Therapeutic drug monitoring in inflammatory bowel disease: implementation, utilization, and barriers in clinical practice in Scandinavia.

BACKGROUND AND AIMS: Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia. METHODS: A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies. RESULTS: In total, 297 IBD physicians prescribing biologic therapies, equally distributed between community and university hospitals, were included (response rate 42%) (Norway 118 (40%), Denmark 86 (29%), Sweden 50 (17%), Finland 33 (11%), Iceland 10 (3%)). Overall, TDM was applied during biologic therapies by 87%, and for TNF-inhibitors >90%. Among the users, reactive and proactive TDM were utilized by 90% and 63%, respectively. Danish physicians were significantly less inclined to use TDM compared to other Scandinavian countries; (58% vs 98%); OR 0.03 [0.01-0.09], p < 0.001). Reactive TDM was commonly applied at primary (74%) and secondary (99%) treatment failure. Proactive TDM was used by 80% during maintenance therapy and 56% during induction and more commonly utilized in Norway (p < 0.001), and by physicians managing >10 IBD patients/week (p = 0.005). TDM scenarios were interpreted in accord with available evidence but with discrepancies for proactive TDM. The main barriers to TDM were lack of guidelines (51%) and time lag between sampling and results (49%). TDM of thiopurines was routinely used by 87%. CONCLUSION: TDM of biologic and thiopurine therapies has been broadly implemented into clinical practice in Scandinavia. However, physicians call for TDM guidelines detailing indications and interpretations of test results along with improved test response times.

Longitudinal evolution of catheter-related bloodstream infections, kidney function and liver status in a nationwide adult intestinal failure cohort.

OBJECTIVES: The development of intestinal failure-related complications in Finnish adults is unknown. This study aimed to investigate the incidence of catheter-related bloodstream infections (CRBSI), and the longitudinal changes in biochemical liver and kidney tests in a nationwide cohort. MATERIALS AND METHODS: The search for Finnish adults with intestinal failure (IF) utilized a survey to Finnish health-care providers (n = 111) with the potential to provide long-term parenteral support (PS) for adult IF. Our nationwide, cross-sectional cohort included all IF patients aged ≥ 18 years who had received PS for ≥ 120 d in 2017. Data regarding CRBSI and biochemical liver and kidney tests were collected from patient records at the start of PS up to the latest available measurement in 2017. RESULTS: In the nationwide cohort of 52 patients, the CRBSI incidence was 1.35/1000 catheter days. Seventy-three percent of CRBSI in a long-term catheter led to catheter replacement. During a median PS duration of 27.5 (interquartile range [IQR] 11.3-57.3) months, a statistically significant median change occurred in estimated glomerular filtration rate (eGFR; -8.5 ml/min/1.73 m2, IQR -30-7, p = .005) and alkaline phosphatase (ALP; 26 U/l, IQR -11-95, p = .019). In a multiple regression model for eGFR at data collection, baseline eGFR and age were strong explanatory variables. CONCLUSIONS: Incidence of CRBSI, but not treatment strategies, in this nationwide adult IF population correspond well to those reported from specialized centers. Decreased kidney function and abnormal liver test results are frequent findings, and even more so over time, emphasizing the importance of regular monitoring.

Combining biological therapies in patients with inflammatory bowel disease: a Finnish multi-centre study.

BACKGROUND AND AIMS: Therapy with two concomitant biologicals targeting different inflammatory pathways has emerged as a new therapy option for treatment refractory inflammatory bowel disease (IBD). Data on the efficacy and safety of dual biological therapy (DBT) are scarce and are investigated in this study. MATERIALS AND METHODS: Data on all patients treated with a combination of two biologicals in four Finnish tertiary centres were collected and analysed. Remission was assessed by a physician on the basis of biomarkers, endoscopic evaluation and alleviation of symptoms. RESULTS: A total of 16 patients with 22 trials of DBT were included. Fifteen patients had Crohn's disease. The most common combination of DBT was adalimumab (ADA) and ustekinumab (USTE; 36%) with median follow-up of nine months (range 2-31). Altogether seven (32%) patients were in remission at the end of follow-up and in two trials response to DBT was assessed to be partial with the relief of patient symptoms. In a total of four trials DBT reduced the need for corticosteroids. The majority of patients achieving a response to DBT were treated with the combination of ADA and USTE (56%). At the end of follow-up all nine (41%) patients responding to DBT continued treatment. Infection complications occurred in three patients (19%). CONCLUSION: DBT is a promising alternative treatment for refractory IBD, and half of our patients benefitted from it. More data on the efficacy and safety of DBT are needed especially in long-term follow up.

Benefit of measuring vedolizumab concentrations in inflammatory bowel disease patients in a real-world setting.

OBJECTIVES: We set out to determine the reasons for serum vedolizumab (VDZ) trough concentration (TC) measurements in inflammatory bowel disease (IBD) patients and to evaluate treatment modifications after therapeutic drug measurement (TDM). We also evaluated the effect of increased dosing on patients' response to VDZ therapy. METHODS: We performed a retrospective cohort study of IBD patients who received VDZ therapy at Helsinki University Hospital and whose VDZ levels were measured between June 2014 and December 2018. RESULTS: Altogether, 90 patients (32 Crohn's disease and 58 ulcerative colitis) and 141 VDZ TC measurements were included. 24.1% of measurements took place during induction and 75.9% during the maintenance phase. During induction, 64.7% reached the target TC >20µg/ml. During maintenance therapy, 82.2% of VDZ TCs were within or exceeded the suggested target range of 5-15µg/ml. Reasons for TDM were: secondary nonresponse (44.0%), assessment of adequate VDZ TC (25.5%), primary nonresponse (12.8%), adverse events (6.4%), and other (11.3%). No treatment changes occurred after 60.3% of VDZ measurements. Increased dose frequency was used after 25.5% of VDZ measurements and 33.3% of these patients experienced improvement. Altogether, 31 (34.4%) patients discontinued the therapy due to inadequate treatment response. No anti-vedolizumab antibodies were detected. CONCLUSIONS: During the maintenance of VDZ therapy, the majority of VDZ TCs were within the suggested range. Measurement of VDZ TC did not lead to any treatment changes in two-thirds of patients. Dose optimization occurred in a quarter of patients and a third of them benefited from it.

A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn's disease patients in Finland.

BACKGROUND: Real-world evidence to support optimal ustekinumab dosing for refractory Crohn's disease (CD) patients remains limited. Data from a retrospective nationwide chart review study was utilized to explore ustekinumab dosing dynamics and optimization, identify possible clinical predictors of dose intensification, and to evaluate ustekinumab trough concentrations (TCs) and concomitant medication use in Finland. METHODS: Information gathered from17 Finnish hospitals included clinical chart data from 155 adult CD patients who received intravenous ustekinumab induction during 2017-2018. Data on ustekinumab dosing and TCs, concomitant corticosteroid and immunosuppressant use, and antiustekinumab antibodies were analyzed in a two-year follow-up, subject to availability. RESULTS: Among 140 patients onustekinumab maintenance therapy, dose optimization was required in 55(39%) of the patients, and 41/47 dose-intensified patients (87%) persisted on ustekinumab. At baseline, dose-intensified patient group had significantly higher C-reactive protein (CRP) levels, and at week 16, significantly lower ustekinumab TCs than in patients without dose intensification. Irrespective of dose optimization, a statistically significant reduction in the use of corticosteroids was observed at both 16 weeks and one year, coupled with an increased proportion of patients on ustekinumab monotherapy. Antiustekinumab antibodies were undetectable in all 28 samples from 25 patients collected throughout the study period. CONCLUSIONS: Nearly a third of all CD patients on ustekinumab maintenance therapy, with a history of treatment-refractory and long-standing disease, required dose intensification. These patients persisted on ustekinumab and had significant reduction of corticosteroid use. Increased baseline CRP was identified as the sole indicator of dose intensification. TRIAL REGISTRATION: EUPAS30920.

Long-term deep remission during maintenance therapy with biological agents in inflammatory bowel diseases.

Background and aims: A multicentre, retrospective, non-interventional, patient chart review study was conducted to investigate deep (DR) and histological remission rates during maintenance therapy with biological agents in inflammatory bowel disease (IBD).Methods: We reviewed clinical, endoscopic, and histological findings, and laboratory markers such as C-reactive protein (CRP) and faecal calprotectin (FC) on average of nine years after the initiation of anti-TNF-therapy. DR was defined as no clinical symptoms (The physicians' global assessment scores; PGA = 0) with endoscopic remission (the Simple Endoscopic Score for Crohn's Disease [SES-CD] ≤ 2 or Mayo endoscopic subscore ≤1). Histological activity was defined as normal if only architectural alterations without cellularity changes occurred.Results: Of 117 IBD patients on maintenance therapy, 72 (62%; CD n = 55 [56%], UC n = 17 [85%]) patients were in DR. Of patients in DR, 76% were also in histological remission. 77% of patients remained on initiated biological treatment. UC patients achieved DR significantly more often than CD patients (p = .016). Both median CRP and FC levels were significantly lower in patients with DR.Conclusion: Reassuringly, almost two thirds of the IBD patients on maintenance therapy with biological agents maintained DR in the long-term, and more than two thirds of patients in DR achieved also histological remission. CD patients in DR had fewer surgical operations due to CD than patients not achieving DR.

Fragmented management of long-term parenteral support for adult intestinal failure in Finland.

Objectives: Parenteral support (PS) is the first-line therapy for intestinal failure (IF). Optimal patient outcomes require experienced multidisciplinary teams adhering to structured protocols. As practices to provide long-term PS for adult IF patients in Finland are unknown, this cross-sectional nationwide study aimed to evaluate current management of PS for adult IF across the country. Materials and methods: An internet-based survey was emailed to all Finnish hospitals and hospital-at-home services with the potential to provide PS for adult IF. The survey included 20 items addressing the provision of long-term PS for adult IF patients (aged ≥18 years). Data were analysed using descriptive statistics. Results: Overall, 52 (47%) of the 111 identified units responded. Of responding units, 38 (73%) had at some point provided long-term (≥120 days) PS for adult IF, and 23 (44%) had done so during the preceding year. Only three units currently managed ≥3 adult patients. Most (65%) of the respondents worked in a hospital and were either physicians (38%) or dietitians (39%). Only 65% of respondents reported that their unit had an assigned physician responsible for PS provision, and 28% reported that a team was responsible for long-term PS. Only 26% of respondents reported having a written protocol to guide PS management. Conclusions: Health care providers with very limited experience and a fragmented approach manage most Finnish adult IF patients. Evidence-based protocols and multidisciplinary teams are scarce. The care for adult IF patients on long-term PS needs to be improved in Finland.

Ustekinumab for Crohn's disease: a nationwide real-life cohort study from Finland (FINUSTE).

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn's Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD. Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48 CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey-Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn's disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up. Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p = .0001) and SES-CD from 12 to 3 (p = .009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up. Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed.

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.

The impact of an adaptation course on health-related quality of life and functional capacity of patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) has a substantial impact on patients health-related quality of life (HRQoL). In this study, we examined the impact of adaptation courses on HRQoL, psychological well-being, depression and number of sick-leave days of IBD patients. METHODS: The study recruited 142 IBD patients attending an adaptation course of 5-12 days. The courses were specially designed for IBD patients and included multidisciplinary information about IBD, peer support, group activities and encouragement for adequate physical exercise. The participants completed the study questionnaire at the beginning and the end of the course and after six and 12 months of follow-up. HRQoL was assessed with the generic 15-dimensional (15D) tool and depression with Beck's Depression Inventory (BDI). Utilization of health care services and work absenteeism was also assessed. Visual analog scales were used for assessing psychological functioning. RESULTS: 15D, BDI scores and scores describing psychological well-being were significantly better at the end of the course when compared to baseline (15D 0.82 vs. 0.84, p < .001; BDI 11.8 vs. 8.5, p < .001). Positive results were maintained during follow up. The percentage of patients receiving peer support rose from 32 to 70% and those with peer support had better HRQoL at the 12-month follow-up (p = .01). No significant change in health care utilization or number of sick-leave days was observed. CONCLUSION: Adaptation training appears to have a positive impact on the psychological well-being of IBD patients. Peer support appears to be an important factor.

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.

Switching maintenance infliximab therapy to biosimilar infliximab in inflammatory bowel disease patients.

BACKGROUND: Clinical use of biosimilar infliximab (CT-P13) in inflammatory bowel diseases (IBDs) is based on extrapolation of indication from clinical studies performed in rheumatological diseases. Only few data exist of behaviour of infliximab trough levels (TLs) and anti-drug antibodies (ADAs) during switching. AIM: The objective of this study was to evaluate changes in TLs, ADA formation and disease activity after switching from originator infliximab to biosimilar one. METHODS: All our IBD patients receiving maintenance infliximab therapy were switched to biosimilar infliximab. TLs and ADAs were measured before the last originator infusion and before the third biosimilar infusion. Laboratory values, disease activity indices (partial Mayo score and Harvey-Bradshaw index) and demographic data were collected from patient records. RESULTS: A total of 62 patients were included in the final analysis (32 Crohn's disease, 30 ulcerative colitis (UC) or IBD-unclassified). No significant changes in median TLs before (5.5 mg/l) and after switching (5.5 mg/l, p = .05) occurred in the entire study group or in the Crohn's disease (CD) subgroup (5.75 and 6.5 mg/l, p = .68). However, in the subgroup of ulcerative colitis, the change in median TL was significantly different (from 5.2 to 4.25 mg/l, p = .019). Two patients developed ADAs after switching. No changes in disease activity were detected during switching and no safety concerns occurred. CONCLUSIONS: Switching from originator to biosimilar infliximab resulted in statistically significant differences in infliximab TLs in patients with UC but not in patients with Crohn's disease. The clinical significance for this difference is doubtful and in neither group changes in disease activity occurred.

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

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.

Detailed Follow-up Study of Pediatric Orofacial Granulomatosis Patients.

OBJECTIVES: Orofacial granulomatosis (OFG) is a chronic inflammatory condition affecting the orofacial area. Its connection to Crohn disease (CD) is debated. Our aim was to describe a cohort of pediatric patients with OFG in detail, study the long-term behavior of OFG, and evaluate factors predicting CD in patients with OFG. METHODS: We invited patients diagnosed with OFG at 2 university hospitals, Finland for a follow-up appointment. Patients (n = 29) were examined by a dentist and an otorhinolaryngologist using a structural schema. Orofacial findings were also recorded using digital photographing. Patients filled in questionnaires about general health and special diets. Patients' nutrition was evaluated from food records. The findings were compared between patients with OFG only and OFG with CD. RESULTS: Patients with CD had more findings in the orofacial area (total score for orofacial findings median 11) compared to patients with OFG only (total score median 7.5). There was no statistically significant difference in the type of lesions between these groups, except the upper lip was more often affected in patients with CD (n = 11) than in patients with OFG only (n = 0). Most of the patients had normal otorhinolaryngological findings. All patients with elevated anti-Saccharomyces cerevisiae antibody A levels had CD (n = 6) and they presented with more orofacial findings (total score) than patients with normal levels of anti-S cerevisiae antibody A (P = 0.0311). CONCLUSIONS: Long-term follow-up of pediatric-onset patients with OFG shows good prognosis. Patients with OFG do not seem to have otorhinolaryngological comorbidity. Anti-S cerevisiae antibody A may serve as a factor to indicate the possible presence of underlying CD in patients with OFG, but further studies are requested.

Does oral α-galactosidase relieve irritable bowel symptoms?

OBJECTIVE: Abdominal bloating is reported by a majority of irritable bowel syndrome (IBS) patients. Excess colonic fermentation may cause gaseous symptoms. Several foodstuffs contain oligosaccharides with an α-galactosidic linkage that is resistant to mammalian hydrolases. Assisted hydrolysis by exogenous α-galactosidase enzyme (AG) could offer a way of controlling IBS symptoms by reducing colonic fermentation and gas production. The aim of this study was to assess the effect of AG on symptom severity and quality of life in IBS patients with abdominal bloating or flatulence. METHODS: A total of 125 subjects with IBS received AG or placebo at meals for 12 weeks. IBS-Symptom Severity Score (IBS-SSS) and quality of life (QoL) were assessed at baseline, during the treatment and at 4-week follow-up. RESULTS: AG showed a trend toward a more prominent decrease in IBS-SSS. The responder rate at week 16 was higher for the AG group. No difference was detected in QoL between AG and placebo groups. A total of 25 patients (18 in AG group and 7 in placebo group, p = 0.016) withdrew from the study. Abdominal pain and diarrhea were more often reported as reason for withdrawal in AG group. CONCLUSIONS: We found no evidence to support the use of AG routinely in IBS patients. Improvement of clinical response at 4-week follow-up may suggest a long-term effect of unknown mechanism, but could also be attributed to non-responder drop out. Gastrointestinal (GI) side effects may be a coincidence in this study, but irritation of GI tract by AG administration cannot be excluded.

Association Between Fecal Calprotectin Levels and Small-bowel Inflammation Score in Capsule Endoscopy: A Multicenter Retrospective Study.

BACKGROUND: Accurate inflammation reporting in capsule endoscopy (CE) is important for diagnosis and monitoring of treatment of inflammatory bowel disease (IBD). Fecal calprotectin (FC) is a highly specific biomarker of gut inflammation. Lewis score (LS) was developed to standardize quantification of inflammation in small-bowel (SB) CE images. GOALS: Multicenter retrospective study aiming to investigate correlation between LS and FC in a large group of patients undergoing CE for suspected or known small-bowel IBD, and to develop a model for prediction of CE results (LS) based on FC levels. STUDY: Five academic centers and a district general hospital offering CE in UK, Finland, Sweden, Canada, and Israel. In total, 333 patients were recruited. They had small-bowel CE and FC done within 3 months. RESULTS: Overall, correlation between FC and LS was weak (r s: 0.232, P < 0.001). When two clinically significant FC thresholds (100 and 250 µg/g) were examined, the r s between FC and LS was 0.247 (weak) and 0.337 (moderate), respectively (P = 0.307). For clinically significant (LS ≥ 135) or negative (LS < 135) for SB inflammation, ROC curves gave an optimum cutoff point of FC 76 µg/g with sensitivity 0.59 and specificity 0.41. LIMITATIONS: Retrospective design. CONCLUSIONS: LS appears to show low correlation with FC as well as other serology markers of inflammation. FC does not appear to be a reliable biomarker for significant small-bowel inflammation. Nevertheless, FC level ≥ 76 µg/g may be associated with appreciable visual inflammation on small-bowel CE in patients with negative prior diagnostic workup.

[Exemplary cases of individualization of biological therapy]. / Esimerkkitapauksia biologisen hoidon yksilöllistämisestä.

The use of biological drugs consisting of large molecules has in recent years expanded to new indications and new specialties. These drugs are most commonly proteins possessing the structure of an antibody or a receptor, and treatment with them is significantly more expensive than that carried out with conventional small molecule drugs. Determination of drug levels and emerging antibodies form the basis of individualization. They will enable better treatment results with simultaneous avoidance of unnecessary medications, excessive doses--and extra costs. We demonstrate the individualization of TNF-α blocker therapy through patient cases in various situations.

Fecal calprotectin in diagnosis and clinical assessment of inflammatory bowel disease.

The fecal neutrophil-derived biomarker calprotectin has several features of an ideal noninvasive test for detecting intestinal inflammation: it is simple, reliable, and low in cost. Its utility in differentiating inflammatory bowel diseases (IBDs) from functional conditions such as irritable bowel syndrome is well documented. Fecal calprotectin (FC) correlates closely with endoscopic activity of IBD. Emerging evidence suggest its usefulness in serial monitoring of disease activity and of therapy success in IBD. A low FC concentration predicts persistence of clinical remission especially in non-symptomatic ulcerative colitis and Crohn's colitis. Here, an overview is given to the current role of FC in diagnosis and clinical assessment of IBD.

Surgical rehabilitation of short and dysmotile intestine in children and adults.

AIMS: This is a descriptive study aiming to compare outcomes of intestinal rehabilitation surgery among pediatric and adult intestinal failure (IF) patients with either primary intestinal motility disorders or short bowel syndrome (SBS) treated by our nationwide program. METHODS: Medical records of IF patients (n = 31, 71% children) having undergone autologous intestinal reconstructions (AIR) (n = 25), intestinal transplantation (ITx) (n = 5), or being listed for ITx (n = 2) between 1994 and 2014 were reviewed. RESULTS: At surgery, median age was 3.4 (interquartile range, 1.0-22.1) in SBS (n = 22) and 16.5 (3.2-26.7) years in dysmotility patients (n = 9) who received median 60% and 83% of energy requirement parenterally, respectively. Median small bowel length was shorter in SBS than dysmotility patients (34 versus 157 cm, p < 0.001). Following AIR, none of the dysmotility patients achieved permanent intestinal autonomy, whereas 68% of SBS patients weaned off parenteral nutrition (PN) (p = 0.022) and none required listing for ITx. Five dysmotility patients who underwent ITx achieved intestinal autonomy. Regarding both AIR and ITx procedures, no significant difference in PN weaning was observed between the two subgroups. At last follow-up, 3.3 (0.6-8.0) years postoperatively, median plasma bilirubin was 6 (4-16) µmol/l, while liver biopsy showed fibrosis (Metavir stage 1-2) in 50% and cholestasis in 8%. Proportion of PN energy requirement had reduced significantly (p = 0.043) among PN-dependent SBS (n = 7) but not among dysmotility patients (n = 5). Overall survival was 90%. CONCLUSION: AIR surgery was beneficial among selected SBS patients, whereas in intestinal dysmotility disorders, permanent PN weaning was only achieved by ITx.

The long-term outcome of anti-tumor necrosis factor-α therapy related to fecal calprotectin values during induction therapy in pediatric inflammatory bowel disease.

OBJECTIVE: Monitoring fecal calprotectin (FC) could assist in the assessment of the therapeutic response of inflammatory bowel disease (IBD). There are few studies on long-term prognosis related to the FC value response to infliximab induction therapy, thus providing the aim of this study on pediatric patients. METHODS: FC levels were measured during the induction and maintenance phase of infliximab therapy (5 mg/kg) in 76 pediatric IBD patients introduced to maintenance therapy. The long-term outcomes and clinical disease activity were retrospectively related to the FC response to induction. RESULTS: The median pretreatment FC level of 817 µg/g stool (range <5-24,000) declined to 372 µg/g (range 5-2430) by week 6, with a low level (<100 µg/g) in 35% (pooled comparable data for ulcerative colitis and Crohn's). Clinical activity indices showed remission in 59% (pediatric Crohn's disease activity index: <10, n = 33; pediatric ulcerative colitis activity index: <10 n = 12). In 49 patients (64%), infliximab therapy was discontinued (inadequate effect/surgery = 27; remission/bridging to azathioprine = 12; adverse effect = 6; antibodies to infliximab n = 4) during the study period with a median follow up of 1.1 years (interquartile range [IQR]: 0.71-4.4). Those who discontinued the therapy within the first year due to an inadequate effect had higher median FC level during induction than the other patients (median 633 µg/g, IQR: 197-819 and median 219 µg/g, IQR: 71-508, respectively; p < 0.025) and were less frequently in clinical remission at week 6 (p < 0.01). CONCLUSIONS: The long-term prognosis of infliximab therapy is related to the response to induction therapy in pediatric IBD and reflected in low FC values between weeks 2 and 6 and clinical remission.