Faculty Bibliography

Patients with elderly-onset IBD are more likely to have marked comorbidities and polypharmacy than those diagnosed at a younger age, which might affect therapeutic decision-making. Increased knowledge of this higher-risk group might guide patient management. Data from a large population-based study evaluating the clinical presentation and course of elderly-onset IBD are discussed.

BACKGROUND: 6-Mercaptopurine (6-MP) and azathioprine (AZA) are effective for induction and maintenance therapy of Crohn's disease (CD) and ulcerative colitis (UC). There is an increased risk of lymphoma in patients with inflammatory bowel disease (IBD) treated with 6-MP/AZA. Little, however, is known about the prognosis of IBD patients treated with 6-MP/AZA who develop lymphoma. METHODS: We conducted a retrospective review of 8780 records from three tertiary IBD centers and the records of 600 lymphoma patients from an academic Hematology and Oncology Center. The primary endpoint variable was survival of IBD patients with a lymphoma diagnosis treated or not treated with 6-MP/AZA. A secondary endpoint was the relative survival rate (by gender, race, and ethnicity) extrapolated from the Surveillance Epidemiology and End Results (SEER) database, computed for each subject. RESULTS: Fourteen IBD patients were diagnosed with lymphoma. Twelve had CD and two had UC. Seven patients had treatment with 6-MP/AZA and seven had not. Two patients who received 6-MP/AZA died (both 1 year after diagnosis) and two patients who had not received 6-MP/AZA died (one after 2 years, another 3 years after diagnosis), all from lymphoma. Survival at last follow-up was similar to expected survival based on extrapolated SEER data for both 6-MP/AZA treated and untreated patients. CONCLUSIONS: We found no differences of survival with lymphoma between IBD patients and expected survival for the general population. Also, the prognosis for those IBD patients treated with 6-MP/AZA was not worse than lymphoma patients not treated with 6-MP/AZA. Statistical analysis, however, was limited by the small sample size and heterogeneity of the patients studied.

BACKGROUND: This was a phase IV, multicenter, open-label, 12-14-month study to assess clinical recurrence in patients with ulcerative colitis (UC) who received maintenance treatment with MMX Multi Matrix System (MMX) mesalamine. A secondary outcome was the relationship between long-term efficacy and adherence. METHODS: Patients with quiescent UC (no rectal bleeding; 0-1 bowel movements more than normal per day) were enrolled directly into a 12-month maintenance phase of the study during which they received MMX mesalamine 2.4 g/day given once daily (QD). Patients with active, mild-to-moderate UC at screening were enrolled into a 2-month acute phase; those who achieved quiescence could continue into the maintenance phase. The primary endpoint was clinical recurrence at Month 6. RESULTS: Of the 290 patients enrolled, 208 entered the maintenance phase; 152 directly and 56 via the acute phase. Following 6 and 12 months of treatment, 76.5% and 64.4% of evaluable patients, respectively, were recurrence-free. The majority of evaluable patients at Month 6 (81.6%) and Month 12 (79.4%) in the maintenance phase were >/= 80% adherent to MMX mesalamine. At Month 6, clinical recurrence was observed in 20.6% of patients who were >/= 80% adherent and 36.1% of patients with <80% adherence (P = 0.05 [post-hoc chi-square analysis]); 31.2% and 52.5% at Month 12 (P = 0.01 [post-hoc chi-square analysis]). CONCLUSIONS: MMX mesalamine 2.4 g/day QD is effective for maintaining quiescence in patients with UC. Furthermore, adherence to prescribed treatment yielded lower rates of clinical recurrence. Continued education regarding the importance of long-term 5-aminosalicylic acid therapy is warranted.

Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD-susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2-4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5x10(-)(6)). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2x10(-)(8); combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7x10(-)(9); OR = 1.16), 8q21.11 (rs12677663, p = 2x10(-)(8); OR = 1.15), 10q26.3 (rs10734105, p = 3x10(-)(8); OR = 1.27), and 11q12.1 (rs11229030, p = 8x10(-)(9); OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim.