0.28±1.61) and BASMI (-0.51±1.02 vs -0.21±0.67); however, differences did not achieve statistical significance. The clinical indices returned to baseline values by 4 weeks after cessation of apremilast. Six apremilast patients (35.3%) vs 3 placebo (15.8%) achieved ASAS20 responses (p=0.25). There were statistically significant decreases in serum RANKL and RANKL:osteoprotegrin ratio and plasma sclerostin but no significant changes in serum DKK-1, bone alkaline phosphatase, TRAP5b, MMP3, osteoprotegrin, or osteocalcin. CONCLUSIONS: Although a small pilot study, these results suggest that apremilast may be effective and well tolerated in AS and modulates biomarkers of bone biology. These data support further research of apremilast in axial inflammation.

Original publication

DOI

10.1136/annrheumdis-2012-201915

Type

Journal article

Journal

Annals of the rheumatic diseases

Publication Date

09/2013

Volume

72

Pages

1475 - 1480

Addresses

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, London, UK.

Keywords

Bone and Bones, Humans, Spondylitis, Ankylosing, Thalidomide, Bone Morphogenetic Proteins, Anti-Inflammatory Agents, Non-Steroidal, Biological Markers, Genetic Markers, Disability Evaluation, Treatment Outcome, Administration, Oral, Severity of Illness Index, Pilot Projects, Double-Blind Method, Health Status, Adult, Aged, Middle Aged, Female, Male, RANK Ligand, Osteoprotegerin, Phosphodiesterase 4 Inhibitors