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Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis
  1. Ejaz Pathan1,
  2. Sonya Abraham2,
  3. Elizabeth Van Rossen3,
  4. Robin Withrington3,
  5. Andrew Keat4,
  6. Peter J Charles1,
  7. Erin Paterson1,
  8. Muslima Chowdhury1,
  9. Catherine McClinton5,
  10. Peter C Taylor5
  1. 1Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, London, UK
  2. 2Faculty of Medicine, Imperial College London, London, UK
  3. 3Department of Physiotherapy, Kent and Canterbury Hospital, Canterbury, Kent, UK
  4. 4Department of Rheumatology, Northwick Park Hospital, Harrow, UK
  5. 5Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Botnar Research Centre, Oxford, UK
  1. Correspondence to Professor Peter C Taylor, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Windmill Road, Headington, Oxford OX3 7LD, UK; peter.taylor{at}kennedy.ox.ac.uk

Abstract

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.

  • Ankylosing Spondylitis
  • Treatment
  • DMARDs (synthetic)

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