Transcript Scott Posterx - Pacific University

Efficacy of Oral Enzyme Combination vs. Diclofenac in the
Management of Large Joint Osteoarthritis
Scott Tryon Hall
Pacific University School of Physician Assistant Studies, Hillsboro, OR USA
METHOD
Search Strategy
An extensive literature search was done using the following databases
accessed through Pacific University Library: CINHAL, Medline, EvidenceBased Medicine Reviews Multifile (EBMRM), and Web of Science (WOS).
The search included the following search terms: Bromelain, Arthritis, and
Non-Steroidal Anti-inflammatory agents. These terms were used individually
and in combination. These articles were then screened by reviewing the titles
and abstracts. The articles were then reviewed for quality and validity using
the Grading of Recommendations Assessment, Development and Evaluation
(GRADE) scale. (See table I.)
Discussion
Although oral enzyme therapy has proven to be better tolerated and
have fewer adverse effects as compared to NSAIDs4 and although some of
the studies in this review make mention of the tolerance and adverse effects
of the oral enzyme, that was not the outcome to be considered in this review.
The purpose of this review was only to show the effectiveness of oral enzyme
therapy when compared to NSAIDs. Studies addressing the long term adverse
effects of oral enzyme therapy should be investigated to more accurately address
tolerance and risk.
All five studies included in this review were very similar in study design
and the results were consistent across all studies in regards to diclofenac vs. oral
enzymes (Tables I & II). However, there were found to be some variation and
limitations among them that should be noted.
Four of the five studies were double-blinded randomized control trials
(RCT) that used a double-dummy technique in the administration of the
medications. The Tilwe et al study was an open randomized single-blinded
study and did not use the double-dummy technique in the administration of
the medications. All five studies used the same study drug and the same drug for
control, which is an important consistency among the studies.
Three of the studies followed the intention-to-treat (ITT) analysis
(Table II). Prognostic balance between the study group and the control group
was not shown in the Klein et al 2000 study (Table II). This could have an
impact on results if the groups were not similar at the start of the study. Each
study however, was similar with respect to the inclusion and exclusion
criteria of the patients.
All five studies included in this review had very small sample sizes, the
largest being 103 total patients (Table II). This was one of the reasons for the
downgrade on the GRADE scale.
The similarities mentioned across studies helps support the validity of
their result and helps make the overall conclusion that oral the enzyme
combination is as effective as diclofenac in the treatment of OA.
Acknowledgements:
To my wife Lauren: I can’t begin to tell you how much you mean to me and how much I love you. Your support and selflessness throughout this journey has been amazing to me and can’t express how grateful I am to you for that.
Your hard work, your sacrifice, all the dinners you ate alone while I was studying, all the months we spent apart; you put up with a lot and never complained. I know it has been hard on both of us but your support made it so much
easier. We have surely had our highs and also some of our very lows these past couple of years but I am glad I have had you to go through it with. This chapter is now over and we are beginning a new one. I can’t wait for the
adventures we will have together. I LOVE YOU!
Study
Design
Findings
Starting Grade
Indirectness
Imprecision
Publication Bias
A comprehensive literature search of four databases using the specified
search strategy, resulted in 78 total articles of which five met the inclusion
criteria and were relevant to the clinical question of, the efficacy of oral
enzyme therapy as compared to NSAIDs in the treatment of osteoarthritis. All
five articles included in this review were double-blinded randomized control
trials comparing PhlogenzmTM to diclofenac. (See Table I.)
The Primary outcomes measured in each study were pain and function,
measured most often with the Lequesne Index, the VAS or a variation of the
two. Each of the five studies showed no statistically significant difference
between the two treatment groups. Repeatedly the oral enzyme combination
containing bromelain proved to be as effective as diclofenac in the treatment
of osteoarthritis with regards to the primary outcome. (See Table II.)
Decrease Grade
Inconsistencies
Osteoarthritis (OA) is the most common joint disorder in the world and
is one of the most frequent causes of pain and loss of function in adults. The
Rate of OA in the US has increased from 21 million in 1995 to over 27
million in 2008.1
Standard treatment of OA is the use of a class of medications known as
NSAIDs. NSAIDs are symptom modifying drugs and do not modify the
disease itself. However, the prolonged use of NSAIDs increases the risks of
adverse effects, the most common being the risk of gastric and duodenal
ulcers and upper gastrointestinal perforation and bleeding.
Bromelain, a proteolytic enzyme derived from the stem of the
pineapple plant, may be an effective alternative to NSAIDs as the standard of
care in the treatment of OA. Bromelain is found most commonly in
combination with other enzymes. PhlogenzymTM contains 90mg bromelain,
48mg trypsin and 100mg rutin. Proteolytic enzymes such as trypsin and
bromelain have shown in vivo and in vitro to have anti-inflammatory, antiedematous, antithrombotic and fibrinolytic effects.2 Enzymes have also
shown to be better tolerated when compared to NSAIDS and do not have the
same gastrointestinal effects.3 Diclofenac sodium is a prescription strength
NSAID and is among the more potent NSAIDs used in acute and chronic
pain. Diclofenac is also one of the most commonly prescribed NSAIDs in
the treatment of OA. Because of the high prevalence of OA and the risks
associated with the standard use of NSAIDs, it is important to consider
alternative treatments. The objective of this review was to evaluate the
efficacy of oral enzyme combination in the management of large joint
osteoarthritis as compared to traditional NSAIDs, in this case diclofenac.
Results
Limitations
BACKGROUND
Table I. Grade of Evidence
Akhtar et al12
RCT
No inferiority
High
0
0
0
-1c
0
Moderate
Klein et al10
2000
RCT
No inferiority
High
-1a
0
0
-1c
0
Low
Singer et al6
RCT
No inferiority
High
0
0
0
-1c
0
Moderate
Klein et al11
2006
RCT
No inferiority
High
0
0
0
-1c
0
Moderate
Tilwe et al13
RCT
No inferiority
High
-1b
0
0
-1c
0
Low
Grade of Evidence
Overall Grade of
Evidence
Moderate
a-failure to report prognostic balance, b-no use of double-dummy technique, c-small sample size
Table II. Summary of Findings
Dosing schedule
Study
Lequesne Index (LI) (Mean)
VAS
WOMAC
Mann-Whitney
Length of study
in weeks
ITT Analysis
OE
DC
OE
DC
OE
DC
OE
OE
Akhtar et al12
6
tid
50mg bid
13.0 to 9.4
12.5 to 9.4
4.9 to 3.5
4.9 to 3.6
NA
0.5305
Yes
Klein et al10
(2000)
3
2 tabs tid
50mg tid wk 1 then
50mg bid
13.56 to 3.10
14.04 to 3.50
16.90 to 2.12 @ 3
weeks
17.42 to 2.24
NA
0.5462
No
Singer et al6
3
2 tabs tid
50mg tid wk 1 then
50mg bid
15.48 to 10.97
15.81 to 10.83
12.37 to 5.51
11.05 to 5.36
NA
0.4919
Yes
Klein et al11
(2006)
6
2 tabs tid
50mg bid
P=0.0008
NA
P=0.0025
No
Yes
Tilwe et al13
3
3 tabs bid
50mg bid
NA
NA
NA
NA
No
Conclusion
In conclusion, the main focus of this review was on the efficacy of oral enzyme therapy as
compared to diclofenac. Primary outcomes were in large part measured using either the Lequesne index
or the VAS, or some sort of variation of the two. These measurements mainly focused on the pain and
function of the patient. The efficacy of the oral enzyme was shown to be statistically equivalent to
diclofenac in all outcomes measured across all five studies. Although the overall grade of the studies was
moderate, which means further studies would likely be of benefit in our confidence of the effect but is
not likely to change the effect, a recommendation could be made to use oral enzyme therapy in patients
suffering from OA. This recommendation would be justified because of the nature of the oral enzyme
and its low risk to benefit ratio. This therapy could be especially beneficial in patients that may already
be suffering from AE from NSAIDs or that can no longer take NSAIDs due to AE.
References
1. Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part
II. Arthritis & Rheumatism. 2008;58:26-35.
2. Maurer H. Bromelain: biochemistry, pharmacology and medical use. Cellular and Molecular Life Sciences. 2001;58:1234-1245.
To My Mom and Dad: Thank you for your love and support and thank you for teaching me from a young age the value of hard work and dedication. I may not have always listened at the time but I came around. I am the man I am
today because of you two.
3. Singer F, Singer C, Oberleitner H. Phlogenzym versus diclofenac in the treatment of activated osteoarthritis of the knee. A double-blind
prospective randomized study. Int J Immunother. 2001;17:135-141.
To Brady Norton: Thanks for the conversation that stimulated the idea for this research .
4. Langman MJ, Weil J, Wainwright P, et al. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs.
Lancet. 1994;343:1075-1078.