Ilse Hoffman

Mucosal healing predicts long‐term outcome of maintenance therapy with infliximab in Crohn's disease

Background: Infliximab (IFX) treatment induces mucosal healing (MH) in patients with Crohns disease (CD) but the impact of MH on the long‐term outcome of IFX treatment in CD is still debated. Methods: We studied MH during long‐term treatment with IFX in 214 CD patients. A total of 183 patients (85.5%) responded to induction therapy and 31 patients (14.5%) were primary nonresponders. They underwent lower gastrointestinal (GI) endoscopy within a median of 0.7 months (interquartile range [IQR] 0.1–6.8) prior to first IFX and after a median of 6.7 months (IQR 1.4–24.6) after start of IFX and were further analyzed. The relationship between the outcome of IFX treatment long‐term and MH was studied. Results: MH was observed in 67.8% of the 183 initial responders (n = 124), with 83 patients having complete healing (45.4%) and 41 having partial healing (22.4%). Scheduled IFX treatment from the start resulted in MH more frequently (76.9% MH rate) than episodic treatment (61.0% MH rate; P = 0.0222, odds ratio [OR] 2.14, 95% confidence interval [CI] 1.11–4.12). Concomitant treatment with corticosteroids (CS) had a negative impact on MH (37.9% in patients with CS versus 63.2% in patients without CS; P = 0.021, OR 0.36, 95% CI 0.16–0.80). MH was associated with a significantly lower need for major abdominal surgery (MAS) during long‐term follow‐up (14.1% of patients with MH needed MAS versus 38.4% of patients without MH; P < 0.0001). Conclusions: MH induced by long‐term maintenance IFX treatment is associated with an improved long‐term outcome of the disease especially with a lower need for major abdominal surgeries. (Inflamm Bowel Dis 2009;)

Long-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort

Background and aims: This observational study assessed the long-term clinical benefit of infliximab (IFX) in 614 consecutive patients with Crohn’s disease (CD) from a single centre during a median follow-up of 55 months (interquartile range (IQR) 27–83). Methods: The primary analysis looked at the proportion of patients with initial response to IFX who had sustained clinical benefit at the end of follow-up. The long-term effects of IFX on the course of CD as reflected by the rate of surgery and hospitalisations and need for corticosteroids were also analysed. Results: 10.9% of patients were primary non-responders to IFX. Sustained benefit was observed in 347 of the 547 patients (63.4%) receiving long-term treatment. In 68.3% of these, treatment with IFX was ongoing and in 31.7% IFX was stopped, with the patient being in remission. Seventy patients (12.8%) had to stop IFX due to side effects and 118 (21.6%) due to loss of response. Although the yearly drop-out rates of IFX in patients with episodic (10.7%) and scheduled treatment (7.1%) were similar, the need for hospitalisations and surgery decreased less in the episodic than in the scheduled group. Steroid discontinuation also occurred in a higher proportion of patients in the scheduled group than in the episodic group. Conclusions: In this large real-life cohort of patients with CD, long-term treatment with IFX was very efficacious to maintain improvement during a median follow-up of almost 5 years and changed disease outcome by decreasing the rate of hospitalisations and surgery.

Corticosteroids but not infliximab increase short‐term postoperative infectious complications in patients with ulcerative colitis

Background: Recent reports suggest that the preoperative use of infliximab (IFX) increases postoperative infectious complications in patients with ulcerative colitis (UC). Therefore, we determined the impact of IFX on postoperative infectious complications. Methods: A consecutive group of 141 UC patients (41% female, median age 39.8 years) undergoing (procto)colectomy was studied. Postoperative infectious complications were compared between 22 patients who received IFX within 12 weeks prior to (procto)colectomy (IFX group) and 119 patients who did not (control group). Short‐term infectious complications, consisting of anastomotic leaks, pelvic abscesses, wound infections, and nonsurgical site infections, were recorded within 30 days after primary surgery. Results: At primary surgery there was no significant difference in gender, disease extent, smoking behavior, body mass index, and concomitant medication (including corticosteroids) between the groups. Patients in the IFX group less often underwent restorative proctocolectomy without defunctioning ileostomy (9% versus 34%, P = 0.022), had a significantly shorter median (interquartile range, IQR) disease duration (2.7 [1.2–8.6] versus 5.9 [2.6–13.0] years, P < 0.036) and a significantly higher C‐reactive protein level at primary surgery (51.7 [9.9–103.6] versus 19.1 [7.5–42.6] mg/L, P = 0.023). There was no short‐term mortality. A moderate‐to‐high dose of corticosteroids (≥20 mg methylprednisolone for ≥2 months, odds ratio 5.19 [95% confidence interval [CI]: 1.72–15.66], P = 0.003) and a restorative proctocolectomy without defunctioning ileostomy (odds ratio 6.45 [95% CI: 2.12–19.64], P = 0.001) were independent predictors of short‐term postoperative infectious complications. Conclusion: Corticosteroids and a restorative proctocolectomy without defunctioning ileostomy, but not IFX, are associated with an increased risk of short‐term postoperative infectious complications in UC.

Predictors of early response to infliximab in patients with ulcerative colitis.

Background Our objective is to report the outcome of infliximab (IFX) in ulcerative colitis (UC) patients from a single center and to identify predictors of early clinical response. Methods The first 100 UC patients (45 female; median age, 37.9 years) who received IFX at a single center were included. Eighty‐four patients received 5 mg/kg IFX, and 37 patients received a 3‐dose IFX induction at weeks 0, 2, and 6. The Mayo endoscopic subscore, assessed by sigmoidoscopy before inclusion, was 1, 2, and 3 in 5%, 52%, and 43% of patients, respectively. Sixty percent had pancolitis, 63% were on concomitant immunosuppressive therapy, 9% were active smokers, 64% had C‐reactive protein ≥5 mg/dL, and 44% were pANCA+/ASCA−. Five patients received IFX because of severe acute colitis refractory to intravenous corticosteroids. Results Early complete and partial clinical responses were observed in 41% and 24% of patients. Patients with early clinical response were significantly younger than nonresponders (median age, 35.7 versus 41.6 years, P = 0.041). Patients who were pANCA+/ASCA− had a significantly lower early clinical response (55% versus 76%; odds ratio [OR] = 0.40 (0.16–0.99), P = 0.049). Concomitant immunosuppressive therapy and the use of an IFX induction scheme did not influence early clinical response. Only 1 of 5 patients who received IFX for acute steroid‐refractory colitis required colectomy within 2 months. Conclusions IFX is an efficient therapy in UC, as shown by 65% early clinical response. A pANCA+/ASCA− serotype and an older age at first IFX infusion are associated with a suboptimal early clinical response. (Inflamm Bowel Dis 2006)

Outcome of pregnancy in women with inflammatory bowel disease treated with antitumor necrosis factor therapy

Background: Infliximab (IFX) and adalimumab (ADA) are attractive treatment options in patients with inflammatory bowel disease (IBD) also during pregnancy but there is still limited data on the benefit/risk profile of IFX and ADA during pregnancy. Methods: This observational study assessed pregnancy outcomes in 212 women with IBD under antitumor necrosis factor alpha (TNF) treatment at our IBD unit. Pregnancy outcomes in 42 pregnancies with direct exposure to anti‐TNF treatment (35 IFX, 7 ADA) were compared with that in 23 pregnancies prior to IBD diagnosis, 78 pregnancies before start of IFX, 53 pregnancies with indirect exposure to IFX, and 56 matched pregnancies in healthy women. Results: Thirty‐two of the 42 pregnancies ended in live births with a median gestational age of 38 weeks (interquartile range [IQR] 37–39). There were seven premature deliveries, six children had low birth weight, and there was one stillbirth. One boy weighed 1640 g delivered at week 33, died at age of 13 days because of necrotizing enterocolitis. A total of eight abortions (one patient wish) occurred in seven women. Trisomy 18 was diagnosed in one fetus of a mother with CD at age 37 under ADA treatment (40 mg weekly) and pregnancy was terminated. Pregnancy outcomes after direct exposure to anti‐TNF treatment were not different from those in pregnancies before anti‐TNF treatment or with indirect exposure to anti‐TNF treatment but outcomes were worse than in pregnancies before IBD diagnosis. Conclusions: Direct exposure to anti‐TNF treatment during pregnancy was not related to a higher incidence of adverse pregnancy outcomes than IBD overall. (Inflamm Bowel Dis 2011;)

Levels of C-reactive protein are associated with response to infliximab therapy in patients with Crohn's disease.

BACKGROUND & AIMS Infliximab is an antibody against tumor necrosis factor-α that is used to treat patients with moderate to severe Crohns disease (CD). C-reactive protein (CRP) is a marker used to identify and follow individuals with CD. We analyzed changes in levels of CRP in a large cohort of patients with CD undergoing treatment with infliximab. METHODS Serial levels of CRP were analyzed in 718 CD patients. Blood was collected before each infusion; a total of 8845 CRP levels were available for analysis. The correlations between CRP levels and need for dose adjustment, outcomes, and mucosal healing (based on endoscopic analysis of 253 patients) were evaluated. Therapy adjustment was considered successful if therapy continued without need for change. Subgroup analysis was performed by using data from 268 patients who received 8 weeks of maintenance therapy. RESULTS More patients with high baseline levels of CRP responded to infliximab than patients with normal levels (90.8% vs 82.6%; P = .014). Early normalization of CRP levels correlated with sustained long-term response (P < .001). CRP levels remained significantly higher among patients who lost their response to infliximab, compared with those with a sustained response (P = .001). At time of loss of response, CRP levels were significantly increased (median, 11.2 mg/L) and did not return to baseline levels (median, 18.2 mg/L; P = .039). CRP correlated with mucosal healing (P = .033). CONCLUSIONS CRP is a good marker of disease activity in patients treated with infliximab. Increased levels of CRP indicate mucosal inflammation and a likelihood of clinical relapse.

A Novel Method for the Nonradiological Assessment of Ineffective Swallowing

OBJECTIVES:This validation study evaluates a new manometry impedance-based approach for the objective assessment of pharyngeal function relevant to postswallow bolus residue.METHODS:We studied 23 adult and pediatric dysphagic patients who were all referred for a videofluoroscopy, and compared these patients with 10 adult controls. The pharyngeal phase of swallowing of semisolid boluses was recorded with manometry and impedance. Fluoroscopic evidence of postswallow bolus residue was scored. Pharyngeal pressure impedance profiles were analyzed. Computational algorithms measured peak pressure (Peak P), pressure at nadir impedance (PNadImp), time from nadir impedance to PeakP (PNadImp–PeakP), the duration of impedance drop in the distal pharynx (flow interval), upper esophaghageal sphincter (UES) relaxation interval (UES-RI), nadir UES pressure (NadUESP), UES intrabolus pressure (UES-IBP), and UES resistance. A swallow risk index (SRI) was derived by the formula: SRI=(FI × PNadImp)/(PeakP × (TNadImp-PeakP+1)) × 100.RESULTS:In all, 76 patient swallows (35 with residue) and 39 control swallows (12 with residue) were analyzed. Different functional variables were found to be altered in relation to residue. In both controls and patients, flow interval was longer in relation to residue. In controls, but not patients, residue was associated with an increased PNadImp (suggestive of increased pharyngeal IBP). Controls with residue had increased UES-IBP, NadUESP, and UES resistance compared with patients with residue. Residue in patients was related to a prolonged UES-RI. The SRI was elevated in relation to residue in both controls and patients and an average SRI of 9 was optimally predictive of residue (sensitivity 75% and specificity 80%).CONCLUSIONS:We present novel findings in control subjects and dysphagic patients showing that combined manometry and impedance recordings can be objectively analyzed to derive pressure-flow variables that are altered in relation to the bolus residual and can be combined to predict ineffective pharyngeal swallowing.

Non-invasive liver elastography (Fibroscan) for detection of cystic fibrosis-associated liver disease

BACKGROUND Cystic fibrosis-associated liver disease (CFLD) is the second cause of mortality in CF. The prevalence is estimated to be 26-45%, but sensitive diagnostic tools are lacking. We investigated whether non-invasive liver elastography (Fibroscan) could serve as a screening tool. METHODS Fibroscan measurements were performed in 66 CF patients. Age-specific cutoff values were determined in a control population (n=59). The measurements were compared to clinical data, bi-yearly biochemistry and ultrasound. RESULTS Fibroscan was easy to perform in this patient population. There were 14 patients (21%) with abnormal liver stiffness measurements. Liver stiffness was significantly increased in patients with clinical CFLD (11.2 kPa versus 5.1 kPa), biochemical CFLD (7.4 kPa versus 5.4 kPa) or ultrasonographical CFLD (8.2 versus 4.3 kPa) (p<0.02 for all). CONCLUSIONS Fibroscan is an objective measure and is easy to perform in CF patients, even in children and could provide a valuable tool to detect, and quantify CFLD.

Review article: non-malignant haematological complications of anti-tumour necrosis factor alpha therapy

Tumour necrosis factor‐alpha (TNF‐α) is an important mediator of the molecular cascade leading to chronic inflammation. TNF‐α inhibitors have proven their safety and efficacy in the treatment of inflammatory diseases.

LONG-TERM OUTCOME OF TREATMENT WITH INFLIXIMAB IN 440 CROHN'S DISEASE PATIENTS: RESULTS FROM A SINGLE CENTER COHORT

Background & Aims: This observational study assessed long term clinical benefit of infliximab (IFX) in 614 consecutive Crohn9s disease (CD) patients from a single centre during a median follow-up (FU) of 55 months (IQR 27-83). Methods: The primary analysis looked at the proportion of patients with initial response to IFX who had sustained clinical benefit at the end of FU. Long-term effects of IFX on the course of CD as reflected by the rate of surgeries and hospitalizations and need for corticosteroids were also analyzed. Results: 10.9% of patients were primary non-responders to IFX. Sustained benefit was observed in 347 of the 547 patients (63.4%) receiving long-term therapy. In 68.3% of these therapy with IFX was ongoing and in 31.7% IFX was stopped with the patient being in remission. Seventy patients (12.8%) had to stop IFX for side effects and 118 (21.6%) for loss of response. Although the yearly drop-out rates of IFX in patients with episodic (10.7%) and scheduled treatment (7.1%) were similar, the need for hospitalizations and surgeries decreased less in the episodic than in the scheduled group. Steroid discontinuation also occurred in a higher proportion of patients in the scheduled group than in the episodic group. Conclusions: In this large real-life cohort of CD patients long-term therapy with IFX was very efficacious to maintain improvement during a median FU of almost 5 years and changed disease outcome by decreasing the rate of hospitalizations and surgeries.