19 / 78
DCMS online
. org
Northeast Florida Medicine
Vol. 66, No. 4 2015
19
Guest Editorial
The field of inflammatory bowel disease is mostly uncharted
territory. Like many questions in life, the two points of greatest
interest are usually the least understood. I am referring to the
beginning and the end. We are just starting to figure out how
IBD begins. We are also trying to figure out a cure. It is in
this setting that the study of
inflammatory bowel disease
is so humbling. It is hard to
be an expert in a field where
you cannot tell a patient how
they got the illness and how
they can get rid of it.However,
we are making huge advances.
The field is exploding with
new medications. Gone are
the days when all we had were
steroidsandmesalamine.Now,
physicians are able to offer
something else to patients. It
is called hope.
Cognizant that most of our readers are either approaching
middle age or deep in the throes of it, the question begs itself,
“How did I get here?” This is the question regarding science itself.
If the medications we had were perfect, then no new medications
would be needed. However, that has not been the case with in-
flammatory bowel disease. Meta-analysis studies have shown that
mesalamine-based products are all pretty much equivalent.
1
The
absolute reduction of risk for 5ASA products is approximately
25 percent better than placebo. However, this is only in mild to
moderatedisease.Inmoreadvanceddisease,the5ASAproductsare
almostfutile.Thereinliestheparadox.Themajorityofpatientswith
inflammatory bowel disease do not present withmild tomoderate
disease. They present mostly with moderate to severe disease.
2
As
such, a giant cohort of patients are offered medications that are
doomed to fail. There was a study a long time ago that stated that
perhaps 5ASA products might have a chemotherapeutic effect.
However, amore recent study states this may not be the case either.
And yet even more studies suggest that they might!
3,4,5
As such, it
is unclear what the role of 5ASA products are in the majority of
IBDpatients.Moreover, another study revealed that once a patient
with inflammatory bowel disease has received steroid therapy, the
efficacy of 5ASA products becomes nil.
6
Next came immunotherapy. Medications including azathio-
prine andmethotrexate serve to staunch theunrelenting cascade of
the immune system by inhibiting lymphocyte activity. However,
the risks of immunotherapy are numerous. They include, but
are not necessarily limited to, the following: nausea, vomiting,
fever, hair loss, pancreatitis, hepatitis, drop in white blood cell
count and lymphoma. Moreover, these medications only work
perhaps 35 percent of the time.
7
Then came a beacon of hope. A new day dawned as biologic
therapies began to take hold. Starting with infliximab and now
refined with vedolizumab, physicians are starting to notice that
there is an incredible overlap between seemingly unrelated ill-
nesses. People with psoriasis had severe joint pains. People with
Crohn’s disease had extraintestinal manifestations such as, at
times, psoriasis. IBD patients had joint pains and many of them
hadpositive rheumatoid factors andpositive antinuclear antibody
assays. In essence, the field of inflammatory bowel disease is just
a subsection of the field of immunology. We noticed that an
earlier application of more advanced therapy in patients with
rheumatoid arthritis could change their future. These patients
were treated with disease modifying anti-rheumatologic drugs
(DMARD). It turns out that the earlier you apply biologic drugs
the less likely the patient will develop deleterious and irrevoca-
ble consequences. Actually, this is not a surprise. The Architect
of the human body is a genius. The axiom “time is tissue” is
universally applicable. The longer you have reflux disease that is
untreated the more likely you will develop Barrett’s esophagus
and potentially esophageal cancer. The longer you have low
blood flow to your brain as a stroke evolves the more likely you
are to develop irreparable neurologic consequences. The longer
you have low blood flow to your heart, the more likely you will
have permanent consequences to the myocardium. And so it is
with inflammatory bowel disease. The longer you have unabated
inflammatory changes of the GI tract the more likely you will
have immutable consequences in the form of perhaps a fistula
or an abscess or a stricture and the more likely you will have
intractable disease that will not be amenable to medical therapy.
The purpose of this issue of Northeast Florida Medicine is to
give a cursory overview of numerous subtopics of inflammatory
bowel disease. However, if the only thing you take out of this
edition is the fact that time is tissue and that tissue is the issue,
then we have done our job. Enjoy.
v
Mark Fleisher, MD
Guest Editor
Advances in Inflammatory Bowel Disease
By Mark Fleisher, MD
References
1. Feagan BG, Chande N, MacDonald JK. Are there
any differences in the efficacy and safety of different
formulations of Oral 5-ASA used for induction
and maintenance of remission in ulcerative colitis?
evidence from cochrane reviews.
Inflamm Bowel
Dis.
2013 Aug;19(9):2031-40.
2. Sninsky CA, Cort DH, Shanahan F, Powers BJ, Ses-
sions JT, Pruitt RE, Jacobs WH, Lo SK, Targan SR,
Cerda JJ, et al. Oral mesalamine (Asacol) for mildly
to moderately active ulcerative colitis. A multicenter
study.
Ann Intern Med.
1991 Sep 1;115(5):350-5.
3. Giannini EG, Kane SV, Testa R, Savarino V. 5-ASA
and colorectal cancer chemoprevention in inflam-
matory bowel disease: can we afford to wait for ‘best
evidence’?
Dig Liver Dis.
2005 Oct;37(10):723-31.
4. Ritland SR, Leighton JA, Hirsch RE, Morrow JD,
Weaver AL, Gendler SJ. Evaluation of 5-aminosa-
licylic acid (5-ASA) for cancer chemoprevention:
lack of efficacy against nascent adenomatous polyps
in the Apc(Min) mouse.
Clin Cancer Res.
1999
Apr;5(4):855-63.
5. O’Connor A, Packey CD, Akbari M, Moss AC. Me-
salamine, but Not Sulfasalazine, Reduces the Risk of
Colorectal Neoplasia in Patients with Inflammatory
Bowel Disease: An Agent-specific Systematic Review
and Meta-analysis.
Inflamm Bowel Dis.
2015 Aug
20. [Epub ahead of print]
6. Camma C, Giunta M, Roselli M, Cottone M. Me-
salamine in the Maintenance Treatment of Crohn’s
Disease: A Meta-analysis Adjusted for Confounding
Variables.
Gastroenterol.
1997;113; 1465-73.
7. Warman JI, Korelitz BI, Fleisher MR, Janardhanam
R. Cumulative experience with short- and long-term
toxicity to 6-mercaptopurine in the treatment of Crohn’s
disease and ulcerative colitis.
J Clin Gastroenterol.
2003
Sep;37(3):220-5.