Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee ? a double-blind prospective randomized study

Abstract

The aim of this study was to compare the efficacy and safety of an oral enzyme-rutosid combination (ERC) containing rutosid and the enzymes bromelain and trypsin, with that of diclofenac in patients with osteoarthritis (OA) of the knee. A total of 103 patients presenting with painful episodes of OA of the knee were treated for 6 weeks in two study centers in a randomized, double-blind, parallel group trial. Altogether, 52 patients were treated in the ERC group and 51 patients were treated in the diclofenac group. Primary efficacy criteria were Lequesne's Algofunctional Index (LFI) and a 'complaint index', including pain at rest, pain on motion and restricted function. The efficacy criteria were analyzed by applying the Wilcoxon-Mann-Whitney test that provides the Mann-Whitney estimator (MW) as a measure of relevance. Non-inferiority was considered to be proven if the lower bound of the 97.5% one-sided confidence interval (CI-LB) was higher than MW = 0.36 (benchmark of not yet relevant inferiority). Both treatments resulted in clear improvements. Within the 6-week observation period, the mean value of the LFI decreased from 13.0 to 9.4 in the ERC group and from 12.5 to 9.4 in the diclofenac group. Non-inferiority of ERC was demonstrated by both primary criteria, LFI (MW = 0.5305; CI-LB = 0.4171) and complaint index (MW = 0.5434; CI-LB = 0.4296). Considerable improvements were also seen in secondary efficacy criteria, with a slight tendency towards superiority of ERC. The global judgment of efficacy by physician resulted in at least good ratings for 51.4% of the ERC patients, and for 37.2% of the diclofenac patients. In the majority of patients tolerability was judged in both drug groups as very good or good. The current study indicates that ERC can be considered as an effective and safe alternative to NSAIDs such as diclofenac in the treatment of painful episodes of OA of the knee. Placebo-controlled studies are now needed to confirm these results.

Bromelain treatment decreases neutrophil migration to sites of inflammation

“…These include the experimental allergic encephalomyelitis (EAE) model of the human autoimmune disease multiple sclerosis (3), carrageenan-induced pleurisy in the rat (4)(5)(6), immunologically mediated arteriosclerosis in rat aortic allografts (7), rheumatologic diseases in mice and humans (8)(9)(10)(11)(12)(13), and allergic asthma (14) and rhinitis (15). Some studies demonstrated that bromelain had efficacy similar to standard anti-inflammatory drugs such as dexamethasone (5,6) or non-steroidal anti-inflammatory agents (NSAIDs) (8,10,11,16). Our previous studies showed that oral administration of 5 mg bromelain/day markedly decreased the development and severity of inflammatory bowel disease in IL-10 −/− mice (17).…”

Trypsin, Rutoside and Bromelain Alone and Fixed Dose Combination: A Natural, Safer and Effective Anti-Inflammatory Agent

“…In a clinical study conducted in 2004, the efficacy of an enzyme-flavonoid mixture was compared with diclofenac, a prescription NSAID 28 .The proteolytic enzymes used were bromelain and trypsin. These three agents were used in the form of an enteric-coated tablet (to prevent the enzymes from being destroyed by stomach acid) that contained 90 mg of bromelain, 48 mg of trypsin, and 100 mg of rutoside.…”

Current experience and future perspectives of bromelain application in medicine

“…Bromelain u kombinaciji sa tripsinom i rutozidom, primenjen kod pacijenata (n = 52) sa osteoartiritisom kolena u toku šest nedelja. potvrdio je svoj analgetički efekat i bio je podjednako efikasan kao i diklofenak (n = 51) (30). u svim studijama pacijenti su prema sopstvenoj proceni "dobro", odnosno "vrlo dobro" podnosili bromelain, a u studiji tilwe i saradnika (29) čak i dnevnu dozu bromelaina od oko 1890 mg u obliku Phlogenzyma ® .…”