Characteristics of patients with difficult-to-treat rheumatoid arthritis in a French single-centre hospital.

OBJECTIVES: To compare the features of difficult-to-treat rheumatoid arthritis (D2TRA) patients using two different definitions according to the previous failure of targeted therapies. METHODS: We stratified consecutive RA patients treated at Cochin Hospital into two groups, a D2TRA group and a non-D2TRA group, according to two definitions of D2TRA. Both definitions defined D2TRA as RAs failing at least two targeted therapies, with a different mechanism of action for the EULAR-D2TRA definition or without prejudging the mechanism of action and for the Alternative D2TRA definition. RESULTS: We included 320 consecutive RA patients. We identified 76 EULAR-D2TRA and 244 non-DTRA patients, and 120 Alternative D2TRA and 200 non-DTRA patients. Compared with non-D2TRA, D2TRA patients from both definitions were more likely to have lower socioeconomic level, positive rheumatoid factor, interstitial lung disease, higher DAS28-CRP and were more likely to respond to rituximab and Janus kinase inhibitors. Although EULAR and Alternative D2TRA patients displayed similar clinical and biological features, they were characterized by different therapeutic profiles. We observed fewer patients receiving methotrexate in the Alternative D2TRA group (53% vs 64%, P = 0.046). Patients with Alternative D2TRA not fulfilling the EULAR definition (n = 44) had all received two successive first-line TNF inhibitors, a monoclonal antibody and a soluble receptor, and were comparable to EULAR-D2TRA patients with regards to all other characteristics. CONCLUSION: Low socioeconomic status, diabetes, interstitial lung disease and absence of combination with methotrexate allow identification of D2TRA. In addition, the inclusion as 'early-D2TRA' of patients failing two TNF inhibitors in the EULAR definition of D2TRA would facilitate the rapid identification of D2TRA patients.

Recommendations of the French Society of Rheumatology for the management in current practice of patients with polymyalgia rheumatica.

OBJECTIVE: To develop recommendations for the routine management of patients with polymyalgia rheumatica (PMR). METHODS: Following standard procedures, a systematic review of the literature by five supervised junior rheumatologists, based on the questions selected by the steering committee (5 senior rheumatologists), was used as the basis for working meetings, followed by a one-day plenary meeting with the working group (15 members), leading to the development of the wording and determination of the strength of the recommendations and the level of agreement of the experts. RESULTS: Five general principles and 19 recommendations were drawn up. Three recommendations relate to diagnosis and the use of imaging, and five to the assessment of the disease, its activity and comorbidities. Non-pharmacological therapies are the subject of one recommendation. Three recommendations concern initial treatment based on general corticosteroid therapy, five concern the reduction of corticosteroid therapy and follow-up, and two concern corticosteroid dependence and steroid-sparing treatments (anti-IL-6). CONCLUSION: These recommendations take account of current data on PMR, with the aim of reducing exposure to corticosteroid therapy and its side effects in a fragile population. They are intended to be practical, to help practitioners in the day-to-day management of patients with PMR.

Recommendations for assessing the risk of cardiovascular disease and venous thromboembolism before the initiation of targeted therapies for chronic inflammatory rheumatic diseases.

BACKGROUND: Patients with rheumatoid arthritis (RA) and other chronic inflammatory rheumatic disorders have increased risk of cardiovascular disease (CVD) and venous thromboembolism (VTE) compared with the general population. Moreover, recent data have raised concerns around a possible increased risk of major CV events (MACE) and VTE in patients treated with JAK inhibitors (JAKi). In October 2022, the PRAC has recommended measures to minimize the risk of serious side effects, including CV conditions and VTE, associated with all approved in chronic inflammatory diseases. OBJECTIVE: To provide an adequate and feasible strategy to evaluate, at the individual level, the risk of CVD and VTE in patients with chronic inflammatory rheumatic diseases. METHODS: A multidisciplinary steering committee comprised 11 members including rheumatologists, a cardiologist, a hematologist expert in thrombophilia and fellows. Systematic literature searches were performed and evidence was categorized according to standard guidelines. The evidence was discussed and summarized by the experts in the course of a consensus finding and voting process. RESULTS: Three overarching principles were defined. First, there is a higher risk of MACE and VTE in patients with chronic inflammatory rheumatic diseases compared with the general population. Second, the rheumatologist has a central role in the evaluation of the risk of CVD and VTE in patient with chronic inflammatory rheumatic diseases. Third, the risk of MACE and VTE should be regularly assessed in patients with chronic inflammatory rheumatic diseases, particularly before initiating targeted therapies. Eleven recommendations were defined to prevent potentially life-threatening complications of CVD and VTE in patients with chronic inflammatory rheumatic diseases, providing practical assessment of CVD and VTE before considering the prescription of targeted therapies, and especially JAKi. CONCLUSION: These practical recommendations based on expert opinion and scientific evidence provide consensus for the prevention and the assessment of CVD and VTE.

Increased gut permeability and intestinal inflammation precede arthritis onset in the adjuvant-induced model of arthritis.

BACKGROUND: Intestinal inflammation, dysbiosis, intestinal permeability (IP), and bacterial translocation (BT) have been identified in patients with spondyloarthritis but the time at which they appear and their contribution to the pathogenesis of the disease is still a matter of debate. OBJECTIVES: To study the time-course of intestinal inflammation (I-Inf), IP, microbiota modification BT in a rat model of reactive arthritis, the adjuvant-induced arthritis model (AIA). METHODS: Analysis was performed at 3 phases of arthritis in control and AIA rats: preclinical phase (day 4), onset phase (day 11), and acute phase (day 28). IP was assessed by measuring levels of zonulin and ileal mRNA expression of zonulin. I-inf was assessed by lymphocyte count from rat ileum and by measuring ileal mRNA expression of proinflammatory cytokines. The integrity of the intestinal barrier was evaluated by levels of iFABP. BT and gut microbiota were assessed by LPS, soluble CD14 levels, and 16S RNA sequencing in mesenteric lymph node and by 16S rRNA sequencing in stool, respectively. RESULTS: Plasma zonulin levels increased at the preclinical and onset phase in the AIA group. Plasma levels of iFABP were increased in AIA rats at all stages of the arthritis course. The preclinical phase was characterized by a transient dysbiosis and increased mRNA ileal expression of IL-8, IL-33, and IL-17. At the onset phase, TNF-α, IL-23p19, and IL-8 mRNA expression were increased. No changes in cytokines mRNA expression were observed at the acute phase. Increased CD4+ and CD8+ T cell number was measured in the AIA ileum at day 4 and day 11. No increase in BT was observed. CONCLUSION: These data show that intestinal changes precede the development of arthritis but argue against a strict "correlative" model in which arthritis and gut changes are inseparable.

Frequency and anatomic distribution of magnetic resonance imaging lesions in the sacroiliac joints of spondyloarthritis and non-spondyloarthritis patients.

Background: Lesions detected by magnetic resonance imaging (MRI) of the sacroiliac joints are critical to the diagnosis of non-radiographic axial spondyloarthritis. However, inflammatory and structural lesions may be encountered in other conditions. Objectives: The objective of this study was to evaluate and compare the frequency and localization of inflammatory and structural lesions on MRIs of the sacroiliac joint of spondyloarthritis (SpA) and non-spondyloarthritis (non-SpA) patients. Design: This is a retrospective study including 200 patients, each having undergone an MRI of the sacroiliac joints. Methods: Two experienced readers evaluated the whole set of images to detect erosions, subchondral sclerosis, fatty lesions, bone marrow edema (BME) and ankylosis according to the definitions established by the ASAS MRI working group. We divided sacroiliac joints into five segments: upper, antero-middle, intermediate-middle, postero-middle and lower. Results: A total of 96 subjects with SpA (mean age 37.4 ± 11.8 years) and 104 without SpA (mean age 39.9 ± 11.6 years) were included. Of the 96 SpA patients, 65% had inflammatory buttock pain compared with 25% in the non-SpA group. BME was seen in 65% of SpA patients, mainly in the intermediate-middle segment, and in 20% of non-SpA patients, predominantly in the antero-middle segment. Subchondral sclerosis occurred in 44% of non-SpA patients, mostly in the antero-middle segment, and in 36% of SpA patients. Fatty lesions were present in 34% of SpA and in 21% of non-SpA patients. Erosions were seen in 25% of non-SpA and in 60% of SpA patients. BME and structural lesions were minimally observed in the postero-middle segment in non-SpA patients. Conclusion: Inflammatory and structural lesions were observed in all segments of the joint in SpA, mainly in the middle segments, while lesions predominantly affected the antero-middle segment in non-SpA, and were uncommon in the postero-middle segment.

2022 French Society for Rheumatology (SFR) recommendations on the everyday management of patients with spondyloarthritis, including psoriatic arthritis.

OBJECTIVE: Update the French Society for Rheumatology (SFR) recommendations on the everyday management of patients with spondyloarthritis, including psoriatic arthritis. METHODS: Following standardized procedures, a systematic literature review was done by four supervised rheumatology residents based on questions defined by a task force of 16 attending rheumatologists. The findings were reviewed during three working meetings that culminated in each recommendation receiving a grade and the level of agreement among experts being determined. RESULTS: Five general principles and 15 recommendations were developed. They take into account pharmacological and non-pharmacological measures along with treatment methods based on the dominant phenotype present (axial, articular, enthesitis/dactylitis) and the extra-articular manifestations (psoriasis, inflammatory bowel disease, uveitis). NSAIDs are the first-line pharmacological treatment in the various presentations. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are not indicated in the axial and isolated entheseal forms. If the response to conventional treatment is not adequate, targeted therapies (biologics, synthetics) should be considered; the indications depend on the clinical phenotype and presence of extra-articular manifestations. CONCLUSION: This update incorporates recent data (published since the prior update in 2018) and the predominant clinical phenotype concept. It aims to help physicians with the everyday management of patients affected by spondyloarthritis, including psoriatic arthritis.

Interest of Follow-Up Radiological Imaging in Patients with Pyogenic Vertebral Osteomyelitis.

No recommendations are established for monitoring pyogenic vertebral osteomyelitis (PVO). Thus, the realization of systematic follow-up radiological imaging is controversial. The objective of this study was to evaluate the interest in follow-up radiological imaging in patients with PVO. We conducted a retrospective cohort analysis of patients with PVO who had both baseline and follow-up radiological imaging. We classified the follow-up images into two groups, improvement/stability, and deterioration, compared with the baseline data. For each patient, we compared their radiological imaging follow-up to their clinical-biological condition assessed at the same time. Eighty-six patients were included. The mean age was 68 years (±13). A total of 99 radiological imaging examinations at diagnosis and at follow-up were analyzed, 69 Magnetic Resonance Imaging (MRI), and 30 Computerized Tomography (CT scans). The mean delay between the follow-up radiological imaging and clinical evaluation was 2.8 +/- 2.1 months. Of the 36 patients with clinical and biological recovery, 24 patients (67%) had improved radiological imaging and 12 patients (34%) had radiological worsening (new abscesses (n = 4), extension of soft tissue infiltration (n = 2) and/or epiduritis (n = 2) or appearance of new locations (n = 1)). Among the 50 patients considered as unhealed, on the contrary, radiological imaging showed an improvement in imaging in 39 patients (78%) and a worsening in 11 patients (22%). Our study showed that there was no correlation between the clinical condition of patients and their follow-up radiological imaging in the context of PVO.

Intestinal permeability in spondyloarthritis and rheumatoid arthritis: A systematic review of the literature.

OBJECTIVES: To describe the current methods usable to assess intestinal permeability in spondyloarthritis (SpA) and rheumatoid arthritis (RA), to analyze the available data on intestinal permeability in SpA and RA patients and the effects of drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) on intestinal permeability. METHODS: A systematic review was conducted. Medline, Embase, and Cochrane Library databases were searched. Studies published in the last 40 years (January 1980-September 2020) with patients with SpA and/or RA assessing the intestinal permeability were selected. RESULTS: A total of 2916 articles were collected, after discarding 1125 duplicate articles, we analyzed the titles and abstracts of 1791 studies. There were 459 articles that met the inclusion criteria and whose text was read. A total of 23 studies were included in the final analysis. Sample sizes ranged from 6 to 206 participants. In patients with spondyloarthritis, a large majority of studies reported an increase in intestinal permeability regardless of the method used. No increase in intestinal permeability was found in RA patients compared to healthy subject in half of the studies. NSAID treatment does not appear to influence intestinal permeability in SpA and seems to increase the intestinal permeability in RA patients as much as in healthy subjects. CONCLUSION: The results of our review suggest the existence of increased intestinal permeability in SpA patients even in the absence of NSAIDs use and regardless of the method assessing the intestinal permeability. Studies in RA patients are more controversial.