Timo Blomster

Achievement of deep remission during scheduled maintenance therapy with TNFα-blocking agents in IBD

BACKGROUND AND AIMS Deep remission, meaning clinical remission with mucosal healing (MH), with anti-tumor necrosis factor-alpha (TNF-α) agents is a new target for therapy in inflammatory bowel disease (IBD). Our aim was to study how often patients on TNF-α blocking therapy actually achieve deep remission. METHODS The total of 252 IBD patients retrospectively included (183 Crohns disease (CD), 62 ulcerative colitis (CU) or 7 inflammatory bowel disease unclassified-type colitis (IBDU)) received TNFα-antagonists (177 infliximab, 75 adalimumab) for at least 11 months and underwent ileocolonoscopy. We reviewed endoscopic and histological findings, clinical symptoms, C-reactive protein (CRP), and fecal calprotectin (FC) levels, and data on TNF-α blocking therapy. Defining deep remission as no clinical symptoms with endoscopic remission (the simple endoscopic score for Crohns disease, SES-CD 0-2 or Mayo endoscopic subscore 0-1). RESULTS Of the 252 patients, 168 (67%) were in clinical remission and 122 (48%) in deep remission after a median of 23 months of maintenance therapy. Of the 183 CD patients, 117 (64%) reached clinical remission and 79 (43%) deep remission. Of the UC patients, 52 (75%) were in clinical remission and 43 (62%) in deep remission. The majority of patients in deep remission (n=99, 81%) also had histologically inactive disease. Both median CRP and FC levels were significantly lower in patients with deep remission. CONCLUSION Reassuringly, half of the IBD patients on the TNFα-blocking maintenance therapy achieved deep remission. The majority of patients in deep remission also achieved histological remission.

Does Fecal Calprotectin Predict Short-Term Relapse After Stopping Tnfα-Blocking Agents In Inflammatory Bowel Disease Patients In Deep Remission?

BACKGROUND AND AIMS This prospective multicenter study examined whether elevated fecal calprotec tin (FC) concentrations after stopping TNFα-blocking therapy can predict clinical or endoscopic relapse. In addition, we evaluated the impact of histological remission on the relapse risk. METHODS We enrolled inflammatory bowel disease (IBD) patients who were in clinical, endoscopic, and FC-based (< 100 μg/g) remission after a minimum 11 months of TNFα-blocking therapy. The patients were followed-up for 12 months after the discontinuation of TNFα-blocking therapy. FC was collected monthly for the first 6 months and thereafter every second month. Ileocolonoscopy was performed at inclusion, at 4 months, at the study end, and at the time of clinical relapse. RESULTS Of 52 enrolled patients, 49 (16 Crohns disease, 33 ulcerative colitis/IBD unclassified) provided the stool samples requested and comprised the study group. During the follow-up, 15/49 (31%) relapsed, whereas 34 (69%) remained in remission. Patients relapsing showed constantly elevated FC levels for a median of 94 (13-317) days before the relapse. Significant increase in median FC levels was seen 2 (p = 0.0014), 4 (p = 0.0056), and 6 (p = 0.0029) months before endoscopic relapse. Constantly normal FC concentrations during the follow-up were highly predictive for clinical and endoscopic remission. Normal FC concentrations in patients with remission were associated with histological remission. CONCLUSION FC seems to increase and remain elevated before clinical or endoscopic relapse, suggesting that it can be used as a surrogate marker for predicting and identifying patients requiring close follow-up in clinical practice.

Outcome after discontinuation of TNFα-blocking therapy in patients with inflammatory bowel disease in deep remission.

Background:Few data are available on the disease course in patients with inflammatory bowel disease (IBD) in deep remission after discontinuing tumor necrosis factor &agr; (TNF&agr;)–blocking therapy. In this prospective multicenter study, we evaluated the relapse rate, predictive factors, and the response to retreatment after discontinuation of TNF&agr;-blocking therapy in patients with IBD in deep remission. Methods:We recruited 52 patients (17 Crohns disease, 30 ulcerative colitis, and 5 IBD unclassified) in clinical, endoscopic, and fecal calprotectin-based (<100 &mgr;g/g) remission after at least 1 year of TNF&agr;-blocking therapy. Clinical and endoscopic remission and relapse were defined according to validated indices. After discontinuation of therapy, the patients were followed up with endoscopic assessment at 4 and 12 months. In the event of a clinical relapse with endoscopically active disease or minor clinical symptoms but severe endoscopic relapse, TNF&agr;-blocking therapy was restarted. Results:After a median follow-up time of 13 (range, 12–15) months, 17/51 (33%) patients relapsed (5/17 Crohns disease, 12/34 ulcerative colitis/IBD unclassified, 1 patient lost to follow-up at 6 mo). Ten experienced clinical and endoscopic relapse, 5 clinical relapse with mild endoscopic activity, and 2 severe endoscopic relapse. No specific predictive factors were associated with the relapse. Retreatment was effective in 94% of patients. Conclusions:After cessation of TNF&agr;-blocking therapy in patients with IBD in deep remission, up to 67% remained in clinical remission during the 12-month follow-up. Importantly, 85% of these patients sustained endoscopic remission. The response to restart of TNF&agr; antagonists was effective and well tolerated.

Long-term outcome of inflammatory bowel disease patients with deep remission after discontinuation of TNFα-blocking agents.

Abstract Background: Little data exist on the long-term prognosis of patients with inflammatory bowel disease (IBD) after stopping TNFα-blocking therapy in deep remission. Existing data indicate that approximately 50% of patients on combination therapy who discontinued TNFα-blockers are still in remission 24 months later. The aims of this follow-up analysis were to evaluate the long-term remission rate after cessation of TNFα-blocking therapy, the predicting factors of a relapse and the response to restarting TNFα blockers. Methods: The first follow-up data of 51 IBD patients (17 Crohn’s disease [CD], 30 ulcerative colitis [UC] and four inflammatory bowel disease type unclassified [IBDU]) in deep remission at the time of cessation of TNFα-blocking therapy have been published earlier. The long-term data was collected retrospectively after the first follow-up year to evaluate the remission rate and risk factors for the relapse after a median of 36 months. Results: After the first relapse-free year, 14 out of the remaining 34 IBD patients relapsed (41%; 5/12 [42%] CD and 9/22 [41%] UC/IBDU). Univariate analysis indicated no associations with any predictive factors. Re-treatment was effective in 90% (26/29) of patients. Conclusion: Of IBD patients in deep remission at the time of cessation of TNFα-blocking therapy, up to 60% experience a clinical or endoscopic relapse after a median follow-up time of 36 months (95% CI 31–41 months). No individual risk factors predicting relapse could be identified. However, the initial response to a restart of TNFα-blockers seems to be effective and well tolerated.

Su1064 Pain Hypersensitivity Among Women With Gastroesophageal Reflux Disease Is Explained by Psychological Distress

Background and aims: Gastroesophageal reflux disease (GERD) is common in the West and the increased incidence is associated with obesity. A third of those with symptoms of GERD have endoscopic signs of erosive esophagitis. Two thirds have non-erosive reflux disease; esophageal hypersensitivity may explain some but it is controversial whether an association of psychological distress exists with GERD. Epigastric pain and burning have been found to be associatedwith both hypersensitivity to gastric distension and the personality trait of neuroticism. It has also been shown that anxiety induction significantly increases the experienced acid-induced esophageal hyperalgesia. Visceral hypersensitivity has also been identified in a subset, although the relationship between specific gastric symptoms and physiological changes has been inconsistent. Our aim was to study whether nociceptive pressure pain threshold (PPT) or tolerance (PPTo) is decreased in GERD indicating pain hypersensitivity.Methods: The prospectively collected Northern Finland Birth Cohort 1966 (NFBC 1966) population (http://www.oulu.fi/nfbc/) is comprised of children from the two northernmost provinces of Finland, Oulu and Lapland with a date of birth Jan 1st Dec 31st, 1966 (12 231 children, 96.3% of all births during 1966 in that area). Between years 2013 and 2014, at the age of 46 years, a large health examination including both questionnaires (n=6868/10282, 67% response rate) and clinical examination (n=5851/10282, 57% response rate) was performed. For this study, 3810 subjects (n=1761, 46% male) were available. Uncomfortable pressure, i.e. PPT and intolerable pressure, i.e. PPTo were tested using an algometer (Somedic AB, Horby, Sweden) and the pressure was increased from 0 kPa at a constant rate of 50 kPa/s until the safety maximum of 1200 kPa. The measurements were done for four anatomical sites in the following order: 1) the upper trapezius muscle, 2) the tibialis anterior muscle, 3) the dorsal aspect of the wrist joint line, and 4) the L5/S1 interspinous space. GERD was defined according to the Montreal definition. Anxiety and depression were assessed with 25-items Hopkins Symptom Checklist with a cut off of 1.55. Smoking habits were recorded and body mass index (BMI) was calculated (kg/m). Data were analyzed by Tobit regression analysis adjusting for BMI, anxiety, depression and smoking and crude Kaplan-Meier curves were drawn. Results: 524 subjects (14%) had GERD (n=230, 44% male), 509 (13%) had anxiety (n=196, 39% male) and 852 (22%) had depression (n=340, 40% male). In the crude model, PPT and PPTo were decreased only in women with GERD (Fig.).The difference was explained by anxiety and depression based on the adjusted models. (Table) Conclusions: Psychological distress may explain pain hypersensitivity in women with GERD. Tobit regression analysis of pressure pain threshold and pain tolerance in females with GERD.