Adalimumab Treatment After Complete Resolution of Sepsis and Abscess in Patients With Crohn's Disease

Complications in treatment management

Dr. Naik: A really interesting study from DDW answered some of those questions about potential treatment options for patients with Crohn's disease and intra-abdominal abscesses, presumably from intrabdominal penetrating fistulizing disease. And so the management of this is very complicated. There has been some guideline-based therapy approach you have there. But this is a common complicated scenario where we need to have radiologists, interventional radiology, colorectal surgeons, inflammatory bowel disease gastroenterologists, et cetera. And potentially infectious disease colleagues to help really manage these patients when there's malnutrition, there's an infection, there's inflammation from Crohn's at the same time. And certainly things that we're considering are utilizing biologic therapy, utilizing antimicrobial therapy, non-invasive or "less invasive," I should say. Abscess drainage versus abdominal resection. Then how to manage nutrition in these complicated patients, right?

And it's very complicated. It's challenging and we have to think about surgery in these patients, but what this study tried to do is looked at the role of adalimumab after the complete resolution of sepsis and abscess in patients. Interestingly enough, they want to look at the long-term results. Say, "Hey, are we just kind of delaying [things here]?"

Study design

And so this is again, a multicenter, prospective, observational cohort from the GETAID group, in adults, essentially, with ileocolonic Crohn's disease and intraabdominal abscesses confirmed by cross-sectional imaging, with CT-MRE. And many are using ultrasound, trans-abdominal ultrasound, overseas, which I think is also a separate issue to discuss, but certainly something that, I think, has potentially really good potential outcome here, if adopted.

Inclusion criteria for this study were: you got to be less than 12 weeks after the intestinal resection, need for immediate surgery, which included if there were any perineal abscesses, abscesses during previous anti-TNF therapy, or previous failure of, obviously, adalimumab. They looked at success at week 48. They looked for relapse-free, abscess-free survival, intestinal resection. They looked at the baseline factors for these patients. And the doses that they used of adalimumab were the appropriate FDA-approved doses of 160, 80, and 40 every other week.

And these were essentially people who were a little younger, in their 20s. About a third were active smokers. They've had disease for about anywhere from 0 to 16 months, median 2. And I think a third were on systemic corticosteroids, a third were on thiopurines or methotrexate. And this is overwhelmingly a small bowel Crohn's disease abscess study, for 86% of the patients. And I'd say only about 10% of them were drained percutaneously. On most of them you could see the visualized fistula tract, and these abscesses were about 25 mm or so in size. I would like to say everybody, but somehow 97%, or I guess a large percentage of them were systemic antimicrobials for the treatment of this.

Study results

Honesty, a really interesting study. A relapse-free survival, so defined as no intestinal resection or abscess, one year, 77%; two years, over 70%. And then even in adalimumab-exposed patients, obstruction was only in about 13%, recurrence, only 14%. Really, a kind of fascinating study. At four years of follow-up, the cumulative incidence rate of adalimumab failure was 50%, or so, and intestinal resection rates were about 25%.

So, definitely is an option in patients with recently diagnosed, remember it's short disease duration here, complicated with this really small inch abdominal abscess. Once controlling the abdominal sepsis with antimicrobials, you really could consider adalimumab as maintenance therapy, following the resolution of the abscess and in a multidisciplinary fashion.

Considerations for use

What you have to remember, in our practice when we think about this study, how we align these results, is this is patients with early disease, relatively small abscesses, very minimal requirements for percutaneous drainage. I'm not a fan of leaving a potentially drain in place, et cetera. And we don't know how commodating immunomodulators may look. And a very important thing to consider in these patients is whether or not there's element of fibrotic or stricturing disease, which we don't really have a lot of information on.

Certainly, treating when that's on board, maybe potentially an operative approach may be of benefit, honestly. As you know, our antifibrotic therapies are quite limited at this point to almost non-existent. We don't have a lot of other evidence and other biologics, let alone things outside of the TNF inhibitor class. So any extension to that would be exploratory events and that's supported by this study.

I will say in my practice I've had utilized those approaches occasionally, and had varying success. I think it's something to consider, but the most important thing here is to realize that there are patients that you can potentially recuperate and improve. And should there be an operation necessary, there's a lot of data now that TNF inhibitors are safe in patients who require operations downstream. Out of the scope of this trial, but we know stuff from the PUCCINI study that when we were awaiting its final release that operating on patients with TNF inhibitors on board is relatively safe, as long as steroids and nutrition are under good control. So, a really important way that we can potentially help a lot of patients, and feel better about some of our treatment decisions.