High rate of progression to symptomatic multiple myeloma in patients with smoldering myeloma and isolated osteoporotic vertebral fracture.

Multiple myeloma (MM) frequently causes vertebral fractures (VF). Some are lytic lesions and others have the aspect of benign osteoporotic fractures not requiring anti-myeloma treatment. We explored outcome of these patients with smoldering myeloma (SM) and osteoporotic VF. In this retrospective bi-centric study, patients were identified using a systematic keyword search on electronic medical records. Patients with SM and isolated VF of osteoporotic aspect without indications for myeloma-specific therapy were included. Overall, 13 (7 %) of the 184 identified patients had SM and VF confirmed to be osteoporotic (median number of VF was 3). During follow-up, 12 (92 %) patients evolved to symptomatic MM, 7 (54 %) of them within 18 months (early progressors). Myeloma defining events were new lytic bone lesions in 7 patients (53.8 %). The serum calcium level was significantly higher in the early progressor group (median 2.35 IQR [2.31-2.38] and 2.28 IQR [2.21-2.29] respectively, p = 0.003). Early progressors had a higher number of VF at diagnosis (3.0 [2.0-5.5] vs 1.0 [1.0-2.5], p = 0.18) and more frequently evolved to symptomatic MM because of lytic bone lesions (5 [71 %] vs 2 [33 %], p = 0.13) compared to late progressors. VF of osteoporotic appearance in the context of SM is a rare situation but at high risk of rapid progression to symptomatic MM, suggesting that they may represent bone fragility linked to MM infiltration rather than solely osteoporotic fractures. Further studies are needed to assess if earlier treatment might be beneficial in this population.

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.

Accuracy of self-reported diagnoses of polymyalgia rheumatica and giant cell arteritis in the French prospective E3N- EPIC cohort: A validation study.

OBJECTIVES: To assess the accuracy of self-reported giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) diagnoses in a large French population-based prospective cohort, and to devise algorithms to improve their accuracy. METHODS: The E3N-EPIC cohort study (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale) includes 98,995 French women born between 1925 and 1950, recruited in 1990 to study risk factors of cancer and chronic diseases. They completed biennially mailed questionnaires to update their health-related information and lifestyle characteristics. In three questionnaires, women could self-report a diagnosis of GCA/PMR. Those women were additionally sent a specific questionnaire, designed to ascertain self-reported diagnoses of GCA/PMR. Four algorithms were then devised to improve their identification. Accuracies of self-reported diagnoses and of each algorithm were calculated by comparing the diagnoses with a blinded medical chart review. RESULTS: Among 98,995 participants, 1,392 women self-reported GCA/PMR. 830 women sent back the specific questionnaire, and 202 women provided medical charts. After independent review of the 202 medical charts, 87.6 % of the self-reported diagnoses of GCA/PMR were accurate. Using additional data from a specific questionnaire (diagnosis confirmation by a physician, and self-report of >3-month of glucocorticoids), and from a reimbursement database (at least two deliveries of glucocorticoids in less than 3 consecutive months) improved their accuracy (91.8 % to 92.8 %). CONCLUSION: The accuracy of self-reported diagnosis of GCA/PMR was high in the E3N-cohort but using additional data as a specific GCA/PMR questionnaire and/or corticosteroid reimbursement database further improved this accuracy. With nearly 600 detected cases of GCA/PMR, we will be able to investigate risk factors for GCA/PMR in women.

Evolution of monoclonal gammopathy of undetermined significance in patients treated with JAK inhibitors for rheumatic diseases: data from the MAJIK-SFR registry.

OBJECTIVE: Monoclonal gammopathy of undetermined significance (MGUS) is common, but there are scarce data regarding the effect of DMARDs on this premalignant condition. We aimed to evaluate the impact of JAK inhibitors (JAKis) on MGUS when initiated for an active rheumatic disease. METHODS: Patients with monoclonal abnormality prior to JAKi initiation for an active rheumatic disease were identified through the MAJIK-SFR Registry, a French multicentre prospective study. Clinical and biological data were collected using a standardized case report form. RESULTS: Twenty patients were identified with a mean age of 65 years and a diagnosis of RA (n = 15), PsA (n = 3), and axial SpA (n = 2). The JAKi prescribed was baricitinib (n = 9), tofacitinib (n = 6) or upadacitinib (n = 5), with a mean duration of 15.5 months. Seventeen patients had individualized serum monoclonal protein (IgG kappa n = 9; IgG lambda n = 4; IgM kappa n = 3; IgA lambda n = 1) ranging from 0.16 to 2.3 g/dl, and three patients did not have an initial measurable spike but they had a positive serum immunofixation. With a follow-up of 4-28 months, the serum monoclonal protein level decreased in 8 of 17 patients (47%), remained stable in 8 patients (47%) and increased in 1 patient (6%). The maximal decrease observed was an initial IgG kappa of 2.3 g/dl, decreasing to 0.2 g/dl at month 14. CONCLUSION: This study provides reassuring and promising data on MGUS evolution in patients treated with JAKis for rheumatic diseases, which may guide the choice of treatment in patients with both conditions.

Epidemiology of Sjögren syndrome.

Sjögren syndrome is a phenotypically varied autoimmune disorder that can occur alone in primary Sjögren syndrome or in association with other connective tissue diseases (CTDs), including rheumatoid arthritis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). The estimation of the prevalence and incidence of Sjögren syndrome varies depending on diagnostic criteria and study design, making it difficult to estimate geographical and temporal trends. Nonetheless, disease phenotype is influenced by geographical origin, which is a risk factor for systemic activity. Whether mortality in primary Sjögren syndrome is increased compared with that of the general population is not yet known, but extra-glandular manifestations, in particular lymphomas, are clear risk factors for mortality. In CTDs associated with Sjögren syndrome, lymphoma risk seems higher than that of patients with CTD alone, and there is potentially lower disease activity in SLE with Sjögren syndrome and in SSc with Sjögren syndrome than in SLE or SSc alone.

Risk of cancer for patients with rheumatoid arthritis versus general population: a national claims database cohort study.

Background: Older studies uncovered an increased risk of cancer in patients with rheumatoid arthritis between 10% and 30% compared to the general population, with a lack of data concerning infrequent cancers. In recent year, major therapeutic breakthroughs might have affected this risk of cancer by mitigating disease activity or on the contrary by impairing antitumoral immune response. The objectives of this study are to compare cancer risk in patients with treated rheumatoid arthritis to the general population, in all treated patients and according to treatment exposure. Methods: This is a nationwide population-based study within the French national claims database "Système National des Données de Santé" (SNDS) between January 1st 2010 and December 31st 2020, to estimate the age and sex-standardized incidence ratios of cancer (all sites and site specific) of treated rheumatoid arthritis patients, with the French population as reference (by use of the French Network of Population-Based Cancer Registries [FRANCIM]). Findings: During the study period, 257,074 treated patients with rheumatoid arthritis contributed to a total of 2,098,238 person-years for the main analysis. The all-cancer risk was increased in rheumatoid arthritis patients, with a SIR (Standardized Incidence Ratio) of 1.20 (95% CI [1.17-1.23]). This risk was increased particularly for lung (SIR 1.41, 95% CI [1.36-1.46], bladder (SIR 2.38 95% CI [2.25-2.51]), cervix (SIR 1.80, 95% CI [1.62-2.01]), prostate (SIR 1.08, 95% CI [1.04, 1.13]) cancers, melanoma (SIR 1.37, 95% CI [1.29-1.46]), diffuse large B cell lymphoma (SIR 1.79, 95% CI [1.63-1.96], multiple myeloma (SIR 1.42, 95% CI [1.27-1.60]) and Hodgkin's lymphoma (SIR 2.73, 95% CI [2.31-3.23]). Some cancers were less frequent than in the general population such as pancreatic (SIR 0.90, 95% CI [0.83-0.97]) as well as breast and endometrial cancers (SIR 0.91, 95% CI [0.88-0.94] and SIR 0.77, 95% CI [0.71-0.84] respectively). Although we observed a modest but significant relative increase of all-cancer risk over-time in rheumatoid arthritis patients, there was a trend towards a decrease in risk of non-Hodgkin's lymphoma. Patients treated with rituximab were the patients displaying the highest risk of cancer. Interpretation: Compared to the general population, treated rheumatoid arthritis patients were at greater risk of all-cancer and some site specific cancers, except for breast, pancreatic and endometrial cancers which were less frequent than in the general population. Funding: This work was supported by unrestricted grants from the InCA (national institute against cancer) and AP-HP (Assistance Publique des Hôpitaux de Paris).

Comparison between primary Sjögren's disease patients with high or low level of dryness.

OBJECTIVES: To describe primary Sjögren's disease (SjD) patients presenting no or low level of dryness and to compare them with SjD patients with oral or ocular dryness features. METHODS: All patients diagnosed with SjD according to AECG or ACR/EULAR criteria in our tertiary reference centre were included. Patients with high or low subjective symptoms or objective signs of dryness were compared. RESULTS: Overall, 509 patients were included for the comparison of patients with high (n=456) or low (n=53) level of subjective dryness and 472 for the comparison of patients with (n=359) or without (n=113) high objective dryness. Compared with patients with subjective dryness, patients without high subjective dryness were significantly younger (median 49 (39-62) years vs 58 (47-67) years, p<0.01), diagnosed earlier (median time from first symptoms to diagnosis 2 (0.5-4.5) years vs 4 (1-9.25), p=0.0056), more frequently anti-SSA positive ((83% vs 64%, p=0.008) and had less focal sialadenitis in minor salivary gland biopsy (69% vs 83%, p=0.02).The patients without high level of objective dryness (n=113) were also younger (51 (41-60) vs 58 (47-67) years, p<0.001) and were more frequently anti-SSA positive (79% vs 63%, p=0.002).In both groups, no difference was observed regarding disease activity. CONCLUSIONS: Among the patients with SjD, those without high subjective or objective dryness features had a younger profile, a faster diagnosis which may result from a more acute onset, were more frequently anti-SSA positive than patients with high dryness features.

French national diagnostic and care protocol for Sjögren's disease.

Sjögren's disease (SD), also known as Sjögren's syndrome (SS) or Gougerot-Sjögren's syndrome in France, is a rare systemic autoimmune disease in its primary form and is characterised by tropism for the exocrine glandular epithelia, particularly the salivary and lacrimal glands. The lymphocytic infiltration of these epithelia will clinically translate into a dry syndrome which, associated with fatigue and pain, constitutes the symptom triad of the disease. In about one third of patients, SD is associated with systemic complications that can affect the joints, skin, lungs, kidneys, central or peripheral nervous system, and lymphoid organs with an increased risk of B-cell lymphoma. SD affects women more frequently than men (9/1). The peak frequency is around the age of 50. However, the disease can occur at any age, with paediatric forms occurring even though they remain rare. SD can occur alone or in association with other systemic autoimmune diseases. In its isolated or primary form, the prevalence of SD is estimated to be between 1 per 1000 and 1 per 10,000 inhabitants. The most recent classification criteria were developed in 2016 by EULAR and ACR. The course and prognosis of the disease are highly variable and depend on the presence of systemic involvement and the severity of the dryness of the eyes and mouth. The current approach is therefore to identify at an early stage those patients most at risk of systemic complications or lymphoma, who require close follow-up. On the other hand, regular monitoring of the ophthalmological damage and of the dental status should be ensured to reduce the consequences.

Factors associated with COVID-19 severity in patients with spondyloarthritis: Results of the French RMD COVID-19 cohort.

OBJECTIVES: The objective of the current study was to evaluate the severity of COVID-19 and identify factors associated with severe disease outcomes in patients with spondyloarthritis (SpA), a chronic inflammatory rheumatic and musculoskeletal disease (RMD). METHODS: We utilized patient data from the French national multicenter RMD COVID-19 cohort (NCT04353609). The primary outcome was to describe COVID-19 characteristics in patients with SpA based on disease severity of COVID-19 (mild, moderate or severe) with serious infection including moderate and severe cases. The secondary outcome was to identify the factors associated with serious COVID-19 classification. RESULTS: Among the 626 patients with SpA (56% female, mean age 49±14 years) from the French RMD cohort, COVID-19 severity was mild in 508 (81%), moderate in 93 (15%), and severe in 25 (4%) patients. Clinical signs and symptoms of COVID-19 were reported in 587 (94%) patients, with the most frequent presented symptom of fever (63%) and cough (62%), followed by flu-like symptoms (53%), agueusia (39%), anosmia (37%), dyspnea (32%) and diarrhea (19.9%). COVID-19 severity was associated with corticosteroid therapy (OR=3.08 [95% CI: 1.44-6.58], P=0.004) and age (OR=1.06 [95% CI: 1.04-1.08], P<0.001) while use of tumor necrosis factor inhibitor (TNFi, OR=0.27 [95% CI: 0.09-0.78], P=0.01) was associated with less severe disease. We did not identify an association between NSAID use and COVID-19 severity. CONCLUSIONS: In this study, the majority of patients with SpA had a favorable COVID-19 outcome. We confirmed age and corticosteroids therapy had a negative impact on disease outcomes while TNFi use was protective.

Association Between Bruton's Tyrosine Kinase Gene Overexpression and Risk of Lymphoma in Primary Sjögren's Syndrome.

OBJECTIVE: We undertook this study to analyze whole blood gene expression and to investigate the role of B cell genes in primary Sjögren's syndrome-related non-Hodgkin lymphoma (primary SS-NHL). METHODS: Peripheral whole blood samples were collected from 345 well-phenotyped patients with primary SS enrolled in the prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort. Transcriptomic analysis was performed using human Clariom S Arrays (Affymetrix). In our primary analysis, we considered patients with incident lymphoma (i-primary SS-NHL) as the case group and all patients without lymphoma as the comparison group. In our sensitivity analyses, we considered all patients with primary SS-NHL, including those with a history of lymphoma (h-primary SS-NHL), as the case group and primary SS patients without lymphoma, stratified on their risk factors of lymphoma, as the comparison group. RESULTS: Twenty-one patients with primary SS-NHL (including 8 with i-primary SS-NHL and 13 h-primary SS-NHL) were eligible for transcriptomic analysis; we compared these patients to 324 primary SS controls without lymphoma, including 110 with moderate to severe disease activity and 61 with no risk factor of lymphoma. Functional clustering analyses revealed an enrichment of genes related to innate and adaptive immunity, including B cell-related genes. Bruton's tyrosine kinase (BTK) and a proliferation-inducing ligand (APRIL) genes were overexpressed before the occurrence of lymphoma in patients with incident lymphoma compared with patients without lymphoma. In sensitivity analyses, BTK was consistently up-regulated across all comparisons performed. BTK expression was associated with risk of lymphoma on multivariate analyses, which considered 9 validated predictors of lymphoma in primary SS. CONCLUSION: BTK and APRIL were overexpressed in the peripheral blood of primary SS patients prior to lymphoma. The association between BTK, APRIL, and primary SS-NHL requires confirmation in other prospective cohorts.

Cancer screening in chronic inflammatory rheumatic diseases.

Cancer is a major public health concern, and screening for cancer is a on-going issue in our practice. The risk of cancer in patients with chronic inflammatory rheumatic diseases varies according to their personal medical history, underlying rheumatic disease and its treatment. However, to date, no rheumatology learned society has established specific recommendations for cancer screening in patients with chronic inflammatory rheumatic diseases. In this review, we provide an overview of the risk of cancer in chronic inflammatory rheumatic diseases (related to the disease itself or its treatment), cancer screening in the general population and in immunocompromised subjects, and cancer screening in patients with chronic inflammatory rheumatic diseases.

18F-FDG PET molecular imaging: A relevant tool to investigate chronic inflammatory rheumatisms in clinical practice?

18F-Labeled Fluorodeoxyglucose-Positron Emission Tomography (18F-FDG PET) is a molecular imaging tool commonly used in practice for the assessment of many cancers. Thanks to its properties, its use has been progressively extended to numerous inflammatory conditions, including chronic inflammatory rheumatism (CIR) such as rheumatoid arthritis (RA), spondylarthritis (SpAs) and polymyalgia rheumatica (PMR). 18F-FDG PET is currently not recommended for the diagnostic of CIRs. However, this whole-body imaging tool has emerged in clinical practice, providing a general overview of systemic involvement occurring in CIRs. Numerous studies have highlighted the capacity of 18F-FDG PET to detect articular and extra articular involvements in RA and PMR. However, the lack of specificity of 18F-FDG limits its use for diagnosis purpose. Finally, the key question is the definition of the best way to integrate this whole-body imaging tool in the patient's management workflow.

Characterisation of the coexistence between sarcoidosis and Sjögren's syndrome. Analysis of 43 patients.

OBJECTIVES: To characterise the key epidemiological, clinical, immunological, imaging, and pathological features of the coexistence between sarcoidosis and Sjögren's syndrome (SS). METHODS: All centres included in two large multicentre registries (the Sjögren Syndrome Big Data Consortium and the Sarco-GEAS-SEMI Registry) were contacted searching for potential cases of coexistence between SS and sarcoidosis seen in daily practice. Inclusion criteria were the fulfilment of the current classification criteria both for SS (2016 ACR/EULAR) and sarcoidosis (WASOG). The following features were considered for evaluating a coexisting immunopathological scenario between the two diseases: non-caseating granulomas (NCG), focal lymphocytic sialadenitis (FLS) and positive anti-Ro antibodies. RESULTS: We identified 43 patients who fulfilled the inclusion criteria (38 women, with a mean age of 53 years at diagnosis of SS and of 52 years at diagnosis of sarcoidosis). In 28 (65%) cases, sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of patients with an already diagnosed SS, while in the remaining 15 (35%), SS was diagnosed during the follow-up of an already diagnosed sarcoidosis. Patients in whom sarcoidosis was diagnosed first showed a lower mean age (43.88 vs. 55.67 years, p=0.005) and were less frequently women (73% vs. 96%, p=0.04) in comparison with those in whom sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of an already diagnosed SS. We identified the following immunopathological scenarios: a combination of NCG involving extrasalivary tissues and anti-Ro antibodies in 55% of patients, a coexistence of both pathological scenarios (extrasalivary NCG and FLS in MSGB) in 42% (with positive anti-Ro antibodies in two thirds of cases), and NCG involving salivary glands and anti-Ro antibodies in 3% of cases. CONCLUSIONS: We have characterised the largest reported series of patients who fulfilled the current classification criteria for both SS and sarcoidosis. This implies that sarcoidosis (and not just the presence of isolated NCG on salivary gland biopsy) may, like other systemic autoimmune diseases, coexist with SS, and that a sarcoidosis diagnosis does not preclude the development of SS in the future.

Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases).

OBJECTIVES: To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases. METHODS: The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019. RESULTS: Hundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued. CONCLUSION: These initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.

Risk of malignancy in rheumatoid arthritis patients initiating biologics: an historical propensity score matched cohort study within the French nationwide healthcare database.

OBJECTIVE: To compare the risk of malignancy between patients with rheumatoid arthritis (RA) initiating their first biological disease-modifying antirheumatic drug (bDMARD) and those continuing conventional synthetic DMARDs (csDMARDs). METHODS: Nine-year historical Propensity Score (PS) matched cohort study within the French national healthcare database (87% of the French population; ~57 million people), including adults RA without malignancy. Exposures started with the first use of any systemic treatment (csDMARDs and/or bDMARDs). Incident users of bDMARDs were matched on a dynamic PS to patients continuing csDMARDs. Their risk of malignancy was compared by Cox model. RESULTS: From 1 January 2007 to 31 December 2014, 83 706 patients with RA started their first systemic treatment (63 837 remained on csDMARDs and 19 869 initiated a bDMARD during follow-up). After dynamic PS matching, 19 727 bDMARD initiators were compared with 19 727 RA remaining on csDMARDs. They did not statistically differ in risk of overall malignancies (HR 0.99 (95% CI 0.86 to 1.14)), solid cancer (HR 0.95 (95% CI 0.82 to 1.11)), nor lymphoma (HR 1.35 (95% CI 0.72 to 2.53)). Results were similar when bDMARDs were given as monotherapy or in association with csDMARDs. Analyses restricted to patients starting TNF inhibitor as first bDMARD compared with matched RA remaining on csDMARDs, provided similar results (HR for overall malignancy 1.03 (95% CI 0.88 to 1.21)). Sensitivity analyses, varying carry-over periods (up to 5 years) to define risk periods, provided similar results. CONCLUSIONS: In this historical cohort study within the French nationwide healthcare database, the risk of overall, solid or haematological malignancies did not significantly differ between patients with RA initiating bDMARD and those continuing csDMARDs.

Associations between ocular and extra-ocular assessment in primary Sjögren's syndrome.

OBJECTIVES: To assess associations between ophthalmological features and the main systemic biomarkers of primary Sjögren's Syndrome (pSS), and to identify systemic biomarkers associated with severe keratoconjunctivitis sicca (KCS) in pSS patients. METHODS: In this cross-sectional study, data was retrospectively extracted from the monocentric cohort of the French reference centre for pSS. We analysed data from the initial visit of patients admitted for suspicion of pSS and included patients validating pSS ACR/EULAR classification criteria. Ophthalmological assessment included Schirmer's test, tear break-up time, ocular staining score (OSS), and visual analogue scale (DED-VAS) for dry eye disease (DED) symptoms. Results of minor salivary gland biopsy, unstimulated whole salivary flow rate, anti-SSA/Ro antibodies, anti-SSB/La antibodies, and rheumatoid factor (RF) were collected. RESULTS: A total of 253 patients (245 females) with confirmed pSS, aged 56.6±13.0 years, were included, among which 37% had severe KCS. Multivariate analysis showed that the presence of anti-SSA/Ro antibodies, anti-SSB/La antibodies and RF were associated with conjunctival OSS (odds ratio-OR-=1.25 per OSS unit increase; confidence interval-CI-95%=1.05-1.49; P=0.01; OR=1.31 per OSS unit increase; CI95%=1.09-1.58, P=0.002, and OR=1.34 per OSS unit increase; CI95%=1.12-1.59; P=0.001, respectively). Both anti-SSB/La antibodies and DED-VAS ≥ 5 were significantly associated with severe KCS (OR=2.03; CI95%=1.03-4.00; P<0.05 and OR=2.52, CI95%=1.31-4.90; P<0.01, respectively). CONCLUSION: Association between conjunctival OSS and systemic biomarkers of pSS indicate the crucial importance of conjunctival staining when pSS is suspected as a cause of DED. Conversely, patients with anti-SSB and DED-VAS ≥ 5 features should be prioritized for extensive evaluation by an ophthalmologist due to their association with severe KCS.

Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies.

OBJECTIVE: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. METHODS: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. RESULTS: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). CONCLUSION: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.

Anthropometric Measures and Risk of Rheumatoid Arthritis in the French E3N Cohort Study.

We aimed to assess the relationships between anthropometric measures and risk of rheumatoid arthritis (RA). The E3N cohort included 98,995 women (aged 40−65 years at the recruitment) who completed mailed questionnaires on reproductive factors, lifestyle, and health-related information, including anthropometric measures, every 2−3 years. Cox proportional hazards regression models with age as the time scale and adjusted on known RA risk factors were used to estimate hazard ratios (HRs) and 95% confidence intervals for the risk of incident RA in the overall population (n = 78,452) and after stratification on smoking exposure. Incident RA diagnosis was validated in 698 women. Abdominal obesity (waist circumference >88 cm) was associated with RA (HR = 1.2 (1.0−1.5)), independent of BMI; whereas obesity, defined as BMI ≥ 30 kg/m2, was marginally associated with RA (HR = 1.26 (0.9−1.5), ptrend = 0.0559). Taking lean body shape (BS) as reference, medium BS at puberty (HR = 1.3 (1.0−1.7)) and medium-large BS at perimenopausal period (HR = 1.5 (1.1−1.9)) were associated with the risk of RA among never-smoker women, independent of BMI. Regarding BS trajectory, taking constantly lean BS as reference, constantly large BS from puberty to perimenopause was associated with RA among non-smokers (HR = 2.10 (1.2−3.6)), independent of BMI.