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.

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.
To investigate how smoking influence the levels of soluble PD-1 ligand (sPD-L1).
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).
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-1β 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).
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.