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Proactive therapeutic drug monitoring (TDM) is often challenged by long turnaround time when using enzyme-linked immunosorbent assays (ELISAs), especially when analyses are centralised. Point-of-care tests (POCTs) allow rapid assessments, but data on their agreement with existing in-house methodologies are scarce. To examine the agreement between a POCT by ProciseDx (San Diego, CA) and the most frequently used in-house ELISA for infliximab (IFX) quantification in Sweden. Serum samples were analysed using the in-house ELISA, Karolinska University Hospital, Stockholm, Sweden and a POCT by ProciseDx (San Diego, CA). Agreement was assessed and differences were examined. Samples from 61 inflammatory bowel disease (IBD) patients were analysed with a median IFX concentration of 7.9 μg/mL (interquartile range (IQR) 5.5–13) for the POCT and 7.9 μg/mL (IQR 5.2–12) for the ELISA (Pearson's correlation coefficient = 0.95 (95% CI 0.92–0.97, p <.01)). A Passing–Bablok regression yielded an intercept of −0.44 and a slope of 1.09. The Bland–Altman plot showed a systemic bias of −0.77 μg/mL (95% CI −0.18 to −1.4) between the methods. The upper limit of agreement was 3.7 (95% CI 2.7–4.8) (μg/mL), whereas the lower limit agreement was −5.3 (95% CI −6.3 to −4.3) (μg/mL). An excellent reliability was observed, intraclass correlation showed = 0.94 (95% CI 0.89–0.96, p <.0001). When defining IFX concentration as subtherapeutic (<3.0 μg/mL), therapeutic (3.0–7.0 μg/mL) or supratherapeutic (>7.0 μg/mL) drug levels, Kappa statistics showed a substantial agreement (0.79). The POCT by ProciseDx (San Diego, CA) demonstrated a good agreement with the in-house ELISA, supporting its use for rapid IFX quantification. [ABSTRACT FROM AUTHOR]

Some studies have suggested a reduced life expectancy in patients with Crohn's disease (CD) compared with the general population. The evidence, however, is inconsistent. Prompted by such studies, we studied survival of CD patients in Örebro county, Sweden. From the medical records, we identified all patients diagnosed with CD during 1963–2010 with follow-up to the end of 2011. We estimated: overall survival, net and crude probabilities of dying from CD, relative survival ratio (RSR), and excess mortality rate ratios (EMRR) at 10-year follow-up. The study included 492 patients (226 males, 266 females). Median age at diagnosis was 32 years (3–87). Net and crude probabilities of dying from CD increased with increasing age and were higher for women. Net survival of patients aged ≥60 at diagnosis was worse for patients diagnosed during 1963–1985 (54%) than for patients diagnosed during 1986–1999 (88%) or 2000–2010 (93%). Overall, CD patients' survival was comparable to that in the general population [RSR = 0.98; 95% CI: (0.95–1.00)]. However, significantly lower than expected survival was suggested for female patients aged ≥60 diagnosed during the 1963–1985 [RSR = 0.47 (0.07–0.95)]. The adjusted model suggested that, compared with diagnostic period 1963–1985, disease-related excess mortality declined during 2000–2010 [EMRR = 0.36 (0.07–1.96)]; and age ≥60 at diagnosis [EMRR = 7.99 (1.64–39.00), reference: age 40–59], female sex [EMRR = 4.16 (0.62–27.85)], colonic localization [EMRR = 4.20 (0.81–21.88), reference: ileal localization], and stricturing/penetrating disease [EMRR = 2.56 (0.52–12.58), reference: inflammatory disease behaviour] were associated with poorer survival. CD-related excess mortality may vary with diagnostic period, age, sex and disease phenotype. There is inconsistent evidence on life expectancy of patients with Crohn's disease Crohn's disease-specific survival improved over time. Earlier diagnosis period, older age at diagnosis, female sex, colonic disease and complicated disease behaviour seems to be associated with excess Crohn's disease-related mortality. [ABSTRACT FROM AUTHOR]

Clinical trials demonstrated that golimumab is effective in anti-TNF naïve patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore ≥2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by ≥3 points or 30% from baseline) and remission (defined as a Mayo score of ≤2 with no individual subscores >1). Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6–9) at baseline to 1 (0–5) at 52 weeks (p <.01) and the faecal calprotectin decreased from 862 (335–1759) µg/g to 90 (34–169) µg/g (p <.01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5‒1188.9). The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis. [ABSTRACT FROM AUTHOR]

Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohn's disease (CD) are still limited. To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (≥3-point-decrease of Harvey–Bradshaw index (HBI)) and remission (HBI ≤4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. Of 114 included patients, 107 (94%) had failed ≥ 1 and 58 (51%) ≥ 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p =.006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option. [ABSTRACT FROM AUTHOR]

It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/− one year and within +/− three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005–2008, 2009–2012, and 2013–2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4–81.7) were ever captured in the PDR/NPR in. A time window of +/− one year or +/− three months reduced the sensitivity to 63.3% (95% CI: 61.3–65.3) and 52.6% (95% CI: 50.5–54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG. [ABSTRACT FROM AUTHOR]

Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown. Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals. Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96–99)% for Crohn's disease, 98 (97–100)% for ulcerative colitis, and 8 (4–11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32–40)% for colonic Crohn's disease (L2), 61 (56–65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78–87)% for perianal disease. Correspondingly, the PPV was 80 (71–89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis. Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients. [ABSTRACT FROM AUTHOR]

Objectives:Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness. Materials and methods:Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index <5 in Crohn’s disease (CD) and Patient Simple Clinical Colitis Activity index <3 in ulcerative colitis (UC). Results:Two-hundred forty-six patients (147 CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone ≥1 surgical resection. After a median follow-up of 17 (IQR: 14–20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p < .0001 in both groups). Faecal-calprotectin decreased in CD (p < .0001) and in UC (p = .001), whereas CRP decreased in CD (p = .002) but not in UC (p = .11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96–16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10–4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16–6.48). Conclusion:Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment. [ABSTRACT FROM AUTHOR]

Objective:With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time. Material and methods:IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA – (Bühlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia). Results:In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Bühlmann 845 (1061–226) μg/g versus 62 (224–39) μg/g, Phadia 369 (975–122) μg/g versus 11 (52–11) μg/g, and Immundiagnostik 135 (302–69) μg/g versus 8 (56–4) μg/g. The Bühlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia – (ratio of means 8.5; 95% CI 3.3–21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1–17.6) than by the Bühlmann assay (ratio of means 5.3; 95% CI 2.7–10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34–75%) when the cut-off 50 μg/g was used, whereas the differences in sensitivity were less pronounced. Conclusions:Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale. [ABSTRACT FROM PUBLISHER]

Background:Both the Swedish National Patient Register (NPR) and the Swedish Quality Register for inflammatory bowel disease (IBD, SWIBREG) are important sources of research data and information. However, the validity of a diagnosis of IBD in these registers is unknown. Methods:Medical charts of 129 randomly selected patients from the NPR and 165 patients registered both in SWIBREG and the NPR were reviewed. Patients were classified according to standardized criteria for ulcerative colitis (UC), Crohn’s disease (CD), or IBD unclassified (IBD-U). Positive predictive values (PPVs) for UC, CD, IBD-U (only SWIBREG), or having any form of IBD were then calculated. Results:For cases with ≥2 diagnoses of IBD in the NPR (hospitalizations or non-primary care outpatient visits), the PPV was 93% (95% CI: 87–97) for any IBD, 79% (66–88) for UC and 72% (60–82) for CD. In UC patients with ≥2 UC diagnoses but never a CD diagnosis, the PPV increased to 90% (77–97). The PPV for CD in patients with ≥2 CD diagnoses but never a UC diagnosis was 81% (67–91)). Combining data from SWIBREG (≥1 record) and the NPR (≥1 record), the PPV was 99% for any IBD (97–100), 96% (89–99) for UC, and 90% (82–96) for CD. Conclusion:The validity of the UC, CD, and IBD diagnoses is high in the NPR but even higher when cases were identified both in SWIBREG and the NPR. These results underline the need for a well-functioning Swedish Quality Register for IBD as a complement to the NPR. [ABSTRACT FROM PUBLISHER]

Objective: Changes in medical therapy and surgery might have influenced the natural history of Crohn’s disease (CD). Our aim was to explore the short-term outcome of CD and to specifically assess trends in disease phenotype, medications and surgery in the first five years from diagnosis.Material and methods: A population-based cohort comprising 472 CD patients diagnosed within the primary catchment area of Örebro University Hospital 1963–2005 were identified retrospectively and described. Data on medication, surgery, progression in disease location and behavior, were extracted from the medical records. Patients were divided into three cohorts based on year of diagnosis.Results: The proportion of patients with complicated disease behavior five years after diagnosis decreased from 54.4% (95%CI, 43.9–65.6) to 33.3% (27.4–40.0) in patients diagnosed 1963–1975 and 1991–2005, respectively (p = 0.002), whereas the proportion of patients progressing to complicated disease behavior was stable among those with non-stricturing, non-penetrating disease at diagnosis (p = 0.435). The proportion of patients undergoing surgery decreased from 65.8% (55.4–76.0) to 34.6% (28.6–41.5) in patients diagnosed 1963–1975 and 1991–2005, respectively (p < 0.001). The reduction in surgery preceded an increased use of immunomodulators and was explained by a decrease in surgery within three months from diagnosis (p = 0.001).Conclusions: We observed a striking decrease in complicated disease behavior and surgery five years after CD diagnosis, the latter largely due to a decrease in early surgery. Our findings suggest that the introduction of new treatments alone does not explain the reduction in surgery rates, the increasing proportion of patients with inflammatory disease at diagnosis also play an important role. [ABSTRACT FROM PUBLISHER]