[Proteolytic enzymes as an alternative in comparison with nonsteroidal anti-inflammatory drugs (NSAID) in the treatment of degenerative and inflammatory rheumatic disease: systematic review]

Med Klin (Munich). 2003 Nov 15;98(11):609-15. doi: 10.1007/s00063-003-1306-5.
[Article in German]


Background and purpose: The comparably high number of severe side effects due to treatment with nonsteroidal anti-inflammatory drugs (NSAID) calls for better tolerated substances. One possible alternative is seen in the systemic treatment with proteolytic enzyme preparations for oral administration. The aim of this study was to determine whether the results from controlled randomized trials on enzyme therapy prove equal anti-inflammatory effectiveness compared to NSAID in the treatment of degenerative or inflammatory rheumatic disease.

Methods: All drug preparations registered in Germany as having anti-inflammatory properties were listed. Among these preparations, a systematic search was carried out for randomized clinical therapeutic trials giving evidence for the anti-inflammatory effectiveness of enzyme preparations or their components.

Results: The anti-inflammatory effectiveness of three out of eight registered enzyme preparations was investigated in randomized trials. In total, seven trials were judged to be sufficiently documented and to allow valuation. All studies show severe methodical deficits, and the standard trial design (clinical trials during inpatient rehabilitation in combination with extensive accompanying treatment) does not allow clear-cut conclusions.

Conclusion: According to the present state of knowledge, oral proteolytic enzyme treatment does not offer a justified alternative in comparison with NSAID in the anti-inflammatory treatment of rheumatic disease.

Publication types

  • Comparative Study
  • Review
  • Systematic Review

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / therapeutic use
  • Administration, Oral
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Bromelains / administration & dosage
  • Bromelains / therapeutic use
  • Double-Blind Method
  • Drug Combinations
  • Humans
  • Hydrolases / administration & dosage
  • Hydrolases / therapeutic use
  • Peptide Hydrolases / administration & dosage
  • Peptide Hydrolases / therapeutic use*
  • Placebos
  • Randomized Controlled Trials as Topic
  • Rheumatic Diseases / drug therapy*
  • Rutin / administration & dosage
  • Rutin / analogs & derivatives*
  • Rutin / therapeutic use
  • Trypsin / administration & dosage
  • Trypsin / therapeutic use


  • Adjuvants, Immunologic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antirheumatic Agents
  • Drug Combinations
  • Phlogenzym
  • Placebos
  • Rutin
  • Wobenzym
  • Bromelains
  • Hydrolases
  • mulsal
  • Peptide Hydrolases
  • Trypsin