Drug Survival, Effectiveness and Safety of Secukinumab in Axial Spondyloarthritis up to 4 Years: A Real-Life Single Center Experience.

(1) Objective: The main aims of our study were to explore the drug survival and effectiveness of secukinumab in patients with axial spondyloarthritis (axSpA). (2) Methods: We underwent a retrospective analysis of consecutive axSpA treated with secukinumab as a first line of biologics or at switch in a biologic-experienced population. Efficacy data, indicating improvement in inflammation parameters (such as C-reactive protein and erythrocyte sedimentation rate) and disease activity scores (such as Ankylosing Spondylitis Disease Activity Score [ASDAS-CRP], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and patient-reported outcomes (pain), were assessed at 6, 12, 24, 36 and 48 months. The drug survival rate, dropout rate and discontinuation reasons (efficacy versus safety) of secukinumab were assessed in subgroup analysis (axSpA with and without exposure to biologics). (3) Results: In total, 46 patients were exposed to the IL-17A inhibitor secukinumab. The drug survival for axSpA patients 59.7% at 12 months and 31.3% at 24 months. There were no statistically significant differences in the median drug survival between biologic-naïve versus biologic-experienced subgroups. (4) Conclusions: Secukinumab has demonstrated effectiveness and safety in treating a cohort of axSpA patients in real-world settings, with a notable retention rate of the drug.

The Complement System, T Cell Response, and Cytokine Shift in Normotensive versus Pre-Eclamptic and Lupus Pregnancy.

Successful pregnancy requires an immunological shift with T helper CD4+ bias based on disbalance Th1/Th17 versus Th2/T regulatory (Tregs) required to induce tolerance against the semi-allogeneic fetus and placenta and to support fetal growth. Considered a pregnancy-specific hypertensive disorder, pre-eclampsia is characterized by multifaceted organ involvement related to impaired maternal immune tolerance to paternal antigens triggered by hypoxic placental injury as well as excessive local and systemic anti-angiogenic and inflammatory factor synthesis. Both systemic and local Th1/Th2 shift further expands to Th17 cells and their cytokines (IL-17) complemented by suppressive Treg and Th2 cytokines (IL-10, IL-4); alterations in Th17 and Tregs cause hypertension during pregnancy throughout vasoactive factors and endothelial dysfunction, providing an explanatory link between immunological and vascular events in the pathobiology of pre-eclamptic pregnancy. Apart from immunological changes representative of normotensive pregnancy, lupus pregnancy is generally defined by higher serum pro-inflammatory cytokines, lower Th2 polarization, defective and lower number of Tregs, potential blockade of complement inhibitors by anti-phospholipid antibodies, and similar immune alterations to those seen in pre-eclampsia. The current review underpins the immune mechanisms of pre-eclampsia focusing on local (placental) and systemic (maternal) aberrant adaptive and innate immune response versus normotensive pregnancy and pregnancy in systemic autoimmune conditions, particularly lupus.

Exploring the Role of Interleukin-6 Receptor Inhibitor Tocilizumab in Patients with Active Rheumatoid Arthritis and Periodontal Disease.

BACKGROUND: The aim of our study was to explore the influence of weekly subcutaneous administration of interleukin-6 (IL-6) receptor inhibitor tocilizumab (TCZ) on periodontal status in a local longitudinal study of patients with rheumatoid arthritis (RA) and periodontal disease (PD). METHODS: We performed a 6-month prospective study in 51 patients with chronic periodontitis and moderate-to-severe RA starting TCZ in accordance with local recommendations. Extensive rheumatologic (clinical activity, inflammatory, serological biomarkers) and periodontal (visible plaque index, gingival index, bleeding on probing, probing pocket depth, clinical attachment loss) assessments were done. Changes in RA activity and periodontal status were reassessed after 3 and 6 months. RESULTS: We demonstrated significant correlations between periodontal status, disease activity, and serologic biomarkers (p < 0.05). Tocilizumab significantly improved the gingival index scores and decreased the number of sites with bleeding on probing after only 3 months (p < 0.05), while the probing pocket depth significantly decreased after 6 months; overall, clinical attachment loss presented only slight changes without any statistical significance as well as teeth count and plaque levels (p > 0.05). CONCLUSION: IL-6 inhibition is able to improve periodontal outcomes in patients with RA and concomitant PD, which is essentially related to a dramatic decrease in serum inflammatory mediators.

The Prevalence of Atopy in Biologically Treated Spondyloarthropathies: A Retrospective Study of 200 Patients.

(1) Background: Recent data shed light on the association between atopic disorders (ADs) (atopic dermatitis, allergic asthma, allergic rhinitis) and spondyloarthropathies (SpAs), underpinning the critical role of T helper (Th)1-Th17/Th2-T regulatory cells disbalance. We evaluated the prevalence of AD in axial SpAs (axSpAs) and psoriatic arthritis (PsA) and explored the potential association between atopic status, disease-related parameters, and biological therapy. (2) Methods: A monocentric, retrospective study was conducted that enrolled 200 patients taking biologics. Demographics, disease, and drug-related variables, along with a screening questionnaire focused on Ads, were systematically collected. (3) Results: Overall, 51 patients (25.5%) had atopy-namely, 24.4% of axSpA and 28% of PsA, with a higher frequency of rhinitis (43%) vs. atopic dermatitis (37.2%) or asthma (21.5%). We failed to demonstrate any statistically significant difference in demographics, SpA-related parameters excepting concomitant inflammatory bowel disease, and biologic drug exposure in patients with and without atopy (p > 0.05). However, significantly more non-atopic patients need only one TNF inhibitor (54%) vs. atopic patients (28%) (p < 0.05) to control active SpA. (4) Conclusions: We successfully demonstrated that AD is associated with one out of four SpA. Irrespective of the SpA subtype, atopic patients require more frequent switching among biologics, as significantly more non-atopic patients remain on their first anti-TNF.

Efficacy of baricitinib on periodontal inflammation in patients with rheumatoid arthritis.

OBJECTIVE: Despite a widely recognized bidirectional pathobiologic relationship between rheumatoid arthritis (RA) and periodontal disease, the impact of innovative anti-rheumatic drugs in modulating not only inflammatory and immune articular damage, but also periodontal microenvironment remains debatable. We aimed to evaluate the periodontal status in RA with and without baricitinib, a Janus kinase (JAK) inhibitor, and to better describe association between these entities. METHODS: We performed a prospective longitudinal 24-weeks study in 21 active RA initiating baricitinib. Standard assessments included a dual rheumatologic (RA activity, disability, serological, inflammatory profile) and dental evaluation comprising plaque index, gingival index, bleeding on probing, probing depth, clinical attachment level. RESULTS: More than half of RA presented at baseline with chronic periodontitis, as suggested by high prevalence of sites with dental plaque, abnormal bleeding on probing, probing depth and clinical attachment level. Aggressive periodontal disease was reported particularly in disease subsets with excessive inflammatory (serumC reactive protein level) and serologic biomarkers (anti-citrullinated peptide antibodies). Furthermore, significant correlations between dental pathology, disease activity and ACPA levels were also reported (P<0.05). Consistent improvement was noticed in both rheumatoid arthritis characteristics and periodontal status after 24 weeks of baricitinib (P<0.05). CONCLUSION: RA, particularly severe active ACPA-positive disease, is basically associated with altered periodontal health. JAK blockade through oral baricitinib may be efficient in patients with active RA and potentially able to modulate the inflammatory process in the periodontal tissue.

Volumetric Cone Beam Computed Tomography for the Assessment of Oral Manifestations in Systemic Sclerosis: Data from an EUSTAR Cohort.

Background: Oral health issues are commonly reported in systemic sclerosis (SSc), comprising a broad spectrum of manifestations, e.g., reduced mouth opening, periodontal disease, increased periodontal ligament (PDL) space width, and mandibular resorption. We aimed to assess oral radiographic abnormalities, particularly PDL space widening and erosions, and to identify potential relations with disease measures. Methods: cross-sectional study in 43 SSc and matching controls receiving systematic oral assessments (full mouth dental/periodontal) and imaging (radiographs and cone beam computed tomography (CBCT)). Associations between disease variables and radiologic findings were investigated by univariate and multivariate analysis (SPSS-v.20, p < 0.05). Results: CBCT demonstrated generalized PDL space widening in up to half SSc, with at least one tooth involved, essentially in the posterior region (p < 0.05). Significant correlations between number of teeth with PDL space widening and disease severity, skin score, disease subset, topoisomerase I specificity, age, and disease duration were reported (p < 0.05). Additionally, mandibular erosions were described in one out of four patients, commonly condylar erosions. Conclusions: Tridimensional CBCT approach confirmed widening of PDL and mandibular erosions as common dental findings in scleroderma. Furthermore, widened PDL spaces correlated with several disease characteristics including severity, skin extent, and antibody profile.