INTRODUCTION:The prevalence of systemic sclerosis (SSc), as well as obesity, has significantly increased in recent decades. To address the lack of data on obese SSc patients, we conducted a retrospective comparative study to assess the prevalence, clinical characteristics, and long-term consequences of obesity in SSc patients. METHODS:We conducted a retrospective comparative study at the Cochin University Hospital's Department of Internal Medicine (Paris) from 2000 to 2019. RESULTS:Of the 911 SSc patients included, 90 (9.9%) were obese, comprising 79 females and 11 males. The median weight for obese patients was 90 [82-98] kg, compared to 60 [53-67] kg for non-obese patients, corresponding to a median body mass index of 33 [31-37] kg/m2 and 23 [20-25] kg/m2, respectively. Obese patients exhibited a higher prevalence of cardiovascular risk factors. The median modified Rodnan skin score was significantly higher in non-obese patients than in obese patients (6 [2-16] vs 3 [2-7]; P<0.05). Organ involvement did not differ significantly between obese and non-obese patients. We observed a lower number of deaths in obese SSc patients compared to non-obese SSc patients (6 [11%] vs. 26 deaths [25%], P=0.06). Analysis of 30-year Kaplan Meier survival curves did not show significant survival difference between obese and non-obese SSc patients. CONCLUSIONS:This study of obese ScS patients reveals that they have a higher prevalence of cardiovascular risk factors, lower mRSS, less calcinosis, and similar rates of organ damage and mortality compared to non-obese ScS patients.

INTRODUCTION:Mixed connective tissue disease (MCTD) is a rare systemic disorder that belongs to connective tissue diseases (CTD). Few studies are available on MCTD treatment. METHODS:We conducted an observational study within the French MCTD cohort. Data were collected at diagnosis, during follow-up, and at the last follow-up (LFU). We studied three treatment groups i) no treatment, ii) hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and iii) disease-modifying antirheumatic drugs (DMARDs)/immunosuppressant (IS). RESULTS:Three hundred and fifteen patients were included and followed for 96 [40-156] months. At MCTD diagnosis, 52 (16.5 %) patients were treatment-free, while 224 (71.1 %) received GC and/or HCQ and 39 (12.4 %) received DMARDs and/or IS. During follow-up, 10 (3.2 %) patients remained treatment-free, and 77 (24.4 %) were GC-free. Most patients (n = 271; 85.8 %) received HCQ, and 161 (51.1 %) were treated with DMARDs and/or IS. DMARDs and/or IS, including anti-B cell therapeutics, were more frequently prescribed in patients with musculoskeletal involvement (p < 0.0001), interstitial lung disease (ILD, p < 0.0001) and/or pulmonary arterial hypertension (PAH, p < 0.01). Patients in clinical remission and those who did not evolve to a differentiated CTD (MCTD-dCTD) received significantly less frequently DMARDs and/or IS (including anti-B cell therapeutics; p < 0.0001 for both). Patients who received HCQ at MCTD diagnosis appeared to develop less frequently ILD or PAH (p < 0.05). CONCLUSION:HCQ and GC were the cornerstones of MCTD treatment and were sufficient to control disease manifestations in nearly half of the patients, reflecting the good prognosis of this disease. DMARDs and IS were used for musculoskeletal involvement, PAH/ILD, and in MCTD-dCTD patients.

BACKGROUND:Mixed connective tissue disease (MCTD) has long been debated as an early nonspecific phase/symptom of differentiated connective tissue diseases (dCTD), similarly to interstitial pneumonia with autoimmune features (IPAF) and very early diagnosis of systemic sclerosis (SSc) (VEDOSS). OBJECTIVE:We aimed to evaluate the predictive value of IPAF, VEDOSS and dCTD classification criteria variables in MCTD patients. METHODS:We conducted an observational study within the French MCTD cohort. IPAF, VEDOSS and current dCTD classification criteria were used to classify patients. RESULTS:Three hundred and twenty-four MCTD patients were included and followed for 8 (3.3-13) years. Among them, 111 (34.3%) progressed into a dCTD, that is, 50 (15.4%) SSc, 40 (12.3%) systemic lupus erythematosus (SLE) and 11 (3.4%) Sjögren's disease. At diagnosis, 38 (11.7%) patients fulfilled IPAF criteria, among which 15 (39.5%) progressed into a dCTD (vs 75 (26.2%) in patients who did not fulfil IPAF criteria; p=0.09). At diagnosis, 293 (90.4%) patients fulfilled VEDOSS criteria but did not progress significantly more frequently to SSc than MCTD patients without VEDOSS criteria (46 (15.7%) vs 4 (12.9%); p=0.8). At baseline, SSc classification criteria did not predict evolution toward SSc, whereas antiphospholipid antibodies and low C3 and/or C4 were predictive of an evolution toward SLE (p=0.01 and p=0.04, respectively). CONCLUSION:At MCTD diagnosis, fulfilment of IPAF and/or VEDOSS criteria was not predictive of evolution toward SSc, whereas antiphospholipid antibodies and low C3 and/or C4 were predictive of an evolution toward SLE. This suggests that MCTD patients should be excluded from IPAF and VEDOSS.

OBJECTIVES:To describe the characteristics and outcome of patients with the association of large vessel vasculitis (LVV, Takayasu arteritis [TA] or GCA) and IBD. METHODS:An observational, multicentre, retrospective case-control study. Cases were LVV-IBD patients from European countries, whereas controls had isolated LVV (iLVV). RESULTS:A total of 39 TA-IBD and 12 GCA-IBD cases were enrolled, compared with 52 isolated GCA (iGCA) and 93 isolated TA (iTA) controls. LVV occurred after IBD in 56% in TA-IBD and 75% in GCA-IBD, with a median interval of 1 year (interquartile range [IQR] 1-7) in TA-IBD and 8.6 years (IQR 1-17.7) in GCA-IBD. Crohn's disease was more common in TA-IBD (67%), whereas ulcerative colitis was more common in GCA-IBD (58%). Compared with iTA, TA-IBD were significantly younger at diagnosis of TA (median age 27 vs 37 years, P < 0.001) and had more upper limb claudication (36% vs 12%, P = 0.006). GCA-IBD patients had more frequent arterial thickening or stenosis than controls (75% vs 30%, respectively, P = 0.044) and tended to more frequently involve gastrointestinal arteries (20% vs 0%, respectively, P = 0.06). LVV occurred in IBD patients despite treatment with glucocorticoids (36%), azathioprine (25%) or TNF-alpha blockers (29%). The presence of the IBD was not associated with a higher LVV relapse rate in multivariate analysis (adjusted hazard ratio [aHR] 0.62 [0.13-2.83] for GCA and aHR 0.92 [0.44-1.89] for TA). CONCLUSION:This study identifies specific clinical and imaging characteristics of LVV-IBD patients, in particular a more severe vascular presentation of GCA-IBD patients compared with iGCA patients.

Objective To investigate the concordance between organ involvement at diagnosis and relapse in granulomatosis with polyangiitis and factors associated with new disease features at relapse.Methods Data from a national database of newly diagnosed patients was analysed. Clinical features were recorded at diagnosis and relapse, grouped by organ system. ORs and HRs were used to assess associations between baseline features and first relapse. Factors independently associated with new organ involvement at relapse were identified using multivariable logistic regression.Results Among 795 patients (median follow-up 3.5 years), 394 (50%) relapsed; organ involvement at relapse was available for 376 patients. Relapses most often affected ear, nose and throat (ENT), lungs and kidneys. Organ involvement at diagnosis was associated with a higher likelihood of relapse in the same organ: eyes (OR 6.69), lungs (OR 3.35), kidneys (OR 3.58), nervous system (OR 2.90), and mucocutaneous (OR 4.53). Major manifestations associated with a higher likelihood of recurrence were scleritis, pachymeningitis, subglottic stenosis and worsening renal function. For 56% of patients, the first relapse affected only the initially involved organs. Of the 165 patients with new organ manifestations, these were rarely isolated (n=34) and usually occurred alongside involvement of at least one previously affected organ (n=131). In multivariable analysis, systemic, ENT and lung manifestations at diagnosis were associated with a lower risk of new organ disease at relapse.Conclusion Although new features can still emerge, organ involvement at diagnosis is associated with a higher likelihood of relapse in the same organ.

OBJECTIVES:Juvenile-onset mixed connective tissue disease (jMCTD) accounts for 7-23 % of MCTD cases but remains poorly described. We aimed to characterize clinical features, treatments, and outcomes of patients with jMCTD, and compare them to adult-onset MCTD (aMCTD) patients. METHODS:We conducted a multicenter, retrospective, case-control study within the French MCTD cohort. Each jMCTD patient was compared to 3 matched aMCTD patients. RESULTS:Forty-seven jMCTD patients (93.6 % girls; median age at onset 14 [11-16] years) were included. Forty-four (93.6 %) jMCTD patients fulfilled either Sharp or Kasukawa diagnostic criteria. None of them met other diagnostic criteria without fulfilling Sharp or Kasukawa criteria. At diagnosis, jMCTD patients' main manifestations were Raynaud's phenomenon, arthralgia, and myalgia. jMCTD patients had less frequently puffy fingers than aMCTD (p < 0.0001). Cumulatively, jMCTD patients mainly received glucocorticoids (80.9 %), hydroxychloroquine (95.7 %) and immunosuppressants (93.6 %). They received a higher initial dose of glucocorticoids (30 [20-60] mg/day vs. 15 [10-35] mg/day, p = 0.02), and significantly more frequently methotrexate (Methotrexate) and rituximab (p = 0.01) over time compared to aMCTD. After a median follow-up of 9.8 [6.6-16.2] years, 29 (61.7 %) jMCTD patients were in remission (vs. 62 (44.0 %) aMCTD; p < 0.05), 36 % had progressed to another CTD (vs. 30.5 % aMCTD; p = 0.5), mainly systemic lupus erythematosus, 11 (23.4 %) had developed interstitial lung disease, 2 (4.3 %) pulmonary arterial hypertension, and 1 (2.1 %) died. CONCLUSIONS:jMCTD share the same clinical characteristics as aMCTD patients, but less frequently have puffy fingers. Outcomes appear more favorable in jMCTD than aMCTD, with higher remission rates, albeit at the cost of more intensive treatment.

BACKGROUND:We aimed to provide pharmacokinetic-pharmacodynamic (PK/PD) rationale for selecting the optimal induction and maintenance dosing regimens in ANCA-associated vasculitis (AAV) using a population modelling approach based on PK, ANCA, and gammaglobulins data from a real-world cohort. METHODS:A total of 121 patients with 296 plasma rituximab concentrations (99 and 197 in the induction and maintenance phases, respectively), 439 ANCA levels and 559 gammaglobulin levels were included in the analysis. Simulations of induction (375 mg/m2 weekly for 4 weeks and 1000 mg on day 0 and 14) and maintenance regimens (500 mg every 6 months [Q6M], 500 mg Q6M starting at month 4, 1000 mg Q4M, 500 mg Q4M) were performed in 1000 virtual patients. Dosing regimens were compared using a clinical utility score that equally weighted the percentage of patients in serological remission and at risk of hypogammaglobulinaemia (<6 g/L). FINDINGS:The PK/PD model satisfactorily described the relationship between rituximab, gammaglobulins and ANCA concentrations over time. Both induction regimens resulted in a similar number of patients achieving serological remission and hypogammaglobulinaemia at 6 months. In the maintenance phase, increasing the dose (to 1000 mg) or the frequency of administration (Q4M versus Q6M) was associated with a higher number of patients with serological remission at month 24, but also with a higher risk of hypogammaglobulinaemia. In the maintenance phase, 500 mg Q6M (start at month 4 or 6), had a significantly higher utility score than 1000 mg Q4M. INTERPRETATION:This PK/PD study can inform clinical decisions regarding the choice between different rituximab induction and maintenance regimens in patients with AAV in daily practice. FUNDING:This study received no funding.

Introduction La prévalence de la sclérodermie systémique (ScS) et de l’obésité a considérablement augmenté au cours des dernières décennies. Pour pallier au manque de données concernant les patients obèses atteints de ScS, nous avons mené une étude comparative rétrospective afin d’évaluer la prévalence, les caractéristiques cliniques et les conséquences à long terme de l’obésité chez les patients atteints de ScS. Patients et méthodes Nous avons mené une étude rétrospective cas-témoins dans le service de médecine interne de l’hôpital Cochin (Paris) de 2000 à 2019. Résultats Sur les 911 patients atteints de ScS éligibles, 90 (9,9 %) étaient obèses, dont 79 femmes et 11 hommes. Le poids médian [interquartile] des patients obèses était de 90 [82–98] kg/m2 versus 60 [53–67] kg/m2 pour les patients non obèses, correspondant à un indice de masse corporelle médian de 33 [31–37] et 23 [20–25] kg/m2, respectivement. Les patients obèses présentaient davantage de facteurs de risque cardiovasculaires, tels que l’hypertension (39 [43 %] contre 35 [19 %] ; p<0,0001), le diabète de type 2 (10 [11 %] contre 3 [2 %] ; p<0,01) et le syndrome d’apnée obstructive du sommeil (6 [7 %] contre 0 [0 %] ; p<0,01). La médiane du score cutané de Rodnan modifié était significativement plus élevée chez les patients non obèses que chez les patients obèses (6 [2–16] versus 3 [2–7] ; p<0,05). Les patients obèses présentaient également moins de calcinose (8 [9 %] contre 33 [18 %] ; p<0,05) et une distance inter-incisive significativement plus grande (médiane [IQR], 40 [35–45] contre 38 [31–42] ; p<0,05). La fréquence des complications systémiques de ScS ne différait pas significativement entre les patients obèses et non obèses. Nous avons observé un nombre plus faible de décès chez les patients obèses que chez les patients non obèses (6 [11 %] versus 26 décès [25 %], p=0,06). L’analyse des courbes de survie de Kaplan-Meier à 30 ans ne montrait pas de différence significative de survie entre les patients obèses et non obèses atteints de ScS. Conclusion Cette étude portant sur des patients obèses atteints de ScS révèle que, malgré une prévalence plus élevée de facteurs de risque cardiovasculaires, les patients obèses atteints de ScS présentent un mRSS plus faible, moins de calcinose et un pronostic similaire en ce qui concerne l’atteinte d’organes et la mortalité.

ObjectiveTo compare the long-term efficacy and safety of azathioprine (AZA), 18-month fixed-schedule rituximab (RTX), 18-month tailored RTX and 36-month RTX in preventing relapses in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who achieved a complete remission after induction therapy. Patients treated with 36-month RTX received either a fixed or a tailored regimen for the first 18 months and a fixed regimen for the last 18 months (36-month fixed/fixed RTX and 36-month tailored/fixed RTX, respectively).MethodsThe Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trials sequentially compared: 18-month fixed-schedule RTX versus AZA (MAINRITSAN); 18-month fixed-schedule RTX versus 18-month tailored-RTX (MAINRITSAN2); and extended therapy to 36 months with four additional RTX infusions after MAINRITSAN2 versus placebo (MAINRITSAN3). Patients were then followed prospectively through month 84 and their data were pooled to analyse relapses and adverse events. The primary endpoint was relapse-free survival at month 84.Results277 patients were enrolled and divided in 5 groups: AZA (n=58), 18-month fixed-schedule RTX (n=97), 18-month tailored-RTX (n=40), 36-month tailored/fixed RTX (n=42), 36-month fixed/fixed RTX (n=41). After adjustment for prognostic factors, 18-month fixed-schedule RTX was superior to AZA in preventing major relapses at month 84 (HR 0.38, 95% CI 0.20 to 0.71). The 18-month tailored-RTX regimen was associated with an increased risk of major relapse compared with fixed-schedule regimen (HR 2.92, 95% CI 1.43 to 5.96). The risk of major relapse was similar between 36-month fixed/fixed and 18-month fixed-RTX (HR 0.69, 95% CI 0.38 to 1.25).ConclusionsAccording to these results, it appears that the 84-month remission rate is higher with an 18-month fixed RTX regimen compared with AZA and 18-month tailored RTX. Also, extending RTX to 36 months does not appear to reduce the long-term relapse rate compared with the 18-month fixed RTX regimen. However, as this study was underpowered to make this comparison, further prospective studies are needed to determine the potential long-term benefits of extending treatment in these patients.

Purpose: The purpose of this study was to describe lung abnormalities observed on computed tomography (CT) in patients meeting the 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria for primary Sjogren's disease (pSD). Materials and methods: All patients with pSD seen between January 2009 and December 2020 in the day care centre of our National Reference Center for rare systemic autoimmune diseases, who had at least one chest CT examination available for review and for whom the cumulative EULAR Sjogren's Syndrome Disease Activity Index (cumESSDAI) could be calculated were retrospectively evaluated. CT examinations were reviewed, together with clinical symptoms and pulmonary functional results. Results: Seventy-seven patients (73 women, four men) with a median age of 51 years at pSD diagnosis (age range: 17-79 years), a median follow-up time of 6 years and a median cumESSDAI of 7 were included. Sixtysix patients (86%) had anti-SSA antibodies. Thirty-three patients (33/77; 43%) had respiratory symptoms, without significant alteration in pulmonary function tests. Forty patients (40/77; 52%) had abnormal lung CT findings of whom almost half of them had no respiratory symptoms. Abnormalities on chest CT were more frequently observed in patients with anti-SSA positivity and a history of lymphoma. Air cysts (28/77; 36%) and mosaic perfusion (35/77; 35%) were the predominant abnormalities, whereas lung fibrosis was observed in five patients (5/77; 6%). Conclusion: More than half of patients with pSD have abnormal CT findings, mainly air cysts and mosaic perfusion, indicative of small airways disease, whereas lung fibrosis is rare, observed in less than 10% of such patients. (c) 2024 Published by Elsevier Masson SAS on behalf of Soci & eacute;t & eacute; fran & ccedil;aise de radiologie.

ObjectivesPolypharmacy, drug-drug interactions (DDI) and related adverse drug reaction (ADR) are understudied in SSc. The aim of this work was to determine the prevalence and determinants of DDI and ADR in a real-life prospective cohort of SSc patients.MethodsWe performed a retrospective analysis of the drug prescriptions of SSc patients admitted to the daily scleroderma clinic between January 2020 and April 2022. DDI were identified using 2 prescription analysis applications, and adjudicated related ADRs occurring during a one-year follow-up were reported. Risk factors for DDI and ADR were identified using multivariate analysis.ResultsOne hundred and eight SSc patients were included. The median number of medications per patient was 6 [4-9]. Seventy-one (65.7%) patients had 5 or more medications, and 23 (21.3%) had 10 or more. Seventy-two (66.7%) patients had DDIs on their prescriptions at inclusion. Patients with DDIs had more medications than patients without DDIs (7 [5-10] versus 3 [2-5], p<0.0001). Six (8.3) patients experienced ADRs during the one-year follow-up. Patients with ADRs had more medications (14 [10-18] versus 7 [5-10] p<0.001) and more DDIs (12 [7-32] versus 3 [1-6]; p<0.001) than patients without ADRs. Multivariate analysis confirmed that the number of prescribed medications was independently positively associated with DDIs (OR: 2.25 [1.52-3.32], p<0.0001) as well as with ADRs (OR: 1.68 [1.17 - 2.40], p<0.01).ConclusionsSSc patients are significantly exposed to polypharmacy, DDIs and related ADRs, particularly in cases of severe illness, and especially if 5 or more medications are prescribed.

Introduction La polymédication, les interactions médicamenteuses (IM) et les effets indésirables (EI) sont peu étudiés chez les patients atteints de sclérodermie systémique. Ces patients sont pourtant traités pour leurs différentes atteintes d’organes et parfois par immunosuppresseurs. L’objectif de ce travail est d’étudier la prévalence et les facteurs de risques des IM et EI au sein d’une cohorte prospective de patients sclérodermiques. Patients et méthodes Une analyse des ordonnances de 108 patients consécutifs suivis en centre de référence de la sclérodermie systémique a été réalisée entre janvier 2020 et avril 2022. Les caractéristiques cliniques des patients inclus ont été recensées. Les IM ont été identifiées en utilisant les applications VIDAL et POSOS et les EI survenus au cours de l’année suivant la rédaction de l’ordonnance ont été adjudiqués par le centre de pharmacovigilance. Les facteurs de risque d’IM et EI ont été déterminés par analyses multivariées. Résultats La médiane du nombre de médicaments par patient était de 6 [4–9]. Au total, 93,5 % des patients avaient au moins 2 et 65,7 % des patients avaient au moins 5 médicaments sur leurs ordonnances. Les médicaments les plus prescrits étaient les inhibiteurs calciques, les inhibiteurs de la pompe à protons et la vitamine D chez respectivement 81,5 %, 74,1 %, et 53,7 % des patients.Deux-tiers (66,7 %) des patients inclus présentaient des IM. Le nombre médian d’IM par patient était de 3 [1-8]. Les patients avec IM prenaient plus de médicaments que ceux sans IM (7 [5–10] versus 3 [2–5], p<0,0001). Les patients avec IM étaient significativement plus souvent traités par inhibiteurs de la pompe à protons (p<0,0001), prednisone (p<0,0001), mycophenolate mofetil (p<0,001), alginate de sodium (p<0,001), hypolipémiants (p<0,05), et domperidone (p<0,01) que les patients sans IM.Six patients ont présenté un EI au cours du suivi. Un EI (arrêt cardiaque sur tachycardie ventriculaire) était déclaré en grade IV selon la classification CTCAE (1,4 % des patients avec IM), 4 (5,6 %) en grade III (chutes, hypotension orthostatique et rupture tendineuse), et 1 (1,4 %) en grade II (maladie de Bowen). Les patients avec EI avaient plus de traitements (14 [10–18] versus 7 [5–10] p<0,001) et d’IM (12 [7–32] versus 3 [1–6] ; p<0,001) que les patients sans EI. Le nombre de médicaments prescrits était positivement associé aux IM (OR : 2,25 [1,52–3,32], p<0,0001) et EI (OR : 1,68 [1,17–2,40], p<0,01).Les patients masculins, avec une forme diffuse de sclérodermie, un score de Rodnan modifié élevé, et une pneumopathie interstitielle étaient significativement plus à risque d’IM. Conclusion Les patients atteints de sclérodermie systémique sont exposés à la polymédication, aux IM et aux EI. Les patients atteints de formes sévères de la maladie ou ceux traités par au moins 5 médicaments sont les plus à risque.