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P129 RESPONSE TO CERTOLIZUMAB PEGOL INDUCTION IS NOT STEROID-DEPENDENT IN PATIENTS WITH ACTIVE CROHN'S DISEASE
44
Poster Presentations
slope, maximum peak intensity, area under the curve, and wash out) were compared among patients scoring as inactive or active as above defined. The slope and the maximum peak intensity were significantly higher in the HDI-QLab elaborated curves from US performed in patients with active vs. inactive CD (p<0.05 by T test). Moreover, PCR values were significantly correlated with the time to peak and wash in (r = 0.46, p < 0.002 and r = 0.31, p < 0.05, respectively). Conclusion: This preliminary study suggests the possibility to correlate quantitative HDI-QLab software elaborated contrast-enhanced wideband harmonic imaging US with clinical activity parameters in CD. Quantitative contrast-enhanced wideband harmonic imaging US could improve the reliability of conventional US to detect active bowel inflammation in CD.
P129 RESPONSE TO CERTOLIZUMAB PEGOL INDUCTION IS NOT STEROID-DEPENDENT IN PATIENTS WITH ACTIVE CROHN' S DISEASE D. Hommes. Leiden University Medical Centre, Leiden, The Netherlands Background: Recently, it was shown that Crohn' s disease (CD) can be effectively treated with a combination of immunesuppressives and infliximab without the use of corticosteroids (Hommes et al, DDW 2006). However, it is recommended that the anti-TNF adalimumab is used concomitantly with a corticosteroid during induction to optimize its clinical efficacy in Crohn' s disease (CD). Certolizumab pegol, a PEGylated Fab' anti-TNF agent has demonstrated efficacy and tolerability in patients with CD in the PRECiSE studies.1,2 We investigated the effect of steroids on response (reduction in CDAI ≥100 points) to induction with certolizumab pegol. Methods: Induction response rates at Week 6 were analyzed by corticosteroid use in one phase II (Study 005, n=292) and two phase III (PRECiSE 1 [(P1) n=659] and 2 [(P2) n=668]) studies. P1 and P2, induction treatment comprised three subcutaneous doses of certolizumab pegol at Weeks 0, 2 and 4. Concomitant corticosteroid treatment was permitted provided the dose had been stable for ≥2 weeks at study entry. Any increase from the entry dose was deemed a treatment failure and the patient was withdrawn. Results: Across studies, the No Steroids had longer disease duration (especially P1), more resections (P2) and more Immunosuppressants (P1). However, the Steroid group did have a slightly higher CDAI baseline (10 point difference).Response rates were not correlated with the use of corticosteroid at entry, but with a trend towards a better response in patients without steroids (table). For patients with either a history of corticosteroid use or current use, Week 6 response rates varied from 36.3% in PRECiSE 1 to 44.0% in Study 005 (400 mg group). Corresponding values for non-corticosteroid users were 34.8% and 45.5%, respectively. Similarly, corticosteroid use was not found to affect remission rates (data not shown). Table 1 Study and certolizumab pegol dose PRECiSE 1, 400 mg PRECiSE 2, 400 mg 005, 100 mg 005, 200 mg 005, 400 mg
Use of corticosteroids at entry
No corticosteroid use at entry
n
Week 6 response, n (%)
n
Week 6 response, n (%)
127 245 26 27 22
43 (33.9) 145 (59.2) 6 (23.1) 6 (22.2) 10 (45.5)
200 423 48 45 50
72 (36.0) 256 (60.5) 22 (45.8) 20 (44.4) 22 (44.0)
Conclusions: Response to certolizumab pegol induction treatment is apparently not affected by concomitant administration of corticosteroids. This steroid -independent response could be advantageous in a clinical setting where patients are suffering from steroids side effects. References: 1. Sandborn W et al. N Engl J Med 2007;357:228-238. 2. Schreiber S et al. N Engl J Med 2007;357:239-250.
reactions in the treatment of severe and refractory CD and UC in the Munich IBD was analyzed prospectively starting in February 2007. In all patients, infliximab infusions were performed every 8 weeks after an induction treatment at weeks 0, 2, and 6. 5 mg/kg infliximab were infused over 2 hours in 250 ml of NaCl solution for injection. No patient was given antihistamines or steroids other than baseline treatment of their UC or CD. In all patients who once experienced allergic reaction due to infliximab, study participation was terminated. Results: So far, 148 patients have received treatment with a median of 3 (range 1 - 7) infusions each. Overall 502 infusions were performed containing a median dose of 350 mg (range 200 - 600 mg). During so far 9 months of observation, 23 anaphylactic reactions appeared, resulting in a overall rate of 4.6% based on the number of infusions and of 15.5% based on the number of treated patients. In the median, allergic reaction occurred at the second infusion (range 1 - 6) and 10 minutes (range 5 - 50 minutes) after start of the infusion. They consisted of flush, dyspnea, abdominal spasms and edema. Infusions were stopped immediately at the onset of clear symptoms. All patients recovered completely within 40 minutes after anti-allergic medication regimen consisting of antihistamines and prednisolone (150 - 250 mg) was given. No patient had to be admitted to the hospital. Conclusion: In 15% of all patients who obtained infliximab therapy at a large IBD center anaphylactic reactions occur due to infliximab. Anaphylactic reactions seem to be the most frequent side effect of infliximab. Most reactions are mild to moderate characterized by flush and edema.
P131 ANXIETY AND DEPRESSION IN INFLAMMATORY BOWEL DISEASE PATIENTS: CONTROL STUDY M. Peñate 1 , V. Malo de Molina 1 , J.M. Marrero 1 , A. García 2 , P. Saiz 1 , N. Hernández 1, V. Sosa 1 , L. Betancor 1 , A. Monescillo 1 , A. Cruz 1 , A. Castellot 1 , E. Jiménez 1 , C. Guevara 1 , M. Jorge 1 , A. Sierra 1 . 1 Gastroenterology, Hospital Universitario Insular De Gran Canaria; 2 Psiquiatry, Hospital Universitario Insular de Gran Canaria, Spain Introduction: Psychological disorders are highly prevalent in inflammatory bowel disease (IBD), 29-35% during remission. Anxiety and depression have an independent effect on the patients' quality of life. There are few studies comparing psychological disorders and chronic symptoms in patient with IBD in remission. Objectives: We prospectively evaluate the prevalence of anxiety, anxious personality and melancholic depression in IBD patients in clinical remission attending a monographic out-patient clinic, and compare them with a control group of healthy individuals, matched by age and sex. Methods: Three different self-administered questionnaires were used to measure: present anxiety status (STAI-E), existence of an anxious personality (STAI-R), melancholic depression (BECK scale). An additional questionnaire was used to evaluate the IBD characteristics and the patient-doctor and patient-environment relationships. IBD activity was quantified through standard clinical activity indexes. A threshold of 27+ was considered as diagnostic for the STAI tests, and 18+ for the BECK scale. In all cases, a larger numerical result implied a greater presence of symptoms. Results: N Average Sex Average Years Months Surgery Immuno- Biological Gcap age age when since until modu- treatment diagnosed onset diagnosed lators IBD 71 Control 84
M. Jürgens, C. Tillack, J. Seiderer, S. Pfennig, B. Göke, S. Brand, T. Ochsenkühn. Klinikum Grosshadern, Munich, Germany Introduction: Antagonizing Tumor Necrosis Factor alpha (TNF-a) has become an effective strategy in treatment of moderate and severe Crohn' s disease (CD) and ulcerative colitis (UC). Infliximab (Remicade), a recombinant IgG1 monoclonal antibody, was the first TNF-a-antibody approved for the treatment of CD and UC, respectively. Anaphylactic reactions occur frequently with infliximab, however the exact frequency of these reactions in a normal clinical single center setting has not been assessed. Methods: The frequency and character of infliximab induced anaphylactic
41 F 52 F
32
7,6
13,8
11
34
11
2
Chronic symptoms:
IBD
P130 THE FREQUENCY OF ANAPHYLACTIC REACTIONS IN THE USE OF INFLIXIMAB IN A LARGE SINGLE CENTER - A PROSPECTIVE STUDY
38 35
Generalized abdominal pain
Loss of appetite
Diarrhea
Rectal bleeding
Weight loss
Fatigue
50%
35%
65%
30%
33%
42%
Disease impact
IBD
Work Responsability Tell doctor animic state Doctor asks about psychological status
19% 29% 49% 70%
Test average results:
IBD Control
STAI-E
STAI-R
BECK
24,69 24,14 (NS)
28,8 26,59 (p=0,03)
11,8 5,37 (p=0,001)
Poster Presentations
slope, maximum peak intensity, area under the curve, and wash out) were compared among patients scoring as inactive or active as above defined. The slope and the maximum peak intensity were significantly higher in the HDI-QLab elaborated curves from US performed in patients with active vs. inactive CD (p<0.05 by T test). Moreover, PCR values were significantly correlated with the time to peak and wash in (r = 0.46, p < 0.002 and r = 0.31, p < 0.05, respectively). Conclusion: This preliminary study suggests the possibility to correlate quantitative HDI-QLab software elaborated contrast-enhanced wideband harmonic imaging US with clinical activity parameters in CD. Quantitative contrast-enhanced wideband harmonic imaging US could improve the reliability of conventional US to detect active bowel inflammation in CD.
P129 RESPONSE TO CERTOLIZUMAB PEGOL INDUCTION IS NOT STEROID-DEPENDENT IN PATIENTS WITH ACTIVE CROHN' S DISEASE D. Hommes. Leiden University Medical Centre, Leiden, The Netherlands Background: Recently, it was shown that Crohn' s disease (CD) can be effectively treated with a combination of immunesuppressives and infliximab without the use of corticosteroids (Hommes et al, DDW 2006). However, it is recommended that the anti-TNF adalimumab is used concomitantly with a corticosteroid during induction to optimize its clinical efficacy in Crohn' s disease (CD). Certolizumab pegol, a PEGylated Fab' anti-TNF agent has demonstrated efficacy and tolerability in patients with CD in the PRECiSE studies.1,2 We investigated the effect of steroids on response (reduction in CDAI ≥100 points) to induction with certolizumab pegol. Methods: Induction response rates at Week 6 were analyzed by corticosteroid use in one phase II (Study 005, n=292) and two phase III (PRECiSE 1 [(P1) n=659] and 2 [(P2) n=668]) studies. P1 and P2, induction treatment comprised three subcutaneous doses of certolizumab pegol at Weeks 0, 2 and 4. Concomitant corticosteroid treatment was permitted provided the dose had been stable for ≥2 weeks at study entry. Any increase from the entry dose was deemed a treatment failure and the patient was withdrawn. Results: Across studies, the No Steroids had longer disease duration (especially P1), more resections (P2) and more Immunosuppressants (P1). However, the Steroid group did have a slightly higher CDAI baseline (10 point difference).Response rates were not correlated with the use of corticosteroid at entry, but with a trend towards a better response in patients without steroids (table). For patients with either a history of corticosteroid use or current use, Week 6 response rates varied from 36.3% in PRECiSE 1 to 44.0% in Study 005 (400 mg group). Corresponding values for non-corticosteroid users were 34.8% and 45.5%, respectively. Similarly, corticosteroid use was not found to affect remission rates (data not shown). Table 1 Study and certolizumab pegol dose PRECiSE 1, 400 mg PRECiSE 2, 400 mg 005, 100 mg 005, 200 mg 005, 400 mg
Use of corticosteroids at entry
No corticosteroid use at entry
n
Week 6 response, n (%)
n
Week 6 response, n (%)
127 245 26 27 22
43 (33.9) 145 (59.2) 6 (23.1) 6 (22.2) 10 (45.5)
200 423 48 45 50
72 (36.0) 256 (60.5) 22 (45.8) 20 (44.4) 22 (44.0)
Conclusions: Response to certolizumab pegol induction treatment is apparently not affected by concomitant administration of corticosteroids. This steroid -independent response could be advantageous in a clinical setting where patients are suffering from steroids side effects. References: 1. Sandborn W et al. N Engl J Med 2007;357:228-238. 2. Schreiber S et al. N Engl J Med 2007;357:239-250.
reactions in the treatment of severe and refractory CD and UC in the Munich IBD was analyzed prospectively starting in February 2007. In all patients, infliximab infusions were performed every 8 weeks after an induction treatment at weeks 0, 2, and 6. 5 mg/kg infliximab were infused over 2 hours in 250 ml of NaCl solution for injection. No patient was given antihistamines or steroids other than baseline treatment of their UC or CD. In all patients who once experienced allergic reaction due to infliximab, study participation was terminated. Results: So far, 148 patients have received treatment with a median of 3 (range 1 - 7) infusions each. Overall 502 infusions were performed containing a median dose of 350 mg (range 200 - 600 mg). During so far 9 months of observation, 23 anaphylactic reactions appeared, resulting in a overall rate of 4.6% based on the number of infusions and of 15.5% based on the number of treated patients. In the median, allergic reaction occurred at the second infusion (range 1 - 6) and 10 minutes (range 5 - 50 minutes) after start of the infusion. They consisted of flush, dyspnea, abdominal spasms and edema. Infusions were stopped immediately at the onset of clear symptoms. All patients recovered completely within 40 minutes after anti-allergic medication regimen consisting of antihistamines and prednisolone (150 - 250 mg) was given. No patient had to be admitted to the hospital. Conclusion: In 15% of all patients who obtained infliximab therapy at a large IBD center anaphylactic reactions occur due to infliximab. Anaphylactic reactions seem to be the most frequent side effect of infliximab. Most reactions are mild to moderate characterized by flush and edema.
P131 ANXIETY AND DEPRESSION IN INFLAMMATORY BOWEL DISEASE PATIENTS: CONTROL STUDY M. Peñate 1 , V. Malo de Molina 1 , J.M. Marrero 1 , A. García 2 , P. Saiz 1 , N. Hernández 1, V. Sosa 1 , L. Betancor 1 , A. Monescillo 1 , A. Cruz 1 , A. Castellot 1 , E. Jiménez 1 , C. Guevara 1 , M. Jorge 1 , A. Sierra 1 . 1 Gastroenterology, Hospital Universitario Insular De Gran Canaria; 2 Psiquiatry, Hospital Universitario Insular de Gran Canaria, Spain Introduction: Psychological disorders are highly prevalent in inflammatory bowel disease (IBD), 29-35% during remission. Anxiety and depression have an independent effect on the patients' quality of life. There are few studies comparing psychological disorders and chronic symptoms in patient with IBD in remission. Objectives: We prospectively evaluate the prevalence of anxiety, anxious personality and melancholic depression in IBD patients in clinical remission attending a monographic out-patient clinic, and compare them with a control group of healthy individuals, matched by age and sex. Methods: Three different self-administered questionnaires were used to measure: present anxiety status (STAI-E), existence of an anxious personality (STAI-R), melancholic depression (BECK scale). An additional questionnaire was used to evaluate the IBD characteristics and the patient-doctor and patient-environment relationships. IBD activity was quantified through standard clinical activity indexes. A threshold of 27+ was considered as diagnostic for the STAI tests, and 18+ for the BECK scale. In all cases, a larger numerical result implied a greater presence of symptoms. Results: N Average Sex Average Years Months Surgery Immuno- Biological Gcap age age when since until modu- treatment diagnosed onset diagnosed lators IBD 71 Control 84
M. Jürgens, C. Tillack, J. Seiderer, S. Pfennig, B. Göke, S. Brand, T. Ochsenkühn. Klinikum Grosshadern, Munich, Germany Introduction: Antagonizing Tumor Necrosis Factor alpha (TNF-a) has become an effective strategy in treatment of moderate and severe Crohn' s disease (CD) and ulcerative colitis (UC). Infliximab (Remicade), a recombinant IgG1 monoclonal antibody, was the first TNF-a-antibody approved for the treatment of CD and UC, respectively. Anaphylactic reactions occur frequently with infliximab, however the exact frequency of these reactions in a normal clinical single center setting has not been assessed. Methods: The frequency and character of infliximab induced anaphylactic
41 F 52 F
32
7,6
13,8
11
34
11
2
Chronic symptoms:
IBD
P130 THE FREQUENCY OF ANAPHYLACTIC REACTIONS IN THE USE OF INFLIXIMAB IN A LARGE SINGLE CENTER - A PROSPECTIVE STUDY
38 35
Generalized abdominal pain
Loss of appetite
Diarrhea
Rectal bleeding
Weight loss
Fatigue
50%
35%
65%
30%
33%
42%
Disease impact
IBD
Work Responsability Tell doctor animic state Doctor asks about psychological status
19% 29% 49% 70%
Test average results:
IBD Control
STAI-E
STAI-R
BECK
24,69 24,14 (NS)
28,8 26,59 (p=0,03)
11,8 5,37 (p=0,001)