Risk of Vaccine-Preventable Infections in Swiss Adults with Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a higher risk of infection and are frequently not up to date with their immunizations. OBJECTIVES: This study aims to review vaccination status and evaluate whether age, disease type, or treatment regimen could predict the absence of seroprotection against selected vaccine-preventable infection in adults with IBD. METHODS: Cross-sectional study using questionnaire, immunization records review, and assessment of tetanus-specific, varicella-specific, and measles-specific immunoglobulin G concentrations. ClinicalTrials.gov: NCT01908283. RESULTS: Among the 306 adults assessed (median age 42.7 years old, 70% with Crohn's disease, 78% receiving immunosuppressive treatment), only 33% had an immunization record available. Absence of seroprotection against tetanus (6%) was associated with increasing age and absence of booster dose; absence of seroprotection against varicella (1%) or measles (3%) was exclusively observed in younger patients with Crohn's disease. There was no statistically significant difference in immunoglobulin concentrations among treatment groups. Although vaccinations are strongly recommended in IBD patients, the frequencies of participants with at least 1 dose of vaccine recorded were low for nearly all antigens: tetanus 94%, diphtheria 87%, pertussis 54%, poliovirus 22%, measles-mumps-rubella 47%, varicella-zoster 0%, Streptococcus pneumoniae 5%, Neisseria meningitidis 12%, hepatitis A 41%, hepatitis B 48%, human papillomavirus 5%, and tick-borne encephalitis 6%. CONCLUSIONS: Although many guidelines recommend the vaccination of IBD patients, disease prevention through immunization is still often overlooked, including in Switzerland, increasing their risk of vaccine-preventable diseases. Serological testing should be standardized to monitor patients' protection during follow-up as immunity may wane faster in this population.

Vaccination in Patients with Inflammatory Bowel Diseases.

During the course of disease, a majority of inflammatory bowel disease (IBD) patients requires long-term immunosuppressive therapy with either immunomodulatory agents, biologics, or newer immunosuppressive therapies such as Vedolizumab, a selective α4ß7 inhibitor, Ustekinumab, an IL 12/23 p40 inhibitor, or the Janus kinase inhibitor Tofacitinib. Due to this, they are at increased risk for infectious diseases, many of which are possible to prevent by vaccination. This review focuses on recommended vaccinations in IBD patients and stresses special issues which have to be paid attention to. The aim of the review is to increase gastroenterologists' awareness of the importance of vaccination and to stress why especially the gastroenterologist should assess the vaccination status of the patient and initiate vaccination as soon as diagnosis is established.

Treatment Algorithm for Mild and Moderate-to-Severe Ulcerative Colitis: An Update.

BACKGROUND: Patient care in ulcerative colitis (UC) remains challenging despite an array of established treatment options and emerging new therapies. The management of UC therapy should be guided by the endoscopic extent of inflammation, disease severity, and prognostic factors of poor outcome. Complete remission, defined as durable symptomatic and endoscopic remission without corticosteroid therapy, is the desired treatment goal. SUMMARY: This review focuses on treatment recommendations for different clinical scenarios in moderate-to-severe UC: Active UC of any extent not responding to aminosalicylates, steroid-dependent UC, steroid-refractory UC, immunomodulator-refractory UC, and acute severe UC. Comprehensive treatment algorithms for daily clinical practice were developed based on published guidelines and current literature. Key Messages: While current treatment options including a number of biologicals and small molecules have evolved UC treatment to achieve sustained remission in a majority of patients, upcoming treatment options with different molecular pathways and different modes of actions will further increase the need for personalized medicine.

Therapeutic Drug Monitoring to Guide Clinical Decision Making in Inflammatory Bowel Disease Patients with Loss of Response to Anti-TNF: A Delphi Technique-Based Consensus.

BACKGROUND: Loss of response is frequently encountered in patients with inflammatory bowel disease (IBD) treated with antitumor necrosis factor (TNF) agents. Therapeutic drug monitoring (TDM) and antidrug antibody measurement are increasingly used in this setting. METHODS: To establish a consensus on the use of TDM in the context of loss of response to anti-TNFs, we performed a vote using a Delphi-style process followed by an expert panel discussion among 8 IBD specialists practicing in Switzerland, Europe. Statements were rated on an even Likert-scale ranging from 1 (strong disagreement) to 4 (strong agreement), based on expert opinion and the available literature. RESULTS: The experts agreed on the following statements: (i) loss of response is associated with inadequate drug levels in both Crohn's disease and ulcerative colitis; (ii) best timepoint for measuring drug levels is prior to the next application (= trough levels) with different thresholds for anti-TNF agents (infliximab 5 µg/mL, adalimumab 8 µg/mL, certolizumab pegol 10 µg/mL); (iii) antidrug antibodies are predictive for loss of response; and (iv) antidrug-antibody titers and drug trough levels are key determinants in the treatment algorithm. Data about non-anti-TNF biologics were considered too limited to propose recommendations. CONCLUSION: A Delphi-style consensus among 8 IBD experts shows that TDM and measurement of antidrug-antibody titers are useful in the context of loss of response to anti-TNF. Optimal cutoff levels depend on the type of anti-TNF. These values are critical in the decision making process. More studies are needed to address the value of such measurements for non-anti-TNF biologics.

[Management of gastrointestinal and hepatic diseases during the COVID-19 outbreak]. / Prise en charge des patients avec maladies digestives et hépatiques durant la pandémie COVID-19.

The current epidemic of SARS-CoV-2 infection poses new challenges in the management of patients with gastrointestinal or liver disease. Consultations with patients with chronic diseases should ideally be done via telemedicine and treatments administered at home if possible. The latter should be maintained in non-infected subjects to limit the risk of decompensation of their underlying disease. In the event of proven infection, immunomodulatory or biological treatments will tend to be reduced or discontinued unless the disease is in a severely active phase. Elective endoscopy should be postponed, and urgent procedures should be performed with appropriate personal protective equipment.

L'épidémie actuelle d'infection par le SARS-CoV-2 pose de nouveaux défis dans la prise en charge des patients avec pathologies gastroentérologique ou hépatologique. Les consultations avec les patients atteints de maladies chroniques devraient se faire idéalement par télémédecine et les traitements administrés à domicile si possible. Ces derniers doivent être maintenus chez les sujets non infectés pour limiter le risque de décompensation de leur maladie de base. En cas d'infection avérée, on aura tendance à diminuer voire interrompre les traitements immunomodulateurs ou biologiques sauf si la maladie est en phase sévèrement active. Les examens endoscopiques électifs doivent être reportés. Les interventions urgentes doivent être effectuées en appliquant des mesures de protection adéquates.

New therapeutic perspectives to manage refractory immune checkpoint-related toxicities.

Immune checkpoint inhibitors are reshaping the prognosis of many cancer and are progressively becoming the standard of care in the treatment of many tumour types. Immunotherapy is bringing new hope to patients, but also a whole new spectrum of toxicities for healthcare practitioners to manage. Oncologists and specialists involved in the pluridisciplinary management of patients with cancer are increasingly confronted with the therapeutic challenge of treating patients with severe and refractory immune-related adverse events. In this Personal View, we summarise the therapeutic strategies that have been used to manage such toxicities resulting from immune checkpoint inhibitor treatment. On the basis of current knowledge about their pathogenesis, we discuss the use of new biological and non-biological immunosuppressive drugs to treat severe and steroid refractory immune-related adverse events. Depending on the immune infiltrate type that is predominant, we propose a treatment algorithm for personalised management that goes beyond typical corticosteroid use. We propose a so-called shut-off strategy that aims at inhibiting key inflammatory components involved in the pathophysiological processes of immune-related adverse events, and limits potential adverse effects of drug immunosuppression on tumour response. This approach develops on current guidelines and challenges the step-by-step increase approach to drug immunosuppression.

Differences in Outcomes Reported by Patients With Inflammatory Bowel Diseases vs Their Health Care Professionals.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) scoring systems combine patient-reported data with physicians' observations to determine patient outcomes, but these systems are believed to have limitations. We used real-world data from a large IBD cohort in Switzerland to compare results between patients and healthcare professionals from scoring systems for Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We collected data from the Swiss IBD cohort, beginning in 2006, using 2453 reports for 1385 patients (52% female, 58% with CD). During office visits, physicians asked patients about signs and symptoms and recorded their answers (health care professional-reported outcomes). On a later date, patients received a questionnaire at home (independently of the medical visit), complete it, and sent it back to the data center. Patients also completed the short form 36 and IBD quality of life (QoL) questionnaires. We calculated Cohen's kappa (κ) statistics to assess the level of agreement in scores between patients and health care professionals (Δt between reports collected less than 2 months apart). We used Spearman correlation coefficients (ρ) to compare general well-being (GWB) and QoL scores determined by patients vs health care professionals. Our primary aim was to investigate the overall and individual level of agreement on signs and symptoms reported by health care professionals vs patients. RESULTS: The best level of agreement (although moderate) was observed for number of stools last week in patients with CD (κ = 0.47), and nocturnal diarrhea in patients with UC (κ = 0.52). Agreement was low on level of abdominal pain (κ = 0.31 for patients with CD and κ = 0.37 for patients with UC) and GWB (κ = 0.23 for patients with CD and κ = 0.26 for patients with UC). Patients reported less severe abdominal pain and worse GWB (CD) or better GWB (UC) than that determined by health care professionals. Patient self-rated GWB correlated with IBD quality of life (ρ = 0.68 for patients with CD and ρ = 0.70 for patients with UC) and SF-36 physical scores (ρ = 0.55 for patients with CD and ρ = 0.60 for patients with UC); there was no correlation between health care professional-rated GWB and QoL. CONCLUSIONS: In a comparison of patient vs health care provider-reported outcomes in a Swiss IBD cohort, we found that health care professionals seem to misinterpret patients' complaints. Patients self-rated GWB correlated with QoL scores, indicating that reporting GWB in a single question is possible and relevant, but can vary based on how the data are collected.

High Immunogenicity of the Pneumococcal Conjugated Vaccine in Immunocompromised Adults With Inflammatory Bowel Disease.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are predisposed to pneumococcal infections due to their underlying disease and iatrogenic immunosuppression. Vaccination with the 13-valent pneumococcal conjugated vaccine (PCV13) is recommended, but with poor take-up and few data available. We performed an open-label, phase IV, multicenter study to evaluate the safety and immunogenicity of PCV13 in adults with IBD and to analyze the influence of immunomodulating treatments on anti-pneumococcal seroresponses. METHODS: We enrolled 306 patients with IBD from March 2014 through February 2016, with the following exclusion criteria: current IBD flare, pregnancy, pneumococcal immunization in the previous 5 years, and influenza immunization in the previous 4 weeks. PCV13 was administered intramuscularly. Serotype-specific vaccine responses were evaluated using an opsonophagocytic assay. Adverse events were monitored by diary cards and standardized phone interviews. RESULTS: The median seroprotection rate increased significantly from 43.9% (95% confidence interval [CI], 42.3-45.5) at inclusion to 90.4% (95% CI, 89.5-91.3%; P < 0.001) after vaccination. Patients receiving anti-tumor necrosis factor agents achieved a slightly lower seroprotection rate (from 44.5% [95% CI, 42.3%-46.8%] to 86.6% [95% CI, 84.9%-88.1%]) than patients treated with other types of immunosuppressive regimens (thiopurine, methotrexate, oral corticosteroids; from 44.7% [95% CI, 41.7%-47.7%] to 93.8% [95% CI, 92.1%-95.2%]) or nonimmunosuppressive treatment (5-aminosalicylate, topical corticosteroids, vedolizumab; from 41.3% [95% CI, 37.9%-44.8%] to 95.2% [95% CI, 93.4%-96.6%]). There were no safety issues. DISCUSSION: Overall, the administration of PCV13 was highly immunogenic and well tolerated, irrespective of the baseline treatment, and should be encouraged in all adults with IBD.

Development and characterization of a CNS-penetrant benzhydryl hydroxamic acid class IIa histone deacetylase inhibitor.

We have identified a potent, cell permeable and CNS penetrant class IIa histone deacetylase (HDAC) inhibitor 22, with >500-fold selectivity over class I HDACs (1,2,3) and ∼150-fold selectivity over HDAC8 and the class IIb HDAC6 isoform. Dose escalation pharmacokinetic analysis demonstrated that upon oral administration, compound 22 can reach exposure levels in mouse plasma, muscle and brain in excess of cellular class IIa HDAC IC50 levels for ∼8 h. Given the interest in aberrant class IIa HDAC function for a number of neurodegenerative, neuromuscular, cardiac and oncology indications, compound 22 (also known as CHDI-390576) provides a selective and potent compound to query the role of class IIa HDAC biology, and the impact of class IIa catalytic site occupancy in vitro and in vivo.

[Management of ulcerative colitis in 2017]. / Mise au point sur la rectocolite ulcéro-hémorragique en 2017.

Ulcerative colitis (UC) has a prevalence of 1 in 1000 inhabitants in Switzerland. The diagnosis of UC is based on a typical clinical presentation that involves bloody diarrhea, characteristic endoscopic features with continuous inflammation involving the rectum, and compatible histology. UC develops in genetically susceptible individuals with a dysregulated mucosal immune system. This article highlights latest insights into the pathogenesis, diagnosis, and therapy of UC.

La rectocolite ulcéro-hémorragique (RCUH) représente une maladie fréquente en Suisse avec une prévalence de 1 sur 1000 habitants. Le diagnostic se base sur la présentation clinique typique avec des diarrhées sanglantes, une image endoscopique caractéristique avec une inflammation continue qui touche pratiquement toujours le rectum, et une image histologique compatible. La RCUH se développe chez des individus avec prédisposition génétique et une dérégulation du système immunitaire colique. Cet article fait le point sur la pathogenèse, le diagnostic et les approches thérapeutiques de cette maladie.

Patients and gastroenterologists' perceptions of treatments for inflammatory bowel diseases: do their perspectives match?

BACKGROUND: Perceptions of appropriateness of treatments may differ between gastroenterologists (GIs) and inflammatory bowel disease (IBD) patients. The aim of this study was to explore and compare GIs' and patients' perceptions of risks and benefits of treatments and prioritization of expected outcomes. METHODS: Four vignette cases were drawn from clinical situations and used in three independent focus groups with GIs (n = 7), ulcerative colitis (UC-p, n = 8) and Crohn's disease patients (CD-p, n = 6). Content analysis was performed based on the conversation transcripts. RESULTS: UC-p agreed more often with GIs' treatment choices than CD-p. CD-p often considered 5-ASA as a placebo. UC-p saw topical 5-ASA as a temporary solution, neither comfortable nor practical when professionally active. Azathioprine was considered as the treatment for which the risks versus benefits were perceived as the highest. The main risk perceived by patients on anti-TNFs was a potential loss of response. Divergences were observed on 1) stop of treatment: UC-p did not easily concur with stopping a treatment, which differed from GIs' expectation of patients' perceptions; CD-p were more prone to consider stopping treatment than GIs, 2) perception of outcomes: physicians had a focus on long-term objective goals. Patients' expectations were of shorter term and mainly concerned stress management, nutritional advice, and information on the treatments effects. CONCLUSIONS: Overall, patients and GIs agreed on perceptions of IBD treatments. GIs seemed more concerned about objective and scientific measures of remission whereas patients focused on quality of life and social outcomes when it came to evaluating a therapy.

[Diagnostic and treatment of mesenteric ischemia]. / Diagnostic et traitement des ischémies mésentériques.

Mesenteric ischemia results from acute or chronic blood flow reduction in the mesenteric arterial or venous vascular supply. This is usually due to an embolus, thrombosis or intestinal hypoperfusion. Radiologic and / or endoscopic imaging and histology allow for diagnosis in high-risk patients with suggestive clinical symptoms and signs. Treatment aims at preventing multi-organ failure through medical treatment, saving intestinal integrity and resecting necrotic bowel segments. Rapid and multidisciplinary management is key in order to optimize treatment and avoid long-term debilitating consequences.

L'ischémie mésentérique est provoquée par l'interruption aiguë ou chronique du flux sanguin splanchno-mésentérique par des mécanismes comme l'embolie, la thrombose ou l'hypoperfusion intestinale. Le diagnostic est posé par imagerie et / ou endoscopie face à un tableau clinique évocateur dans un contexte à risque. La prise en charge vise la prévention d'une défaillance multiviscérale par un traitement médical, la préservation de l'intestin par une revascularisation et la résection des segments nécrotiques. Une prise en charge rapide et multidisciplinaire est cardinale afin d'optimiser le traitement et éviter des séquelles fonctionnelles graves à long terme.

Lack of Mycobacterium tuberculosis-specific interleukin-17A-producing CD4+ T cells in active disease.

Protective immunity to Mycobacterium tuberculosis (Mtb) is commonly ascribed to a Th1 profile; however, the involvement of Th17 cells remains to be clarified. Here, we characterized Mtb-specific CD4(+) T cells in blood and bronchoalveolar lavages (BALs) from untreated subjects with either active tuberculosis disease (TB) or latent Mtb infection (LTBI), considered as prototypic models of uncontrolled or controlled infection, respectively. The production of IL-17A, IFN-γ, TNF-α, and IL-2 by Mtb-specific CD4(+) T cells was assessed both directly ex vivo and following in vitro antigen-specific T-cell expansion. Unlike for extracellular bacteria, Mtb-specific CD4(+) T-cell responses lacked immediate ex vivo IL-17A effector function in both LTBI and TB individuals. Furthermore, Mtb-specific Th17 cells were absent in BALs, while extracellular bacteria-specific Th17 cells were identified in gut biopsies of healthy individuals. Interestingly, only Mtb-specific CD4(+) T cells from 50% of LTBI but not from TB subjects acquired the ability to produce IL-17A following Mtb-specific T-cell expansion. Finally, IL-17A acquisition by Mtb-specific CD4(+) T cells correlated with the coexpression of CXCR3 and CCR6, currently associated to Th1 or Th17 profiles, respectively. Our data demonstrate that Mtb-specific Th17 cells are selectively undetectable in peripheral blood and BALs from TB patients.

The Wiskott-Aldrich syndrome protein is required for the function of CD4(+)CD25(+)Foxp3(+) regulatory T cells.

The Wiskott-Aldrich syndrome, a primary human immunodeficiency, results from defective expression of the hematopoietic-specific cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASP). Because CD4(+)CD25(+)Foxp3(+) naturally occurring regulatory T (nTreg) cells control autoimmunity, we asked whether colitis in WASP knockout (WKO) mice is associated with aberrant development/function of nTreg cells. We show that WKO mice have decreased numbers of CD4(+)CD25(+)Foxp3(+) nTreg cells in both the thymus and peripheral lymphoid organs. Moreover, we demonstrate that WKO nTreg cells are markedly defective in both their ability to ameliorate the colitis induced by the transfer of CD45RB(hi) T cells and in functional suppression assays in vitro. Compared with wild-type (WT) nTreg cells, WKO nTreg cells show significantly impaired homing to both mucosal (mesenteric) and peripheral sites upon adoptive transfer into WT recipient mice. Suppression defects may be independent of antigen receptor-mediated actin rearrangement because both WT and WKO nTreg cells remodeled their actin cytoskeleton inefficiently upon T cell receptor stimulation. Preincubation of WKO nTreg cells with exogenous interleukin (IL)-2, combined with antigen receptor-mediated activation, substantially rescues the suppression defects. WKO nTreg cells are also defective in the secretion of the immunomodulatory cytokine IL-10. Overall, our data reveal a critical role for WASP in nTreg cell function and implicate nTreg cell dysfunction in the autoimmunity associated with WASP deficiency.

Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: prime side chromane-containing inhibitors.

The structure activity relationship of the prime region of conformationally restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the P1' region provided selectivity over Cat-D with a series of 2,2-dioxo-isothiochromanes and optimization of the P2' substituent of chromane-HEA(s) with polar substituents provided improvements in the compound's in vitro permeability. Significant potency gains were observed with small aliphatic substituents such as methyl, n-propyl, and cyclopropyl when placed at the C-2 position of the chromane.

Alcohol and cannabis consumption in patients with inflammatory bowel disease: prevalence, pattern of consumption and impact on the disease.

OBJECTIVES OF THE STUDY: There is little guidance regarding the impact of alcohol and cannabis on the clinical course of inflammatory bowel disease. The aim of this study was to assess the prevalence, sociodemographic characteristics and impact of alcohol and cannabis use on the clinical course of the disease. METHODS: We performed an analysis of prospectively collected data within the Swiss Inflammatory Bowel Disease Cohort Study with yearly follow-ups and substance-specific questionnaires. We analyzed the prevalence of use, the profile of users at risk for addiction and the impact of alcohol and cannabis on the course of the disease. RESULTS: We collected data of 2828 patients included between 2006 and 2018 and analyzed it according to their completion of specific surveys on alcohol and cannabis use. The prevalence of patient-reported active use was 41.3% for alcohol and 6% for cannabis. Heavy drinkers were over-represented among retired, married smokers receiving mostly aminosalicylates and less immunosuppression. In ulcerative colitis patients, low-to-moderate drinking was associated with less extensive disease. Cannabis users were often students with ileal Crohn's disease. CONCLUSION: A significant proportion of patients with inflammatory bowel disease consume alcohol or cannabis. Heavy alcohol consumption is most likely in male smokers >50 years, whereas young men with ileal disease rather use cannabis.

PAR2 promotes vaccine-induced protection against Helicobacter infection in mice.

BACKGROUND & AIMS: Protective immunization limits Helicobacter infection of mice by undetermined mechanisms. Protease-activated receptor 2 (PAR2) signaling is believed to regulate immune and inflammatory responses. We investigated the role of PAR2 in vaccine-induced immunity against Helicobacter infection. METHODS: Immune responses against Helicobacter infection were compared between vaccinated PAR2-/- and wild-type (WT) mice. Bacterial persistence, gastric pathology, and inflammatory and cellular responses were assessed using the rapid urease test (RUT), histologic analyses, quantitative polymerase chain reaction, and flow cytometry, respectively. RESULTS: Following vaccination, PAR2-/- mice did not have reductions in Helicobacter felis infection (RUT values were 0.01±0.01 for WT mice and 0.11±0.13 for PAR2-/- mice; P<.05). The vaccinated PAR2-/- mice had reduced inflammation-induced stomach tissue damage (tissue damage scores were 8.83±1.47 for WT mice and 4.86±1.35 for PAR2-/- mice; P<.002) and reduced T-helper (Th)17 responses, based on reduced urease-induced interleukin (IL)-17 secretion by stomach mononuclear cells (5182 ± 1265 pg/mL for WT mice and 350±436 pg/mL for PAR2-/- mice; P<.03) and reduced recruitment of CD4+ IL-17+ T cells into the gastric mucosa of PAR2-/- mice following bacterial challenge (3.7%±1.5% for WT mice and 2.6%±1.1% for PAR2-/- mice; P<.05). In vitro, H felis-stimulated dendritic cells (DCs) from WT mice induced greater secretion of IL-17 by ovalbumin-stimulated OT-II transgenic CD4+ T cells compared with DCs from PAR2-/- mice (4298±347 and 3230±779; P<.04), indicating that PAR2-/- DCs are impaired in priming of Th17 cells. Adoptive transfer of PAR2+/+ DCs into vaccinated PAR2-/- mice increased vaccine-induced protection (RUT values were 0.11±0.10 and 0.26±0.15 for injected and noninjected mice, respectively; P<.03). CONCLUSIONS: PAR2 activates DCs to mediate vaccine-induced protection against Helicobacter infection in mice.

DNA/NYVAC vaccine regimen induces HIV-specific CD4 and CD8 T-cell responses in intestinal mucosa.

In the present study, we have investigated the anatomic distribution in blood and gut mucosal tissues of memory poxvirus-specific CD4 and CD8 T cells in subjects vaccinated with smallpox and compared it with vector (NYVAC)-specific and HIV insert-specific T-cell responses induced by an experimental DNA-C/ NYVAC-C vaccine regimen. Smallpox-specific CD4 T-cell responses were present in the blood of 52% of the subjects studied, while smallpox-specific CD8 T cells were rarely detected (12%). With one exception, smallpox-specific T cells were not measurable in gut tissues. Interestingly, NYVAC vector-specific and HIV-specific CD4 and CD8 T-cell responses were detected in almost 100% of the subjects immunized with DNA-C/NYVAC-C in blood and gut tissues. The large majority (83%) of NYVAC-specific CD4 T cells expressed α4ß7 integrins and the HIV coreceptor CCR5. These results demonstrate that the experimental DNA-C/NYVAC-C HIV vaccine regimen induces the homing of potentially protective HIV-specific CD4 and CD8 T cells in the gut, the port of entry of HIV and one of the major sites for HIV spreading and the depletion of CD4 T cells.

Primary Hypogammaglobulinaemia with Inflammatory Bowel Disease-Like Features: An ECCO CONFER Multicentre Case Series.

BACKGROUND: Hypogammaglobulinaemia is a disorder characterized by low serum immunoglobulin levels and a high prevalence of gastrointestinal manifestations. In some cases, clinical and endoscopic features are indistinguishable from those of inflammatory bowel disease [IBD]. METHODS: This was a multicentre case series performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. RESULTS: This report includes 27 patients with primary hypogammaglobulinaemia and IBD-like features: 20 males and seven females, median age 45.6 years (interquartile range [IQR] 35.2-59). Crohn's disease-like features were noted in 23 patients, and four patients had ulcerative colitis-like features. The diagnosis of hypogammaglobulinaemia preceded a diagnosis of IBD-like features in 20 patients [median of 7 years prior, IQR 2.6-20.6 years], and followed the appearance of IBD-like features in seven cases [median of 1 year after, IQR 0.45-5.6 years]. Hypogammaglobulinaemia aetiologies were common variable immunodeficiency [66.6%], agammaglobulinaemia [7.4%], selective IgA-deficiency [11.1%], Good's syndrome [7.4%], IgG subclass deficiency with IgA deficiency [3.7%] and hyper-IgM [3.7%]. In addition to antibiotics and intravenous immunoglobulin [IVIG] for hypogammaglobulinaemia, 12 patients received IBD-related treatment including 5-aminosalicylate agents [two patients], corticosteroids [one patient], thiopurines [three patients], anti-tumour necrosis factor [four patients] and vedolizumab [two patients]. By the end of the follow-up (44.5 months [IQR 18-81]), 21/27 [77%] patients were in clinical remission. CONCLUSION: This case series describes IBD-like features in patients with hypogammaglobulinaemia. The diagnosis of IBD-like features mainly occurred after that of hypogammaglobulinaemia, with successful recovery in the majority of cases after appropriate treatment.

Effectiveness of golimumab in patients with ulcerative colitis: results of a real-life study in Switzerland.

BACKGROUND: Tumor necrosis factor (TNF) inhibitors have improved treatment of ulcerative colitis (UC), but loss of response remains a frequent problem. The anti-TNF agent, golimumab, was approved in Switzerland for the treatment of UC in 2014. This study aims to summarize the experience of golimumab in a real-world setting in Switzerland. METHODS: We analyzed real-world data from 1769 UC patients from the Swiss Inflammatory Bowel Disease Cohort (SIBDC) study and performed a chart review of golimumab-treated patients. We extracted the partial Mayo score at t0 (baseline), t1 (2-16 weeks), t2 (17-35 weeks), and t3 (36-89 weeks). The primary endpoint was clinical response at t1, defined as marked improvement in partial Mayo score and objective parameters. Clinical remission was defined as resolution of symptoms and normalization of objective parameters. RESULTS: Our chart review included 103 UC patients with golimumab treatment (5.8% of all SIBDC UC patients); only 16 (15.5%) were anti-TNF naïve. Sixty-three patients remained on golimumab (61.2%) after 180 days, 51 (44.7%) after 365 days, and 34 (33%) after 630 days after the start of treatment. Upon golimumab treatment, the partial Mayo score decreased from 4 [interquartile range (IQR): 2-6] at t0 to 2 (IQR: 0-4) at t1, 1 (IQR: 0-3.5) at t2, and 1 (IQR: 0-3) at t3 (p < 0.001 for all comparisons with t0). The primary endpoint, clinical response at t1, could be evaluated in 52 patients and was met in 15 individuals (28.8%). Clinical remission at t1 was observed in 8 out of 52 patients (15.4%). Golimumab was generally well tolerated, one patient developed meningitis. The most frequent reasons to stop treatment were primary and secondary non-response. CONCLUSION: Golimumab was used in 5.8% of Swiss UC patients, mainly in biologic-experienced individuals. Golimumab treatment was associated with a sustained reduction of symptoms and clinical response in approximately 30% of patients.[ClinicalTrials.gov identifier: NCT00488631].