A randomized, triple-blinded controlled clinical study with a novel disease-modifying drug combination in equine lameness-associated osteoarthritis

E Skiöldebrand; S Adepu; C Lützelschwab; S Nyström; A Lindahl; K Abrahamsson-Aurell; E Hansson

doi:10.1016/j.ocarto.2023.100381

A randomized, triple-blinded controlled clinical study with a novel disease-modifying drug combination in equine lameness-associated osteoarthritis

Osteoarthr Cartil Open. 2023 Jun 16;5(3):100381. doi: 10.1016/j.ocarto.2023.100381. eCollection 2023 Sep.

Authors

E Skiöldebrand¹, S Adepu¹, C Lützelschwab¹, S Nyström², A Lindahl², K Abrahamsson-Aurell³, E Hansson⁴

Affiliations

¹ Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
² Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
³ Hallands Djursjukhus Kungsbacka Hästklinik, Älvsåkers Byväg 20, 434 95 Kungsbacka, Sweden.
⁴ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Abstract

Objective: This study aimed to test a novel treatment combination (TC) (equivalent to sildenafil, mepivacaine, and glucose) with disease-modifying properties compared to Celestone® bifas® (CB) in a randomized triple-blinded phase III clinical study in horses with mild osteoarthritis (OA). Joint biomarkers (reflecting the articular cartilage and subchondral bone remodelling) and clinical lameness were used as readouts to evaluate the treatment efficacy.

Methods: Twenty horses with OA-associated lameness in the carpal joint were included in the study and received either TC (n = 10) or CB (n = 10) drug intra-articularly-twice in the middle carpal joint with an interval of 2 weeks (visit 1 & 2). Clinical lameness was assessed both objectively (Lameness locator) and subjectively (visually). Synovial fluid and serum were sampled for quantification of the extracellular matrix (ECM) neo-epitope joint biomarkers represented by biglycan (BGN²⁶²) and cartilage oligomeric matrix protein (COMP¹⁵⁶). Another two weeks later clinical lameness was recorded, and serum was collected for biomarkers analysis. The overall health status was compared pre and post-intervention by interviewing the trainer.

Results: Post-intervention, SF BGN²⁶² levels significantly declined in TC (P = 0.002) and COMP¹⁵⁶ levels significantly increased in CB (P = 0.002). The flexion test scores improved in the TC compared to CB (P =0.033) and also had an improved trotting gait quality (P =0.044). No adverse events were reported.

Conclusion: This is the first clinical study presenting companion diagnostics assisting in identifying OA phenotype and evaluating the efficacy and safety of a novel disease-modifying osteoarthritic drug.

Keywords: Anaesthetic agents; Biomarkers; Companion diagnostics; DMOAD; Glucose; Osteoarthritis; Sildenafil.