[en] [en] OBJECTIVES: Oral enzyme combination (OEC) therapy with bromelain, trypsin and rutoside reduces pain and improves function in patients with knee osteoarthritis (OA). Here, we investigated several potential biological mechanisms underlying the clinical effects of OEC therapy in patients with established knee OA with respect to innate immunity, systemic inflammation and cartilage turnover (EudraCT 2020-003154-80, NCT05038410).
METHODS: Patients (age ≥40 years, body mass index (BMI) ≤35 kg/m2) with symptomatic knee OA were randomised to either placebo or OEC, administered 2×3 tablets/day, for 8 weeks before crossing over after a 4-week washout period. Different markers exploring innate immunity, inflammation and cartilage matrix degradation have been measured in the blood using immunoassays or cytometric methods. Data from the modified intention-to-treat population (mITT) were analysed using a generalised linear mixed model. No correction for multiple comparisons was made due to the exploratory nature of the study.
RESULTS: Altogether, 45 patients were randomised; 43 completed both treatment sequences (mITT; mean age: 63.3 years; mean BMI: 27.4 kg/m2; mean global Knee injury and Osteoarthritis Outcome Score (KOOS): 48.7). OEC significantly increased levels of α2-macroglobulin (p=0.038) and interleukin-10 (p<0.0001) while decreasing urinary carboxyl-terminal cross-linked telopeptide of type II collagen (p=0.038). Patients administered OEC exhibited significant improvements in KOOS Pain (p=0.0464) and Symptoms (p=0.026) subdomains but not globally. OEC was well tolerated, with no serious related adverse events reported in either group.
CONCLUSIONS: One of the key findings of this proof-of-mechanism study is that OEC modulates IL-10 production, suggesting an anti-inflammatory effect in patients with knee OA. This main finding contributes to explaining the effects of OEC on pain and function in these patients.
TRIAL REGISTRATION NUMBER: NCT05038410.
Disciplines :
Rheumatology
Author, co-author :
Henrotin, Yves ; Université de Liège - ULiège > Département des Sciences de l'activité physique et de la réadaptation > Pathologie générale et physiopathologie - Techniques particulières de kinésithérapie
Pap, Thomas ; Institute of Musculoskeletal Medicine, University Hospital Münster, Münster, Germany
Lieten, Siddhartha; Department of Geriatrics, Universitair Ziekenhuis Brussel, Brussels, Belgium
Badot, Valérie; Department of Rheumatology, CHU Brugmann, Brussels, Belgium
The trial and investigational product were fully sponsored by Nestl Health Science. The Sponsor was involved in the study design; participated in data collection, analysis and interpretation; funded medical writing support and agreed to submit the manuscript for publicationThe authors acknowledge Ananya Das, Constantinos Bezos of Porterhouse Medical UK and Amy Chee of Porterhouse Medical US for medical writing support, which was funded by Nestl\u00E9 Health Sciences, and Isma\u00EFl Aouadi, Nestl\u00E9 Health Science, for the statistical evaluation.
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