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Objective. This paper aims to provide an overview of the use of treatments available for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) during pregnancy and breastfeeding, according to current national recommendations and international guidelines, as well as data on the impact on pregnancy outcomes of paternal exposure to treatment. Methods. We performed a narrative review of national and international recommendations and guidelines on the reproductive health of patients suffering from rheumatic diseases. The last updated recommendations and guidelines were considered source data. Results. We reported updated information regarding the treatment of axSpA and PsA with nonsteroidal anti-inflammatory drugs, intra-articular glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and targeted synthetic DMARDs during the preconception period, pregnancy, and breastfeeding, as well as data related to paternal exposure. We highlighted any medications that should be discontinued and/or not used in the reproductive age group and also treatments that may be continued, avoiding the withdrawal of drugs that can be used in the different phases, thus preventing the risk of increasing disease activity and flares before, during, and after pregnancy in SpA patients. Conclusions. The best management of pregnancy in patients with SpA is based on knowledge of updated drug recommendations, a careful and wise evaluation of the risks/benefits of starting or continuing treatment from the SpA diagnosis in a woman of childbearing age through pregnancy and lactation, and sharing therapeutic choices with other healthcare providers (in particular, gynecologists/obstetricians) and the patient.

The objective of this study was to evaluate biological disease-modifying anti-rheumatic drugs (bDMARDs) survival in several therapy courses of patients affected by psoriatic arthritis (PsA) and to compare tumor necrosis factor inhibitors (TNFi) and non-TNFi retention rates. A total of 241 bDMARD therapy courses (155 TNFi drugs, 65 anti-interleukin (IL)-17 drugs, and 21 anti-IL12/23) were analyzed. Bivariate analyses were performed to assess the presence of demographic and clinical features, as well as comorbidities, associated with bDMARD discontinuation in TNFi and non-TNFi groups. In the bivariate analyses of TNFi and non-TNFi groups, we found a lower age at the start of TNFi therapy in the former group [46 years, interquartile range (IQR) 45-54 vs 50.5 years, IQR 42-61; p=0.004] as well as a lower proportion of patients with skin psoriasis (65.8% vs 88.4%; p

Objectives: The study aims to evaluate the applicability of the D2T psoriatic arthritis (PsA) definition, adapted from rheumatoid arthritis, within a single-center observational cohort of PsA patients treated with b/tsDMARDs. In addition, we aimed to establish a numerical index defining D2T-PsA based on the ratio of observed to expected failed b/tsDMARDs and to develop a predictive model identifying features associated with the D2T condition., Methods: The study included 267 consecutive adult PsA patients receiving b/tsDMARDs, collecting demographic, clinical, and clinimetric data. The prevalence of D2T PsA patients was assessed using a proposed definition. We then developed a predictive model to assess treatment difficulty, utilizing PsA-normalized failed b/tsDMARDs. A generalized linear model was applied to identify clinical and demographic features associated with D2T PsA, employing a bagging procedure for robust variable selection, followed by univariate and multivariable analyses., Results: Among the 267 patients, only 8 of them (2.9%) met the proposed D2T PsA criteria. In a subset of 177 patients analyzed using the predictive model, 17.2% of them demonstrated higher treatment difficulty. Univariate analysis revealed associations between treatment difficulty and female sex, psoriasis pattern, fibromyalgia, and steroid therapy. Multivariate analysis confirmed significant associations between fibromyalgia, nail and pustular psoriasis, and steroid use., Conclusion: According to the predictive model, the proposed D2T PsA definition identified a small subset of patients with increased treatment difficulty. These findings highlight the need for refining the criteria to better define D2T PsA patients, providing valuable insights into managing complex treatment challenges in PsA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Favalli, Biganzoli, Cincinelli, Ferrito, Luconi, Manara, Biggioggero, Boracchi and Caporali.)

Competing Interests: Competing interests: None declared.

Background: The purpose of the authors' narrative review was to outline the current literature regarding the use of ultrasound in main rheumatic disorders and summarize the updates, specifically about rheumatoid arthritis, psoriatic arthritis, and crystal-induced arthropathies., Methods: The authors searched on PubMed for articles discussing the major updates regarding the role of ultrasound in the previously mentioned rheumatic conditions., Results: The authors have provided the updated definitions, new criteria, and diagnostic scores., Conclusions: In rheumatology's dynamic landscape, this review provides valuable insights for researchers and clinicians on ultrasound's role in improving patient care and outcomes in rheumatic diseases., Competing Interests: Disclosure L.M. Sconfienza has financial relationship with Esaote SpA and Samsung Medison, all unrelated to the present paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: This study aims to examine the potential effectiveness of intravenous neridronate (IVNer) on axial involvement in patients with spondyloarthritis (SpA) refractory to non-steroidal anti-inflammatory drugs (NSAIDs) but not eligible for biological disease-modifying antirheumatic drugs (bDMARDs)., Method: Patients with active SpA (BASDAI score ≥ 4) and active sacroiliitis (SI) on MRI (according to ASAS MRI definition), who were NSAID-insufficient responder/intolerant but not eligible for bDMARDs, were retrospectively recruited in a tertiary rheumatology centre between September 2015 and December 2021. IVNer (100 mg) was administered to the patients on days 1, 4, 7, and 10. Responses were evaluated 60 days after the last infusion as the median changes from the baseline of BASDAI and Visual Analogue Scale (VAS) pain and there are improvements on MRI signs., Results: A total of 38 patients (26 axial SpA, 3 enteropathic arthritis, and 9 axial psoriatic arthritis) were included [66% women, mean age ± SD: 38.0 ± 14.1 years, mean disease duration: 30.5 ± 49.5 months (range 1.0-298), 47% HLAB27+]. The reason for bDMARD ineligibility was concurrent solid tumors ( n  = 6) or hematological ( n  = 1) malignancy, comorbidities ( n  = 11), or patient preference ( n  = 20). Both median BASDAI [5.83 (4.2-8.33) versus 3.66 (1.1-6.85), p  < 0.001] and VAS pain [7 (5.75-8.0) versus 3 (1.0-7.0), p  < 0.0001] significantly decreased after IVNer. Of 28 available MRI at follow-up, we observed a complete (36%) or partial (39%) resolution of sacroiliitis or a persistent activity (25%)., Discussion: IVNer was effective in improving axial involvement in patients with SpA refractory to NSAIDs but not eligible for bDMARDs. IVNer can be considered as a potential alternative therapeutic option in selected settings., Competing Interests: MV served as a consultant for Abiogen. RC received speaker’s fee and consultation fee from Abbvie, BMS, Lilly, Galapgos, Fresenius-Kabi, MSD, UCB, and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Crotti, Di Taranto, Orsini, Ferrito, Varenna, Favalli and Caporali.)

Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, which not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying specific bone involvement, focusing on the complex interactions that occur between bone tissue's own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined as osteoimmunology. Specifically, we comprehensively elaborate on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis leads to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility.

Objective: To evaluate in patients with rheumatoid arthritis (RA) the impact of EMA recommendations on the real-life prescription of JAK inhibitors (JAKis) and the use of the Expanded Risk Score in RA (ERS-RA) to quantify the risk of major adverse cardiac events (MACE)., Methods: We conducted a retrospective analysis of real-life RA patients treated with JAKis. Patients were classified as ineligible for JAKis if they fulfilled EMA criteria (>65 years-old, history of malignancy, or increased risk of venous thromboembolic events [VTE] or MACE including smoking). Risk of MACE was defined according to ORAL Surveillance trial inclusion criteria (ORALSURV) or by using the ERS-RA., Results: Of 194 patients enrolled, 57.9% were classified as ineligible according to EMA definition (ORALSURV criteria). The most frequent reason for ineligibility was increased MACE risk (70.2%), followed by age>65 (34.2%), smoking (30.7%), and increased risk of VTE (20.2%) or malignancy (7%). The use of the ERS-RA reduced the rate of patients carrying an increased CV risk to 18.6% (p<0.001 versus ORALSURV), leading to 46.4% overall ineligible patients. Over a drug-exposure of 337 patient/years, we observed 2 VTE, one MACE (non-fatal stroke), and one solid malignancy (all in the group of patients classified as ineligible according to both the definitions)., Conclusions: Rigorous application of EMA indications in clinical practice could result in the exclusion of a large proportion of RA patients from treatment with JAKis. A proper quantification of the risk for MACE by dedicated tools as ERS-RA is advocated to better tailor the management of RA., Competing Interests: Author EF has been a consultant for and/or received honoraria as a speaker for the companies AbbVie, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, and UCB Pharma. Author MB received honoraria as a speaker for the company Galapagos. Author RC has been a consultant for and/or received honoraria as a speaker for the companies AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Favalli, Cincinelli, Germinario, Di Taranto, Orsini, Maioli, Biggioggero, Ferrito and Caporali.)

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, while multiple sclerosis (MS) is a demyelinating disease of the central nervous system, characterized by remission and exacerbation phases. An association between MS and rheumatologic diseases, in particular rheumatoid arthritis, has been described and numerous studies acknowledge anti-TNF-α drugs as MS triggers. Conversely, the association between MS and JIA has been reported merely in five cases in the literature. We describe two cases of adult patients with longstanding JIA and JIA-associated uveitis, who developed MS. The first patient was on methotrexate and adalimumab when she developed dizziness and nausea. Characteristic MRI lesions and oligoclonal bands in cerebrospinal fluid led to MS diagnosis. Adalimumab was discontinued, and she was treated with three pulses of intravenous methylprednisolone. After a few months, rituximab was started. The second patient had been treated with anti-TNF-α and then switched to abatacept. She complained of unilateral arm and facial paraesthesias; brain MRI showed characteristic lesions, and MS was diagnosed. Three pulses of intravenous methylprednisolone were administered; neurological disease remained stable, and abatacept was reintroduced. Further studies are warranted to define if there is an association between JIA and MS, if MS represents JIA comorbidity or if anti-TNF-α underpins MS development.

Background : the endocannabinoid 2-arachidonoylglycerol (2-AG) plays a pivotal role in immune cells regulation. The plasma levels of 2-AG are increased in patients with systemic lupus erythematosus (SLE) and correlate with disease activity. Moreover, in plasmacytoid dendritic cells from SLE patients, 2-AG is able to control the production of type 1 interferon (IFN) through CB 2 activation. The aim of this study was to evaluate the potential role of 2-AG on T lymphocytes from SLE patients. Methods : peripheral blood mononuclear cells (PBMCs) from SLE participants and age- and sex-matched healthy donors (HD) were isolated by Ficoll-Hypaque density-gradient centrifugation. The PBMCs were treated with increasing concentrations of 2-AG, and AM251 and AM630 were used to antagonize CB 1 and CB 2, respectively. Flow cytometry was used to assess the expression of CD3, CD4, CD8, CD25, IFN-ɣ, IL-4, and IL-17A. Results : 2-AG (1 μM) decreased IFN-ɣ expression ( p = 0.0005) in the Th1 lymphocytes of SLE patients. 2-AG did not modulate the cytokine expression of any other T lymphocyte population from either SLE or HD. Treatment with both 2-AG and AM630 increased the IFN-ɣ expression in Th1 lymphocytes of SLE patients ( p = 0.03). Discussion : 2-AG is able to modulate type 2 IFN production from CD4+ T lymphocytes from SLE patients through CB 2 activation.