Performance of a diagnostic score for gouty arthritis: results from a cohort of acute arthritis suspected of being septic.

Septic arthritis (SA) and gout are the main suspected etiologies of acute monoarthritis. Differentiating them is essential because SA is an emergency. The performance of a gout diagnostic score developed by Janssens et al. was investigated in a cohort of patients with acute arthritis suspected of being septic. This was an ancillary study of a single-center cohort of patients with suspected SA. Patients were classified into three groups according to the final diagnosis (gout, SA or other diagnosis). We assessed the performance of the score (sensitivity [Se], specificity [Sp], positive and negative predictive value [PPV, NPV], area under the receiver operating characteristic [ROC] curve) for the diagnosis of gouty arthritis. In total, 138 patients were included: 28 (20.3%) had gout, 42 (30.4%) SA, and 68 (49.3%) another diagnosis. The median diagnostic score was 7.0 [4.5; 8.8] for patients with gout, 3.5 [2.5; 6.0] for those with SA and 3.0 [2.0-5.0] for those with another diagnosis. With a score threshold of ≥ 8, the Se for a diagnosis of gout was 28.6%, Sp 96.4%, PPV 66.7%, and NPV 84.1%. With a threshold of ≤ 4, the Se was 82.1%, Sp 64.5%, PPV 37.1%, and NPV 93.4%. The area under the ROC for the diagnostic score was 0.79. The performance of the clinico-biological score of Janssens et al. for a diagnosis of gout applied to a cohort of patients with acute arthritis and suspected of being septic was poor. Joint aspiration remains necessary to differentiate SA from another etiology.

Comparison of the cardiovascular risk profile of rheumatoid arthritis versus hand osteoarthritis patients.

It is clear that there is an increased cardiovascular (CV) risk in rheumatoid arthritis (RA) as a result of systemic inflammation. Hand osteoarthritis (HOA) patients, also have an increased CV risk, but the causes are still debated. Our objective was to compare CV risk factors and risk scores between HOA and RA patients. Thirty-five HOA patients were matched by age (< 3 years) and sex to 35 RA patients in a case-control study. We compared their CV risk profiles and their risk of occurrence of CV events at 10 years using the risk equations SCORE1, SCORE2, and QRISK3. There was a significant increase in SCORE1, SCORE2, but not in QRISK3 in the RA group compared to the HOA group, provided that the multiplication coefficient for RA was applied. This increase was found to no longer be significant for SCORE1 when RA patients have low disease activity (DAS28 ≤ 3.2; n = 8). There was no difference between groups in the frequency of metabolic syndrome, blood pressure, abdominal circumference, body mass index, uricemia, triglyceridemia, HDL cholesterolemia, or pain intensity. Conversely, HOA patients had higher LDL cholesterol and fasting blood glucose levels, in the main analysis and in the subgroup of moderate/high RA activity patients (DAS28 > 3.2; n = 26). We found a higher CV risk in RA compared to HOA patients with moderate/high disease activity. The increased CV risk reported in OA remains to be confirmed in HOA, but these patients appear to have a pro-atherogenic lipid and glycemic profile.

Pregnancy and neonatal outcomes in women with axial spondyloarthritis: pooled data analysis from the European Network of Pregnancy Registries in Rheumatology (EuNeP).

OBJECTIVE: To investigate outcome and course of pregnancies in women with axial spondyloarthritis (axSpA) in a pooled data analysis of pregnancy registries in rheumatology. METHODS: Prospectively followed women with axSpA, fulfilling ASAS classification criteria and for whom a pregnancy outcome was reported, were eligible for the analysis. Anonymised data of four registries was pooled. Rates of adverse pregnancy outcomes were calculated. Systemic inflammation, disease activity and treatment patterns with tumour necrosis factor inhibitor (TNFi) before, during and after pregnancy were analysed. RESULTS: In a total of 332 pregnancies from 304 axSpA women, 98.8% of the pregnancies resulted in live birth. Mean maternal age was 31 years and disease duration 5 years. Most of these patients received pre-conception counselling (78.4%). Before pregnancy, 53% received TNFi treatment, 27.5% in first and 21.4% in third trimester. Pregnancy and neonatal outcomes were favourable with rates of 2.2% for pre-eclampsia, 4.9% for preterm birth, 3.1% for low birth weight and 9.5% for small for gestational age. Neonates were delivered by caesarean section in 27.7% of pregnancies, of which 47.4% were emergencies. Pooled mean CRP was 4 mg/L before conception peaking in the second trimester at 9.4 mg/L. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was below 4 at all time-points. CONCLUSIONS: Pooled rates of most outcomes were better than what had been reported in the literature and within expected rates of those reported for the general population. Pre-conception counselling, planned pregnancies and a tight management in expert centres applying a tailored treatment approach may have contributed to the favourable pregnancy outcomes.

Management and outcome of native joint septic arthritis: a nationwide survey in French rheumatology departments, 2016-2017.

OBJECTIVES: To describe current management and outcome of native joint septic arthritis (NJSA) in French rheumatology departments. METHODS: For this retrospective, nationwide multicentric study, 127 French rheumatology departments were contacted to report up to 12 cases of NJSA that occurred between 1 January 2016 and 31 December 2017. Characteristics, diagnosis procedures, therapeutic management and outcome were recorded. RESULTS: Overall, 362 patients were included (mean age 64.0±18.6 years, median Charlson comorbidity index 3.5 (0-14)). Knee was the most frequent site (n=160 (38.9%)), and Staphylococcus sp (n=185 (51.4%)), the most frequent pathogen. All patients received antibiotics for a mean duration of 46.8 (±22.0) days, including intravenous route for a mean of 17.2 (±15.4) days. Management was heterogeneous. Surgical procedure was performed in 171 (48.3%), joint immobilisation in 128 (43.8%). During follow-up, 91 (28.3%) patients have had serious complications and 28 (9.2%) of them died. Factors associated with 1-year mortality were age (OR 1.08, 95% CI 1.04 to 1.13; p<0.001), Charlson's index (OR 1.30, 95% CI 1.06 to 1.58; p=0.012), presence of bacteraemia (OR 4.02, 95% CI 1.35 to 11.99; p=0.008), antibiotic use in the previous 3 months (OR 3.32, 95% CI 1.11 to 9.87; p=0.029) and Staphylococcus aureus NJSA compared with Streptococcus sp. NJSA (OR 7.24, 95% CI 1.26 to 41.68, p=0.027). The complete recovery with no adverse joint outcome at 1 year was observed in n=125/278 patients (55.0%). CONCLUSION: Prognosis of NJSA remained severe with a high rate of morbimortality. Its management was very heterogeneous. This study highlights the importance of the new French recommendations, published after the completion of the study, in order to facilitate NJSA management.

Concomitant fibromyalgia in primary Sjögren's syndrome in the French ASSESS cohort: comparison of the ACR 1990 and ACR 2016 criteria, FiRST questionnaire and physician's opinion.

OBJECTIVES: Dryness, fatigue, and pain are classic symptoms in primary Sjögren's syndrome (pSS) but are also common in fibromyalgia (FM). We compared the characteristics of FM assessed by different criteria (American College of Rheumatology (ACR) 2016 and 1990 criteria), physician's opinion and Fibromyalgia Rapid Screening Tool (FiRST) questionnaire) in a cohort of patients with pSS. METHODS: Eight hospital departments tested 134 patients with pSS according to AECG criteria from the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort. RESUKLTS: FM was present in 19%, 18%, 20%, and 29% of cases according to ACR 2016, ACR 1990 criteria, physician's opinion and the FiRST questionnaire, respectively. FM criteria-positive patients had higher EULAR SS Patient-Reported Index (ESSPRI) score, but not higher EULAR SS Disease Activity Index (ESSDAI) score. The objective measurements of dryness and the use of corticosteroids and immunosuppressive drugs did not differ between FM positive and negative patients. Regarding the ESSPRI dryness and fatigue subscale scores, depression and anxiety scores and the use of anxiolytics and antidepressants, the FiRST questionnaire exhibited a higher difference between positive and negative patients than ACR 2016 criteria. ACR 1990 and physician's opinion were somewhere in the middle. ACR 2016 exhibited moderate agreement with ACR 1990 (κ=0.52) and the physician's opinion (κ=0.60) and poor agreement with FiRST (κ=0.39). CONCLUSIONS: The FM criteria identified pSS patients with higher ESSPRI scores but not higher ESSDAI systemic disease scores. Agreement between the different FM criteria was moderate, and the characteristics they described did not fully coincide.

ACPA-positive versus ACPA-negative rheumatoid arthritis: two distinct erosive disease entities on radiography and ultrasonography.

The objective of this study is to assess the prevalence, localization, and severity of bone erosions on radiography (RX) and ultrasonography (US) according to ACPA status in patients with rheumatoid arthritis (RA). 78 patients with ACPA-positive (ACPA+) RA and 30 patients with ACPA-negative (ACPA-) RA fulfilling the ACR 1987 and/or ACR/EULAR 2010 criteria were consecutively included. On RX, a modified Sharp erosion score (SHSe) was evaluated by two blinded readers and one adjudicator for discordant cases (number of eroded joints ≤ three). On US, erosions were scored on six bilateral joints (MCP2, 3, 5; MTP2, 3, 5) with a four-point scale to calculate the total US score for erosions (USSe). The mean total SHSe and USSe were 3.7 and 4.4 times higher in the ACPA+ group than in the ACPA- group, respectively (P < 0.001). On both RX and US, the most discriminating joint between the two groups was MTP5, especially in cases with bilateral erosion. Based on multivariate analyses, ACPA + status was associated with erosive RA on RX according to the EULAR 2013 definition criteria [OR 4.4 (95% CI 1.2-16.4)], and on US according to the following two definitions: the presence of at least two eroded joint facets [OR 3.7 (95% CI 1.4-9.9)] or at least one grade 2 joint facet erosion [OR 9.0 (95% CI 2.8-28.4)]. Compared to ACPA- RA, ACPA + RA is associated independently with more severe erosive disease on RX and US. Both US and RX bilateral erosions in MTP5 joints are highly discriminant for ACPA + RA patients (97.8% in US and 100% in RX).

Characteristics of spontaneous coagulase-negative staphylococcal spondylodiscitis: a retrospective comparative study versus Staphylococcus aureus spondylodiscitis.

BACKGROUND: Coagulase-negative staphylococci (CoNS) are increasingly implicated in recent patient series of spondylodiscitis, but there are no series of CoNS-spondylodiscitis available. The objective of this study was to compare the characteristics of patients with spontaneous CoNS-spondylodiscitis with those patients with Staphylococcus aureus (SA) spondylodiscitis. METHODS: This was a retrospective single center study involving 147 spontaneous infectious spondylodiscitis cases observed between 2000 and 2015. The 26 cases of CoNS-spondylodiscitis (15 confirmed) were compared with 30 cases of SA-spondylodiscitis. CoNS infection was considered confirmed if the same CoNS was isolated in at least two samples at two different times. RESULT: Patients with CoNS-spondylodiscitis were older (70 vs. 61 years of age; p = 0.01), had associated cancer more often (15% vs. 0%; p = 0.04) and had a longer diagnostic delay (>15 days in 88% vs. 60%; p = 0.01); experienced fever less often (19% vs. 50%; p = 0.01), and had lower white blood cell (7.6 vs. 9.9G/L; p = 0.01) and polymorphonuclear leucocyte counts (5.6 vs. 7.5G/L; p = 0.04). Patients with CoNS spondylodiscitis had less pronounced inflammatory syndrome (erythrocyte sedimentation rate [ESR]: 62 vs. 81 mm at 1 h; p = 0.03; CRP: 60 vs. 147 mg/L; p = 0.0003) and less common (ESR < 30 mm: 23% vs. 0%; p = 0.01; CRP < 10 mg/L: 23% vs. 0%; p = 0.005) in comparison with patients with SA infection. The infection entry site was most often an intravascular catheter (20% vs. 3%; p = 0.008). The level of positive percutaneous needle biopsies was comparable between CoNS and SA. Two patients who died both had SA infections. CONCLUSION: CoNS-spondylodiscitis involved at least 10% of spontaneous spondylodiscitis cases and was more common in elderly patients, afflicted by comorbidities, and its presentation was less virulent than that of those with SA-spondylodiscitis.

Does rheumatoid synovitis activity vary during the day? Evaluation with color doppler sonography.

BACKGROUND: Clinical symptoms of rheumatoid arthritis (RA) improve in the course of the day, as can synovitis activity, reported via doppler ultrasound (US). The aim of the study was to establish whether the Color Doppler (CD) scores of synovitis in RA changes throughout the day. METHODS: In total, 27 patients with active RA, including 14 patients receiving corticosteroids were studied. US evaluation was performed twice in each patient, at 9 a.m. (T0) and after 4 p.m. (T1) on the same day by a single radiologist and using the same instrument. Overall, 30 joints were assessed, including grey scale and CD (S0 = no flow [no detectable CD)]; S1 = mild [CD <1/3 of the synovium]; S2 = moderate [CD <2/3]; S3 = pronounced [CD >2/3]). RESULTS: In the total population, synovitis was detected more often in the evening than in the morning (39% vs. 33%, p = 0.02). The difference remained significant only in patients without corticosteroid administration (44% vs. 37%, p = 0.04). Moreover, a greater number of CD-positive joints were likewise found (S0 vs. S1 + S2 + S3) in the evening (57% vs. 51%, p = 0.04) in patients not receiving corticosteroids (67% vs. 41%, p = 0.002). More moderate (S2) and pronounced (S3) than mild (S1) synovitis was observed at T1 vs. T0 (39% vs. 24%, p = 0.03) in patients not receiving corticosteroids. More synovitis (40% vs 36% p = 0.02) in the dominant hand were found in the evening than in the morning. CONCLUSION: Synovitis and CD activity increase during the day in RA patients, especially in joints of the dominant hands and in patients without corticosteroids.

Performance of Fibromyalgia Rapid Screening Tool (FiRST) to detect fibromyalgia syndrome in rheumatic diseases.

OBJECTIVE: To evaluate the performance of the Fibromyalgia Rapid Screening Tool (FiRST) self-questionnaire for the detection of FM associated with inflammatory rheumatic diseases. METHODS: This cross-sectional, French single-centre study was carried out between September 2014 and April 2015 in all patients who consulted for RA, SpA or CTD. Diagnosis of FM was based on ACR 90 criteria and rheumatologist opinion. RESULTS: The self-questionnaire was completed by 605 patients (279 RA, 271 SpA, 57 CTD). It detected 143 concomitant FMs (24.4%). When assessed against ACR 90 criteria, FiRST had a sensitivity of 74.5%, a specificity of 80.4%, a positive predictive value of 26.6% and a negative predictive value (NPV) of 97.1%. Specificity was lower in the CTD group (RA: 84.4%, SpA: 80.2%, CTD: 59.6%) (P = 0.001). When assessed against the rheumatologist's opinion, FiRST had a sensitivity of 75.8%, a specificity of 85.1%, a positive predictive value of 48.3% and an NPV of 95%. Sensitivity was lower in the SpA group than in the CTD group (66% vs 94.4%) (P = 0.004). Performance varied according to self-questionnaire items. CONCLUSION: Although it performs less well in inflammatory rheumatic disease, FiRST's opinion is close to that of the rheumatologist. It can be used by the rheumatologist in clinical practice for patients facing an apparent treatment failure and to rule out a potential FM diagnosis which could interfere with the treatment response.

Psoriatic arthritis treated by anti-TNFs: a monocentric trial of 102 cases in Auvergne, France.

OBJECTIVES: While several registries have already evaluated the retention of anti-TNF therapy in psoriatic arthritis (PsA), they sometimes reach divergent conclusions. Our study therefore sought to assess therapeutic retention rates and predictive factors of response in a patient cohort from Auvergne, France, followed up in routine clinical practice. METHODS: Medical records of all PsA patients treated from 2002 to May 2015 were analysed. PsA diagnosis was established based on the CASPAR criteria. RESULTS: In total, 102 patients were analysed, comprising 62 men (44.6±12.6 years) and 40 women (37.8±13.4). Mean PsA evolution was 2.7 years (0.8-11.2). The most common forms were peripheral (47/102, 45.1%) and mixed (46/102, 46.1%) PsA. The anti-TNF treatment initiated was etanercept in 47 cases (45.2%), adalimumab in 29 (27.9%), infliximab in 20 (19.2%), and golimumab in six [5.8%]. In 28 cases (27.4%), anti-TNF was associated with methotrexate (MTX). Overall, the median duration of anti-TNF retention was 76.5 months. The hazard ratios (HR) for treatment cessation did not significantly differ between the etanercept and monoclonal antibody groups (HR=1.35[0.96-1.93], p=0.08). After 5 years, approximately 30.8% of etanercept patients and 68.8% of monoclonal antibody patients (adalimumab 71.2%; infliximab 67.2%) were still being treated. Combining with MTX did not prolong the overall retention rate (HR=0.85[0.37-1.96], p=0.71). Tobacco use was predictive of discontinuation (p=0.03). CONCLUSIONS: Our study demonstrates good anti-TNF treatment retention in PsA patients, as well as confirming the deleterious effect of smoking while providing no argument in favour of combined treatment with MTX to improve maintenance.

Influence of gender on response to rituximab in patients with rheumatoid arthritis: results from the Autoimmunity and Rituximab registry.

OBJECTIVE: The response rate to many therapies for RA is lower in women. The aim of this study was to analyse the influence of gender on the response to rituximab (RTX) in patients with RA. METHODS: A total of 1709 RA patients were included in the French Autoimmunity and Rituximab (AIR) registry. Disease activity assessed by the 28-joint DAS (DAS28) was recorded at baseline and at follow-up (6, 12, 18 and 24 months). Response criteria [European League Against Rheumatism (EULAR) remission defined as a DAS28 < 2.6 and EULAR response] were compared in both sexes. RESULTS: Seventy-seven per cent of the patients were female (age 61.4 years, disease duration 16 years). Approximately 78.6% of the patients were positive for RF and 75.8% for anti-CCP. Women had a longer disease duration (P < 0.001), less frequently had anti-CCP (P = 0.03) and had lower CRP levels at baseline (P < 0.001). Six months after RTX, 11% were in remission and 62% had a good to moderate EULAR response, irrespective of gender (P = 0.81 and P = 0.38, respectively). No differences were observed in terms of remission or EULAR response during the follow-up except at 12 months, when men achieved remission more frequently (18% vs 12%, P = 0.045). In the cases of anti-TNF failure, remission rates were higher in men than in women at 6, 12 and 18 months. Re-treatment delay between the first and second courses was similar in both genders (P = 0.26). CONCLUSION: In this large cohort of RA patients we found no significant differences in EULAR response to RTX between men and women during the 2-years of follow-up, but there was a previous anti-TNF exposure-dependent effect of gender on remission rate.

Treatment modalities of marginal zone lymphoma and overall survival, haematological response, and underlying Sjögren's disease activity: a multicentre, retrospective, observational study.

BACKGROUND: Sjögren's disease is the autoimmune disease with the highest risk of lymphoma development. There is no consensus on the optimal way to manage Sjögren's disease complicated by lymphoma. We aimed to describe characteristics, therapeutic strategies, and outcomes of non-Hodgkin lymphoma associated with Sjögren's disease, and their effect on lymphoma and Sjögren's disease prognoses. METHODS: We did a multicentre, retrospective, observational study including patients with Sjögren's disease according to the 2016 American College of Rheumatology-European League Against Rheumatism criteria who did not fulfil diagnostic criteria for other connective tissue diseases. We included patients with a lymphoma diagnosis made before Jan 1, 2020, from two expert centres in Paris (France); from the French, multicentre, prospective Assessment of Systemic Signs and Evolution of Sjögren's Syndrome cohort; and via practitioners registered with the Club Rhumatismes et Inflammation. Using inverse probability of treatment weighting, the effect of lymphoma treatment was compared in relation to three endpoints: lymphoma progression-free survival, new Sjögren's disease systemic activity, and overall survival. Exploratory analyses also aimed to identify factors associated with lymphoma relapse, new Sjögren's disease systemic activity, and overall survival. People with lived experience were not involved in this research. FINDINGS: 106 patients with Sjögren's disease who developed lymphoma were included in the study. The most frequent histological subtype was mucosa-associated lymphoid tissue lymphoma (68 [64%] of 106 patients), followed by other marginal zone subtypes (14 [13%] of 106 patients) and diffuse large B-cell lymphoma (14 [13%] of 106 patients). Among the 82 patients with marginal zone lymphoma (72 [88%] women and ten (12%) men; mean age at lymphoma diagnosis 57·5 years [SD 14·8]), multivariable analysis showed that pulmonary localisation was associated with mortality (hazard ratio [HR] 7·92 [95% CI 1·70-37·0]). A watch and wait approach was proposed in 19 (23%) of 82 patients with marginal zone lymphoma, 13 (16%) had first-line localised treatment (surgery or radiotherapy), and 50 (61%) had first-line systemic treatment. After a median follow-up of 7 years, 26 patients (32%) had lymphoma relapse, nine (11%) died, and 27 (33%) had new Sjögren's disease systemic activity. After inverse probability of treatment weighting, patients with systemic treatment at lymphoma diagnosis had a reduced risk of new Sjögren's disease activity (HR 0·43 [95% CI 0·21-0·90]). When comparing patients treated with a combination of chemotherapy and anti-CD20 therapy (n=32) with patients treated with monotherapy (n=18) as a first-line therapy for lymphoma, lymphoma-progression-free survival was improved in patients treated with combination therapy (HR 0·36 [95% CI 0·14-0·94]). The were no differences in new Sjögren's disease systemic activity or overall survival according to combination therapy or monotherapy. INTERPRETATION: A systemic treatment strategy for Sjögren's disease-associated lymphoma, rather than localised treatment or a watch and wait strategy, reduces the risk of new Sjögren's disease systemic activity and combination therapy is associated with decreased risk of lymphoma relapse. FUNDING: None.

2023 French recommendations for diagnosing and managing prepatellar and olecranon septic bursitis.

Septic bursitis (SB) is a common condition accounting for one third of all cases of inflammatory bursitis. It is often related to professional activities. Management is heterogeneous and either ambulatory or hospital-based, with no recommendations available. This article presents recommendations for managing patients with septic bursitis gathered by 18 rheumatologists from the French Society for Rheumatology work group on bone and joint infections, 1 infectious diseases specialist, 2 orthopedic surgeons, 1 general practitioner and 1 emergency physician. This group used a literature review and expert opinions to establish 3 general principles and 11 recommendations for managing olecranon and prepatellar SB. The French Health authority (Haute Autorité de santé [HAS]) methodology was used for these recommendations. Designed for rheumatologists, general practitioners, emergency physicians and orthopedic surgeons, they focus on the use of biological tests and imaging in both outpatient and inpatient management. Antibiotic treatment options (drugs and duration) are proposed for both treatment modalities. Finally, surgical indications, non-drug treatments and prevention are covered by specific recommendations.

Identification of distinct subgroups of Sjögren's disease by cluster analysis based on clinical and biological manifestations: data from the cross-sectional Paris-Saclay and the prospective ASSESS cohorts.

BACKGROUND: Sjögren's disease is a heterogenous autoimmune disease with a wide range of symptoms-including dryness, fatigue, and pain-in addition to systemic manifestations and an increased risk of lymphoma. We aimed to identify distinct subgroups of the disease, using cluster analysis based on subjective symptoms and clinical and biological manifestations, and to compare the prognoses of patients in these subgroups. METHODS: This study included patients with Sjögren's disease from two independent cohorts in France: the cross-sectional Paris-Saclay cohort and the prospective Assessment of Systemic Signs and Evolution of Sjögren's Syndrome (ASSESS) cohort. We first used an unsupervised multiple correspondence analysis to identify clusters within the Paris-Saclay cohort using 26 variables comprising patient-reported symptoms and clinical and biological manifestations. Next, we validated these clusters using patients from the ASSESS cohort. Changes in disease activity (measured by the European Alliance of Associations for Rheumatology [EULAR] Sjögren's Syndrome Disease Activity Index [ESSDAI]), patient-acceptable symptom state (measured by the EULAR Sjögren's Syndrome Patient Reported Index [ESSPRI]), and lymphoma incidence during follow-up were compared between clusters. Finally, we compared our clusters with the symptom-based subgroups previously described by Tarn and colleagues. FINDINGS: 534 patients from the Paris-Saclay cohort (502 [94%] women, 32 [6%] men, median age 54 years [IQR 43-64]), recruited between 1999 and 2022, and 395 patients from the ASSESS cohort (370 [94%] women, 25 [6%] men, median age 53 years [43-63]), recruited between 2006 and 2009, were included in this study. In both cohorts, hierarchical cluster analysis revealed three distinct subgroups of patients: those with B-cell active disease and low symptom burden (BALS), those with high systemic disease activity (HSA), and those with low systemic disease activity and high symptom burden (LSAHS). During follow-up in the ASSESS cohort, disease activity and symptom states worsened for patients in the BALS cluster (67 [36%] of 186 patients with ESSPRI score <5 at month 60 vs 92 [49%] of 186 at inclusion; p<0·0001). Lymphomas occurred in patients in the BALS cluster (five [3%] of 186 patients; diagnosed a median of 70 months [IQR 42-104] after inclusion) and the HSA cluster (six [4%] of 158 patients; diagnosed 23 months [13-83] after inclusion). All patients from the Paris-Saclay cohort with a history of lymphoma were in the BALS and HSA clusters. This unsupervised clustering classification based on symptoms and clinical and biological manifestations did not correlate with a previous classification based on symptoms only. INTERPRETATION: On the basis of symptoms and clinical and biological manifestations, we identified three distinct subgroups of patients with Sjögren's disease with different prognoses. Our results suggest that these subgroups represent different heterogeneous pathophysiological disease mechanisms, stages of disease, or both. These findings could be of interest when stratifying patients in future therapeutic trials. FUNDING: Fondation pour la Recherche Médicale, French Ministry of Health, French Society of Rheumatology, Innovative Medicines Initiative 2 Joint Undertaking, Medical Research Council UK, and Foundation for Research in Rheumatology.