A Randomized, Clinical Trial to Evaluate Efficacy and Tolerability of Trypsin:Chymotrypsin as Compared to Serratiopeptidase and Trypsin:Bromelain:Rutoside in Wound Management.

INTRODUCTION: Systemic enzyme therapy can play an important role in maintaining normal inflammatory processes within the body and thereby helps support and speed up healing. In the course of the anti-inflammatory action, enzymes degrade damaged cells and necrotic material and, through the inactivation of mediators and toxic products, they restrict the edema and pain. METHOD: The study conducted at Grant Medical College, Mumbai, India was a clinical trial comparing the efficacy and tolerability of three oral enzyme treatment groups-oral tablets containing trypsin:chymotrypsin (TC) (Chymoral Forte®), serratiopeptidase (S) 5 mg oral tablets, and oral enzyme tablets containing trypsin 48 mg, bromelain 90 mg, and rutoside 100 mg (TBR)-to evaluate their healing potential in surgical wounds after orthopedic surgery. RESULTS: A total of 75 patients were screened, randomized, and divided into three groups in 1:1:1 ratio receiving either of the three treatments. In the TC group, erythema was significantly reduced from 3.44 on day 3 to 1.16 on day 10 (p < 0.01). There was significantly better reduction in erythema scores in the TC group as compared to S and TBR groups (p < 0.05) at each follow-up visit. Similarly reduction in the local irritation, wound discharge, edema, induration, and tenderness score with TC treatment at the end of the study was significantly higher than that observed in the other two groups. In addition TC showed significant reduction in pain on the VAS scale (p < 0.01). Global assessment of response to therapy for efficacy and tolerability was reported to be good to excellent in 88% and 92% of the patients on TC as compared to 12% and 8% with S and 12% and 8% with TBR. CONCLUSION: TC provides a better resolution of symptoms of inflammation after orthopedic surgery as compared to S and TBR, thus facilitating better wound healing. Further studies are warranted to confirm the findings. TRIAL REGISTRATION: Clinical Trial Registry of India (Reg. No. CTRI/2011/07/001920).

A prospective, randomized, double-blind, placebo-controlled clinical trial comparing the efficacy of systemic enzyme therapy for edema control in orthognathic surgery using ultrasound scan to measure facial swelling.

PURPOSE: To evaluate the effectiveness of systemic enzyme therapy for the control of edema in patients who undergo bimaxillary orthognathic surgery. MATERIALS AND METHODS: Thirty patients were included in this double-blinded, randomized, control trial. Before surgery, each patient was allotted a code (study or control group). Nine anthropometric points were selected. Thickness of the soft tissue at each of these points was measured using an ultrasound device. These measurements were performed on the day before surgery and 1, 5, and 15 days after surgery. The study group was given a twice-daily dose of systemic enzyme therapy from the first postoperative day for 5 days; the control group was given placebo. The percentage of difference in the thickness of the soft tissue was calculated at each of the 9 points on postoperative days 1, 5, and 15. These data were analyzed and compared using the Mann-Whitney test. RESULTS: The statistical evaluation showed a significant difference in soft tissue thickness between the 2 groups, especially on days 5 and 15, at most assessed points. CONCLUSION: The results of this study suggest that systemic enzyme therapy significantly decreases postoperative edema in orthognathic surgery, precluding long-term corticosteroid use.

Effect of trypsin and mucin on heme iron bioavailability in humans.

UNLABELLED: In the human gastrointestinal tract, trypsin and mucin may affect the absorption of heme iron. However, these interactions have not been well-established. We determined the effect of trypsin and mucin on heme iron absorption in humans. DESIGN: Twenty-eight apparently healthy females participated in two studies (14 per study). Study A evaluated the effect of trypsin on iron bioavailability. Subjects ingested 100 mg trypsin and 1.7 g mucin on 5 mg heme iron bioavailability on days 1, 2, 14, and 15, respectively. In study B, which assessed the effect of mucin on heme iron bioavailability, the subjects ingested hemin, hemin plus mucin, hemoglobin (Hb), and Hb plus mucin, on days 1, 2, 14, and 15, respectively. RESULTS: In study A, the geometric means ± 1 SD of heme iron absorption were 5.1 % (3.1-8.3), 2.9 % (1.6-5.1), 7.3 % (4.1-13.1), and 6 % (2.7-13) for hemin, hemin plus trypsin, Hb plus trypsin, and Hb plus mucin plus trypsin, respectively. In study B, the geometric means ± 1 SD of heme iron absorption were 16.4 % (10.5-25.7), 13.1 % (9.0-18.9), 13.7 % (9.0-20.7), and 11.8 % (7.6-18.3) for hemin, hemin plus mucin, Hb, and Hb plus mucin, respectively. The ratio increased when Hb plus trypsin was ingested and decreased when hemin plus trypsin was ingested. There were no differences in other ratios with respect to the ratio on day 1 (P < 0.05). CONCLUSION: Trypsin is the only human gastrointestinal protein that evaluated the affects of heme iron absorption. However, this effect depends on how heme iron is ingested.

Naturopathic treatment of rotator cuff tendinitis among Canadian postal workers: a randomized controlled trial.

OBJECTIVE: To explore the effectiveness of naturopathic care (NC) on rotator cuff tendinitis using a prospective randomized clinical trial design. METHODS: Canadian postal workers with rotator cuff tendinitis for a duration of >6 weeks were randomized to receive NC (n = 43) or standardized physical exercises (PEs; n = 42) over 12 weeks. Participants in the NC group received dietary counseling, acupuncture, and Phlogenzym (2 tablets 3 times/day). The PE intervention group received passive, active-assisted, and active range of motion exercises and matched placebo. The primary outcome measure was the Shoulder Pain and Disability Index (SPADI), and secondary outcomes were the pain visual analog scale (VAS), Short Form 36 (SF-36), Measure Yourself Medical Outcomes Profile (MYMOP), and shoulder maximal range of motion. Participants and assessors were blinded to group and placebo allocation. RESULTS: Seventy-seven participants (87%) completed >or=8 weeks of the trial. Final total SPADI scores decreased by 54.5% (P < 0.0001) in the NC group and by 18% (P = 0.0241) in the PE group. Between-group differences in changes to SPADI scores showed statistically significant decreases in shoulder pain and disability in the NC group compared with the PE group (P < 0.0001). Significant differences between groups were also observed in the pain VAS, MYMOP, SF-36, and shoulder extension, flexion, and abduction, with the NC group showing superiority in each outcome. No serious adverse reactions were observed. CONCLUSION: NC and PE provided significant improvements, with greater improvement in shoulder function in the NC group compared with the PE group. Statistically significant improvements in quality of life measures were observed in the NC group as compared with the PE group.

Acoustic pressure wound therapy in the treatment of stage II pressure ulcers.

Pressure ulcers are localized skin injuries secondary to unrelieved pressure or friction. Patients with immobility issues are at increased risk for developing pressure ulcers. In 2004, stricter federal regulations for prevention and treatment of pressure ulcers in institutional settings--eg, long-term care facilities--were introduced. Effective, low-cost treatments for pressure ulcers are needed; acoustic pressure wound therapy (APWT), a noncontact, low-frequency, therapeutic ultrasound system, is one option. A retrospective case series of six long-term care patients (two men and one woman, age range 61 to 92 years), each with one Stage II pressure ulcer, is presented. Acoustic pressure wound therapy was provided as an adjunct to standard treatment that included balsam of Peru/castor oil/trypsin ointment, hydrogel, hydrocolloid dressings, silver dressings, and offloading. Outcomes (days to healing) were determined through changes in wound dimensions. Study participants each received APWT for 3 to 4 minutes three to four times weekly. In four of the six wounds, the average number of days to healing was 22. One of the two remaining patients discontinued treatment at 95% healed; treatment for the sixth patient was ongoing due to hospitalization that delayed APWT. In a long-term care setting, APWT added to standard of care may accelerate healing of Stage II pressure ulcers.

Use of microcirculatory parameters to evaluate clinical treatments of chronic venous disorder (CVD).

OBJECTIVES: To evaluate changes on cutaneous microangiopathy in chronic venous disorder (CVD) after use of Cirkan [venotonic drug containing Ruscus aculeatus (plant extract), hesperidine methylchalcone (flavonoid) and vitamin C], elastic compression stockings (ECS) or no treatment for four weeks. PATIENTS AND METHODS: Fifty-five female patients (85 legs), 25 to 57 years, with at least one limb classified as C2,s or C2,3,s (CEAP classification), were allocated consecutively, according to entrance order, in these three groups. Ten healthy women age-matched were also investigated. Using orthogonal polarization spectral technique (noninvasive method), measurements of functional capillary density (FCD, number of capillaries with flowing red blood cells/mm(2)), capillary morphology (CM, % of abnormal capillaries/mm(2)) and diameters (mum) of dermal papilla (DDP), capillary bulk (DCB) and capillary limb (CD) were obtained on the medial perimalleolar region and later analyzed using CapImage software. RESULTS AND CONCLUSIONS: CVD patients showed significant changes on CD and CM compared to healthy subjects in agreement with our previous findings (J Vasc Surg 43:1037-1044, 2006). On Cirkan-treated patients, after 4 weeks, CD decreased on both limbs and CM improved on the left one, suggesting an amelioration of the chronic venous hypertension. No significant changes could be detected on other patient groups. These results confirm the existence of microcirculatory dysfunction in early stages of CVD, probably due to post-capillary hypertension, and further support the venotonic action of Cirkan.

Enzymes, trophoblasts, and cancer: the afterlife of an idea (1924-2008).

In the early 20th century, advocacy of the enzyme therapy of cancer was primarily the work of one man, John Beard, DSc (1858-1924). He and his collaborators made a determined effort to establish this mode of therapy, especially in the years 1905 to 1911. Despite a brief flowering of international interest, Beard's efforts came to naught. During the 20th century, there was a succession of American researchers who continued to investigate this topic. This included Marshall William McDuffie, MD (1882-1945), Frank LeForest Morse, MD (1876-1953), Franklin Lloyd Shively, MD (1887-1971), and William Donald Kelley (1926-2005). In central Europe, India, and other parts of the globe, the use of pancreatic enzymes as an adjuvant treatment for cancer has become a fairly routine practice, at least among those doctors who utilize complementary and alternative medicine (CAM). It is also a well-established method for reducing inflammation and mitigating the adverse effects of cytotoxic treatment.

[Effect of flogensim in the treatment of postischemic inflammation (according to results of using interleukin-6 in patients with acute brain infarction)].

I1-6 in blood serum 109 patients with ischemic stroke was tested on 1st and 7 day after developing the disease. The decrease in concentration of I1-6 on 7 day was found after a complex therapy with Flogensim in the study group in comparison with the control group where a traditional therapy was used. The authors found considerable difference in consequences of the ischemic stroke on 21 day among patients pertaining to different group: the number of patients of the study group where results were better increases and number of the patients of this group with no dynamic or even worsening in neurological status decreases.

Where do the immunostimulatory effects of oral proteolytic enzymes ('systemic enzyme therapy') come from? Microbial proteolysis as a possible starting point.

Enteric-coated proteolytic enzyme preparations like Wobenzym and Phlogenzym are widely used for the so-called 'systemic enzyme therapy' both in humans and animals. Numerous publications reveal that oral proteolytic enzymes are able to stimulate directly the activity of immune competent cells as well as to increase efficiency of some of their products. But origins of the immunostimulatory effects of oral proteolytic enzymes are still unclear. The hypothesis described here suggests that it may be proteolysis of intestinal microorganisms that makes the immune competent cells to work in the immunostimulatory manner. The hypothesis was largely formed by several scientific observations: First, microbial lysis products (lipopolysaccharides, muropeptides and other peptidoglycan fragments, beta-glucans, etc.) are well known for their immunostimulatory action. Second, a normal human being hosts a mass of intestinal microorganisms equivalent to about 1 kg. The biomass (mainly due to naturally occurring autolysis) continuously supplies the host's organism with immunostimulatory microbial cell components. Third, the immunostimulatory effects resulting from the oral application of exogenously acting antimicrobial (lytic) enzyme preparations, such as lysozyme and lysosubtilin, are likely to be a result of the action of microbial lysis products. Fourth, cell walls of most microorganisms contain a considerable amount of proteins/peptides, a possible target for exogenous proteolytic enzymes. In fact, several authors have already shown that a number of proteases possess an ability to lyse the microbial cells in vitro. Fifth, the pretreatment of microbial cells (at least of some species) in vitro with proteolytic enzymes makes them more sensitive to the lytic action of lysozyme and, otherwise, pretreatment with lysozyme makes them more susceptible to proteolytic degradation. Sixth, exogenous proteases, when in the intestines, may participate in final steps of food-protein digestion. The resulting food-borne peptides have recently been shown to be potential activators of microbial autolysis. The main question that needs to be answered in order to verify the hypothesis is whether oral proteases are able (and to what extent) to lyse/mediate lysis of intestinal microorganisms in situ. Methods based on up-to-date molecular biology techniques to allow investigation of the influence of exogenous proteases on microbial lysis processes in vivo (in the intestines) need to be developed. Research testing of this hypothesis may have an important impact in development of novel preparations for the systemic enzyme therapy.

Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs.

OBJECTIVE: The objective of this study was to establish the non-inferiority of an oral enzyme therapy (Phlogenzym-(PE)) as compared to the non-steroidal anti-inflammatory drug (NSAID) diclofenac (DC) in patients with osteoarthritis (OA) of the hip. METHODS: Ninety patients presenting with painful episodes of OA of the hip were treated for 6 weeks in one study centre in a phase III, randomised, double blind, parallel group trial. Altogether, 45 patients were treated in the PE group and 45 patients were treated in the DC group. Primary efficacy criteria were: WOMAC dimensions pain, joint stiffness and function, and Lequesne index as multiple endpoint according to O'Brien. The efficacy criteria were analysed applying the test of non-inferiority with regard to mean changes and frequencies, t-test, U test, ANCOVA and descriptive methods. RESULTS: Within the 6 weeks observation period, the adjusted changes from baseline to endpoint of the target parameters worked out as follows (adjusted differences, mean +/- SEM): WOMAC subscale pain (PE -10.3 +/- 1.2, DC -9.5 +/- 1.2), WOMAC subscale joint stiffness (PE -3.9 +/- 0.5, DC -3.6 +/- 0.5), WOMAC subscale physical function (PE -31.7 +/- 3.5, DC -29.7 +/- 3.5), Lequesne's index (PE -2.89 +/- 0.47, DC -2.27 +/- 0.47). Non-inferiority of PE as compared to DC with regard to the O'Brien's global sum of the standardised adjusted changes from baseline to endpoint in pain, stiffness, physical function, and Lequesne's index was established with p = 0.0025. PE was simultaneously non-inferior as compared to DC with regard to the 4 single endpoints: WOMAC subscale pain (p = 0.0033), WOMAC subscale joint stiffness (p = 0.0061), WOMAC subscale physical function (p = 0.0039), Lequesne's index (p = 0.0008) (closed test procedure). The equivalence tests remained insignificant due to comparatively lower effects of DC. For 71.1% of the PE patients and for 61.4% of the DC patients rates of good or very good global investigator assessments of efficacy were calculated (test of non-inferiority: p = 0.0011). In the majority of patients, tolerability was judged in both drug groups as very good or good. CONCLUSION: This trial showed significant non-inferiority from 6 weeks treatment with PE in patients with OA of the hip with regard to the WOMAC dimensions pain, stiffness and physical function, to Lequesne's index, to the investigator and patients assessments of efficacy, and to the responder rates based on pain, physical function, and patient assessment of efficacy. With regard to drug tolerability some tendencies in favour of PE were detected. However, in this study there was no real difference between PE and DC 100 mg/day, implying an equal benefit-risk relation between the substances. PE may well be recommended for the treatment of patients with osteoarthritis of the hip with signs of inflammation as indicated by a high pain level.

Heparin-induced thrombocytopenia syndrome bullous lesions treated with trypsin-balsam of peru-castor oil ointment: a case study.

Heparin-induced thrombocytopenia syndrome is a serious, potentially life-threatening adverse reaction to the use of heparin anticoagulation therapy that can result in significant skin damage and organ morbidity. A case study design is used to describe the innovative use of a topical wound treatment (trypsin-balsam of Peru-castor oil ointment) on bullous lesions related to the effects of this syndrome. An elderly, morbidly obese woman was treated for 2 weeks with twice-daily applications of the product along with non-adherent oil emulsion dressings. Oozing decreased substantially within a few days and open blisters closed within 1 week. After 2 weeks of therapy, the bullous skin reaction was fully resolved with no recurrence. The results of this case study suggest that this topical product may have had a positive effect on the bullous lesions and should be considered for use in other similar significant integumentary reactions.

Comparison of pressure ulcer treatments in long-term care facilities: clinical outcomes and impact on cost.

This study compared clinical outcomes and nursing labor costs associated with (a) balsam Peru, hydrogenated castor oil, and trypsin (BCT) ointment; (b) BCT + Other; and (c) Other treatments in 2014 wound episodes occurring in 861 patients (mean 2.34 wounds/patient). Treatment with BCT ointment or BCT + Other was associated with a higher healing rate (P < .05). No Stage 1 or 2 ulcer treated with BCT ointment progressed, compared with 13.8% treated with BCT + Other and 13.4% treated with Other. The reported mean duration of treatment and time to heal were shorter for ulcers treated with BCT ointment, but differences did not reach significance, possibly because of the variability in reported treatment times. Mean daily nursing labor costs were lower for treatment with BCT than Other ($50.8 vs $61.7, P < .05). These data suggest that treatment of Stage 1 or 2 ulcers with BCT may be associated with shorter treatment time and time to heal and a potential reduction in treatment-related nursing labor costs.

[Oral enzyme therapy for chronic hepatitis C--a retrospective analysis]. / Orale Enzymtherapie bei chronischer Hepatitis C -- eine retrospektive Analyse.

BACKGROUND AND OBJECTIVE: Data from a randomized trial in hepatitis C infected Egyptian patients suggest that the oral intake of the enzyme preparation Phlogenzym results in a significant reduction of aminotransferase levels and is equally effective to the therapy with interferon alpha. In our study, we investigated whether comparable effects can be found in daily practice in German patients. PATIENTS AND METHODS: We retrospectively evaluated the aminotransferase levels of all patients with chronic hepatitis C who were treated with Phlogenzym at a dose of 6 tablets/day in our outpatient department between 1998 and 2003. Inclusion criteria for the study were treatment duration >3 weeks and elevated alanine-aminotransferase (ALT)levels 6 months prior to and at the beginning of the treatment with Phlogenzym. Liver cirrhosis Child B or C, interferon therapy within the last 3 months before treatment with Phlogenzym and alcohol intake >30 g/day were exclusion criteria. RESULTS: 22 patients were included into the analyses. The mean duration of treatment with Phlogenzym was 77 +/- 41 days. ALT, aspartate-aminotransferase (AST) and gamma glutamyl transpeptidase (GGT) levels did not change significantly during treatment. Fitting a generalized linear model, we estimated that a hypothetical patient who started with a baseline value of 50 U/I after 90 days of treatment ends up in an ALT level of 52 U/I (95%-CI:27-77 U/I), an AST level of 51 U/I (35-67 U/I) and a GGT level of 42 U/I (22-61 U/I). 5 out of 22 patients had to stop treatment because of side effects. CONCLUSION: 6 tablets Phlogenzym per day do not seem to reduce permanently elevated aminotransferases in patients with chronic hepatitis C.

A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes.

OBJECTIVE: To compare the effectiveness and safety of the triple combination Phlogenzym (rutoside, bromelain, and trypsin) with double combinations, the single substances, and placebo. DESIGN: Multinational, multicentre, double blind, randomised, parallel group design with eight groups structured according to a factorial design. SETTING: Orthopaedic surgery and emergency departments in 27 European hospitals. PARTICIPANTS: A total of 721 patients aged 16-53 years presenting with acute unilateral sprain of the lateral ankle joint. PRIMARY EFFICACY CRITERIA: (a) Pain on walking one or two steps, as defined by the patient on a visual analogue scale. (b) The range of motion, as measured by the investigator and expressed as a sum of flexion and extension. (c) The volume of the injured ankle measured with a volometer. RESULTS: At the primary end point at seven days, the greatest reduction in pain was in the bromelain/trypsin group (73.7%). The Phlogenzym group showed a median reduction of 60.3%, and the placebo group showed a median reduction of 73.3%. The largest increase in range of motion (median) was in the placebo group (60% change from baseline). The Phlogenzym group showed a median increase of 42.9%. The biggest decrease in swelling was in the trypsin group (3.9% change from baseline). The Phlogenzym group showed a -2.30% change from baseline and the placebo group a -2.90% change. In the subgroup analysis of patients who did not use a Caligamed brace, Phlogenzym was superior to placebo for the summarising directional test of the primary efficacy criteria (MW = 0.621; LB-CI 0.496; p = 0.029; one sided Wei-Lachin procedure). The vast majority of doctors and patients rated the tolerability of all treatments tested as very good or at least good. CONCLUSIONS: Phlogenzym was not found to be superior to the three two-drug combinations, the three single substances, or placebo for treatment of patients with acute unilateral sprain of the lateral ankle joint. The small subgroup of patients treated without the support of a Caligamed brace showed evidence of superiority of Phlogenzym over placebo. Further research is warranted to study this effect of Phlogenzym in patients treated without ankle support.

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

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.

[Proteolytic enzymes as an alternative in comparison with nonsteroidal anti-inflammatory drugs (NSAID) in the treatment of degenerative and inflammatory rheumatic disease: systematic review]. / Proteolytische Enzyme als therapeutische Alternative zu nichtsteroidalen Antirheumatika (NSAR) in der antiphlogistischen Therapie degenerativer und entzündlich-rheumatischer Erkrankungen. Systematischer Review.

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.