CME

Practical Considerations for the Use of First-Line Therapies in Ulcerative Colitis: A Case-Based Approach

Seymour Katz, MD

Albert Einstein College of Medicine
Yeshiva University
Bronx, New York

The questions below were submitted by your peers based on a recent CME activity.
The Course Director, Dr. Seymour Katz, provides his answers below.

Question 1: I'm having trouble with the seesawing of the recommendation of immunomodulators with or without biologics. Together, they may achieve remission quicker and more often and have less antibiologic antibody development, but what about the infection risk and neoplasia risk? Should I reserve combination therapy for only the sickest patients? Is there less potential for favorable response with starting one class then adding another later?

Question 2: I have a 50-year-old patient with proctosigmoiditis who has, over 20 years, transitioned to universal colitis. She is not responsive to 5-ASA preparation or steroids and could not tolerate 6-MP due to nausea and abdominal pain. She has a history of untreated hepatitis C type 1b with minimal change on biopsy 8 years ago. What is your next choice of treatment?

Question 3: My patient has a 20-year history of ulcerative colitis (UC) with no acute episodes in the past 8 years. A colonoscopy 4 years ago showed "burnt-out colitis” but no evidence of active disease. What is this patient’s risk for colorectal cancer (CRC) and the suggested follow-up?

Question 4: Compliance is a huge issue, particularly for proctitis and proctosigmoiditis. Is there a reliable maintenance regimen? And, how soon after the first flare (diagnosis) would one consider transition to maintenance?

I'm having trouble with the seesawing of the recommendation of immunomodulators with or without biologics. Together, they may achieve remission quicker and more often and have less antibiologic antibody development, but what about the infection risk and neoplasia risk? Should I reserve combination therapy for only the sickest patients? Is there less potential for favorable response with starting one class then adding another later?

The initial clinical trials of biologics have uniformly revealed a lack of immunomodulators’ contribution to the efficacy of these agents [Oussalah A et al. Am J Gastroenterol. 2010;105:1142-1149]. The SONIC trial, which definitely showed a benefit to dual therapy (biologic and immunomodulators) was conducted in a unique group of patients who were naïve to immunomodulators at entry, generally young (average, 32 years), and with a shorter duration of disease [Colombel JF et al. N Engl J Med. 2010;362:1383-1395]. Thus, the comparison with prior trials of mixed ages, disease duration, and multidrug exposure is not appropriate.

The risks of opportunistic infections [Pepio A et al. Am J Gastroenterol. 2010;105(Suppl 1):S431-S432. Abstract 1184] and fears of hepatosplenic T-cell lymphoma (HSTCL) [Ehrenpreis E et al. Am J Gastroenterol. 2010;105(Suppl 1):S475-S476. Abstract 1291], albeit small, still lurk in the minds of patients. Based on the present data, my recommendations are:

Limit biologics to the “severe” patient category.
Limit monotherapy (ie, biologics) to young males under 30, which is the most vulnerable group to HSTCL, or the elderly with risk of prostate, breast, or ovarian cancer unless severe fistulizing disease or multicentric inflammatory disease co-exists.
Many patients will respond to immunomodulators alone, provided they are not too sick to wait the 6 to 8 weeks before drug impact. If they are too ill, biologic therapy at the onset is always best given on a maintenance schedule.

I have a 50-year-old patient with proctosigmoiditis who has, over 20 years, transitioned to universal colitis. She is not responsive to 5-ASA preparation or steroids and could not tolerate 6-MP due to nausea and abdominal pain. She has a history of untreated hepatitis C type 1b with minimal change on biopsy 8 years ago. What is your next choice of treatment?

I would advise biologic therapy at this point, provided an adequate course of topical therapy has been given concomitantly with prior oral therapy. Often, alternating hydrocortisone enemas every other night with 5-ASA enemas can “turn the corner.”

The risks of biologics in liver disease appear to be limited to patients with hepatitis B [Loras C et al. Gut. 2010;59:1340-1346]. Indeed, fatal hepatitis has been described with such therapy in that population alone [Elkayam O et al. Ann Rheum Dis. 2002;61:623-625]. If the viral PCR RNA level is measured as an index of activity, then hepatitis C therapy should commence and subsequently be followed with biologic therapy for intractable left-sided IBD. I would be sure that the patient is vaccinated against hepatitis A and B.

My patient has a 20-year history of ulcerative colitis (UC) with no acute episodes in the past 8 years. A colonoscopy 4 years ago showed "burnt-out colitis” but no evidence of active disease. What is this patient’s risk for colorectal cancer (CRC) and the suggested follow-up?

Surveillance colonoscopy is appropriate for your patient. Although the present thrust is to control inflammation as a precursor to dysplasia [Rubin DT, Sederman R. Gastroenterol. 2009;136(Suppl 1):959. Bupta PB et al. Gastroenterol. 2007;133:1099-1105], we always worry about the silent quiescent UC patient with the disease duration of your patient. There is conflicting data about 5-ASA’s role as a chemo protective agent, but the UCSF meta-analysis and a recent French experience appear supportive of this role [Carrat F et al. Digestive Disease Week 2010. Abstract 255. Velayos FS et al. Gastroenterol. 2004;126:A20(A536)].

Our experience of an 8% incidence of CRC in our IBD patients with risk factors of long disease duration, pancolitis, and positive family history of CRC forces us to follow a scheduled yearly colonoscopy program.

Compliance is a huge issue, particularly for proctitis and proctosigmoiditis. Is there a reliable maintenance regimen? And, how soon after the first flare (diagnosis) would one consider transition to maintenance?

Proctitis and proctosigmoiditis patients can represent a formidable compliance challenge once they feel “better.” Considerable support from the physician and medical team is needed to keep such patients in control. I have found that the adage “the dose that gets you into remission should be the dose that keeps you in remission” resonates well. Topical therapy combined with dual therapy is best [Safdi M et al. Am J Gastroenterol. 1997;92:1867-1871. Regueiro MD. J Clin Gastroenterol. 2004;38:733-740], but this dual therapy is often hard to enforce once the fear of urgency and incontinence has passed. Regularly scheduled visits with the medical team have been our most effective maintenance tactic.