Long-term cost and complications of surgery in patients with ulcerative colitis: a claims data analysis.

OBJECTIVES: Use claims data to assess healthcare resource utilization (HCRU) and cost for patients with ulcerative colitis (UC) who had surgery and patients who did not. METHODS: UC patients from a German health insurance were included between 01/01/2010-31/12/2017. Patients with proctocolectomy or colectomy between 01/07/2010 and 31/12/2014 were identified, and surgery date was set as index. For patients with IPAA, the last surgery in the 6 months was taken as index. Non-surgery patients received random index. After propensity score matching, UC-related HCRU and cost were observed for three years post-index. RESULTS: Of 21,392 UC patients, 85 underwent surgery and 2655 did not. After matching, 76 were included in the surgery group and 114 in the non-surgery group. Matched cohorts did not differ in baseline characteristics and mortality rates where high in both groups (21.1% and 29.0%, respectively). The percentage of patients with at least one hospitalization in the follow-up period was higher in the surgery (53.9%) compared to the non-surgery group (25.4%, p<0.001). In contrast, the number of outpatient prescriptions of UC-related drugs in the non-surgery group (11.2) was almost twice as large as in the surgery group (5.8, p<0.001). Hospitalization cost was 4.6 times higher in the surgery (1955.5€) than in the non-surgery group (419.6€, p<0.001). Medication cost was three times higher in the non-surgery group (6519€) compared to the surgery group (2151.7€, p<0.001). CONCLUSIONS: Based on hospitalizations, outpatient visits, and medical treatment, results show a considerable patient burden in UC from surgery complications or disease exacerbation in case of colectomy.

Relationship of faecal calprotectin and long-term outcomes in Finnish patients with Crohn's disease: retrospective multi-centre chart review study.

Background and Aims: A retrospective non-interventional, multi-centre patient chart review study was conducted to investigate the association of faecal calprotectin (FC) 1 year (±2 months) after biological therapy initiation with composite event-free survival (CEFS) consisting of surgical procedures, corticosteroid initiation, treatment failure or dose increase in patients with Crohn's disease (CD). In addition, the correlations of FC and other tests of disease activity were assessed.Materials and methods: Data on Finnish CD patients initiating a biological therapy between 2010 and 2016, were collected. The association of FC and CEFS was analysed with Kaplan-Meier and Cox proportional hazard modelling. The correlations were tested with Pearson's test.Results: Biological therapy was initiated in 186 patients, of which 87 (46.8%) had FC results available at 1 year and 80 had follow-up exceeding 14 months. The characteristics of patients with and without FC results were similar. Patients with elevated FC (>250 µg/g) had a significantly increased risk of experiencing composite event (HR 3.4, 95% CI: 1.3-8.9; p = .013) when compared to patients with normal FC (FC ≤ 100). No such risk was observed in patients with intermediately increased FC level (100 µg/g < FC ≤ 250 µg/g) (HR 2.2 (95% CI: 0.8-6.2; p = .120). FC value had significant positive correlation with CRP, HBI and leukocyte values when measured at similar timepoints.Conclusions: Elevated level of FC approximately 1 year after the initiation of biological therapy was associated with an increased risk of either surgical procedures, corticosteroid initiation, treatment failure or dose increase (i.e. composite outcome) in patients with CD.

Quality of life and patient benefit following transition from methotrexate to ustekinumab in psoriasis.

BACKGROUND: TRANSIT (NCT01059773) compared immediate and gradual transition from methotrexate to ustekinumab in psoriasis patients via multiple measures, including patient-reported outcomes. OBJECTIVE: To evaluate patient perception of treatment benefits in TRANSIT. METHODS: A total of 489 psoriasis patients received ustekinumab, with immediate cessation of methotrexate (Arm 1) or 4 weeks' overlap with decreasing methotrexate dose (Arm 2). Ustekinumab was administered at weeks 0, 4, 16, 28 and 40. Dermatology Life Quality Index (DLQI), EuroQol 5-item (EQ-5D), visual analogue scale (VAS) valuation technique and patient benefit index (PBI) were employed. Mean global PBI and sub-scores were calculated from the sum of the benefit items weighted by their respective relevance at baseline. Patient-relevant benefit was defined as PBI ≥1 (scale: 0 [no benefit] to 4 [maximum benefit]). Correlations of global PBI with Psoriasis Area and Severity Index (PASI) and DLQI were examined. RESULTS: Relationships between PBI and clinical data were evaluable in 340 patients. The most important treatment goals at baseline included: 'be healed of all skin defects', 'have confidence in therapy', 'get better skin quickly' and 'regain control of the disease'. Benefit in PBI global score was achieved at week 4 by 93% of patients in Arm 1 and 91% in Arm 2. Global PBI scores increased in both Arms between weeks 4 and 52. Global PBI correlated weakly with PASI change from baseline (correlation coefficient range: -0.22 to -0.40), and moderately with DLQI (-0.29 to -0.54). Overall DLQI score was lower than baseline at all times; and the percentage of patients with an overall score of 0 or 1 increased with time. Correspondingly, EQ VAS scores increased with time. DLQI and EQ VAS results were similar between arms. CONCLUSIONS: Regardless of the strategy for transitioning from methotrexate, ustekinumab was associated with rapid and sustained improvement in patient-reported outcomes. PBI appears a suitable tool for assessing patient-relevant treatment benefits in psoriasis patients.

Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: Drug survival is a marker for treatment sustainability in chronic diseases such as psoriasis. OBJECTIVE: The aim of these analyses was to assess survival of biologic treatments in the PSOriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: PSOLAR is a large, prospective, international, disease-based registry of patients with psoriasis receiving (or eligible for) systemic therapy in a real-world setting. Drug survival is defined as the time from initiation to discontinuation (stop/switch) of biologic therapy on registry. The number of patients who discontinued each treatment and the duration of therapy were recorded. Using Kaplan-Meier survival curves and Cox-regression analyses [hazard ratios (HR) and 95% confidence intervals (CIs)], time to discontinuation was compared across cohorts undergoing first-, second- or third-line treatment with ustekinumab, infliximab, adalimumab or etanercept. RESULTS: As of the 2013 data cut, 12 095 patients with psoriasis were enrolled in PSOLAR. Of the 4000 patients initiating any new biologic therapy, approximately 3500 started a first-line, second-line or third-line biologic therapy during the registry. Lack of effectiveness was the most common reason for discontinuation across biologic therapies. Based on the multivariate analysis, significantly shorter times to discontinuation were observed for infliximab [HR (95%CI) = 2.73 (1.48-5.04), P = 0.0014]; adalimumab [4.16 (2.80-6.20), P < 0.0001]; and etanercept [4.91 (3.28-7.35) P < 0.0001] compared with ustekinumab [reference treatment]) for first-line biologic use; results were similar for treatment effects for second/third-line therapies. Although limited in power, analyses in patients with concurrent psoriatic arthritis confirmed by a rheumatologist reflect observations in the overall psoriasis population. CONCLUSION: Drug survival was superior for ustekinumab compared with infliximab, adalimumab and etanercept in patients with psoriasis.

Elucidation of a novel epitope of a substrate-inducing monoclonal antibody against the serpin PAI-1.

Plasminogen activator inhibitor-1 (PAI-1) is the most important physiological inhibitor of plasminogen activators. Inhibition of PAI-1 constitutes a putative strategy for the prevention of cardiovascular disease. The monoclonal antibody MA-8H9D4 inhibits PAI-1 activity by inducing a substrate behavior in PAI-1. To identify the epitope, a rational approach was used to design various PAI-1 alanine mutants (n = 16) for evaluation of their affinity. PAI-1-R300A, PAI-1-Q303A and PAI-1-D305A had affinities for MA-8H9D4 of < 10(5) M(-1), 2.0 x 10(8) M(-1) and 2.5 x 10(8) M(-1), respectively, whereas the affinity of wtPAI-1 is 3.3 x 10(9) M(-1). The epitope on the axis of arginine 300, glutamine 303 and aspartic acid 305, located on the loop between alpha-helix I and beta-strand 5A, demonstrates that MA-8H9D4 interferes with the final locking step in the serpin/proteinase interaction, thereby explaining its substrate inducing properties. The location of the epitope as well as the proposed mechanism of action is clearly different from that of other substrate inducing monoclonal antibodies against PAI-1. Elucidation of this novel epitope and the previously unidentified molecular mechanism opens new perspectives for the rational development of PAI-1-neutralizing compounds, as well as for the further exploration of synergistic effects between different PAI-1-inhibiting compounds.

The effect of carbonate content and drying temperature on the ESR-spectrum near g = 2 of carbonated calciumapatites synthesized from aqueous media.

The ESR spectrum of X-irradiated carbonated apatites precipitated from aqueous solutions was studied as a function of their carbonate content and drying temperature. When the latter increases from 25 to 400 degrees C, the ESR spectrum is gradually modified and becomes similar to the spectrum of carbonated apatites, synthesized at high temperatures by solid state reactions. The latter ESR spectrum is dominated by CO3(3-)-contributions whereas the spectrum of precipitated samples dried at 25 degrees C can mainly be interpreted in terms of CO2-, CO3-, and O- ions. The behavior of these earlier-reported CO2-, CO3-, and O- centers is now studied as a function of drying temperature. In addition, the Spin Hamiltonian parameters of the CO3(3-) centers are determined and some other new paramagnetic radicals are discussed. It is shown that a CO3(2-) ion at a phosphate lattice site (B-type substitution) may give rise to either a CO2-, CO3-, or CO3(3-) radical on X-irradiation, depending on the sample preparation conditions. A surface CO3(2-) ion may cause a surface CO2-, CO3-, or O- radical. From the reported results it is not unambiguously clear whether the CO3(3-) ion detected in the samples with the relatively lowest carbonate content should be located on the surface or on a hydroxyl lattice site (A-type substitution). An important result is that the absolute concentration of the B-type CO3(3-) ion increases with increasing carbonate content as was also the case for the earlier reported B-type radicals (isotropic CO2- and CO3-). On the other hand, the absolute concentration of the surface radicals decreases with increasing carbonate content. The reported results show that similar deconvolution techniques can be applied in the future for the study of ESR spectra of calcified tissues. This will allow a more efficient phenomenological investigation of the latter.

Effect of carbonate content on the ESR spectrum near g = 2 of carbonated calciumapatites synthesized from aqueous media.

The ESR spectrum of X-irradiated carbonated apatites synthesized at low temperature was studied as a function of their carbonate content. Using 13C-enriched samples, four different carbonate-derived radicals and a surface O- ion could be identified. Isotropic CO3- and CO2- ions are present at a B site in the apatite lattice, and anisotropic CO3- and CO2- radicals are located at the surface of the crystallites. Only the isotropic ESR signals increase with increasing carbonate content. The anisotropic signal ascribed to a surface CO2- radical is mainly responsible for the so-called asymmetric ESR signal near g = 2. It is argued that this surface signal may still be composite and caused by several very similar CO2- ions. The consequences for phenomenological ESR studies of calcified tissues are discussed.

ESR study of 13C-enriched carbonated calciumapatites precipitated from aqueous solutions.

The ESR spectrum of X-irradiated carbonated apatites precipitated from aqueous solutions was studied at carbonate contents ranging from approximately 5.4 up to 12.4 wt%. 12C- as well as 13C-enriched samples were prepared and examined with ESR after dying until constant weight at 25 degrees C and 400 degrees C. In these carbonated apatites, two CO3(3-) radicals were detected, one of which is derived from B-type carbonate situated at a phosphate lattice site. The other CO3(3-) most probably arises from CO3(2-) ions situated at OH- lattice sites. In contradistinction to the B-type contribution, the A-type contribution to the overall ESR signal decreases in absolute terms with increasing carbonate concentration. In addition, the line shape and the complete set of principal g-values of the A1-signal found in previous studies could be determined, corroborating the assignment of A1 to a surface O- ion.