Efficacy of systemic enzyme therapy as an anti-inflammatory agent when used as monotherapy or in combination with NSAIDs: A systematic review

Systemic enzyme therapy (SET) has emerged as a potential anti-inflammatory intervention, either as monotherapy or in combination with non-steroidal anti-inflammatory drugs (NSAIDs).Despite its increasing clinical application, the comparative efficacy of SET in various inflammatory conditions remains insufficiently explored.A systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines to evaluate the effectiveness of SET as an anti-inflammatory therapy.Databases were searched for studies meeting predefined eligibility criteria, including randomized and non-randomized trials.Study characteristics, intervention protocols and outcomes were extracted and analyzed.The risk of bias was assessed using the ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions) and Cochrane risk-of-bias (RoB) 2.0 tools.Eleven studies with sample sizes ranging from 30 to 487,372 participants were included.Systemic enzyme therapy demonstrated comparable efficacy to diclofenac in terms of pain relief and functional improvement across various conditions, including joint disorders and temporomandibular disorders (TMD).Combination therapy resulted in significantly greater pain reduction (p < 0.05) and improved functional outcomes, as reported in several studies.In most cases, adverse effects were mild, and the safety profile of SET was more favorable than that of NSAIDs.One study reported that the concomitant use of NSAIDs and antihypertensive medications was associated with a 31% increased risk of acute kidney injury during the first 30 days.Systemic enzyme therapy demonstrated efficacy comparable to that of NSAIDs, with a potentially more favorable safety profile in the management of inflammatory conditions.Combination therapy may provide additional benefits in terms of pain reduction and functional improvement.However, the heterogeneity of study designs and the limited number of large-scale trials warrant further research.