By Henry Ehrlich
The founding premise for this website, which was launched simultaneously with the publication of Asthma Allergies Children: a parent’s guide, was “medicine moves faster than print.” Here it is four weeks after the publication of my new book about the work of Dr. Xiu-Min Li, and there are already new things to talk about. I promise this website will not become “all Dr. Li, all the time” but this is a hot subject in allergy circles, so I will be updating at seemly intervals.
We have returned repeatedly on this website to the issue of medication compliance to control chronic asthma and environmental allergies, most recently featuring the charming cartoon by Elizabeth Bostic, which summed up the special challenges posed by small children. Dr. Larry Chiaramonte, particularly, has written about the difference between that which is possible medically when people use their medication as directed and that which is probable, given human nature. In analyzing a Dutch study that shows patients are (fractionally) more compliant when they receive allergy shots than when they receive sub-lingual immunotherapy, he ponders why “Patients give up the ‘easy’ medication (administered at home, under the tongue) more readily than the ‘difficult’ one (which involves shots at the doctor’s office)…All I do know is that anyone who thinks the work is done when efficacy has been proved without considering patient behavior over time is kidding himself.” Successful therapy, as Dr. Wesley Burks has said, must be safe, effective, and convenient.
With food allergies, the big compliance issues have been avoidance and emergency treatment protocols. Even when faced with life-threatening reactions, however, compliance is an issue. The recent study “Anaphylaxis in America: The prevalence and characteristics of anaphylaxis in the United States” showed that only 11% of people experiencing anaphylaxis, including those who had done so repeatedly, self-administered epinephrine. Three times as many went to the ER, and of course that’s also way too low. And of course there’s the problem of EMTs and ER doctors misunderstanding of anaphylaxis to begin with, as Dr. Ehrlich has discussed.
However, I think we’re about to enter a new dimension of compliance issues because of burgeoning research into treating food-allergies, whether through desensitization—oral immunotherapy (OIT)—or immune modulation via the traditional Chinese medicine-based treatments of Dr. Xiu-Min Li.
I am not going to wade into the debate over whether OIT is ready for private-practice “prime time. However, one issue that I do think about quite a bit is the ability of desensitized patients to go on taking maintenance doses of their allergens in perpetuity, which I discussed in my new book: “As I can attest to personally, a daily handful of peanuts or Peanut M&Ms sounds better than Grandpa’s Lipitor, but I believe that as these mostly very young patients grow up, they will tire of maintenance dosing.” If they are desensitized to more than one food, the problem will grow even more difficult.
Compliance also factors in the development of a TCM-based treatment. Since the new book came out, a time period that happen to encompass the AAAAI meetings in San Diego at the end of February into early March, several things have popped up that bear talking about.
One was an abstract presented at the meeting entitled “Food Allergy Herbal Formula-2 (FAHF-2) – Adherence To Treatment” by Jaime Ross, RN, et al, which said, “Subjects aged 12-45 years were randomized to receive active FAHF-2 or placebo, 10 tablets three times a day for 6 months (30 tablets daily)… Adherence was calculated based on number of tablets taken in relation to expected number taken during the study time frame. Adherence was defined by medication completion > 80%….
“Of the 59 subjects who completed 6 months of therapy, 16 (27%) were non-adherent for 1/3 of the study period, 8 (13.6%) were non-adherent for 2/3 of the study and 2 (3%) were non-adherent for the entire study. Twenty-six (44%) of the subjects were non-adherent to either part or all of the 6 month study.” The researchers concluded, “Almost half of study participants had difficulties with medication adherence in this 6 month study, suggesting that the intervention may be too demanding.”
In retrospect, Dr. Li has pointed out to me that the problems with this regimen stem not only from the number of pills but the three-times-a-day dosing. “Taking 15 or 18 pills in one sitting twice a day is too much,” she says, “But it’s also hard to take time out in the middle of the day to take lots of pills. The standard TCM protocol is to take medicine at breakfast time and again in the late afternoon or early evening.”
Originally, the effective dose was 56 pills a day. I wrote about this process in my chapter “Too Many Pills.” Fifty-six were reduced to 36 using ethanol, or grain alcohol, which became 30 for the Phase II clinical trials. Subsequently, another form of alcohol, butanol, was used to refine it further into the second-generation drug, B-FAHF-2, which will be used for the next round of studies, as Dr. Li told Gina Clowes in their latest interview. The adult dose will be four pills twice a day, morning and evening. And the child dose will be 1-2. This level of refinement is absolutely vital to the next phase of trials, which will last for two years instead of six months, as in the last round.
Among other exciting news from Gina’s interview, which Dr. Li also reported at the AAAAI, B-FAHF-2 also directly suppresses IgE production of human memory B cells and peripheral blood mononuclear cells nine times more potently than FAHF-2. This effect on IgE should be good news for those who would like a convenient marker for progress in treating food allergies. B-FAHF-2 will also be tested as an adjunctive therapy with OIT, as covered a year ago on this website, and with sub-lingual immunotherapy (SLIT).
Another piece of the compliance equation stems from Dr. Li’s clinical practice, which, as I point out in the book, helps inform the research and set the agenda for further work. In his piece on the Dutch immunotherapy study, Larry pointed out that there are two kinds of people who quit their therapy early. Those who feel better and those who don’t feel better; i.e. those who think that the medicine has done its work and those who don’t feel it’s helping, so why bother?
“I worry,” Dr. Li told me, “That when some patients start to improve they will start to cut down on their medication. In my private practice, we are often treating several conditions, such as eczema and asthma as well as food allergies, with several causes. We do this with baths and lotions as well as pills because oral medication is not the best way to absorb some ingredients in therapeutic doses. If the patient starts to feel some relief in their skin and breathing, they may be tempted to cut down on the baths and lotions, but this will hurt the treatment of food allergies, which is less of a problem, day to day.
“I know little boys and girls don’t like to take pills. Some of them don’t like to take a bath every day with Mommy watching. But this is long-term treatment. No shortcuts. I reduce dosing or even stop some parts of treatment based on clinical improvement and certain bio-markers.”
This is an issue even in clinical trials, which are heavily supervised. Dr. Li says, “In a blind placebo-controlled trial, we have to deal with everyone the same. We can’t make adjustments. It’s easy with mice. The researchers just ‘garage’ them. Our subjects are human. They make their own adjustments, which affects outcomes.”
Then Dr. Li pointed out that logic alone is not enough to keep people compliant with their medicines. After years of illness, patients and moms may say, “We’ll do anything no matter how long it takes.” But that’s a hard promise to keep, month in, month out, even when someone’s life is at stake. “In your other book [Asthma Allergies Children: a parent’s guide] there’s a story about a boy who was going to die from his asthma, and still he didn’t take the medicine.”
I remember this story very well. It was told to me by a Connecticut allergist who was ready to inform the state health authorities that this teenager was in imminent danger of dying. He and an army of nurses and doctors were convinced the boy was compliant with his steroids and other medication. At the last moment, however, this doctor got the patient to blow into a machine called Niox Mino that measured exhaled nitric oxide (eNO), which indicates levels of lung inflammation from asthma. The doctor confronted the boy and said there’s no way the levels could be so high if he were taking his steroids, at which point the boy confessed that he was jealous of all the attention his seriously ill sister got and had hidden all the meds under his bed. He started taking it, along with psychotherapy, and his lungs got better.
“We want to gently monitor compliance while we are studying whether the medication is working,” says Dr. Li. “We developed a technique to detect the active ingredients in blood samples or urine samples so we can quantitatively measure absorption. We are also working on biomarkers as accurate and convincing as eNO. It’s easier if the patient has bad eczema or asthma that you can treat while working on the food allergy because you can see progress. Food allergy is invisible, unless you have a reaction. We want to be able to measure that, too.”
With this expansive view of patients’ nature in mind, Dr. Li is doing everything she can to make compliance easier by developing a third generation of food allergy herbal formula. “In my lab we are trying to isolate all the active ingredients. Even after butanol extraction, there are compounds with no therapeutic value. Eventually we will get down from 6 or 8 pills to just 1, which will make both research and clinical treatment much easier.”
As Larry has said to me, no medicine works if you don’t take it.