Research: Early introduction of biologic therapy improves Crohn's disease outcomes

[zumone2002]

http://www.eurekalert.org/pub_releases/2012-04/uocm-eio041712.php

Early introduction of biologic therapy improves Crohn's disease
outcomes

A large-scale study of medical claims data shows that introducing
sophisticated biologic therapies early in the course of treatment for
Crohn's disease improves response to medication and reduces the need
for surgery.

There is no known cure for Crohn's disease, and traditional treatment
is focused on a "step-up" strategy of managing inflammatory symptoms,
starting with simpler and less costly oral medications such as
aminosalicylates (5-ASAs) and corticosteroids, and escalating through
a series of steps to more expensive biological therapies that target
specific proteins in the immune system's inflammatory response.

David Rubin, MD, associate professor of medicine and co-director of
the University of Chicago Medicine's Inflammatory Bowel Disease
Center, studied a newer "top-down" strategy that reverses this order
of treatment. He found that patients treated with biologic therapies
earlier were significantly less likely to need steroids, lose response
to their biologic therapy, and require surgery related to their
Crohn's disease. "We're essentially reversing the management strategy
in Crohn's disease," Rubin said.

He emphasized that the medications often used first for patients with
Crohn's are also the least effective and carry risks for side effects.
"We've long discussed and debated that 5-ASAs don't work in the
majority of Crohn's patients, and certainly don't change any
outcomes," he said. "Steroids are ineffective long-term and are also
dangerous because they have significant side effects such as
infections."

Crohn's is a disorder in which the body's immune system appears to
have lost the ability to regulate itself and becomes overactive,
causing progressive damage to the bowel structure and function.
Patients often need bowel surgery to repair this damage. Researchers
have made great progress finding genetic and environmental
contributors to Crohn's disease, but the actual cause is unknown.

Rubin said that physicians have questioned the effectiveness of the
step-up strategy because patients experience little relief while being
treated with medications before they receive the biological therapies.
During that time, they suffer from active disease, have low rates of
remission and often appear to lose response to the biological
therapies.

In recent years a treatment strategy that starts with the targeted
biologic therapy as a first option has been explored in controlled
clinical trials. The encouraging results suggested that such an
approach results in higher remission rates. However, it was not clear
whether this top-down approach would translate to the general
population of patients with Crohn's disease, or whether such an
approach would maintain the response to biologic therapy and decrease
the need for surgery.

The Food and Drug Administration approved the first targeted biologic
therapy for Crohn's disease in 1998 and the second two in 2007 and
2008. Rubin said physicians are hesitant to prescribe them earlier
because they are expensive, must be administered through injections
instead of pills and are typically saved until last,. "Patients and
doctors are nervous about immune suppressive therapies. The perception
in the current treatment algorithm is that the therapies saved for
last must also be the most dangerous," he said. "But that's the wrong
thinking, and by delaying their prescription it may be a self-
fulfilling prophecy because by then patients have suffered more damage
to their bowels and are less likely to respond favorably."

In the study, published in the journal Inflammatory Bowel Diseases,
Rubin and his colleagues analyzed health insurance claims from a
database that includes records from more than 94 commercial health
plans throughout the United States. Patients eligible for the study
had to be enrolled in the same health plan continuously for at least
six months before the first claim related to Crohn's and stay enrolled
for at least 12 months after the first claim for anti-TNF treatments.

Rubin then separated these patients into three groups: those who
followed the traditional step-up therapy starting with 5-ASAs or
corticosteroids before anti-TNF treatment, those who had
immunosuppressive therapy (but not 5-ASAs) before anti-TNF treatment,
and those who started anti-TNF treatment within 30 days of their first
prescription for Crohn's disease.

In general, the group that started anti-TNF treatment early had
significantly lower rates of continuous steroid use to treat flare-ups
than the other groups, lower rates of escalation of dosage for their
medications and needed fewer surgeries related to Crohn's disease.
"This is the first time we did a large assessment of the top-down,
early-TNF strategy using claims databases," Rubin said. "It gave us
lots of detail and lots of information, much larger than with a
controlled trial. We could look at hundreds of thousands of patients
in order to get a big picture of how effective these approaches are in
treating Crohn's. It's also the first time we were able to examine
surgical outcomes associated with this strategy."

"Having a new class of therapies and having a culture change in GI
takes a lot of discussions," he said. "This paper contributes to the
discussion about how important this kind of treatment is because it
changes the outcomes for people suffering from Crohn's disease."

--
Luke

[Jeff]

what a novel idea "let's give the most effective treatments first",
sounds like a break through in thinking, makes sense!

[zumone2002]

Hi Jeff,

> what a novel idea "let's give the most effective treatments first",
> sounds like a break through in thinking, makes sense!

Doctor's usually go with the the safest treatment first. Most of the
new biologics have death as a rare side effect. Its one reason meds
like 5 ASA get tried even though they don't work well for CD.

Using your “reasoning” people with UC should immediately get their
colon removed, no colon, no disease. The most effective treatment.

--
Luke

[Jeff]

comments embedded below, and sorry for late posts, I don't check here
every day but try to catch up when I can.

On 5/23/2012 1:04 AM, zumone2002 wrote:
> Hi Jeff,
>
>> what a novel idea "let's give the most effective treatments first",
>> sounds like a break through in thinking, makes sense!
>
> Doctor's usually go with the the safest treatment first. Most of the
> new biologics have death as a rare side effect. Its one reason meds
> like 5 ASA get tried even though they don't work well for CD.

I am well of the treatment progressions, and reasons, for the most part,
that hasn't changed much for as long as I can remember, or at least the
last 12 years since I've been a member of this group. Start with the
safest, etc etc.

But what I didn't know is that the 5 ASA's are not that effective for
CD. IBD is a disease of progression. If left untreated or poorly treated
it will likely progress and affect larger parts of which ever organ(s)
it is affecting. Therefore giving more effective treatments earlier on
could save people a lot of suffering and possible irreversible damage.
Actually the main point of this article is exactly that. I understand
the dangers and death is a serious side-effect but correct me if I'm
wrong they have made progress in understanding and reducing those risk
factors. Of course people should be informed of any and all serious
side-effects so they can make an informed decision about their treatment
selection.

In any case I was merely summarizing the main thrust of the article.

>
> Using your “reasoning” people with UC should immediately get their
> colon removed, no colon, no disease. The most effective treatment.

Not so fast. It's a huge jump between taking drugs and/or making
lifestyle changes to effectively reduce symptoms to a manageable state -
to removing your colon which is an irreversible and life changing event.
Removing the colon carries a very significant lifestyle adaptation. I
have seen people post who say it's the best thing they've ever done,
but those people continued to suffer before making that decision. Having
your colon removed can have substantial social consequences for some. My
father had colon cancer and he eventually had his entire lower colon
removed, he had a stoma and a bag somewhere around mid-chest level. I
witnessed first hand what had to be done to attach, detach and empty the
bag. So please don't assume to think I don't know what that entails. My
father was retired, and had my mother and family for support. It would
be not so easy if you still had to show up at the office and had to deal
with that. Or imagine dating and springing that little surprise on
someone. I have the utmost compassion for anyone who can and has to deal
with all those issues. In my case and many others there are much better
options so there is no point in jumping to the extremes. And as we all
hope, there is new information and hopefully promising new treatments
coming down the pike which may obviate the need for extreme measures.
But again, making that decision is a big one and each individual must
weigh all the factors carefully.

>
> --
> Luke