The North American EPD Study
73 physicians participated in the study at different centers (multi-center) in the USA and Canada. Patients were selected randomly for this study in many or most instances. However, a quite significant percentage of these of patients were selected because they had previously failed on treatment with both medications and conventional immunotherapy.
EPD treatment was administered every two to three months, generally by one to five small (1/20 c.c.) intradermal (in the first layer of skin) injections which were generally administered in the skin of the inner aspect of the forearm.
Patients were evaluated by the use of initial and interim questionnaires. The initial questionnaires were completed by patients prior to receiving EPD, and the interim questionnaires were completed immediately prior to receiving each subsequent treatment. Patients evaluated how they responded to EPD "overall" and how they responded to each specific condition they had recorded. Overall and individual categories were evaluated for both the effect on the frequency of their symptoms and the effect upon severity of symptoms.
Patients were allowed to evaluate as few as one and as many as six conditions for which they were being treated. Patients were required to choose one of the following categories for both their "overall" response for each evaluation and their response to EPD treatment for each specific condition were evaluated:
Terrible (worse than the before starting treatment)
Patients also recorded their frequency of use of self-selected medications at the onset of treatment and for their evaluation after each treatment (over 600 medications were listed by patients).
EPD - Frequency of Treatment
EPD treatments were given every 2 to 3 months at first, then less often. Generally, patients with multiple problems were treated every two to three months for six to eight times. After that, treatments usually decreased to every four to six months and then less often as needed. Once therapy reached once yearly, treatments were often stretched to as little as once every 6-12 months. 68,428 treatments were given to 10,372 patients. Since "treatments" consisted of 1 to as many as 7 injections, the total number of actual injections given is not known exactly, but was between 175,000 and 179,000.
EPD - Conditions Treated
Over 60 conditions were treated with EPD in this study. The conditions treated are listed here
EPD - Complications and Adverse Reactions
There were 3 patients reported with possible complications to EPD to the IRB over the period of 1994-1999. None of these complications were serious or life threatening.
The study evaluated 10,372 patients over 7 years. Of those patients, 60% (6261) were female and 40% (4111) were male. Average age of females was 45, and the average for males was 33.
Of the 10,372 patients enrolled in the study, 6030 were evaluated as to overall response, response as to improvement in frequency (see Table I below) and response as to improvement in severity (see Table II below). The "dropout" rate was 41% over the 7-year period of the study. This compares to 50% for much shorter-term studies of escalating dose immunotherapy, where only very few conditions (4 or less) were studied.
It has been established by previous studies that it may take up to three treatments with EPD to determine whether the therapy may be effective. Considering this, the 1160 patients who stopped treatment prior to three treatments were counted as dropouts, but really cannot be counted as treatment failures.
Responses were scored numerically by computer. For specific conditions evaluated, for the purposes of this paper, patients who reported a response of "excellent", "very good" or "good" were grouped together as "satisfactory"). Patients who reported "fair" results were classified as "fair", and patients who reported "poor" or "terrible" were reported as "no change" or "worse".
The "overall" response showed that 20% of patients reported excellent, 30% reported very good and 26% good, with an overall "satisfactory" response rate of 76%. Fourteen percent (14%) reported fair and 8% reported no change. Two percent (2%) of patients felt they were worse after receiving EPD than they had been prior to starting EPD; most investigators suspected that many of these patients worsened despite EPD, rather than as a result of EPD, though this could not be determined.
The American EPD Society study is the largest outcome-based study ever undertaken of any type of immunotherapy, with over 10,000 patients. We believe that this study demonstrated the significant clinical value of EPD as a treatment tool. We have listed a brief comparison of EPD immunotherapy to conventional immunotherapy in Table IV.
Conventional escalating dose immunotherapy is the immunotherapy most widely used in the United States. Most classically trained allergists employ this type of treatment in some form. It should be made clear, however, that this type of immunotherapy is effective for only a relatively few conditions. According to the medical literature, these conditions are fairly limited to seasonal hay fever, dust mite allergy, cat (and perhaps dog) allergy, and possibly seasonal asthma.
Most studies done of patients treated with conventional immunotherapy for classical pollen allergy claim an overall success rate of between about 60 and 80 percent for highly selected patients.
Although every condition evaluated in our study did not necessarily appear to respond dramatically to EPD immunotherapy, most responded quite favorably. Most importantly, a large number of conditions which do not respond at all to conventional immunotherapy, and many which do not respond well to any type of therapy - appear to have responded to EPD.
For example, there is no effective immunotherapy for angioedema, which consists of facial swelling, swelling of the lips or eyes or swelling of other parts of the body, primarily as a result of acute food allergy. 78% of 180 patients reported satisfactory (excellent, very good or good) results with EPD immunotherapy. Conventional therapy dictates treatment primarily with drugs.
Likewise, immediate food allergy, which includes anaphylaxis (a condition that is generally life-threatening) has no effective treatment except for emergency drug treatment and avoidance of the offending food or foods. This includes such potentially fatal problems as peanut and shrimp or shellfish allergy. In the group of 519 patients who had some type of immediate food allergy, EPD was effective in 72%. Conventional immunotherapy has no effect for anaphylaxis to foods or chemicals, and is in fact dangerous and contraindicated. The only exception is a type of immunotherapy (Rush desensitization) that has been employed for penicillin, bee sting and a few other problems.
Several conditions that are difficult to treat don't respond extremely well to drug therapy and cannot be treated with conventional immunotherapy. Yet many appeared to respond well to EPD in this study. The quite successful response (in regards to severity) of such conditions as perennial asthma, (732 patients with 75% success), headaches (1186 patients with 75% success), food intolerance - or food reactions, which in most cases was moderate to moderately severe (2857 patients with 74% success), chronic perennial rhinitis (2258 patients with 74% success), hyperactivity/attention deficit disorder (578 patients with 70% success) and eczema or severe dermatitis (669 patients with 69% success), are just a few conditions that response to any type of immunotherapy should be considered dramatic.
Although the results of treatment with EPD of some of the autoimmune diseases studied here may not appear to be dramatic, treatment of these conditions with any type of immunotherapy has been extremely disappointing or has not been considered possible.
Results for certain autoimmune conditions varied from center to center, primarily as a result of specific treatment protocols employed by physicians that were used in addition to the fundamental study protocol. For example, in this study, 14 patients with ankylosing spondylitis (severe, debilitating arthritis of the spinal column) had a modest success rate of 64%. However, in one treatment center, likely as a result of the specific protocol chosen by the physician, all four patients treated for ankylosing spondylitis with EPD responded extremely well.
The same case can be made for rheumatoid arthritis. This is a typically debilitating and progressive disease for which the only available treatment is the employment of a specific regimen of drug therapy. For the 76 patients with rheumatoid arthritis in the study, most would consider a 57 percent rate of success - which means patients were satisfied with the results - remarkable. 79% of patients with rheumatoid arthritis in the study reported a decrease in the medications needed to treat symptoms.
Although the final statistics of this study have not yet been published, the considerably large numbers of patients in fairly well defined groups gives a strong indication that the conclusions are reliable. Also, the success rate of EPD (78%) for seasonal rhinitis (1361 patients) compares favorably to that of conventional immunotherapy.
The results for the treatment, listed by response to Frequency and Severity, appear below, sorted from greatest to least effect. Groups of patients with less than 20 individuals (N< 20) should not be considered accurate enough to be statistically significant.
A comparison of EPD immunotherapy and conventional immunotherapy appears in Table III.
Table I. American EPD Trial Outcome Results
Improvement in Frequency of Symptoms (Nov., 1993 - Nov., 2000)
Table II: American EPD Trial Outcome Results
Improvement in Severity of Symptoms (Nov., 1993 - Nov., 2000)
Table III: Comparison of EPD Immunotherapy to Conventional Immunotherapy
At the end of this 7-year study of 10,372 patients who received at least 175,000 injections of EPD, the physicians who participated in this study concluded that the healing and health potential of EPD for use to treat allergy and autoimmune disease is significant.
As a result of the findings of this study, and in comparison to conventional immunotherapy, we must conclude that EPD:
Is extremely safe, without incidence of fatality or serious side effects
Is virtually the only option available to actually prevent the occurrence of life-threatening reactions or death as a result of acute food allergy
Is as successful as conventional immunotherapy for the very limited conditions for which conventional immunotherapy is used to treat.
Can be used to successfully treat a vastly greater number of conditions, and is more convenient than conventional immunotherapy (i.e. treatment every 2 weeks)
Reduces the amount and/or number of drugs required to be taken by patients by at least 50 percent on the average.
Has several major advantages over conventional escalating dose immunotherapy:
o is 30-60% more cost-effective
o is administered far less frequently with an earlier and more complete endpoint
o can be discontinued without complete relapse of symptoms, or treatments can be extended to very long intervals of a year or more
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Santa Fe Center for Allergy and Environmental Medicine