Potential efficacy of T and B lymphocyte-targeted therapies on articular involvement of patients with rheumatoid arthritis and systemic sclerosis overlap syndrome. Results from a 2-centre series of 19 cases.

OBJECTIVES: To analyse in routine practice the efficacy of targeted therapies on joint involvement of patients with rheumatoid arthritis/systemic sclerosis (RA/SSc) overlap syndrome. METHODS: This was a retrospective analysis of medical records of two academic centres over a 10-year period. Joint response to targeted therapies was measured according to EULAR criteria based on Disease Activity Score (DAS)-28. In addition, changes in CRP level and glucocorticoid consumption were recorded. RESULTS: Nineteen patients were included. Methotrexate (n=11) and hydroxychloroquine (n=4) were the most used first-line treatments. Targeted therapies were frequently used (n=14). Tocilizumab was the most selected therapy (n=8), then rituximab (n=5), abatacept and anti-tumour necrosis factor (n=4). Twenty-one treatment sequences were assessed, including 18 with EULAR response criteria. Responses were "good" or "moderate" in 100% (4/4) of patients treated with abatacept, 80% (4/5) with rituximab, 40% (2/5) with tocilizumab, and 25% (1/4) with anti-TNF. T and B lymphocyte-targeted therapies (abatacept, rituximab) resulted more frequently in a "good" or "moderate" response compared to cytokine inhibitors (tocilizumab, etanercept, infliximab) with a significant decrease in DAS-28 at 6 months (-1.75; p=0.016) and a trend to a lower consumption of glucocorticoids. CONCLUSIONS: In patients with RA/SSc overlap syndrome refractory to conventional synthetic-DMARDs, T and B lymphocyte-targeted therapies seem to be a promising therapeutic option to control joint activity.

Evaluation of the nocebo effect after switching from etanercept or adalimumab originator to a biosimilar: a retrospective study of patients with inflammatory rheumatism.

OBJECTIVES: Despite significant savings with biosimilars, their negative perception can lead to the occurrence of a nocebo effect (NE), therefore we aimed to quantify the NE in inflammatory rheumatism after switching from adalimumab or etanercept originators to biosimilars. METHODS: This retrospective study was conducted in 4 hospitals in Normandy, France between January 2018 and July 2022. The study included patients with rheumatoid arthritis or spondyloarthritis in remission under adalimumab or etanercept originators before switching to biosimilars. The occurrence of a NE was considered in patients who did not maintain biosimilars at 12 months and who presented a subjective adverse event (AE). A comparative analysis of the quantitative data collected before and after switching was performed. The AE that led to biosimilar discontinuation was identified. Additional analyses were performed to identify potential risk factors for the occurrence of a NE. RESULTS: Among 183 patients included,13.1% presented a NE. Objective AEs were observed, including rheumatism reactivation (15.3%), intolerance (8.2%), infection (1.6%) and allergic reactions (0.5%). Morning stiffness duration was significantly different before and after the switch in the spondyloarthritis group (p=0.01). No risk factors were associated with the occurrence of a NE within the limits of the studied parameters. CONCLUSIONS: The occurrence of a NE after switching to a biosimilar remains acceptable. It appears less frequent when the switch is supervised by the practitioner rather than being systematic (up to 33% in some countries). A shared medical decision seems to be essential in a subset of patients, which remains to be defined.

Clinical and ultrasonographic evaluation of the window of opportunity for retreatment with rituximab in rheumatoid arthritis patients from a multicentre real-life study.

OBJECTIVES: To determine a potential window of opportunity for retreatment with rituximab in patients with rheumatoid arthritis (RA) from a multicentre longitudinal real-life study based on tight monitoring with ultrasonography (US). METHODS: Thirty RA patients treated with rituximab were included. US parameters were collected at each time (8 visits) of the 18-month follow-up, notably the global score of power Doppler (PD) activity. Clinical relapse was defined as a DAS28 ESR of >3.2 after 6 months in responders while US relapse was defined as an increase of ≥20% of the global score of PD activity. The decision of retreatment was based exclusively on clinical findings. RESULTS: A total of 29 patients were analysed (mean (SD) age: 57.2 (12.2) years; female gender: 66%). The mean (SD) PD score decreased from 8.8 (5.2) at baseline to 4.9 (4.3) at 6 months (p <0.0001). A clinical response was observed at Month 4 or Month 6 for 93% of patients. A total of 19 patients had a first clinical relapse (with or without US relapse) after Month 6 (18 of them were retreated with rituximab). Among 10 patients without clinical relapse, 3 had US relapse (only one was retreated) and 7 had no US relapse (but 4 were retreated). CONCLUSIONS: This study highlights a great heterogeneity in terms of sequence of clinical relapse, US relapse and retreatment in RA patients receiving rituximab. Therefore, US monitoring does not seem to be relevant to determine the best time for retreatment with rituximab.

AA amyloidosis complicating cryopyrin-associated periodic syndrome: a study of 86 cases including 23 French patients and systematic review.

OBJECTIVE: Cryopyrin-associated periodic syndrome (CAPS) is a rare but treatable inherited autoinflammatory condition including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurologic cutaneous articular syndrome (CINCA). Our objective was to describe the main features of CAPS AA amyloidosis (AA-CAPS) associated and the efficacy of IL-1 inhibitors in this indication. METHODS: Retrospective study in France associated with a systematic literature review. RESULTS: Eighty-six patients were identified: 23 new French cases and 63 from the literature, with a median age at amyloidosis diagnosis of 39 years old. CAPS subtypes were MWS (n = 62), FCAS (n = 9), frontier forms between MWS and FCAS (n = 12) and between CINCA and MWS (n = 3). NLRP3 had been sequenced in 60 patients (70%) and the most frequent mutation was R260W (60%). Three AA-CAPS patients displayed somatic NLRP3 mutations. Death occurred in 35 patients (41%), none of whom having ever received IL-1 inhibitors. Twenty-eight patients (33%) received IL-1 inhibitors, with a >50% decrease in proteinuria in 89% of cases. CONCLUSION: AA amyloidosis can occur in nearly all CAPS subtypes. IL-1 inhibitors are effective, underlining the necessity of an early diagnosis of CAPS in order to start this treatment as soon as possible among AA-CAPS patients.

Potential Benefit of Rituximab in Rhupus Patients From a Single-Center: A Series of 16 Cases.

BACKGROUND: Rhupus syndrome is better characterized, but uncertainties remain, and therapeutic management must be defined. The objective was to analyze therapeutic procedures with a focus on biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: This 10-year medical records review was based on diagnosis codes (rheumatoid arthritis [RA] and systemic lupus erythematosus [SLE]) and biological data (anti-CCP testing, anti-dsDNA, and anti-RNP antibodies). Patients fulfilling 2010 ACR/EULAR and 2012 SLICC and/or 2019 ACR/EULAR classification criteria for RA and SLE, respectively, were included. RESULTS: Sixteen patients were identified. Rheumatoid arthritis most often preceded rhupus, with predominant articular pattern; 11 of them had erosive arthropathy. Skin involvement was the most frequent associated manifestation (n = 12). Serious events were reported, including active glomerulonephritis (n = 3), ischemic stroke (n = 1), and myocardial infarction (n = 1). Immunological profiles showed positivity for antinuclear (n = 16), anti-dsDNA (n = 9), and anti-CCP (n = 9). Ten patients required bDMARDs. All types of RA-approved bDMARDs were used. Abatacept was considered effective in 3 of the 4 patients, with 1 primary failure, 1 secondary escape, and 2 therapeutic maintenances, whereas primary or secondary failure was observed under tocilizimub and TNF-blocking agents. Rituximab was the most prescribed (n = 9) and the most effective with a sustained response in 6 patients. CONCLUSIONS: In rhupus refractory to conventional treatment, T or B lymphocytes targeted therapies, and particularly rituximab, seem to be a relevant therapeutic option unlike anticytokine biologics.

Microbiological diagnosis of suspected vertebral osteomyelitis with a focus on the yield of percutaneous needle biopsy: a 10-year cohort study.

This study aims to evaluate in patients hospitalized for vertebral osteomyelitis (VO) the effectiveness of bacteriological diagnosis and the yield of percutaneous needle biopsy (PNB) and to identify factors associated with the result of PNB. This retrospective, two-centre study was conducted between 2000 and 2009. Data on patients with VO were retrieved from the diagnosis database and confirmed by checking medical records. A total of 300 patients with VO were identified; 31 received antibiotics without bacteriological diagnosis, and 269 patients with spondylodiscitis imaging were included. Eighty-three (30.9%) and 18 (6.7%) infections were documented by blood cultures and by bacteriological samples other than PNB, respectively; 168 patients with no bacteriological diagnosis had PNB. Of these, 92 (54.8%) were positive and identified the pathogen and 76 (45.2%) were negative. The most common bacteria were Staphylococcus aureus (34.3%), Streptococcus spp. (20.6%) and coagulase-negative staphylococcus (14.8%). After multivariate analysis, the only factor associated with negative PNB was previous antibiotic intake (OR: 2.31 [1.07-5.00]). When VO was suspected on imaging, bacteriological investigation identified the microorganism in 209/300 (70%) of the cases. The yield of PNB was 54.8%. The only predictor of PNB negativity was previous antibiotic intake. Therefore, we believe that a second PNB should be done after a sufficient delay withdrawal of antibiotics if the first sample was negative. The study was retrospectively registered by the local ethics committee (N°E2019-61).

Implication of IL-17 in Bone Loss and Structural Damage in Inflammatory Rheumatic Diseases.

Proinflammatory cytokines play an important role in the systemic and focal bone loss associated with chronic inflammatory diseases. Targeting these cytokines with biologics and small molecules has led to a major improvement of the bone health of patients with inflammatory arthritis. Cytokines from the IL-17 family have been shown to be involved in the pathogenesis of several diseases such as spondyloarthritis, psoriatic arthritis, or psoriasis. IL-17A has been the first described and the most studied. The recent development of targeted therapies against IL-17A or its receptor and their efficacy has confirmed the importance of this cytokine in the development of inflammatory diseases. The aim of this review was to describe the effects of the IL-17 family and more particularly of IL-17A on bone and cartilage tissues. At the cellular level, IL-17A is proosteoclastogenic whereas its effects on osteoblasts depend on the stage of differentiation of these cells. In vivo, IL-17A is not required for normal bone homeostasis but plays an important role in bone loss notably in an ovariectomized mouse model of osteoporosis. Preliminary data from clinical trials showed a stabilisation of bone density in patients treated with anti-IL-17A antibodies. IL-17A plays a central role in the cartilage damage through the induction of collagenases and by decreasing the expression of their inhibitors in synergy with the other proinflammatory cytokines. The prevention of structural damage by anti-IL-17A therapies has been demonstrated in several pivotal clinical trials. Overall, blocking the IL-17A pathway seems to have a positive effect on the bone and cartilage damage observed in inflammatory arthritis. Differences and specificity of these effects compared to those already described with other biologics such as anti-TNF therapies remain to be explored.

Variations in the metabolome in response to disease activity of rheumatoid arthritis.

BACKGROUND: Anti-Tumor Necrosis Factor (TNF) therapies are able to control rheumatoid arthritis (RA) disease activity and limit structural damage. Yet no predictive factor of response to anti-TNF has been identified. Metabolomic profile is known to vary in response to different inflammatory rheumatisms so determining it could substantially improve diagnosis and, consequently, prognosis. The aim of this study was to use mass spectrometry to determine whether there is variation in the metabolome in patients treated with anti-TNF and whether any particular metabolomic profile can serve as a predictor of therapeutic response. METHODS: Blood samples were analyzed in 140 patients with active RA before initiation of anti-TNF treatment and after 6 months of Anti-TNF treatment (100 good responders and 40 non-responders). Plasma was deproteinized, extracted and analyzed by reverse-phase chromatography-QToF mass spectrometry. Extracted and normalized ions were tested by univariate and ANOVA analysis followed by partial least-squares regression-discriminant analysis (PLS-DA). Orthogonal Signal Correction (OSC) was also used to filter data from unwanted non-related effects. Disease activity scores (DAS 28) obtained at 6 months were correlated with metabolome variation findings to identify a metabolite that is predictive of therapeutic response to anti-TNF. RESULTS: After 6 months of anti-TNF therapy, 100 patients rated as good responders and 40 patients as non-responders according to EULAR criteria. Metabolomic investigations suggested two different metabolic fingerprints splitting the good-responders group and the non-responders group, without differences in anti-TNF therapies. Univariate analysis revealed 24 significant ions in positive mode (p < 0.05) and 31 significant ions in negative mode (p < 0.05). Once intersected with PLS results, only 35 ions remained. Carbohydrate derivates emerged as strong candidate determinants of therapeutic response. CONCLUSIONS: This is the first study describing metabolic profiling in response to anti-TNF treatments using plasma samples. The study highlighted two different metabolic profiles splitting good responders from non-responders.

Seronegative polyarthritis revealing antisynthetase syndrome: a multicentre study of 40 patients.

OBJECTIVE: The aim of this study was to determine the frequency and characteristics of antisynthetase syndrome (ASS) revealed by polyarthritis. METHODS: First we conducted a retrospective single-centre study to assess the frequency of ASS patients who presented with polyarthritis without pulmonary and/or muscle symptoms. Secondly, we conducted a larger, multicentre study in order to describe the clinical characteristics of these patients. Exclusion criteria were the presence of RF, the presence of ACPA and overlap with another CTD. RESULTS: In the single-centre study, polyarthritis was the first manifestation in 12 of 45 ASS patients (27%). An additional 28 patients were collected for the multicentre study, resulting in a total population of 40 ASS patients who presented with polyarthritis. The mean delay from polyarthritis onset to ASS diagnosis was 27 months (s.d. 40). Pulmonary and muscle symptoms were uncommon at ASS diagnosis (40% and 32.5%, respectively) and were dramatically delayed [mean delay after polyarthritis onset of 41 months (s.d. 53) and 21 months (s.d. 14), respectively]. Mechanic's hands and cutaneous signs of DM occurred in 25% and 22.5%, respectively, with a mean delay of 10 months (s.d. 10) and 31 months (s.d. 21), respectively. When present (32%), RP was the earliest non-articular manifestation [mean delay 3 months (s.d. 23) after polyarthritis onset]. On HEp-2 cells, antinuclear and/or cytoplasmic fluorescence was found in 70% of cases, with specificity for various anti-aminoacyl tRNA synthetase (anti-ARS) antibodies. CONCLUSION: ASS may be revealed by polyarthritis. To decrease the delay in diagnosis of ASS, pulmonary and muscle symptoms and anti-ARS antibodies might usefully be searched for in seronegative polyarthritis patients, especially in those with RP.

Pharmacokinetics and concentration-effect relationship of adalimumab in rheumatoid arthritis.

AIMS: This study aimed at describing adalimumab pharmacokinetics (PK) and the concentration-effect relationship of adalimumab using pharmacokinetic-pharmacodynamic (PK-PD) modelling in patients with rheumatoid arthritis (RA). METHODS: Adalimumab PK and PK-PD data were obtained from a multicentric observational study. Adalimumab (40 mg) was administered subcutaneously every other week, and its pharmacokinetics was described using a one-compartment model. The relationship between adalimumab concentration and C-reactive protein (CRP) concentration was described using an indirect response model with inhibition of CRP input, whereas the relationship between adalimumab concentration and disease activity score in 28 joints (DAS28) was described using a direct inhibition model. Dose regimens that included a loading dose of adalimumab were simulated. RESULTS: Thirty patients treated for RA were analysed. The following pharmacokinetic and PK-PD parameters were estimated (interidividual coefficient of variation): apparent volume of distribution (Vd /F) = 10.8 l (92%); apparent clearance (CL/F) = 0.32 l day(-1) (17%); first-order absorption rate (ka ) = 0.28 day(-1) ; CRP input (kin ) = 22.0 mg l(-1) day(-1) (65%); adalimumab concentration leading to a 50% decrease in kin (C50 ) = 3.6 mg l(-1) (88%); baseline DAS28 (DAS0 ) = 5.5 mg l(-1) (11%); and adalimumab concentration leading to 50% decrease of DAS0 (IC50 ) = 11.0 mg l(-1) (71%). Simulations showed that a 160 mg loading dose should reduce the time to reach efficacy in terms of both CRP and DAS28 after the first injection. CONCLUSIONS: This is the first study to describe adalimumab pharmacokinetics and the concentration-effect relationship in RA. A 160 mg loading dose may lead to an increased benefit from treatment in RA patients.

On difficulties to define prognostic factors for clinical practice in rheumatoid arthritis.

In rheumatoid arthritis (RA), the identification of prognostic factors (PF) capable of predicting disease outcome, response to treatment or success of dose reduction is an important issue, as these factors are intended to serve as a basis for decision-making. The task is complex from the outset, as the definition of disease prognosis or therapeutic prognosis is not uniquevocal. The heterogeneity of the definitions used partly explains the failure to identify PF that can be applied at an individual level. But other factors also contribute. First, the scope of the disease studied is too broad, including nosologically different entities. Second, potential PF are only measured at a single point of time, whereas changes over a period of time should be taken into account to a greater extent, not forgetting the potential impact of the treatment received during this period. Beyond these limiting factors, one of the main obstacles to the identification of PF is probably the fact that the phase of the disease is not sufficiently taken into account. Predicting the disease outcome when it is well established is a more complex challenge than when it is just beginning, as many factors are likely to interfere. The same applies to therapeutic PF, which should be determined according to disease duration. Difficulties also arise from the approaches used, which are often restricted to a single field of interest whereas they should be much more integrative and call on new large-scale data analysis tools with a view to precision medicine.In RA, prognosis can be defined at two levels: disease outcome, including joint damage and risk of extra-articular manifestations and/or complications, and treatment outcome, including response to therapy, risk of adverse effects and drug-free remission.

Determinants associated with the prescription of a first biologic therapy in patients with axial spondyloarthritis and concomitant fibromyalgia in daily practice.

OBJECTIVES: There is no consensus on the therapeutic strategy of rheumatologists for patients with spondyloarthritis (SpA) and concomitant fibromyalgia (FM). The main aim of this study was to identify, in a population of rheumatologists practicing in Normandy, France, the determinants associated with their decision to prescribe a first biologic DMARD (bDMARD) in patients with Spa/FM. Specific objectives were to evaluate professional prescribing practices to identify a set of criteria likely to contribute to the therapeutic decision of rheumatologists, and to validate the relevance of these criteria. METHOD: This is a cross-sectional survey-based study using a mixed (qualitative and quantitative) method. The quantitative approach was web-based and conducted among rheumatologists in Normandy. RESULTS: The qualitative study allowed us to identify a set of criteria likely to contribute to the therapeutic decision of rheumatologists. In the quantitative study, 54/113 rheumatologists filled the questionnaire. Four criteria were considered by all respondents to contribute to their decision to prescribe a first bDMARD: arthritis on physical examination, extra-articular manifestations, systemic inflammation and structural damage on imaging. CONCLUSIONS: The determinants associated with the decision of rheumatologists to prescribe a first bDMARD in patients with SpA/FM were mostly objective, in line with the recommendations in the literature. Most criteria were more related to an approach aimed at ensuring the diagnosis of SpA than evaluating its activity or severity.

Diagnosis challenges in inception cohorts in axial spondyloarthritis: the case of the French national DESIR cohort.

BACKGROUND: Inception cohorts aim to describe chronic diseases from diagnosis and over years of follow-up. Axial spondyloarthritis (axSpA) diagnosis might be challenging during the first years of the disease. Thus, identifying the features that will be associated with a confirmed diagnosis over time is key. OBJECTIVES: To assess the frequency and the predisposing factors for a change of an initial diagnosis in an inception axSpA cohort. METHODS: DESIR is an ongoing national multicentre inception axSpA cohort with currently 12.5 years of follow-up. At the entry visit and confirmed at each visit, the diagnosis of axSpA was based on the opinion of the treating rheumatologist. Follow-up was interrupted in case of a change in this initial diagnosis. Multiple imputation was used to estimate the probability of a change in the initial diagnosis of axSpA for each patient lost to follow-up. Factors predisposing to an unchanged diagnosis of axSpA were then assessed using a multivariate logistic regression model on the imputed data sets. RESULTS: Of the 708 patients included, over 10 years of follow-up, 45 (6.4%) were excluded due to a diagnosis change and 300 (42.4%) patients were lost to follow-up. Based on the imputation of these 300 patients, a change in their initial axSpA diagnosis was estimated in 42 (14.0%). Factors predisposing to an unchanged initial axSpA diagnosis during follow-up were (ORs (95% CIs)): radiographic sacroiliitis: 17.0 (4.1 to 71.0); psoriasis: 5.3 (2.0 to 14.3); CRP≥6 mg/L: 2.7 (1.3 to 5.3); good NSAID response: 2.5 (1.5 to 4.2); HLA B27+: 2.0 (1.3 to 3.3); anterior chest wall pain: 2.0 (1.2 to 3.3) and female sex: 1.9 (1.2 to 3.0). CONCLUSION: These data suggest that a change in diagnosis in recent onset axSpA exists, but is not frequent, and is less likely to occur in the presence of objective features at baseline.

Impact of the Clinical Pharmacist in Rheumatology Practice: A Systematic Review.

This is a systematic literature review on the impact of pharmacists in rheumatology, conducted using the PubMed®, CINAHL®, Cochrane Library®, and Web of science® databases and using the PRISMA 2020 checklist. This review was conducted from 2000 to June 2024. A quality analysis was performed. The selection of articles, as well as all analyses, including quality analyses, were conducted by a pair of pharmacists with experience in rheumatology, and included 24 articles. This study highlights the growth of clinical pharmacy activities in rheumatology and the positive influence of clinical pharmacists on patient care. The implementation of such initiatives has the potential to improve medication adherence, reduce medication-related risks, and optimize associated healthcare costs. All these pharmaceutical interventions aim to make the patient care journey smoother and safer. Additionally, the diversity of available pharmaceutical services caters to the varied needs of rheumatology. Furthermore, outpatient clinical pharmacy is also explored in this field and garners interest from patients. The vast majority of studies demonstrate significant improvement in patient care with promising performance outcomes when pharmacists are involved. This review highlights the diverse range of interventions by clinical pharmacists in rheumatology, which is very promising. However, to better assess the benefits of clinical pharmacists, this activity needs further development and evaluation through controlled and randomized clinical research programs.

Unmet needs in axial spondyloarthritis. Proceedings of the French spondyloarthritis taskforce workshop.

The progress observed over the last 30 years in the field of axial spondyloarthritis (axSpA) has not made it possible to answer all the current questions. This manuscript represents the proceedings of the meeting of the French spondyloArthitiS Task force (FAST) in Besançon on September 28 and 29, 2023. Different points of discussion were thus individualized as unmet needs: biomarkers for early diagnosis and disease activity, a common electronic file dedicated to SpA nationwide, a better comprehension of dysbiosis in the disease, a check-list for addressing to the rheumatologist, adapt patient reported outcomes thresholds for female gender, implementation of comorbidities screening programs, new imaging tools, in research cellular and multi omics approaches, grouping, at a nationwide level, different cohorts and registries, therapeutic strategy studies, consensual definition of difficult to treat disease and management, preclinical stage of the disease, mastering AI as a tool in the various aspects of research. These elements may represent a framework for the research agenda in axSpA for the years to come.

Efficacy of rituximab in systemic manifestations of primary Sjogren's syndrome: results in 78 patients of the AutoImmune and Rituximab registry.

OBJECTIVES: To evaluate the efficacy and safety of rituximab in patients with primary Sjögren's syndrome (pSS). METHODS: The AutoImmune and Rituximab registry has included 86 patients with pSS treated with rituximab, prospectivey followed up every 6 months for 5 years. RESULTS: Seventy-eight patients with pSS (11 men, 67 women), who already had at least one follow-up visit, were analysed. Median age was 59.8 years (29-83), median duration of disease was 11.9 years (3-32). Indications for treatment were systemic involvement for 74 patients and only severe glandular involvement in four patients. The median European Sjögren's Syndrome disease activity index (ESSDAI) was 11 (2-31). 17 patients were concomitantly treated with another immunosuppressant agent. Median follow-up was 34.9 months (6-81.4) (226 patient-years). Overall efficacy according to the treating physician was observed in 47 patients (60%) after the first cycle of rituximab. Median ESSDAI decreased from 11 (2-31) to 7.5 (0-26) (p<0.0001). Median dosage of corticosteroid decreased from 17.6 mg/day (3-60) to 10.8 mg/day (p=0.1). Forty-one patients were retreated with rituximab. Four infusion reactions and one delayed serum sickness-like disease resulted in rituximab discontinuation. Three serious infections (1.3/100 patient-years) and two cancer-related deaths occurred. CONCLUSIONS: In common practice, the use of rituximab in pSS is mostly restricted to patients with systemic involvement. This prospective study shows good efficacy and tolerance of rituximab in patients with pSS and systemic involvement.

Novel insights into the anatomy and histopathology of the sacroiliac joint and correlations with imaging signs of sacroiliitis in case of axial spondyloarthritis.

For a better understanding of the pathophysiology of spondyloarthropathy (SpA), a detailed anatomical description of the sacroiliac joint is required because sacroiliitis is the earliest and most common sign of SpA and an essential feature for the diagnosis of ankylosing spondylitis. Beyond the anatomy, the histopathology of sacroiliac entheses and immunological mechanisms involved in sacroiliitis are crucial for a better understanding of disease causation. In this narrative review, we discuss the core anatomical, histological, and immunohistological observations involved in the development of sacroiliitis, focusing particularly on imaging-based information associated with sacroiliitis. Finally, we try to answer the question of whether at the sacroiliac joint, enthesitis precedes synovitis and subchondral bone changes in SpA.