Sa1925

Does Obesity Impact Treatment Efficacy of Adalimumab and CertolizumabPegol in Crohn's Disease?Benjamin Click, Anne G. Tuskey, Brian W. Behm

BACKGROUND: Adalimumab (ADA) and certolizumab pegol (CZP) are injectable biologicscurrently approved for moderate to severe Crohn's disease (CD) failing to respond adequatelyto conventional therapy. Unlike infliximab, ADA and CZP do not use weight-based dosing.Recent data involving patients with psoriasis suggest that the efficacy of adalimumab maybe reduced in obese patients, although this association has not been found in CD. The aimof this study was to determine whether obesity influences treatment efficacy and need fordose escalation of ADA or CZP in patients with CD. METHODS: A retrospective chart reviewwas performed to identify patients with CD treated with ADA or CZP at our institutionfrom January 2006 to October 2011. The primary outcomes of interest were the proportionof patients with a clinical response to induction with ADA and CZP, and the proportion ofpatients that underwent dose escalation (for ADA) or reinduction (for CZP) in obese vnonobese patients. Patients were defined as nonobese (body mass index (BMI) <30) or obese(BMI >30). Patients were excluded if less than 3 months of follow up data were available.Statistical analysis was done by chi-square analysis and student's t-test. RESULTS: 135Crohn's patients (107 ADA, 28 CZP) were included. 35/135 patients had a BMI >30. Medianage was 38 (range 19-73), 63% were female, and median disease duration was 11 years(range 0-37). There were no significant differences in clinical response to ADA induction(obese 23/29 79.3%, nonobese 58/78 74.4%; p =.80). A higher proportion of obese patientsunderwent dose escalation with ADA although this was not statistically significant (obese12/29 41.4%, nonobese 21/78 26.9%; p =.16). There were no differences in response todose escalation (obese 58%, nonobese 62%) or proportion of patients that remain on therapy(obese 55%, nonobese 55%). Patients receiving CZP had no significant differences in clinicalresponse to induction (obese 2/6 33%, nonobese 12/22 54%; p=.64) or rates of reinduction(obese 20%, nonobese 36%; p=.64) and proportion of patients remaining on therapy (obese17%, nonobese 14%). However these numbers are limited by small sample size. The meanduration of therapy was 12 months (range 4-56) for ADA and 7 months (range 3-26) forCZP. CONCLUSIONS: In this cohort of Crohn's patients, obesity was associated with similarrates of clinical response to ADA and CZP compared with nonobese patients. Obese patientshad higher rates of dose escalation of ADA, although this difference was not statisticallysignificant. Obesity did not impact the proportion of patients that remain on therapy.

Sa1926

Durability of Anti TNF α Therapy in Ulcerative Colitis: Switching is anEffective Strategy in a Small Subset of PatientsLilani P. Perera, Yelena Zadvornova, Kia Saeian, Corinne Guilday, Daniel J. Stein, Amar S.Naik

Background: Infliximab is an effective maintenance for moderate to severe Ulcerative colitis(UC); however, problems with immunogenicity and decreased efficacy often complicatelong-term use. Durability of other anti TNF agents (adalimumab and Certolizumab) andmaintenance therapy over multiple years has not been well defined. Methods: A retrospective,observational study of UC patients who received maintenance anti TNF (ATNF) for ≥ 6months with the intention of ongoing maintenance. Patients were categorized into thosewho either continued treatment or discontinued maintenance therapy. We examined theimpact of demographic, clinical characteristics, and Clostridium difficile infection on long-term durability of ATNF therapy and also examined the reasons for discontinuation oftherapy including colectomy. Subgroup analysis was performed to study the use of first,second or third ATNF agent. Results: A total of 145 UC patients received maintenance ATNFtreatment ≥ 6 months and 37 (26%) ultimately discontinued treatment. The mean durationof maintenance treatment at the time of discontinuation was 1.7± 1.5 yrs compared 3.4±1.9 yrs in the group continuing therapy (p=0.0001). There was no difference in age at firstATNF, disease duration at first ATNF, gender, or ESR between groups. The main reasonsfor discontinuation were allergy/adverse reaction 15 (41%) and loss of response/colectomy22 (59%). Use of concomitant immunosuppression was similar between the 2 groups (82%versus 79%, p= 0.84). However, the discontinued group had significantly high rate ofsurgeries, hospitalizations CRP and UCDAI (table). Discontinued group had significantlylower SIBDQ score (45±11 vs 50±10, p=0.005). In continued group 90 (83%) patients wereon their first ATNF and 17 (16%) were on the 2nd ATNF agent. Conclusions: 62% ofpatients on long-term ATNF maintenance successfully continue their initial treatment. Anadditional 12% canmaintain remission by switching to a second ATNF. These data emphasizethe need to change ATNF therapy for a significant minority of patients to have successfullong-term management of their UC.

S-361 AGA Abstracts

Sa1927

The use of Infliximab in Older Inflammatory Bowel Disease PatientsStephanie M. Moleski, Christina C. Lindenmeyer, Patricia L. Kozuch

BACKGROUND: The limited data regarding treatment of inflammatory bowel disease (IBD)with anti-tumor necrosis factor (TNF) antibodies in older patients suggests equal efficacybut higher morbidity and mortality in this cohort compared to younger patients. METHODS:IBD patients ≥ 60 y.o. treated with infliximab (IFX) from 2006-11 were identified fromICD-9 codes. A retrospective chart review evaluated clinical and endoscopic response aswell as adverse events related to treatment in this age group. RESULTS: Among IBD patientstreated with IFX (n=253) during this time period, 27 (11%) were ≥ 60 y.o. An additional4 patients received IFX elsewhere but were subsequently followed at our center. There were18 women and 13 men, with a mean age of 69.3 (60-81). Fourteen patients had Crohn'sdisease (45%), 15 had ulcerative colitis (48%) and 2 had indeterminate colitis (7%). Themean duration of treatment was 26.5 mos (2-86 mos). Eleven (35%) were on concomitantimmunomodulators (IMM). Ten (32%) patients achieved clinical remission (as definedby physician global assessment and no pain medications/steroids/additional medications/hospitalizations for IBD); eight (26%) patients had a partial clinical response and 13 (42%)had no clinical response. Of the patients with endoscopic data available both pre and posttreatment (n=17), 4 (24%) had mucosal healing, 5 (29%) had endoscopic improvement,and 8 (47%) had no endoscopic improvement. Ten (32%) patients experienced 13 adverseevents (AEs) thought reasonably related to IFX treatment, with 6 (19%) considered seriousAEs. Eight (31%) developed infections requiring antimicrobial therapy, but only 2 (6%)required hospitalization. Two (6%) patients had infusion reactions. One patient developedtwo malignancies (melanomas) during treatment, another congestive heart failure, and onea lupus-like reaction. Three of the 11 (27%) patients on concomitant IMMs experiencedAEs. There were no deaths. CONCLUSIONS: IBD patients ≥ 60 y.o. treated with IFX havea similar rate of clinical response but a higher rate of serious AEs compared to younger IBDpatients as previously reported in randomized controlled trials (e.g. ACCENT I). While thiscase series is relatively small, the data suggests that IFX is an effective therapy in olderpatients but should be used judiciously secondary to a higher rate of complications.

Sa1928

Reduced Fatigue in IBD Patients Undergoing Psychotherapy is AssociatedWith a Reduction in Serum IL-12 LevelsColin de Haar, Lauran Vogelaar, Bas Aerts, Maikel P. Peppelenbosch, Ernst J. Kuipers,Christien J. van der Woude

BACKGROUND Fatigue is an important factor in the decreased quality of life of inflammatorybowel disease (IBD) patients. A direct link between fatigue and the immune system issuggested in a variety of diseases. We previously showed that serum levels of variouscytokines differed between fatigue and non-fatigue patients with IBD in complete remission.In the current study we investigated whether psychotherapy-induced reduction in fatiguewas associated with changes in serum cytokine levels as well. METHODS IBD patients inclinical and biological remission, defined by a normal Harvey Bradshaw Index (< 5) andColitis activity index (< 10) were included. The Checklist Individual Strength (CIS) wasused to assess fatigue. Patients with fatigue received psychotherapy that consisted of 7sessions over a period of 6 months. Response to therapy was defined as a drop in CIS scoreof at least 5 points. Serum samples were collected before, during, after psychotherapy andthe levels of IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNFα and IFNg were measured usingELISA. The changes and differences in serum cytokines between responders and non-responders were assessed. Change over time was modeled for measures of different cytokinesusing mixed-effects regression analyses. RESULTS In total 55 fatigue patients (CIS score of≥ 35) were included, of whom 58% responded to the psychotherapy whereas 42% didnot. Of the cytokines measured we only detected an overall significant drop in IL-12 levelsin the responders vs. non-responders (p=0.028). The levels in the responders were already

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