Effect of neridronate on axial involvement in patients with spondyloarthritis when biologics are not possible. Results of a monocentric study.

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.

Bone Involvement in Rheumatoid Arthritis and Spondyloartritis: An Updated Review.

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.

The impact of EMA recommendations on the real-life use of Janus kinases inhibitors for rheumatoid arthritis: the Expanded Risk Score in RA as a tool to quantify the risk of cardiovascular events.

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.

Juvenile Idiopathic Arthritis, Uveitis and Multiple Sclerosis: Description of Two Patients and Literature Review.

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.

2-Arachidonoylglycerol Reduces the Production of Interferon-Gamma in T Lymphocytes from Patients with Systemic Lupus Erythematosus.

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 CB2 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 CB1 and CB2, respectively. Flow cytometry was used to assess the expression of CD3, CD4, CD8, CD25, IFN-É£, IL-4, and IL-17A. Results: 2-AG (1 µM) decreased IFN-É£ 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-É£ 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 CB2 activation.