Comparative Epidemiological Study in Patients with Rheumatic
Diseases Illustrated in an Example of a Treatment with Non-Steroidal
Anti-inflammatory Drugs versus an Oral Enzyme Combination
Wittenborga
A., Bockb P. R., Hanischb J., Sailerc R., and Schneiderd B.
Comparative Epidemiological Study in Patients with Rheumatic
Diseases Illustrated in an Example of a Treatment with Non-Steroidal
Anti-inflammatory Drugs versus an Oral Enzyme Combination.
Arzneimittel-Forschung/Drug Research 2000, Vol. 50 (II), No. 8, pp.
728-738. PZ 20 (3-14-2)
Rheumazentrum Ruhrgebieta, Herne (Germany), IFAG AG Basel, Institut
fur Medizin und Statistikb, Basel (Switzerland), Department Innere
Medizin, Abteilung Naturheilkundec, Universitätsspital Zürich
(Switzerland), and Institut für Biometried der Medizinischen
Hochschule Hannover (Germany)
To establish the safety and efficacy of an oral
enzyme-combination product (OE; Phlogenzym®, containing
trypsin, bromelain and rutin) in the treatment of rheumatic diseases
a retrolective cohort study with parallel groups was undertaken as
an epidemiological study, in which the enzyme combination was
compared with non steroidal anti-inflammatory drugs (NSAID). Data of
3326 patients treated for rheumatic diseases between January 1993
and the end of March 1995 were registered by 380 physicians. From
the patient file age, gender, indication for treatment (diagnostic
group), anamnestic data (especially pre-treatment), complaints at
the beginning and end of treatment, treatment duration, prescribed
drugs (OE, NSAID), additional treatment and adverse events were
transferred into case report forms (CRFs). The quality of the data
was monitored and additionally checked by internal and external
quality audits.
Included in the efficacy analysis were 2139 patients which were
treated either only with OE or only with NSAID and could be
classified unambiguously into one of the following diagnostic
groups: joint diseases, spinal diseases, rheumatic soft tissue
diseases. As clinically relevant and reliably evaluable criterion
freedom from rheumatic complaints at the end of treatment was
considered. For evaluation of safety the documented adverse events
of all patients were considered. Two thirds of the OE patients
received the recommended dose of 6 tablets/day, taken for 23 to 35
days. The respective mean values for NSAID patients were 16 to 25
days, and the patients were treated with the recommended
symptomatically effective doses of NSAID.
As the allocation of the compared treatment options (OE or NSAID) to
the patients was not randomized, a mixing of treatment effects with
other factors cannot be excluded. For adjustment of these
confounding factors two methods were applied: a) logistic regression
of the relative ratio of the main criterion and all confounding
factors and b) stratification of data according to the propensity
score i.e. the probability of a treatment with OE. Both methods
yielded similar results: A 50 % higher success rate can be expected
in total for OE than for NSAID at comparable initial and treatment
situations (95 % confidence interval with logistic regression =
1,218-1,96, with stratification according to propensity score =
1,16-1,84). As significant negative indicators for response age over
50 years, pre-treatment with antirheumatic or analgetic drugs,
treatment duration more than 30 days and joint diseases or
fibromyalgias could be revealed. Since there was no interaction
between these indicators and the type of treatment also in patients
presenting with these indicators a treatment success (freedom from
symptoms) with OE can be expected with a higher probability than
with NSAID. OE were well tolerated showing much less adverse events
when compared with conventional doses of NSAID.
Key words: Anti-inflammatory drugs, non-, Logistic regression,
Phlogenzym®, comparative epidemiological study,
Propensity score, Proteolytic enzymes, Rheumatic diseases