The Use of TNF-α Inhibitors in Active Ankylosing Spondylitis Treatment.

Ankylosing spondylitis (AS) is a challenging disease, characterized by chronic inflammation and structural damage primarily affecting the axial skeleton, while extra-articular manifestations may also appear. This results in the deterioration of patients' quality of life. Over the past few decades, tumor necrosis factor-α (TNF-α) inhibitors have revolutionized the management of AS, offering substantial relief from symptoms and improving patient outcomes. The aim of this review is to assess the efficacy of TNF-α inhibitors in patients with active AS. A search was performed in the PubMed database using the following keywords: ("TNF alpha inhibitors" OR "anti TNF-a" OR "TNF-a inhibitors" OR "anti TNF-alpha" OR "Etanercept " OR "Golimumab" OR "Infliximab" OR "Certolizumab pegol" OR "Adalimumab") AND "ankylosing spondylitis". The search was completed in February 2024, and 35 studies were included in this review following PRISMA guidelines. The findings reveal evidence supporting the efficacy of TNF-α inhibitors in reducing inflammation, preventing structural damage, and enhancing overall well-being in AS patients. Overall, TNF-α inhibitors have emerged as a cornerstone in the therapeutic algorithm against AS with a very satisfactory safety profile.

Terapias biológicas y tuberculosis en pediatría / Biological therapies and tuberculosis in pediatrics

En los últimos años, ha habido un aumento sostenido del uso de terapias inmunomoduladoras como las terapias biológicas y en un período más reciente, de las terapias con moléculas pequeñas. Estos tratamientos constituyen un factor de riesgo más para enfermar de tuberculosis en adultos y aunque en menor grado, también en niños, especialmente con el uso de anti TNF-α, por lo que antes de iniciar una terapia biológica, hay que descartar la tuberculosis activa y la latente. En el tratamiento de una tuberculosis activa producida por un biológico se debe prolongar la etapa de continuación a 9 meses. Es importante el seguimiento clínico prolongado en años de quienes usan o han completado el uso de estas terapias. Hay que posponer la vacunación BCG en los hijos de madres que usaron terapias biológicas durante la gestación hasta la edad 6 a 12 meses de los niños. El foco de esta revisión está centrado en la tuberculosis por progresión de una forma latente a una activa o por un contacto estrecho con una persona con tuberculosis pulmonar en pacientes que reciben terapias biológicas anti TNF alfa de uso inmunoreumatológico.

In recent years, there has been a sustained increase in the use of immunomodulatory therapies such as biologic therapies and, more recently, small molecule therapies. Those therapies have become another risk factor for tuberculosis in adults and, although to lesser degree, also in children, especially some of them, such as anti-TNF α. Before starting biological therapy, active tuberculosis and latent tuberculosis must be ruled out. In the treatment of active tuberculosis caused by a biologic, the continuation stage should be extended to 9 months. Long-term clinical follow-up in years of those who use them or have completed their use, is important. BCG vaccine should be postponed in children of mother who used biologic therapies during pregnancy until the children ́s age 6 to 12 months. The focus of this review is centered on tuberculosis due to progression from a latent to an active form or due to close contact with a person with pulmonary tuberculosis in patients receiving anti-TNF alpha biological therapies for immunorheumatology use.

Assessing the efficacy of TNF-alpha inhibitors in preventing emergency and emergent colectomies.

BACKGROUND AND AIM: Severe ulcerative colitis (UC) is potentially life threatening and is associated with significant morbidity. TNF-∝ inhibitors (Infliximab) were introduced in Australia for the management of medically resistant, acute, severe flares of UC in 2008. The aim of this study is to assess the efficacy of Infliximab in preventing emergent and emergency colectomies for patients with moderate to severe UC by comparing colectomy rates before and after its introduction at our institution. METHODS: This was a retrospective cohort study of all patients who were admitted to the Royal Perth Hospital with a flare of UC between 2002 and 2017. Patients were divided into two cohorts: those admitted prior to the introduction of Infliximab (pre-2008) and those admitted after. We compared data between these two groups, including age, gender, length of admission, use of Infliximab, colectomy, and complications of surgery. We defined emergency surgery as requiring surgery during the index admission and emergent surgery as an operation within 54 weeks. RESULTS: A total of 313 UC cases from 2002 to 2017 were analyzed. There was a decrease in emergency and emergent colectomies from 19.4 to 8% in the post-2008 cohort (P = 0.008). Furthermore, there was a decrease in the proportion of operations performed as emergencies, from 36 to 20%. This resulted in a significantly reduced length of stay (13.4-9.7 days, P < 0.05) and complication rate (36 to 20%, P < 0.05). CONCLUSION: Overall, the need for emergency and emergent operations has drastically reduced at our institution with the introduction of Infliximab. This study has confirmed the efficacy of Infliximab in reducing colectomy rates at our institution.

Smoking Is Associated With Low Levels of Soluble PD-L1 in Rheumatoid Arthritis.

Background: Smoking is a risk factor for developing rheumatoid arthritis (RA), but the mechanism remains uncertain. We previously demonstrated that smoking lowers the T cell activation threshold by limiting programmed death protein 1 (PD-1) expression. Aim: To investigate how smoking influence the levels of soluble PD-1 ligand (sPD-L1). Method: Serum levels of sPD-L1 were measured in 246 RA patients and in 168 healthy subjects. The analysis was done with respect to inflammation, smoking, treatments, and autoantibody status. The effect of therapeutic TNF-inhibiting antibodies (TNFi) on sPD-L1 was studied in 16 RA patients at their first infliximab infusion. The expression of Fcγ-receptor (FcγR) subclass IIB and IIIA was analyzed with quantitative polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) from 12 RA patients and 15 healthy controls, and in healthy PBMC exposed to IgG containing antibodies to cyclic citrullinated peptides (aCCP). Results: The negative association between smoking and sPD-L1 in RA patients was established by multiple logistic regression (OR = 0.52, p = 0.038). Other covariates in the regression model were serum levels of IL-1ß representing inflammation (OR = 1.6, p = 0.0076) and aCCP positivity (OR = 1.9, p = 0.047). First infliximab infusion repressed sPD-L1 (p = 0.023) in patients, and low levels of sPD-L1 were found in patients with early RA treated with TNFi (p = 0.018). Treatment with TNFi was associated with higher sPD-L1 in patients with long disease duration (p = 0.041) and restored levels in smokers. In vitro exposure to aCCP+ IgG suppressed sPD-L1 (p = 0.036), but aCCP+ patients with long disease duration had higher sPD-L1 (p = 0.016). High ratio of the inhibitory FcγR subclass IIB over the stimulatory IIIA resulted in low sPD-L1 release (p = 0.029). Smoking was associated with a higher FcγR IIB/IIIA ratio (p = 0.00062) and lower levels of sPD-L1 (p = 0.013). Conclusion: In RA, serum sPD-L1 was related to systemic inflammation and aCCP positivity. Smoking altered the expression of FcγRs and limited sPD-L1 in RA patients, permitting inappropriate T cell responses. Differential regulation of sPD-L1 during the early and late RA may indicate transposition from acute to chronic inflammation.

Biological evaluation of novel 6-Arylbenzimidazo [1.2-c] quinazoline derivatives as inhibitors of LPS-induced TNF- alpha secretion

This study describes the effect of novel 6-Arylbenzimidazo [1,2-c] quinazoline derivatives as tumor necrosis factor alpha (TNF-á) production inhibitors. The newly synthesized compounds were tested for their in vitro ability to inhibit the lipolysaccharide (LPS) induced TNF-á secretion in the human promyelocytic cell line HL-60. The compound 6-Phenyl-benzimidazo [1,2-c] quinazoline, coded as Gl, resulted as the most potent inhibitor and with no significant cytotoxic activity. Thus, 6-Arylbenzimidazo [1,2-c] quinazoline derivatives may have a potential as anti-inflammatory agents.