Update on the management of inflammatory bowel disease: specific role of adalimumab

Anti-tumor necrosis factor alpha (TNF-α) medications are a class of biologics employed in the treatment of patients with inflammatory bowel disease (IBD). Adalimumab is the first fully human monoclonal immunoglobulin directed against TNF-α, which binds with high affinity and specificity to membrane and soluble TNF. Adalimumab administered subcutaneously has demonstrated efficacy in the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and severe chronic psoriasis. Studies have shown that adalimumab is effective for inducing and maintaining remission of moderate-to-severe active Crohn’s disease (CD) patients at an induction dose of 160/80 mg (week 0 and 2) and at a maintenance dose of 40 mg every other week. The efficacy of adalimumab as a second-line therapy has also been documented for patients with loss of response or intolerance to infliximab. Adalimumab is also superior to placebo for inducing and maintaining complete perianal fistula closure. It also seems effective for reducing extraintestinal manifestations. The safety profile is similar to that of other anti-TNF therapy in CD patients, with lower immunogenicity and rate of adverse injection reactions than infliximab. Adalimumab is not approved for the treatment of ulcerative colitis (UC). Recently, however, the results of the first randomized, controlled trial on adalimumab for UC showed that adalimumab at 160/80 mg induction dose was safe and effective for inducing remission and clinical response after 8 weeks in patients with moderately-to-severely active UC failing treatment with corticosteroids and/or immunosuppressants. More data are necessary to clarify the therapeutic role of adalimumab in UC. This review of the literature summarizes available data on the efficacy and safety profile adalimumab in patients with IBD

Late-Onset Hepatic Veno-Occlusive Disease after Allografting: Report of Two Cases with Atypical Clinical Features Successfully Treated with Defibrotide

Hepatic Veno-occlusive disease (VOD) is a potentially severe complication of hematopoietic stem cell transplantation (HSCT). Here we report two patients receiving an allogeneic HSCT  who developed late onset VOD with atypical clinical features. The two  patients presented with only few risk factors, namely, advanced acute leukemia, a myeloablative busulphan-containing regimen and received grafts from an unrelated donor. The first patient did not experience painful hepatomegaly and weight gain and both  patients showed only a mild elevation in total serum bilirubin level. Most importantly, the two patients developed clinical signs beyond day 21 post-HSCT. Hepatic transjugular biopsy confirmed the diagnosis of VOD. Intravenous defibrotide was promptly started leading to a marked clinical improvement. Based on our experience, liver biopsy may represent a useful diagnostic tool when the clinical features of VOD are ambiguous. Early therapeutic intervention with defibrotide  represents a crucial issue for the successful outcome of patients with VOD

Switching from IFX originator to biosimilar CT-P13 does not impact effectiveness,safety and immunogenicity in a large cohort of IBD patients

Background: Switching from IFX originator to CT-P13 is safe; however, little data on immunogenicity exists. Research design and methods: Consecutive IBD patients on IFX originator were switched to CT-P13 and followed-up for 12 months. Clinical activity, infliximab trough levels (ITLs), anti-drug antibodies (ATIs), and adverse events were recorded at predefined timepoints (baseline, second CT-P13 infusion, 6 and 12 months). The outcomes investigated were immunogenicity, pharmacokinetics, effectiveness and safety. Results: 119 patients were switched to CT-P13 after a median time with IFX of 5.8 years. No changes in mean ITLs were observed. ATIs were detected in 30 patients (25.2%): 14 before and 16 after switch. Mean persistent ATIs were significantly higher compared to mean transient ones (109.74 ng/mL ±84.70 vs 18.22 ng/mL ±11.37, p < 0.001), with significantly lower ITLs associated (mean 0.32 µg/mL ±0.6 vs 3.08 µg/mL ±3.22, p < 0.001). A significant decrease of patients in steroid-fee clinical remission was observed after the switch (p = 0.004), with subsequent improvement at 6 months (p = 0.005). Eighteen patients (15.1%) discontinued IFX, only 6 (5%) for loss of response. Conclusions: Switching from infliximab originator to CT-P13 seems safe and effective, without differences in immunogenicity. A temporary reduction of clinical benefit after switching could be potentially explained by a ‘nocebo-effect response’

Allogeneic hematopoietic cell transplantation from unrelated donors in multiple myeloma: study from the italian bone marrow donor registry.

AbstractTo evaluate trends in allografting from unrelated donors, we conducted a study on 196 consecutive myeloma patients transplanted between 2000 and 2009 in Italy. Twenty-eight percent, 37%, and 35%, respectively, received myeloablative, reduced-intensity, and nonmyeloablative conditioning. In these 3 cohorts, 1-year and 5-year transplantation-related mortalities were 28.8% and 37.0%, 20.3% and 31.3%, and 25.0% and 30.3%, respectively (P = .745). Median overall survival (OS) and event-free survival from transplantation for the 3 cohorts were 29 and 10 months, 11 and 6 months, and 32 and 13 months, respectively (P = .039 and P = .049). Overall cumulative incidences of acute and chronic graft-versus-host-disease (GVHD) were 46.1% and 51.1%. By Cox multivariate analyses, chronic GVHD was significantly associated with longer OS (hazard ratio [HR], .51; P = .009), whereas the use of peripheral blood stem cells was borderline significant (HR, .55; P = .051). Better response posttransplantation was associated with longer event-free survival (HR, 2.13 to 4.25; P < .001). Acute GVHD was associated with poorer OS (HR, 2.53; P = .001). This analysis showed a strong association of acute and chronic GVHD and depth of response posttransplantation with clinical outcomes. Long-term disease control remains challenging regardless of the conditioning. In the light of these results, prospective trials may be designed to better define the role of allografting from unrelated donors in myeloma

QUIN 2.0 - new release of the QUaternary fault strain INdicators database from the Southern Apennines of Italy

QUIN database integrates and organizes structural-geological information from published and unpublished sources to constrain deformation in seismotectonic studies. The initial release, QUIN1.0, comprised 3,339 Fault Striation Pairs, mapped on 445 sites exposed along the Quaternary faults of central Italy. The present Data Descriptor introduces the QUIN 2.0 release, which includes 4,297 Fault Striation Pairs on 738 Structural Sites from southern Italy. The newly investigated faults span ~500 km along the Apennines chain, with strikes transitioning from ~SE to ~SW and comprehensively details Fault Striation Pairs’ location, attitude, kinematics, and deformation axes. Additionally, it offers a shapefile of the fault traces hosting the data. The QUIN 2.0 release offers a significant geographic extension to the QUIN 1.0, with comprehensive description of local geometric-kinematic complexities of the regional pattern. The QUIN data may be especially relevant for constraining intra-Apennine potential seismogenic deformation patterns, where earthquake data only offer scattered or incomplete information. QUIN’s data will support studies aimed at enhancing geological understanding, hazard assessment and comprehension of fault rupture propagation and barriers

Testing gravitational-wave searches with numerical relativity waveforms: Results from the first Numerical INJection Analysis (NINJA) project

The Numerical INJection Analysis (NINJA) project is a collaborative effort between members of the numerical relativity and gravitational-wave data analysis communities. The purpose of NINJA is to study the sensitivity of existing gravitational-wave search algorithms using numerically generated waveforms and to foster closer collaboration between the numerical relativity and data analysis communities. We describe the results of the first NINJA analysis which focused on gravitational waveforms from binary black hole coalescence. Ten numerical relativity groups contributed numerical data which were used to generate a set of gravitational-wave signals. These signals were injected into a simulated data set, designed to mimic the response of the initial LIGO and Virgo gravitational-wave detectors. Nine groups analysed this data using search and parameter-estimation pipelines. Matched filter algorithms, un-modelled-burst searches and Bayesian parameter estimation and model-selection algorithms were applied to the data. We report the efficiency of these search methods in detecting the numerical waveforms and measuring their parameters. We describe preliminary comparisons between the different search methods and suggest improvements for future NINJA analyses. © 2009 IOP Publishing Ltd

Status of NINJA: The Numerical INJection Analysis project

The 2008 NRDA conference introduced the Numerical INJection Analysis project (NINJA), a new collaborative effort between the numerical relativity community and the data analysis community. NINJA focuses on modeling and searching for gravitational wave signatures from the coalescence of binary system of compact objects. We review the scope of this collaboration and the components of the first NINJA project, where numerical relativity groups, shared waveforms and data analysis teams applied various techniques to detect them when embedded in colored Gaussian noise. © 2009 IOP Publishing Ltd

Testing gravitational-wave searches with numerical relativity waveforms: Results from the first Numerical INJection Analysis (NINJA) project

The Numerical INJection Analysis (NINJA) project is a collaborative effort between members of the numerical relativity and gravitational-wave data analysis communities. The purpose of NINJA is to study the sensitivity of existing gravitational-wave search algorithms using numerically generated waveforms and to foster closer collaboration between the numerical relativity and data analysis communities. We describe the results of the first NINJA analysis which focused on gravitational waveforms from binary black hole coalescence. Ten numerical relativity groups contributed numerical data which were used to generate a set of gravitational-wave signals. These signals were injected into a simulated data set, designed to mimic the response of the Initial LIGO and Virgo gravitational-wave detectors. Nine groups analysed this data using search and parameter-estimation pipelines. Matched filter algorithms, un-modelled-burst searches and Bayesian parameter-estimation and model-selection algorithms were applied to the data. We report the efficiency of these search methods in detecting the numerical waveforms and measuring their parameters. We describe preliminary comparisons between the different search methods and suggest improvements for future NINJA analyses.Comment: 56 pages, 25 figures; various clarifications; accepted to CQ