- Email: [email protected]
Clinical manifestations of the nod2 gene in familial Crohn’s Disease
S260
Abstracts
AJG – Vol. 97, No. 9, Suppl., 2002
phosphate buffer (pH 7.5) and the experiment was continued for another 8 hours at the same media flow. The budesonide content in the fractions from the release analysis was then investigated by a liquid chromatography system. A reference experiment was performed for comparison where the granules were analyzed in the same way except that they were not exposed to applesauce. Results: Mean Value and Range of 6 Samples % Budesonide % Budesonide release in SGF released in pH 1.2 SIF pH 7.52 Experiment
2h
Applesauce 0.7 (0.5–0.9) experiment Reference 0.5 (0.4–0.6) experiment
1h
2h
4h
8h
29 (28–30)
49 (48–51) 77 (76–80) 97 (95–100)
31 (30–31)
51 (51–52) 79 (77–82) 99 (95–102)
Conclusions: There is no change in the release properties of budesonide capsules 3 mg if the granules are mixed with applesauce for 30 minutes before administration.
792 ENDOSCOPIC HEALING INDUCED BY INFLIXIMAB MAINTENANCE THERAPY CORRELATES WITH LONG–TERM CLINICAL RESPONSE IN PATIENTS WITH ACTIVE CROHNS DISEASE. RESULTS OF ENDOSCOPIC SUBSTUDY OF ACCENT 1 P. Rutgeerts*, J.–F. Colombel, S. van Deventer, M. Vatn, R. Loftberg, S. Schreiber, M. Campieri, H. Malchow, J. Scholmerich, F. Cornillie, A. Olson, W. Bao, S. Katz and H. Lochs. GE, Univ Hosp Gasthuisberg, Leuven, Belgium; GE, Mayo Clinic, Rochester, MN; GE, Afdeling GE Acad Med Ctr, Amsterdam, Netherlands; Oslo, Norway; Huddinge, Sweden; Kiel, Germany; Bologna, Italy; Leverkusen, Germany; Regensburg, Germany; Centocor; Great Neck; and Berlin, Germany. Purpose: Examine patients (pts) achieving endoscopic (ENDO) healing at weeks (wk) 10 and 54 and correlate changes from baseline (BL) in CDEIS and CDAI . Methods: 573 ACCENT I pts received 5mg/kg infliximab (IFX) at wk0 and were randomized to 1 of 3 maintenance regimens (MNT) at wk2: 1)placebo (PBO)wk2, 6, q8wk, 2)5mg/kg IFX wk2, 6, q8wk, and 3)5mg/kg IFX wk2, 6, 10mg/kg IFX q8wk. Starting at wk14, pts who lost response could crossover to IFX episodic retreatment (EPI RETX) at 5mg/kg higher than assigned MNT dose. All pts at 25 selected sites could participate in ENDO substudy with assessments at wk0, 10 and 54. CDEIS and clinical response (CDAI association) were assessed using Spearman correlation coefficients. All wk2 responders were analyzed. Results: 99 pts enrolled in ENDO substudy; 66 responded to single 5mg/kg IFX infusion by wk2 and were randomized to PBO MNT(n⫽24), 5mg/kg IFX(n⫽19), 10mg/kg IFX(n⫽23). At wk10, 0% (0/17) PBO vs. 31% (10/32) IFX had MUC healing (p⫽0.010). At wk54, among pts not losing response, 63% (12/19) IFX showed MUC healing. Including EPI RETX, 7% (1/14) PBO vs 50% (13/26) IFX showed ENDO healing at wk54 (p⫽0.007). Including EPI RETX data, significantly more IFX MNT pts had ENDO healing at wk10 and 54 compared to PBO: 27% (7/26) vs. 0% (0/14) (p⫽0.03). A greater improvement in CDEIS from BL to wk54 was observed in IFX than PBO with EPI RETX (5.1 vs 1.1) or without EPI RETX (5.7 vs 0.7). Changes from BL CDEIS were positively, significantly correlated with changes from BL CDAI at wk10 and 54: r⫽0.307, p⫽0.021, and r⫽0.498, p⬍0.001, respectively. Conclusions: A majority of Crohns pts with sustained response to IFX showed ENDO healing (63%). 50% IFX pts achieved MUC healing at wk54 compared to 7%EPI RETX pts. Improvements in CDEIS and CDAI are positively, significantly correlated during IFX MNT. ENDO healing should be considered as an important treatment goal for pts with active CD.
793 UNEXPECTED DRAMATIC CLINICAL RESPONSE OF PSORIASIS LESIONS AND UNEXPECTED PREGNANCY IN AN INFERTILE PATIENT IN RESPONSE TO TREATMENT WITH ANTI–TUMOR NECROSIS FACTOR (TNFALPHA) MONOCLONAL ANTIBODY FOR CROHN’S DISEASE Leslie Bank* and Belinda Hunt. United Medical Associates, Binghamton, NY and Centocor, Inc, Malvern, PA. Purpose: Infliximab (IFX), a monoclonal antibody that neutralizes the biological activity of tumor necrosis factor alpha, is indicated for the reduction of signs and symptoms of Crohn’s disease (CD). Also, recent data suggest a role for IFX in treating plaque psoriasis. We report on a patient with CD and psoriasis, as well as history of infertility, who experienced clinical improvement after therapy with IFX. Of note, this patient became pregnant unexpectedly by natural means after IFX treatment and is 20 weeks into an apparently normal pregnancy. Recent data suggest that some infertility may be associated with elevated levels of TNF alpha. Methods: This 32–year– old woman had an 11–year history of refractory CD, along with psoriasis and a history of infertility. The patient was treated with IFX 5 mg/kg along with cyclosporine, total parenteral nutrition (TPN; the patient was unable to maintain adequate oral nutrition), mesalamine, and lansoprazole and reported dramatic improvement in her overall well– being within 1 week of the IFX infusion; TPN was discontinued. Results: Within 4 weeks of the IFX infusion, the patient’s CD was in remission and cyclosporine was being discontinued. Approximately 8 weeks following her initial IFX infusion, the patient had an exacerbation of her psoriasis (body surface involved approx. 80%). Cyclosporine was restarted, and her psoriasis improved. Several months following IFX infusion, the patient was scheduled for in vitro fertilization. The procedure was successful, but shortly thereafter the patient had a miscarriage. Three IFX infusions were given and dramatic clinical improvement was noted. After a second in vitro procedure that was unsuccessful, the patient received maintenance IFX infusions (every 8 weeks) for approximately 1 year. At this point the patient became pregnant unexpectedly by natural means. She is now 20 weeks into an apparently normal pregnancy. Conclusions: IFX was effective in treating longstanding refractory CD and psoriasis in a previously infertile woman. After 1 year of IFX maintenance therapy, the patient became pregnant unexpectedly by natural means.
794 CLINICAL MANIFESTATIONS OF THE NOD2 GENE IN FAMILIAL CROHN’S DISEASE Jean–Paul Achkar, M.D., Judy Cho, M.D., Aaron Brzezinski, M.D., Deborah Vogel, M.S. and Richard Duerr, M.D.*. Gastroenterology, Cleveland Clinic Foundation, Cleveland, OH; Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA and Medicine, University of Chicago, Chicago, IL. Purpose: Crohn’s disease (CD) is a heterogeneous disorder with varied clinical manifestations. Recently NOD2 was identified as the first gene associated with CD, allowing for genotype–phenotype correlations to be performed. Our aim was to determine whether the NOD2 gene was associated with specific clinical phenotypes in familial CD. Methods: Detailed CD–related phenotypic information was collected by chart review and telephone interviews for 129 CD–affected individuals from 61 families with 2 or more CD–affected members. Data collected included demographic information, age at diagnosis, disease location, disease behavior, and surgical history. Individuals were genotyped at the NOD2 gene for the Leu1007fsinsC, Gly908Arg, and Arg702Trp polymorphisms and were stratified as having 2 variant NOD2 alleles (N⫽25), 1 variant NOD2 allele (N⫽42) or 0 variant NOD2 alleles (N⫽62). Data analysis was performed using Pearson Chi–square tests. Rao–and–Scott corrections for clustering were used to account for intrafamily correlation.
AJG – September, Suppl., 2002
Abstracts
Results: Demographic data and duration of follow– up were similar for the 3 groups. Patients with 2 NOD2 variants were more likely to have fistulizing or stricturing disease behavior (P⫽0.006) and were more likely to require surgery (P⫽0.005) when compared to those with 0 or 1 NOD2 variants (See table). Trends for younger age at diagnosis and absence of colonic disease were also noted in the group with 2 NOD2 variants. Logistic regression demonstrated that patients with 2 NOD2 variants had an odds ratio of 2.4 (95% CI⫽1.1–5.0; P⫽0.022) for development of fistulizing or stricturing disease when compared to other groups. NOD2 Genotype–Phenotype Correlation
Median age at diagnosis Colon only disease Fistulizing or stricturing disease Surgical resection
0 NOD2 Variants (Nⴝ62)
1 NOD2 Variant (Nⴝ42)
2 NOD2 Variants (Nⴝ25)
P–value
22.0 15% 52%
22.0 12% 68%
19.0 0 79%
0.09 0.055 0.006
65%
81%
92%
0.005
Conclusions: 1. CD–associated NOD2 variants are associated with more aggressive disease behavior and higher frequency of surgical resection in familial CD. 2. CD–associated NOD2 variants may also be associated with younger age at diagnosis and absence of colonic disease.
795 IMPROVED PERI–OPERATIVE SURGICAL OUTCOME IN CROHN’S DISEASE PATIENTS RECEIVING CONCOMITANT IMMUNOMODULATOR THERAPY Grace S. Tay, M.D., Mary F. Otterson, M.D. and David G. Binion, M.D.*. Medicine, Medical College of Wisconsin, Milwaukee, WI and Surgery, Medical College of Wisconsin, Milwaukee, WI. Purpose: Although efficacious, medical management of moderate to severe Crohn’s disease (CD) using immunomodulator and biologic agents has not eliminated the role for surgical treatment of disease complications, specifically intestinal stricture and lumenal obstruction. Intra–abdominal septic complications (IASC: intra–abdominal abscess, anastomotic leak, fistula) are dreaded complications of CD surgery. We hypothesized that medical treatment with immunomodulators improves perioperative surgical outcome, as adequately treated CD decreases the rate of IASC in the 6 weeks following operation in pts requiring intestinal anastomosis and/or strictureplasty. Methods: Surgical outcome was reviewed in 92 pts followed in an IBD referral center, who underwent 101 operations involving primary anastomosis and/or strictureplasty for CD between 1998 –2001. IASC (intra– abdominal abscess, anastomotic leak, and/or enterocutaneous fistulae occurring in 6 weeks following surgery), were compared between pts receiving and not receiving peri– operative immunomodulator agents (azathioprine, 6 –MP, methotrexate, mycophenolate mofetil and/or infliximab during the 2 months prior to surgery). Results: IASC developed in 13 out of 101 (12.9%) operations. Immunomodulator use was associated with fewer IASC (4/72 procedures; 5.6%) compared with 9/29 (31.0%) cases with pts not on immunomodulator therapy (p⫽⬍ 0.05). Length of hospital stay was significantly lower in the immunomodulator treated group (p⫽⬍0.05). Serum albumin levels ⬍ 3.0 g/dl were significantly associated with a higher IASC rate, but were identical in the immmunomodulator and non–immunomodulator treated groups. Rate of IASC was not influenced by steroid use, smoking status, and the presence of pre– operative abscess and/or fistula. Immunomodulator use did not affect length of resected bowel, or the rate and number of strictureplasties. Rate of IASC was not associated with emergent operation and more pts receiving immunomodulator therapy required emergent surgery compared to non–immunomodulator treated group. Conclusions: Optimizing medical management with immunomodulator therapy significantly decreases post– operative intra–abdominal septic com-
S261
plications and length of hospital stay in CD patients undergoing surgical procedures requiring either anastomosis and/or strictureplasty.
796 SUCCESSFUL TREATMENT OF PERISTOMAL PYODERMA GANGRENOSUM WITH INFLIXIMAB Jean–Paul Achkar, M.D.*, Aaron Brzezinski, M.D., Conor Delaney, M.D., Tracy Hull, M.D. and Bret Lashner, M.D. Center for Inflammatory Bowel Diseases, Cleveland Clinic Foundation, Cleveland, OH. Purpose: Following the creation of a stoma in patients with inflammatory bowel disease, peristomal pyoderma gangrenosum (PPG) is an uncommon but difficult condition to treat. The purpose of this study was to evaluate the use of infliximab as therapy for PPG. Methods: Four patients with PPG were seen over the past 2 years and treated with infliximab specifically for this condition. All 4 patients were females with Crohn’s disease and had an ileostomy created following either proctocolectomy (N⫽3) or subtotal colectomy (N⫽1). Ages at the time of development of PPG ranged from 13 to 51 years. Data collected included demographic information, surgical history, and therapy for PPG. Assessment of response to infliximab was classified as complete healing , partial healing, or no response. Results: In all 4 cases the diagnosis of PPG was made within 2 months of creation of the ileostomy. All 4 patients had failed prior therapy for PPG as follows: 1. two patients had received local debridement and steroid injections, 2. one patient had been on longstanding therapy with 6 –MP and had also received local steroid injections, 3. one patient had failed therapy with oral steroids, 6 –MP, and cyclosporine. After therapy with infliximab, 2 patients (including the patient who had failed steroids/6 –MP/cyclosporine) achieved complete healing of PPG with follow– up duration of 13 months and 6 months since healing (see table– patients 1 and 2) . One patient (patient 3) achieved compete healing of PPG but has required maintenance infliximab because the PPG recurred after initial healing. One patient (patient 4) has thus far had a partial response but continues to slowly heal with ongoing infliximab therapy. # infusions Time Concomitant Response to to Patient therapy assessment healing healing 1
6–MP
2
6–MP
3
6–MP
4
Dapsone
Complete healing Complete healing Complete w/ recurrence Partial healing
F/U duration since healing
Maintenance therapy
3
8 mo
13 mo
11
19 mo
6 mo
Infliximab
3
3 mo
12 mo
Infliximab
7*
N/A
N/A
None
N/A
* Infusions to date
Conclusions: 1. Infliximab with concomitant immunosuppression appears to be promising therapy for the management of PPG. 2. Multiple infusions of infliximab may be needed to achieve healing of PPG.
797 METASTATIC CROHN’S DISEASE OF THE LARYNX Kenneth D. Glazier, M.D., Bruce A. Adelman, M.D. and Kiron M. Das, M.D.,FACG*. Division of Gastroenterology and Hepatology, UMDNJ– Robert Wood Johnson Medical School, New Brunswick, NJ. Purpose: Metastatic Crohn’s disease (CD) is the presence of granulomatous tissue outside the intestinal tract. We report a case of metastatic Crohn’s disease of the larynx.
Abstracts
AJG – Vol. 97, No. 9, Suppl., 2002
phosphate buffer (pH 7.5) and the experiment was continued for another 8 hours at the same media flow. The budesonide content in the fractions from the release analysis was then investigated by a liquid chromatography system. A reference experiment was performed for comparison where the granules were analyzed in the same way except that they were not exposed to applesauce. Results: Mean Value and Range of 6 Samples % Budesonide % Budesonide release in SGF released in pH 1.2 SIF pH 7.52 Experiment
2h
Applesauce 0.7 (0.5–0.9) experiment Reference 0.5 (0.4–0.6) experiment
1h
2h
4h
8h
29 (28–30)
49 (48–51) 77 (76–80) 97 (95–100)
31 (30–31)
51 (51–52) 79 (77–82) 99 (95–102)
Conclusions: There is no change in the release properties of budesonide capsules 3 mg if the granules are mixed with applesauce for 30 minutes before administration.
792 ENDOSCOPIC HEALING INDUCED BY INFLIXIMAB MAINTENANCE THERAPY CORRELATES WITH LONG–TERM CLINICAL RESPONSE IN PATIENTS WITH ACTIVE CROHNS DISEASE. RESULTS OF ENDOSCOPIC SUBSTUDY OF ACCENT 1 P. Rutgeerts*, J.–F. Colombel, S. van Deventer, M. Vatn, R. Loftberg, S. Schreiber, M. Campieri, H. Malchow, J. Scholmerich, F. Cornillie, A. Olson, W. Bao, S. Katz and H. Lochs. GE, Univ Hosp Gasthuisberg, Leuven, Belgium; GE, Mayo Clinic, Rochester, MN; GE, Afdeling GE Acad Med Ctr, Amsterdam, Netherlands; Oslo, Norway; Huddinge, Sweden; Kiel, Germany; Bologna, Italy; Leverkusen, Germany; Regensburg, Germany; Centocor; Great Neck; and Berlin, Germany. Purpose: Examine patients (pts) achieving endoscopic (ENDO) healing at weeks (wk) 10 and 54 and correlate changes from baseline (BL) in CDEIS and CDAI . Methods: 573 ACCENT I pts received 5mg/kg infliximab (IFX) at wk0 and were randomized to 1 of 3 maintenance regimens (MNT) at wk2: 1)placebo (PBO)wk2, 6, q8wk, 2)5mg/kg IFX wk2, 6, q8wk, and 3)5mg/kg IFX wk2, 6, 10mg/kg IFX q8wk. Starting at wk14, pts who lost response could crossover to IFX episodic retreatment (EPI RETX) at 5mg/kg higher than assigned MNT dose. All pts at 25 selected sites could participate in ENDO substudy with assessments at wk0, 10 and 54. CDEIS and clinical response (CDAI association) were assessed using Spearman correlation coefficients. All wk2 responders were analyzed. Results: 99 pts enrolled in ENDO substudy; 66 responded to single 5mg/kg IFX infusion by wk2 and were randomized to PBO MNT(n⫽24), 5mg/kg IFX(n⫽19), 10mg/kg IFX(n⫽23). At wk10, 0% (0/17) PBO vs. 31% (10/32) IFX had MUC healing (p⫽0.010). At wk54, among pts not losing response, 63% (12/19) IFX showed MUC healing. Including EPI RETX, 7% (1/14) PBO vs 50% (13/26) IFX showed ENDO healing at wk54 (p⫽0.007). Including EPI RETX data, significantly more IFX MNT pts had ENDO healing at wk10 and 54 compared to PBO: 27% (7/26) vs. 0% (0/14) (p⫽0.03). A greater improvement in CDEIS from BL to wk54 was observed in IFX than PBO with EPI RETX (5.1 vs 1.1) or without EPI RETX (5.7 vs 0.7). Changes from BL CDEIS were positively, significantly correlated with changes from BL CDAI at wk10 and 54: r⫽0.307, p⫽0.021, and r⫽0.498, p⬍0.001, respectively. Conclusions: A majority of Crohns pts with sustained response to IFX showed ENDO healing (63%). 50% IFX pts achieved MUC healing at wk54 compared to 7%EPI RETX pts. Improvements in CDEIS and CDAI are positively, significantly correlated during IFX MNT. ENDO healing should be considered as an important treatment goal for pts with active CD.
793 UNEXPECTED DRAMATIC CLINICAL RESPONSE OF PSORIASIS LESIONS AND UNEXPECTED PREGNANCY IN AN INFERTILE PATIENT IN RESPONSE TO TREATMENT WITH ANTI–TUMOR NECROSIS FACTOR (TNFALPHA) MONOCLONAL ANTIBODY FOR CROHN’S DISEASE Leslie Bank* and Belinda Hunt. United Medical Associates, Binghamton, NY and Centocor, Inc, Malvern, PA. Purpose: Infliximab (IFX), a monoclonal antibody that neutralizes the biological activity of tumor necrosis factor alpha, is indicated for the reduction of signs and symptoms of Crohn’s disease (CD). Also, recent data suggest a role for IFX in treating plaque psoriasis. We report on a patient with CD and psoriasis, as well as history of infertility, who experienced clinical improvement after therapy with IFX. Of note, this patient became pregnant unexpectedly by natural means after IFX treatment and is 20 weeks into an apparently normal pregnancy. Recent data suggest that some infertility may be associated with elevated levels of TNF alpha. Methods: This 32–year– old woman had an 11–year history of refractory CD, along with psoriasis and a history of infertility. The patient was treated with IFX 5 mg/kg along with cyclosporine, total parenteral nutrition (TPN; the patient was unable to maintain adequate oral nutrition), mesalamine, and lansoprazole and reported dramatic improvement in her overall well– being within 1 week of the IFX infusion; TPN was discontinued. Results: Within 4 weeks of the IFX infusion, the patient’s CD was in remission and cyclosporine was being discontinued. Approximately 8 weeks following her initial IFX infusion, the patient had an exacerbation of her psoriasis (body surface involved approx. 80%). Cyclosporine was restarted, and her psoriasis improved. Several months following IFX infusion, the patient was scheduled for in vitro fertilization. The procedure was successful, but shortly thereafter the patient had a miscarriage. Three IFX infusions were given and dramatic clinical improvement was noted. After a second in vitro procedure that was unsuccessful, the patient received maintenance IFX infusions (every 8 weeks) for approximately 1 year. At this point the patient became pregnant unexpectedly by natural means. She is now 20 weeks into an apparently normal pregnancy. Conclusions: IFX was effective in treating longstanding refractory CD and psoriasis in a previously infertile woman. After 1 year of IFX maintenance therapy, the patient became pregnant unexpectedly by natural means.
794 CLINICAL MANIFESTATIONS OF THE NOD2 GENE IN FAMILIAL CROHN’S DISEASE Jean–Paul Achkar, M.D., Judy Cho, M.D., Aaron Brzezinski, M.D., Deborah Vogel, M.S. and Richard Duerr, M.D.*. Gastroenterology, Cleveland Clinic Foundation, Cleveland, OH; Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA and Medicine, University of Chicago, Chicago, IL. Purpose: Crohn’s disease (CD) is a heterogeneous disorder with varied clinical manifestations. Recently NOD2 was identified as the first gene associated with CD, allowing for genotype–phenotype correlations to be performed. Our aim was to determine whether the NOD2 gene was associated with specific clinical phenotypes in familial CD. Methods: Detailed CD–related phenotypic information was collected by chart review and telephone interviews for 129 CD–affected individuals from 61 families with 2 or more CD–affected members. Data collected included demographic information, age at diagnosis, disease location, disease behavior, and surgical history. Individuals were genotyped at the NOD2 gene for the Leu1007fsinsC, Gly908Arg, and Arg702Trp polymorphisms and were stratified as having 2 variant NOD2 alleles (N⫽25), 1 variant NOD2 allele (N⫽42) or 0 variant NOD2 alleles (N⫽62). Data analysis was performed using Pearson Chi–square tests. Rao–and–Scott corrections for clustering were used to account for intrafamily correlation.
AJG – September, Suppl., 2002
Abstracts
Results: Demographic data and duration of follow– up were similar for the 3 groups. Patients with 2 NOD2 variants were more likely to have fistulizing or stricturing disease behavior (P⫽0.006) and were more likely to require surgery (P⫽0.005) when compared to those with 0 or 1 NOD2 variants (See table). Trends for younger age at diagnosis and absence of colonic disease were also noted in the group with 2 NOD2 variants. Logistic regression demonstrated that patients with 2 NOD2 variants had an odds ratio of 2.4 (95% CI⫽1.1–5.0; P⫽0.022) for development of fistulizing or stricturing disease when compared to other groups. NOD2 Genotype–Phenotype Correlation
Median age at diagnosis Colon only disease Fistulizing or stricturing disease Surgical resection
0 NOD2 Variants (Nⴝ62)
1 NOD2 Variant (Nⴝ42)
2 NOD2 Variants (Nⴝ25)
P–value
22.0 15% 52%
22.0 12% 68%
19.0 0 79%
0.09 0.055 0.006
65%
81%
92%
0.005
Conclusions: 1. CD–associated NOD2 variants are associated with more aggressive disease behavior and higher frequency of surgical resection in familial CD. 2. CD–associated NOD2 variants may also be associated with younger age at diagnosis and absence of colonic disease.
795 IMPROVED PERI–OPERATIVE SURGICAL OUTCOME IN CROHN’S DISEASE PATIENTS RECEIVING CONCOMITANT IMMUNOMODULATOR THERAPY Grace S. Tay, M.D., Mary F. Otterson, M.D. and David G. Binion, M.D.*. Medicine, Medical College of Wisconsin, Milwaukee, WI and Surgery, Medical College of Wisconsin, Milwaukee, WI. Purpose: Although efficacious, medical management of moderate to severe Crohn’s disease (CD) using immunomodulator and biologic agents has not eliminated the role for surgical treatment of disease complications, specifically intestinal stricture and lumenal obstruction. Intra–abdominal septic complications (IASC: intra–abdominal abscess, anastomotic leak, fistula) are dreaded complications of CD surgery. We hypothesized that medical treatment with immunomodulators improves perioperative surgical outcome, as adequately treated CD decreases the rate of IASC in the 6 weeks following operation in pts requiring intestinal anastomosis and/or strictureplasty. Methods: Surgical outcome was reviewed in 92 pts followed in an IBD referral center, who underwent 101 operations involving primary anastomosis and/or strictureplasty for CD between 1998 –2001. IASC (intra– abdominal abscess, anastomotic leak, and/or enterocutaneous fistulae occurring in 6 weeks following surgery), were compared between pts receiving and not receiving peri– operative immunomodulator agents (azathioprine, 6 –MP, methotrexate, mycophenolate mofetil and/or infliximab during the 2 months prior to surgery). Results: IASC developed in 13 out of 101 (12.9%) operations. Immunomodulator use was associated with fewer IASC (4/72 procedures; 5.6%) compared with 9/29 (31.0%) cases with pts not on immunomodulator therapy (p⫽⬍ 0.05). Length of hospital stay was significantly lower in the immunomodulator treated group (p⫽⬍0.05). Serum albumin levels ⬍ 3.0 g/dl were significantly associated with a higher IASC rate, but were identical in the immmunomodulator and non–immunomodulator treated groups. Rate of IASC was not influenced by steroid use, smoking status, and the presence of pre– operative abscess and/or fistula. Immunomodulator use did not affect length of resected bowel, or the rate and number of strictureplasties. Rate of IASC was not associated with emergent operation and more pts receiving immunomodulator therapy required emergent surgery compared to non–immunomodulator treated group. Conclusions: Optimizing medical management with immunomodulator therapy significantly decreases post– operative intra–abdominal septic com-
S261
plications and length of hospital stay in CD patients undergoing surgical procedures requiring either anastomosis and/or strictureplasty.
796 SUCCESSFUL TREATMENT OF PERISTOMAL PYODERMA GANGRENOSUM WITH INFLIXIMAB Jean–Paul Achkar, M.D.*, Aaron Brzezinski, M.D., Conor Delaney, M.D., Tracy Hull, M.D. and Bret Lashner, M.D. Center for Inflammatory Bowel Diseases, Cleveland Clinic Foundation, Cleveland, OH. Purpose: Following the creation of a stoma in patients with inflammatory bowel disease, peristomal pyoderma gangrenosum (PPG) is an uncommon but difficult condition to treat. The purpose of this study was to evaluate the use of infliximab as therapy for PPG. Methods: Four patients with PPG were seen over the past 2 years and treated with infliximab specifically for this condition. All 4 patients were females with Crohn’s disease and had an ileostomy created following either proctocolectomy (N⫽3) or subtotal colectomy (N⫽1). Ages at the time of development of PPG ranged from 13 to 51 years. Data collected included demographic information, surgical history, and therapy for PPG. Assessment of response to infliximab was classified as complete healing , partial healing, or no response. Results: In all 4 cases the diagnosis of PPG was made within 2 months of creation of the ileostomy. All 4 patients had failed prior therapy for PPG as follows: 1. two patients had received local debridement and steroid injections, 2. one patient had been on longstanding therapy with 6 –MP and had also received local steroid injections, 3. one patient had failed therapy with oral steroids, 6 –MP, and cyclosporine. After therapy with infliximab, 2 patients (including the patient who had failed steroids/6 –MP/cyclosporine) achieved complete healing of PPG with follow– up duration of 13 months and 6 months since healing (see table– patients 1 and 2) . One patient (patient 3) achieved compete healing of PPG but has required maintenance infliximab because the PPG recurred after initial healing. One patient (patient 4) has thus far had a partial response but continues to slowly heal with ongoing infliximab therapy. # infusions Time Concomitant Response to to Patient therapy assessment healing healing 1
6–MP
2
6–MP
3
6–MP
4
Dapsone
Complete healing Complete healing Complete w/ recurrence Partial healing
F/U duration since healing
Maintenance therapy
3
8 mo
13 mo
11
19 mo
6 mo
Infliximab
3
3 mo
12 mo
Infliximab
7*
N/A
N/A
None
N/A
* Infusions to date
Conclusions: 1. Infliximab with concomitant immunosuppression appears to be promising therapy for the management of PPG. 2. Multiple infusions of infliximab may be needed to achieve healing of PPG.
797 METASTATIC CROHN’S DISEASE OF THE LARYNX Kenneth D. Glazier, M.D., Bruce A. Adelman, M.D. and Kiron M. Das, M.D.,FACG*. Division of Gastroenterology and Hepatology, UMDNJ– Robert Wood Johnson Medical School, New Brunswick, NJ. Purpose: Metastatic Crohn’s disease (CD) is the presence of granulomatous tissue outside the intestinal tract. We report a case of metastatic Crohn’s disease of the larynx.