Characterization of inflammatory bowel disease management by vedolizumab and concomitant treatments in real-life clinical practice.

Limited data is available on vedolizumab combination therapies in real-world clinical practice. Here, we evaluated the concomitant corticosteroid, immunosuppressive, and 5-aminosalicylic acid utilization of inflammatory bowel disease (IBD) patients treated with vedolizumab in a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centres with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) who had at least one vedolizumab infusion since it's availability in Finland were included in the study. Data were collected from medical charts at baseline (vedolizumab treatment initiation), week 14, and month 6. The majority of patients who used corticosteroids at the baseline and persisted on vedolizumab treatment for 6 months were taken off corticosteroid treatment by the 6-month time point (CD, 54.5%; UC, 69.8%). Modest corticosteroid dose reductions were observed among treatment persistent CD patients from the baseline until month 6. Corticosteroid users had less vedolizumab discontinuations due to primary ineffectiveness and more discontinuations due to adverse events than patients not using corticosteroids. Vedolizumab may have a corticosteroid sparing effect in real-world clinical practice. Concomitant corticosteroid use may lead to a lower rate of vedolizumab discontinuation due to primary ineffectiveness, but a higher discontinuation rate due to adverse events.

High treatment persistence rate and significant endoscopic healing among real-life patients treated with vedolizumab - a Finnish Nationwide Inflammatory Bowel Disease Cohort Study (FINVEDO).

OBJECTIVES: The efficacy and tolerability of vedolizumab in the treatment of inflammatory bowel diseases (IBD) has been demonstrated in an extensive GEMINI clinical trial programme. Clinical trials represent highly selected patient populations and, therefore, it is important to demonstrate effectiveness in real-life clinical practice. We set out to assess real-world treatment outcomes of vedolizumab in a nationwide cohort of treatment refractory Finnish Crohn's disease (CD) and ulcerative colitis (UC) patients. METHODS: This was a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centers with a diagnosis of UC or CD who had at least one vedolizumab infusion since the availability of the product in Finland, were included in the study. Data were collected retrospectively from medical charts at baseline, week 14, and month 6. The primary outcome measure was treatment persistence 24 weeks post-vedolizumab initiation. RESULTS: A total of 247 patients were included (108 CD, 139 UC). A total of 75.0% (n = 81) of all CD patients and 66.2% (n = 92) of all UC patients, were persistent on vedolizumab therapy for 6 months post treatment initiation. At month 6, 41.8% (28/67) of the treatment persistent CD patients and 73.3% (63/86) of the treatment persistent UC patients achieved clinical remission. Significant improvement in endoscopic scores were observed among treatment persistent patients (CD, n = 17, ΔSES-CD=-5.5, p = .008; UC, n = 26, ΔMayo endoscopic score =-0.5, p = .003) at month 6. CONCLUSIONS: Vedolizumab provides an effective and well-tolerated treatment option in real-world clinical practice even among treatment refractory IBD patients.

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 Crohn's 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 α (TNFα)-blocking therapy. In this prospective multicenter study, we evaluated the relapse rate, predictive factors, and the response to retreatment after discontinuation of TNFα-blocking therapy in patients with IBD in deep remission. METHODS: We recruited 52 patients (17 Crohn's disease, 30 ulcerative colitis, and 5 IBD unclassified) in clinical, endoscopic, and fecal calprotectin-based (<100 µg/g) remission after at least 1 year of TNFα-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, TNFα-blocking therapy was restarted. RESULTS: After a median follow-up time of 13 (range, 12-15) months, 17/51 (33%) patients relapsed (5/17 Crohn's 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 TNFα-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 TNFα antagonists was effective and well tolerated.

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 Crohn's 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 Crohn's 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.

[Primary biliary cirrhosis (PBC)]. / Primaarinen biliaarikirroosi (PBC).

Primary biliary cirrhosis (PBC) is an inflammatory autoimmune liver disease leading, if untreated, to cholestasis and cirrhosis. The diagnosis is made on the basis of elevated plasma levels of alkaline phosphatase and antimitochondrial antibodies at a stage where the patient usually still remains symptomless. The degree of severity and prognosis of the disease are defined by means of histological findings of the liver. Adequate response for approximately half of the patients is obtained with urodeoxycholic acid treatment. The treatment for advanced disease is hepatic transplantation, which yields excellent results.

Fecal calprotectin and S100A12 have low utility in prediction of small bowel Crohn's disease detected by wireless capsule endoscopy.

OBJECTIVE: Data on fecal calprotectin and S100A12 in predicting wireless capsule endoscopy (WCE) findings in suspicion of Crohn's disease (CD) are scarce. Our aim was to study the role of calprotectin and S100A12 in predicting inflammatory lesions of small bowel in patients undergoing WCE. MATERIAL AND METHODS: 84 patients undergoing WCE (77 for suspicion of CD and 7 CD patients for evaluation of disease extent) were prospectively recruited. WCE findings were scored. Patients provided a stool sample for measurements of biomarkers. Patients underwent an esophagogastroduodenoscopy and ileocolonoscopy before WCE. RESULTS: WCE was abnormal in 35 (42%) of 84 patients: 14 patients with CD, 8 with NSAID enteropathies, 8 with angioectasias, 4 with polyps or tumors, and 1 with ischemic stricture. Median calprotectin concentration in the study population was 22 µg/g (range 2-342) and S100A12 concentration 0.048 µg/g (range 0.003-1.215). Fecal calprotectin was significantly higher in CD patients (median 91, range 2-312) compared with those with normal WCE or other abnormalities (p = 0.008), whereas fecal S100A12 (0.087 µg/g, range 0.008-0.896) did not differ between the groups (p = 0.166). In detecting inflammatory small bowel lesions, sensitivity, specificity, positive predictive value, and negative predictive value for fecal calprotectin (cutoff 50 µg/g) were 59%, 71%, 42%, and 83%, and for S100A12 (cutoff 0.06 µg/g) these were 59%, 66%, 38%, and 82%. CONCLUSIONS: In predicting small bowel inflammatory changes, fecal biomarkers calprotectin and S100A12 have moderate specificity, but low sensitivity. Neither fecal calprotectin nor S100A12 can be used for screening or excluding small bowel CD.

Serological markers for monitoring disease progression in noncirrhotic primary biliary cirrhosis on ursodeoxycholic acid therapy.

BACKGROUND/AIM: Liver biopsy has so far been the only method to accurately follow the progression of primary biliary cirrhosis (PBC). The stage and the severity of lymphocytic piecemeal necrosis (LPN) have been shown to be an independent factor for the development of cirrhosis. In this 3-year prospective study, we evaluated the diagnostic value of several liver function tests, surrogate markers of fibrogenesis, hyaluronic acid (HA), procollagen III N-terminal peptide (S-PIIINP), cholestanol and plant sterols in noncirrhotic PBC patients treated with ursodeoxycholic acid (UDCA) or with UDCA and budesonide to assess the stage, inflammation and fibrosis. METHODS: Seventy-seven stage I-III PBC patients were included into the study, with control biopsy at 36 months. Serum liver enzymes, bile acids (BA), HA, PIIINP, immunoglobulins, lipids and cholesterol precursors and plant sterols were measured at baseline and at 36 months. RESULTS: Aspartate aminotransferase (AST), HA, BA and PIINP were significantly different between stages I to III and differentiated mild (F0F1) from moderate (F2F3) fibrosis. The combination of these variables (PBC score) exhibited best sensitivity and specificity, compared with AST/platelet ratio, Forns' score and fibrosis index. Using a cut-off value of 66 for the PBC score, the sensitivity was 81.4% and specificity was 65.2% for classifying the stage of PBC, regarding the stage the and fibrosis in noncirrhotic PBC. CONCLUSIONS: Serum HA, BA, PIIINP and AST may serve as valuable simple tools to monitor the treatment response to UDCA in early stages of PBC. Combinations of these biomarkers into a single index further potentiate the diagnostic value of such measurements.

Prevalence and incidence of primary biliary cirrhosis are increasing in Finland.

OBJECTIVE: To examine the epidemiology of primary biliary cirrhosis (PBC) in Finland and to evaluate whether the possible increase in prevalence was attributable to the increasing incidence, better survival, or both. MATERIAL AND METHODS: The Hospital Discharge Register, pathology registers, and death certificates for the years 1988 99 were scrutinized, and the patients identified were followed-up for survival until 31 October 2004. The study area covered four university hospital districts: a total of 25 hospitals. The diagnosis of PBC was regarded as definite (or probable) if three (or two) of the following criteria were fulfilled: positive antimitochondrial antibodies, constantly elevated alkaline phosphatase, and compatible liver histology. RESULTS: In the total population of the study areas, the age-standardized prevalence of PBC increased during the study period from 103 (95% CI: 97-110) to 180 (172-189) per million inhabitants. Incidence increased from 12 (10-14) to 17 (15-20) per million inhabitants per year. The annual average increase in prevalence was 5.1% (4.2-5.9%, p <0.0001) and in incidence 3.5% (0.9%-6.0%, p =0.008). In gender-specific analyses among women, the prevalence of PBC increased from 161 (151-171) to 292 (277-207) per million during the study period and the incidence from 20 (16-24) to 27 (23-32) per million per year. The death rate was 4% per year and half the deaths were from liver-related causes. Survival after diagnosis during the study period lengthened. CONCLUSIONS: The prevalence of PBC increased in Finland during 1988-99, owing to both the increased incidence and the prolonged survival.

Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial.

Ursodeoxycholic acid (UDCA) is a safe medical therapy for primary biliary cirrhosis (PBC), but its effect on liver histology remains uncertain. Budesonide is a glucocorticoid with high receptor activity and high first-pass metabolism in liver. We evaluated the combination of budesonide and UDCA on liver histology and compared this with UDCA alone in a 3-year prospective, randomized, open multicenter study. Patients with PBC (n = 77), at stages I to III, were randomized into 2 treatment arms, A (n = 41): budesonide 6 mg/d and UDCA 15 mg/kg/d and B (n = 36): UDCA 15 mg/kg/d. Liver histology was assessed at the beginning and at the end of the study. Liver function tests and glucose and cortisol values were determined every 4 months. Paired liver biopsy specimens were available from 69 patients (A = 37 and B = 32). Stage improved 22% in group A but deteriorated 20% in group B (P = .009). Fibrosis decreased 25% in group A but increased 70% in group B (P = .0009). S-PIIINP decreased significantly in group A. Inflammation decreased in both groups, 34% in group A (P = .02), but only 10% in group B (P = NS). Serum liver enzymes decreased significantly in both treatment arms. Bilirubin values rose in group B but stayed stable in group A (A/B P = .002). A mild systemic glucocorticoid effect from budesonide was evident after 2 years. In conclusion, budesonide combined with UDCA improved liver histology, whereas the effect of UDCA alone was mainly on laboratory values. Studies with longer follow-up using a combination of budesonide and UDCA are warranted to confirm safety and effects.