Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Ixekizumab vs ustekinumab for skin clearance in patients with moderate to severe psoriasis after a year of treatment: Real-world practice.

There is a lack of real practice studies comparing ustekinumab and ixekizumab effectiveness and safety. The main aim of this study was to compare the effectiveness and safety of both drugs used to treat moderate-to-severe psoriasis patients over 52 weeks. The secondary objective was to identify which clinical variables could have an impact on its effectiveness. A retrospective observational study was carried out, comparing the first 28 patients treated with ustekinumab after its commercialization was compared to the first 35 patients treated with ixekizumab. Although a higher level of skin clearance was achieved with ixekizumab with a PASI 90 and 100 response of 54.3% and 40% compared to 42.9% and 25% for ustekinumab, these differences were not statistically significant. Ixekizumab achieved a higher PASI 90 response in those patients with BMI > 27 (slightly overweight), which was statistically significant (P = .024). Ustekinumab had a greater survival at 52 weeks than ixekizumab, with a trend towards statistical significance (P = .052). Ixekizumab achieved higher skin clearance rates (PASI 90 and 100 response) than ustekinumab, with no statistically significant differences. However, ixekizumab should be specially considered in overweight patients.

Is vitamin-D supplementation not useful in patients at risk of fractures and falls?

To evaluate numerous publications that question the bone and extraosseous benefits of vitamin D diet supplementation based on results, which often transcend to public opinion, but are not well interpreted. This may have negative consequences on compliance of patients under vitamin D supplementation. Critical appraisal of several articles on vitamin D supplementation and its relationship with fractures, falls, cardiovascular diseases, and cancer incidence. Such publications have certain limitations (i.e. patients excluded because of a diagnosis of osteoporosis, or at a higher risk for fractures and falls, or because they have a vitamin D deficiency, etc.), and conclusions and/or subsequent recommendations should be approached with caution. Our research shows that patients with osteoporosis, vitamin D deficiency, and at high risk of fractures and falls should not discontinue vitamin D supplementation (often associated with calcium). It is becoming increasingly evident that patients with hypovitaminosis D are those that gain a maximal benefit from vitamin D supplementation.

Muscle MRI in immune-mediated necrotizing myopathy (IMNM): implications for clinical management and treatment strategies.

OBJECTIVES: Immune-mediated necrotizing myopathy (IMNM) is the most severe idiopathic inflammatory myopathy (IIM) and early aggressive poly-immunotherapy is often required to reduce long-term disability. The aim of this study is to investigate muscle MRI in IMNM as outcome measure for disease activity, severity, progression, response to treatment, and to better characterize the pattern of muscle involvement. METHODS: This is a retrospective, observational, cross-sectional, and longitudinal study including 22 IMNM patients, divided into three groups based on timing of first MRI and if performed before or under treatment. T1 score and percentage of STIR positive muscles (STIR%) were considered and analyzed also in relation to demographic, clinical and laboratory characteristics. RESULTS: STIR% was higher in untreated patients and in those who performed MRI earlier (p = 0.001). Pelvic girdle and thighs were in general more affected than legs. T1 score was higher in patients with MRI performed later in disease course (p = 0.004) with a prevalent involvement of the lumbar paraspinal muscles, gluteus medius and minimus, adductor magnus and hamstrings. 22% of STIR positive muscles showed fat replacement progression at second MRI. Higher STIR% at baseline correlated with higher risk of fat replacement at follow-up (p = 0.003); higher T1 score correlated with clinical disability at follow-up, with late treatment start and delayed treatment with IVIG (p = 0.03). INTERPRETATION: Muscle MRI is a sensitive biomarker for monitoring disease activity and therapy response, especially when performed early in disease course and before treatment start, and could represent a supportive outcome measure and early prognostic index in IMNM.

The Essential Role of IL-17 as the Pathogenetic Link between Psoriasis and Metabolic-Associated Fatty Liver Disease.

Interleukin 17 (IL-17) is an effector cytokine that plays a key role in the pathogenesis of both psoriasis and metabolic-associated fatty liver disease (MAFLD), a condition that is more prevalent and severe in patients with psoriasis. In liver inflammation, IL-17 is mainly produced by CD4+ T (TH17) and CD8+ T cells (Tc17), although numerous other cells (macrophages, natural killer cells, neutrophils and Tγδ cells) also contribute to the production of IL-17. In hepatocytes, IL-17 mediates systemic inflammation and the recruitment of inflammatory cells to the liver, and it is also implicated in the development of fibrosis and insulin resistance. IL-17 levels have been correlated with progression from MAFLD to steatohepatitis, cirrhosis, and even hepatocellular carcinoma. Clinical trials have shown that inhibiting IL-17A in patients with psoriasis could potentially contribute to the improvement of metabolic and liver parameters. A better understanding of the key factors involved in the pathogenesis of these chronic inflammatory processes could potentially lead to more efficient treatment for both psoriasis and MAFLD, and help to develop holistic strategies to improve the management of these patients.

Utilidad de la prueba de detección de ácidos nucleicos GeneXpert tuberculosis (MTB/RIF) en muestras respiratorias y no respiratorias en un hospital de referencia / Utility of nucleic acids detection GeneXpert tuberculosis (MTB/RIF) in respiratory and non-respiratory hospital reference samples

Resumen: OBJETIVO Evaluar la sensibilidad y valores predictivos de BAAR-Ziehl-Neelsen y GeneXpert (MTB/RIF) en muestras respiratorias y no respiratorias en población general y con VIH. MATERIAL Y MÉTODO Estudio clínico abierto, sin distribución al azar, prospectivo, descriptivo y observacional efectuado de mayo de 2016 a enero de 2017. Los criterios de inclusión fueron: pacientes con datos clínicos epidemiológicos radiológicos que sugirieran tuberculosis en la evaluación diagnóstica o riesgo de padecerla. Se hizo toma simultánea de expectoración o muestra extrapulmonar para determinación de BAAR-Ziehl-Neelsen, GeneXpert MTB y cultivo; se utilizó como patrón de referencia el cultivo. RESULTADOS Se incluyeron en el estudio 120 pacientes, 88 (73.3%) hombres. La justificación de la realización de la prueba fue enfermedad aguda grave 76 (63.3%), el factor de riesgo de mayor prevalencia fue el VIH-SIDA 54 (45.5%). El mayor porcentaje correspondió a la forma respiratoria (n = 75, 62.5%). El total de las muestras (n = 89, 74.2%) fueron negativas respecto a BAAR en contraste con GeneXpert y cultivo, que fueron positivos en 94 casos (78.3%). CONCLUSIONES Los indicadores estables evaluados en la prueba GeneXpert mostraron que es una prueba útil, sobre todo en muestras extrapulmonares de pacientes con VIH-SIDA.

Abstract: OBJECTIVE To assess the sensitivity and predictive values of BAAR Ziehl-Neelsen and GeneXpert (MTB/RIF) for respiratory and non-respiratory samples in the general population and HIV-patients. MATERIAL AND METHOD A clinical open, not-random, prospective, descriptive and observational study was done from May 2016 to January 2017. Inclusion criteria were: Patients with radiological, clinical and epidemiological data that suggested tuberculosis within the diagnostic evaluation or risk of having it. Simultaneous sputum or extrapulmonary sample was taken for determination of Ziehl-Neelsen, GeneXpert MTB and culture; the crop was used as a gold standard. RESULTS There were included 120 patients, 88 (73.3%) men; the justification for performing the test was severe acute disease (n = 76, 63.3%), the risk factor with the highest prevalence was HIV-AIDS (n = 54, 45.5%) The highest percentage was respiratory (n = 75, 62.5%). The total of samples 89 (74.2%) were negative with respect to BAAR in contrast to GeneXpert and culture, which reported positive in 94 (78.3%). CONCLUSIONS The stable indicators evaluated in the GeneXpert test showed that it is a useful test especially in extralung samples of patients with HIV-AIDS.