Prospective Evaluation of Local Sustained Release of Celecoxib in Dogs with Low Back Pain

Tijn Wiersema,Nina Woike,Jens Thies,Laura Creemers,Marianna Tryfonidou,Martijn Beukers,George Mihov,Marijn Van Stralen,Björn Meij,Anna Tellegen,Erik Wouters,Mandy Van De Vooren

doi:10.3390/pharmaceutics13081178

Tijn Wiersema, Nina Woike + Show 10 more

Open Access

https://doi.org/10.3390/pharmaceutics13081178

Copy DOI

Abstract

Back pain affects millions globally and in 40% of the cases is attributed to intervertebral disc degeneration. Oral analgesics are associated with adverse systemic side-effects and insufficient pain relief. Local drug delivery mitigates systemic effects and accomplishes higher local dosing. Clinical efficacy of intradiscally injected celecoxib (CXB)-loaded polyesteramide microspheres (PEAMs) was studied in a randomized prospective double-blinded placebo controlled veterinary study. Client-owned dog patients suffering from back pain were treated with CXB-loaded (n = 20) or unloaded PEAMs (“placebo”) (n = 10) and evaluated by clinical examination, gait analysis, owners’ questionnaires, and MRI at 6 and 12 weeks follow-up. At 6 and 12 weeks, CXB-treated dogs experienced significantly less pain interference with their daily life activities compared to placebo. The risk ratio for treatment success was 1.90 (95% C.I. 1.24–2.91, p = 0.023) at week 6 and 1.95 (95% C.I. 1.10–3.45, p = 0.036) at week 12. The beneficial effects of CXB-PEAMs were more pronounced for the subpopulation of male dogs and those with no Modic changes in MRI at inclusion in the study; disc protrusion did not affect the outcome. It remains to be determined whether intradiscal injection of CXB-PEAMs, in addition to analgesic properties, has the ability to halt the degenerative process in the long term or restore the disc.

Highlights

The main aim of the present study was to determine the clinical efficacy of local delivery of CXB-loaded polyesteramide microspheres (PEAMs) compared to unloaded PEAMs (“placebo”) in client-owned dog patients suffering from low back pain due to degenerative lumbosacral stenosis (DLSS)
In a placebo-controlled RCT in which the treating veterinarian and the dog owner were blinded to the treatment group, the present study demonstrated that dogs treated with local application of CXB-loaded PEAMs had twice the probability of successful recovery and clinical improvement by at least 10 points
In a placebo-controlled RCT in which the treating veterinarian and the dog owner were blinded to the treatment group, the present study demonstrated that dogs treated with local application of CXB-loaded PEAMs had twice the probability of successful recovery and clinical improvement by at least 10 points compared to dogs treated with placebo

Summary

Introduction

In. 40% of the patient cases, chronic low back pain is attributed to intervertebral disc (IVD). Degeneration [2,3]. The IVD lies between the vertebrae and its main function is to transmit compressive forces, and provide mobility and stability to the spinal column. The core of the IVD, the nucleus pulposus (NP), is contained by the annulus fibrosus (AF), and the two cartilaginous endplates (EPs) of the adjacent vertebrae [4]. IVD degeneration and discogenic pain [5,6] are associated with the local production and influx of pro-inflammatory cytokines, cells, and nociceptive mediators [7], including prostaglandin E2 (PGE2 ) and nerve growth factor (NGF) [8,9].

Objectives

Methods

Results

Conclusion