Publications by authors named "Véronique Le Guern"

84 Publications

Evaluation of the severe preeclampsia classification criterion for antiphospholipid syndrome in a study of 40 patients.

Arthritis Res Ther 2021 05 4;23(1):134. Epub 2021 May 4.

AP-HP, Cochin Hospital, Internal Medicine Department, Centre de référence maladies auto-immunes et systémiques rares d'Ile de France, Paris, France.

Background: The criteria for antiphospholipid syndrome (APS) include severe preeclampsia and/or placental insufficiency leading to preterm delivery before 34 weeks of gestation, but this APS manifestation has been rarely studied. Thus, we report a series of severe preeclampsia occurred in patients with APS.

Methods: We retrospectively analysed data of women with APS (Sydney criteria) who experienced severe preeclampsia with delivery before 34 weeks' gestation between 2000 and 2017 at five French internal medicine departments and one Italian rheumatology unit.

Results: The 40 women had a mean age of 30.5 ± 4.6 years at their first episode of preeclampsia; 21 were nulligravid (52.5%), 12 (30%) had already been diagnosed with APS, and 21 (52.5%) had a triple-positive antiphospholipid (aPL) antibody test. Preeclampsia occurred at a median gestational age of 25.5 weeks (IQR 23-29). It was associated with HELLP in 18 cases (45%), eclampsia in 6 (15%), placental abruption in 3 (7.5%), catastrophic APS in 3 (7.5%), and foetal and neonatal death in 11 and 15 cases. Overall, 14 (35%) children survived, born at a median gestational age of 31 weeks. Among other APS criteria, 16 women (40%) experienced at least one thrombosis, 17 (42.5%) an intrauterine foetal death, and 19 (47.5%) at least one episode of HELLP during follow-up (median 5 years, IQR = 2-8). None had three or more consecutive miscarriages. Notably, 12 women (30%) had systemic lupus erythematosus.

Conclusions: Severe preeclampsia led to high mortality in the offspring. Almost half of these women experienced other APS features, but not three consecutive miscarriages.
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http://dx.doi.org/10.1186/s13075-021-02518-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094564PMC
May 2021

SLE-DAS in the First Trimester of Gestation Predicts Maternal Lupus Flares Later in Pregnancy.

Front Pharmacol 2021 16;12:660123. Epub 2021 Apr 16.

Rheumatology Unit, Department of Medicine, DIMED, University of Padova, Padova, Italy.

Systemic Lupus Erythematosus (SLE) mainly occurs during childbearing age. Remission or low disease activity state (LDAS) before conception are recommended by experts to achieve a favourable lupus pregnancy outcome but little is known on the best way to evaluate remission or activity status during pregnancy. We tested SLE-disease activity score (SLE-DAS) in the first trimester as predictor of maternal flares and obstetrical complications in 2nd and 3rd trimester in a cohort of SLE pregnant women. Inclusion criteria were: 1) women ≥ 18 years; 2) affected with SLE (SLICC 2012); 3) enrolled in two referral centers (Italy and France) 4) with an ongoing singleton pregnancy at 12 weeks (only one pregnancy per patient). Disease activity was assessed at first trimester of pregnancy, using SLE-pregnancy disease activity index (SLEPDAI) and retrospectively applying SLE-DAS. Maternal lupus flares at 2nd and 3rd trimester were defined by the SELENA-SLEDAI Flare Index (SFI). Adverse pregnancy outcome (APO) included: fetal and neonatal death, placental insufficiency with premature delivery <37 weeks, and small for gestational age (SGA) (≤3rd percentile). We included 158 pregnant patients affected with SLE. At first trimester the median SLEPDAI (IQR) was 2 (0-4) and the median SLE-DAS (IQR) 1.32 (0.37-2.08). At least one flare occurred in 25 (15.8%) women during the 2nd and 3rd trimester. APO occurred in 19 (12.0%) patients. A significant correlation between SLE-DAS and SLEPDAI was found in this cohort (Spearman's = 0.97, Figure 1). At multivariate analysis, both SLE-DAS and SLEPDAI predicted maternal flares (adjOR = 1.2; 95% CI = 1.0-1.3, = 0.02; adjOR 1.3, 95% CI = 1.1-1.6 per unit increase, = 0.01, respectively). SLE-DAS and SLEPDAI were associated with APO at univariate analysis ( = 0.02). SLE-DAS was highly correlated with SLEPDAI and its use in the first trimester predicted maternal flares in the 2nd and 3rd trimester, making SLE-DAS a reliable instrument to measure SLE activity during pregnancy.
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http://dx.doi.org/10.3389/fphar.2021.660123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085518PMC
April 2021

Catastrophic antiphospholipid syndrome and posterior ocular involvement: case series of 11 patients and literature review.

Retina 2021 Apr 2. Epub 2021 Apr 2.

AP-HP, Cochin Hospital, Internal Medicine department, Centre de référence maladies auto-immunes et systémiques rares de l'Ile de France, Paris, France. Université Paris-Descartes, Paris, France. AP-HP, Cochin Hospital, Ophthalmology Department, Paris, France. Centre Hospitalier Saint Joseph Saint Luc, Internal medicine department, Lyon, France. Foch Hospital, Internal Medicine department, Suresnes, France. AP-HP, Henri Mondor Hospital, Internal Medicine department, Creteil, France. AP-HP, La Pitié-Salpêtrière Hospital, Internal Medicine department, Centre de référence maladies auto-immunes et systémiques rares de l'Ile de France, Paris, France. Normandie Université, UNIROUEN, Inserm U1096, Rouen university hospital, department of internal medicine, vascular and thrombosis unit, 76000 Rouen, France. Univ. Lille ; INSERM U1167 ; CHU Lille, Internal Medicine department, Centre National de Référence Maladies Systémiques et Auto-Immunes Rares, European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases (ReCONNECT), F-59000 Lille, France Department of Internal Medicine, CHU de Saint-Etienne, France. Université Paris Descartes-Sorbonne Paris Cité, Paris, France ; INSERM U 1153, Center for Epidemiology and Statistics, Sorbonne Paris Cité (CRESS), Paris, France.

Purpose: To describe the posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome (CAPS).

Methods: Retrospective case series of patients presenting with CAPS and posterior segment ocular manifestations. The main outcomes were the type of posterior segment manifestations at CAPS diagnosis, specifically retinal vascular occlusion, vasculitis, or choroidopathy, and the final best corrected visual acuity (BCVA).

Results: This study included 23 patients (11 cases treated by the authors and 12 published case reports), 21 (91%) of them female. Their median age at diagnosis was 28 years (range 16-79). Ophthalmologic manifestations were usually bilateral (n = 19, 83%) and involved vascular occlusive retinopathy (n = 17, 74%), choroidopathy (n=11, 48%), and/or retinal vasculitis (n = 1, 4%). Final BCVA was not significantly worse than BCVA at diagnosis (P = 0.16). Retinal vascular occlusions were associated with poorer final visual acuity than choroidopathy (P = 0.002). After a median follow-up of 14 months [2-132], nearly half the patients (n = 11, 48%) had permanent vision loss including BCVA < 20/400 for 4 patients.

Conclusion: Posterior ophthalmic manifestations of CAPS were mainly bilateral retinal vascular occlusion, which had the worst visual prognosis, followed by choroidopathy and retinal vasculitis. Permanent visual loss was common.
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http://dx.doi.org/10.1097/IAE.0000000000003185DOI Listing
April 2021

Is the presence of antiphospholipid antibodies a poor prognostic factor for patients with hemolysis, elevated liver enzymes, and low platelet count syndrome?

Am J Obstet Gynecol 2021 Apr 1. Epub 2021 Apr 1.

Internal Medicine and Clinical Immunology Department, Reference Center for Rare Systemic Autoimminue Diseases of North and Northwest France (CeRAINO), European Reference Network on Rare Connective Tissues and Musculoskeletal Diseases (ReCONNECT), Centre Hospitalier Universitaire de Lille, Lille, France.

Background: The characteristics of antiphospholipid syndrome-associated hemolysis, elevated liver enzymes, and low platelet count syndrome are poorly described, likely because of the low frequency of this combination of syndromes.

Objective: This study aimed to compare the characteristics and prognosis of hemolysis, elevated liver enzymes, and low platelet count syndrome in patients with and without antiphospholipid syndrome.

Study Design: In this multicenter, case-control study, adult women diagnosed with hemolysis, elevated liver enzymes, and low platelet count syndrome before 34 weeks' gestation and who were also tested for antiphospholipid antibodies according to international diagnostic recommendations were included. Cases labeled "HELLP-APS+" were defined as patients who fulfilled the international classification criteria for antiphospholipid syndrome; they were retrospectively recruited by screening the 672 patients with antiphospholipid syndrome in our antiphospholipid syndrome database. Control cases labeled "HELLP-APS-" were defined as patients who did not fulfill the criteria for antiphospholipid syndrome; they were retrospectively recruited from our hospital admission database.

Results: Overall, 71 patients were included (mean age, 30±5 years), with 23 patients in the hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome group and 48 patients in the hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome group. The live birth rate was significantly lower for patients with hemolysis, elevated liver enzymes, and low platelet count with antiphospholipid syndrome than for those with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (43.5% vs 89.4%; P<.001). The patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome gave birth prematurely more often than the patients without antiphospholipid syndrome (24 weeks' gestation; 22.0-28.0 weeks vs 30 weeks' gestation; 27.0-33.0 weeks; P<.001). Among the patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome, 39% required an induced abortion owing to hemolysis, elevated liver enzymes, and low platelet count syndrome severity vs 8.5% of the patients with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (P=.006). The intensive care unit admission rate was 61.9% in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome, which was significantly higher than the rate of 27.7% in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (P=.007). None of the mothers died.

Conclusion: Our results suggest that the presence of antiphospholipid syndrome is a poor prognostic factor for both the mother and fetus in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome.
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http://dx.doi.org/10.1016/j.ajog.2021.03.039DOI Listing
April 2021

Evolution of kidney antibody secreting cells molecular signature in lupus patients with active nephritis upon immunosuppressive therapy.

Arthritis Rheumatol 2021 Mar 1. Epub 2021 Mar 1.

Institut Necker Enfants Malades, INSERM U1151/CNRS UMS 8253, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Objectives: To characterize kidney and urine antibody secreting cells (ASC) from patients with active lupus nephritis (LN), before and after induction therapy.

Methods: We included patients with biopsy proven active LN and performed anti-CD138 staining of kidney biopsy samples to visualize ASC. We performed single-cell gene expression profiling on sorted ASC from fresh biopsy samples by multiplex RT-PCR. We used a gene set allowing the study of ASC maturation from plasmablast to long-lived plasma cells. We quantified urine ASC from untreated LN patients at diagnosis and after 6 months of prospective follow up during induction therapy.

Results: The number of kidney CD138+ ASC in 46 untreated LN patients correlated with a low estimated glomerular filtration rate and with tubulointerstitial damage. Most kidney ASC from 3 untreated patients had a plasmablast molecular signature, contrasting with ASC from 4 patients refractory to immunosuppressant drugs that expressed long-lived plasma cells genes and clustered with long-lived bone marrow plasma cells from 2 healthy donors. Some urine ASC with plasmablast signature were detected in patients with untreated active LN. The presence of urine ASC at 6 months was associated with treatment failure.

Conclusion: These results suggest a potential interest of ASC-directed therapy in refractory LN.
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http://dx.doi.org/10.1002/art.41703DOI Listing
March 2021

Epidemiology of cutaneous involvement in Sjögren syndrome: Data from three French pSS populations (TEARS, ASSESS, diapSS).

Joint Bone Spine 2021 Jul 19;88(4):105162. Epub 2021 Feb 19.

Inserm 1227, LabEx IGO, rhumatologie, centre de référence maladies rares CERAINO, université de Bretagne Occidentale, CHU de Brest, 29200 Brest, France. Electronic address:

Objective: To determine the prevalence and significance of dermatological disorders in primary Sjögren syndrome (pSS).

Methods: We used 2 pSS French cohorts (ASSESS, in which prevalence of skin disorders in 395 patients was evaluated; and diapSS, in which 76 on 139 pSS patients had an examination by a dermatologist) and baseline data of the TEARS randomized trial (110 patients with recent or active pSS treated with rituximab or placebo and evaluated for skin dryness using a visual analogue scale (VAS) out of 100).

Results: Skin manifestations included in the EULAR Sjögren syndrome disease activity index (ESSDAI) were rare in the ASSESS cohort (n=16/395, 4.1%, mainly purpuras; only 3 had high activity), but they were associated with activity in the other ESSDAI domains (peripheral neurological (P<0.001), muscular (P<0.01), haematological (P<0.05), biological (P<0.05), history of arthritis (P<0.01), splenomegaly (P<0.05) and higher gamma globulin levels (P<0.01)). In the diapSS cohort, compared to pSS patients not receiving a dermatological consultation, the pSS patients who had a dermatological consultation had significantly more dermatological involvement outside the ESSDAI score [38.2% (29/76) versus 15.9% (10/63); P<0.01]. The TEARS study showed a high prevalence of cutaneous dryness (VAS>50; 48.2%) and found that patients with dry skin had higher VAS pain (P<0.01) and drought (P<0.01) scores.

Conclusion: ESSDAI skin activity is rare and associated with hypergammaglobulinemia and ESSDAI activity. Systematic dermatological examination is informative for non-specific lesions. The most common skin disorder is skin dryness, which is associated with a higher pain and overall subjective dryness.
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http://dx.doi.org/10.1016/j.jbspin.2021.105162DOI Listing
July 2021

Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial.

Ann Rheum Dis 2020 Nov 18. Epub 2020 Nov 18.

Rheumatology, CHU Strasbourg, Centre National de Référence des maladies auto-immunes et systémiques rares Est/Sud-Ouest (RESO), Strasbourg, Alsace, France.

Objectives: No immunomodulatory drug has been approved for primary Sjögren's syndrome, a systemic autoimmune disease affecting 0.1% of the population. To demonstrate the efficacy of targeting interleukin 6 receptor in patients with Sjögren's syndrome-related systemic complications.

Methods: Multicentre double-blind randomised placebo-controlled trial between 24 July 2013 and 16 July 2018, with a follow-up of 44 weeks, involving 17 referral centres. Inclusion criteria were primary Sjögren's syndrome according to American European Consensus Group criteria and score ≥5 for the EULAR Sjögren's Syndrome Disease activity Index (ESSDAI, score of systemic complications). Patients were randomised to receive either 6 monthly infusions of tocilizumab or placebo. The primary endpoint was response to treatment at week 24. Response to treatment was defined by the combination of (1) a decrease of at least 3 points in the ESSDAI, (2) no occurrence of moderate or severe activity in any new domain of the ESSDAI and (3) lack of worsening in physician's global assessment on a Visual Numeric Scale ≥1/10, all as compared with enrolment.

Results: 110 patients were randomised, 55 patients to tocilizumab (mean (SD) age: 50.9 (12.4) years; women: 98.2%) and 55 patients to placebo (54.8 (10.7) years; 90.9%). At 24 weeks, the proportion of patients meeting the primary endpoint was 52.7% (29/55) in the tocilizumab group and 63.6% (35/55) in the placebo group, for a difference of -11.4% (95% credible interval -30.6 to 9.0) (Pr[Toc >Pla]=0.14).

Conclusion: Among patients with primary Sjögren's syndrome, the use of tocilizumab did not improve systemic involvement and symptoms over 24 weeks of treatment compared with placebo.

Trial Registration Number: NCT01782235.
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http://dx.doi.org/10.1136/annrheumdis-2020-218467DOI Listing
November 2020

Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence.

Arthritis Res Ther 2020 09 25;22(1):223. Epub 2020 Sep 25.

UPMC, Université Paris 6, Paris, France.

Background: Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients.

Methods: HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ < 200 ng/mL.

Results: The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76-0.94) and specificity of 0.89 (95% CI 0.72-0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level (< 20 ng/mL) were also undetectable (< 20 ng/mL).

Conclusions: These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.
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http://dx.doi.org/10.1186/s13075-020-02291-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517694PMC
September 2020

Highly sensitive serum cardiac troponin T and cardiovascular events in patients with systemic lupus erythematosus (TROPOPLUS study).

Rheumatology (Oxford) 2021 Mar;60(3):1210-1215

Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris (APHP), Institut national de la santé et de la recherche médicale (INSERM) U1149, Université de Paris, France.

Objective: Identification of biological markers able to better stratify cardiovascular risks in SLE patients is needed. We aimed to determine whether serum cardiac troponin T (cTnT) levels measured with a highly sensitive assay [high sensitivity cTnT (HS-cTnT)] may predict cardiovascular events (CVEs) in SLE.

Method: All SLE patients included between 2007 and 2010 in the randomized, double-blind, placebo-controlled, multicentre PLUS trial were screened. Patients with no past history of CVE at inclusion and a follow-up period of >20 months were analysed. HS-cTnT concentration was measured using the electrochemiluminescence method on serum collected at PLUS inclusion. The primary outcome was the incident CVE. Factors associated with the primary outcome were identified and multivariate analysis was performed.

Results: Overall, 442 SLE patients (of the 573 included in the PLUS study) were analysed for the primary outcome with a median follow up of 110 (interquartile range: 99-120) months. Among them, 29 (6.6%) experienced at least one CVE that occurred at a median of 67 (interquartile range: 31-91) months after inclusion. Six out of 29 patients had more than one CVE. In the multivariate analysis, dyslipidaemia, age and HS-cTnT were associated with the occurrence of CVE. Kaplan-Meier analysis showed that a concentration of HS-cTnT > 4.27 ng/l at inclusion increased by 2.7 [hazard ratio 2.7 (95% CI: 1.3, 5.6), P =0.0083] the risk of CVE in SLE.

Conclusion: HS-cTnT measured in serum is the first identified biomarker independently associated with incident CVE in SLE patients.
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http://dx.doi.org/10.1093/rheumatology/keaa434DOI Listing
March 2021

Refining myositis associated with primary Sjögren's syndrome: data from the prospective cohort ASSESS.

Rheumatology (Oxford) 2021 02;60(2):675-681

Service de Rhumatologie, CNR RESO, CHU Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Objectives: To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS).

Methods: The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months' follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed.

Results: Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested 'pure' pSS myositis. Steroids plus MTX was then efficient in achieving remission.

Conclusions: Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.
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http://dx.doi.org/10.1093/rheumatology/keaa257DOI Listing
February 2021

Risk factors for hydroxychloroquine retinopathy in systemic lupus erythematosus: a case-control study with hydroxychloroquine blood-level analysis.

Rheumatology (Oxford) 2020 12;59(12):3807-3816

Department of Internal Medicine, Centre de Référence Maladies Auto-Immunes et Systémiques Rares d'Ile de France, Cochin Hospital, APHP.

Objective: HCQ is an essential medication in SLE, proven to lengthen survival and reduce flares. Its use, however, is limited by its rare but severe ophthalmological complications. Here, we aimed to analyse factors associated with HCQ retinopathy including HCQ blood levels.

Methods: This case-control study compared SLE patients with and without HCQ retinopathy, defined by abnormal results for at least two of the following ophthalmological tests: automated visual fields, spectral-domain optical coherence tomography (SD-OCT), multifocal electroretinogram (mfERG) and fundus autofluorescence. We compared clinical and laboratory findings to assess risk factors for HCQ retinopathy.

Results: The study included 23 patients with confirmed retinopathy (cases) and 547 controls. In the univariate analysis, age (P < 0.001), height (P = 0.045), creatinine clearance (P < 0.001), haemoglobin concentration (P = 0.01), duration of HCQ intake, (P < 0.001), higher cumulative HCQ dose (P < 0.001) and geographical origin (West Indies and sub-Saharan Africa) (P = 0.007) were associated with the risk of retinopathy, while HCQ blood levels were not. In the multivariate analysis, only cumulative dose (P = 0.016), duration of intake (P = 0.039), creatinine clearance (P = 0.002) and geographical origin (P < 0.0001, odds ratio 8.7) remained significantly associated with retinopathy.

Conclusion: SLE patients on HCQ should be closely monitored for retinopathy, especially those from the West Indies or sub-Saharan Africa, or with renal insufficiency, longer HCQ intake or a high cumulative dose. Although reducing the daily dose of HCQ in patients with persistently high HCQ blood levels seems logical, these concentrations were not associated with retinopathy in this study with controls adherent to treatment.
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http://dx.doi.org/10.1093/rheumatology/keaa157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186841PMC
December 2020

Analysis of risk factors for complications and adverse obstetrical outcomes in women with Takayasu arteritis: a French retrospective study and literature review.

Clin Rheumatol 2020 Sep 23;39(9):2707-2713. Epub 2020 Mar 23.

Sorbonne Université, Département Hospitalo-Universitaire-Inflammation-Immunopathologie-Biothérapie (DMU i3), Service de Médecine Interne, F-75005, Paris, France.

Objective: Takayasu arteritis (TAK) is a large vessel vasculitis affecting young women of childbearing age. The outcome of pregnancies in TAK patients, factors associated with maternal and foetal complications and adverse outcomes were analysed.

Methods: All pregnancies in women with a TAK diagnosis were retrospectively included from 20 French hospitals providing care for TAK, until August 2015.

Results: The study consisted of 43 pregnancies in 33 women, including 29 with a pre-existing TAK diagnosis and 4 diagnosed during pregnancy. Complications were observed in 20 pregnancies (47%), including 35% with arterial hypertension (n = 15), 9% with pre-eclampsia (n = 4), 2% with HELLP syndrome (n = 1) and 14% with intrauterine growth restriction (IUGR, n = 6, leading in one case to a medically indicated termination of pregnancy). There were 42 live births (98%) at a median term of 38 [27-42] weeks gestation including 9 before 37 weeks (21%). The median birth weight was 2940 [610-4310] grams. Five children (12%) required transfer to a neonatal intensive care unit. One premature boy (27 weeks gestation) died after 2 days. Treatment during pregnancy included steroids (n = 25/43; 58%), azathioprine (n = 9/43; 21%) and infliximab (n = 1/43; 2%). The risk of developing arterial hypertension during pregnancy was associated with previous chronic arterial hypertension and with an infra-diaphragmatic vasculitis injury (P = 0.01 and P = 0.04, respectively). No correlation was reported between TAK activity and any of the obstetrical complications described in the study.

Conclusion: This study showed a high rate of adverse obstetrical complications without significant impact on live birth rates. Pregnancy did not appear to influence TAK disease activity. Key Points • We observed a high rate of adverse obstetrical complications in women with Takayasu arteritis; however, the rate of live births was high. Pregnancy did not appear to influence TA disease activity.
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http://dx.doi.org/10.1007/s10067-020-05024-4DOI Listing
September 2020

Seasonal effect on fatigue, pain and dryness in primary Sjögren's syndrome.

Arthritis Res Ther 2020 02 24;22(1):39. Epub 2020 Feb 24.

Department of Rheumatology, Referral Center for Rare Autoimmune and Systemic Diseases, Strasbourg University Hospital, Strasbourg, France.

Background: To assess the presence of a seasonal effect on fatigue, pain and dryness in primary Sjögren's syndrome (pSS).

Methods: Data (date; visual analogue scales (VAS) for pain, fatigue and dryness) were extracted from three randomised placebo-controlled trials (RCTs) evaluating infliximab (TRIPSS; n = 103 patients), hydroxychloroquine (JOQUER; n = 120 patients) and rituximab (TEARS; n = 120 patients) and from the 5-year follow-up of the ASSESS prospective cohort (n = 395 patients). Data were analysed at each visit for each patient, according to the day, the month of the year and the season. Linear mixed models were used to take into account the repeated structure of the data and to analyse a potential cyclic effect.

Results: A total of 744, 584, 848 and 682 pain, fatigue and dryness VASs were collected on 632 subjects in spring, summer, fall and winter, respectively. No significant difference was observed in pain, fatigue and dryness, according to the month of the year or the season (all p values > 0.05).

Conclusion: In pSS, seasonality does not affect patient-reported outcomes (PROs) on fatigue, pain and dryness.
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http://dx.doi.org/10.1186/s13075-020-2118-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041128PMC
February 2020

Thrombocytopenia in primary antiphospholipid syndrome, a marker of high-risk patients?

Eur J Intern Med 2020 04 5;74:106-107. Epub 2020 Feb 5.

Univ. Lille, INSERM U995, CHU Lille, Département de Médecine Interne et d'Immunologie clinique, Centre National de Référence Maladies Systémiques et Auto-Immunes Rares, European Reference Network on Rare Connective Tissue and MusculoskeletalDiseases (ReCONNECT), F-59000 Lille, France.

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http://dx.doi.org/10.1016/j.ejim.2020.01.017DOI Listing
April 2020

Is early-onset primary Sjögren's syndrome a worse prognosis form of the disease?

Rheumatology (Oxford) 2019 07;58(7):1163-1167

Service de médecine interne, CHU Claude Huriez, Lille Cedex, France.

Objectives: Onset of primary SS is usually between 40 and 60 years of age, with severe systemic complications in 15% of cases. We sought to determine whether early-onset disease is related to a specific phenotype and if it is predictive of a poor outcome.

Methods: Biological and clinical data from 393 patients recruited in the ASSESS cohort, a French multicentre prospective cohort, were compared according to age at diagnosis.

Results: Fifty-five patients had early-onset disease, defined as age ⩽35 years at diagnosis, and presented a significantly higher frequency of salivary gland enlargement (47.2% vs 33.3%, P = 0.045), adenopathy (25.5% vs 11.8%, P = 0.006), purpura (23.6% vs 9.2%, P = 0.002) and renal involvement (16.4% vs 4.4%, P = 0.003). They had a higher frequency of hypergammaglobulinaemia (60.8% vs 26.6%, P < 0.001), RF positivity (41.5% vs 20.2%, P < 0.001), low C3 level (18.9% vs 9.1%, P = 0.032), low C4 level (54.7% vs 40.2%, P = 0.048) and autoantibodies [84.6% with anti-SSA vs 54.4% (P < 0.001) and 57.7% with anti-SSB vs 29.7% (P < 0.001)]. The change in ESSDAI scores between baseline and the 5-year follow-up was significantly different (P = 0.005) with a trend for worsening in the early-onset group (0.72, P = 0.27) and a significant improvement in the later onset group (-1.27, P < 0.0001).

Conclusion: Early-onset primary SS is associated with a specific phenotype defined by clinical and biological features known to be predictive factors of severe systemic disease. Interestingly, we showed a different evolution of the ESSDAI score depending on the age at disease onset, patients with early-onset disease tending to worsen over time.
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http://dx.doi.org/10.1093/rheumatology/key392DOI Listing
July 2019

Intrauterine fetal deaths related to antiphospholipid syndrome: a descriptive study of 65 women.

Arthritis Res Ther 2018 Nov 6;20(1):249. Epub 2018 Nov 6.

AP-HP, Cochin Hospital, Internal Medicine Department, Centre de référence maladies auto-immunes et systémiques rares d'île de France, 27 Rue du Faubourg Saint Jacques, 75014, Paris, France.

Objective: Although one of the three obstetric manifestations of antiphospholipid syndrome (APS) is intrauterine fetal death (IUFD), little is known about it in this context. We report the first large series of patients with APS and IUFD.

Methods: We retrospectively analyzed the history and clinical data of women at four French hospitals. All had (1) APS diagnosis (Sydney criteria) and (2) IUFD at or after 10 weeks of gestation (weeks) between 2000 and 2016.

Results: The study included 65 women. Their median age at the index IUFD was 29 years (IQR 26-33); 38 (58%) were primigravidas. The index IUFD was the first APS clinical manifestation in 48 women (74%). Overall, 35% had a triple-positive antibody profile. IUFD occurred at a median gestational age of 24 weeks (IQR 18-27) and was associated with maternal obstetric complications in 16 women (25%), namely, preeclampsia (n = 12), hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP) (n = 6), and/or placental abruption (n = 5). Half of the 50 women with available data had a small-for-gestational-age fetus. Overall, including during the follow-up period of 4 years (IQR 2-9), 28 women (43%) had at least one thrombosis, and 29% were diagnosed with systemic lupus erythematosus (SLE). Ultimately, 54 women (83%) had at least one live birth. Only one woman had three consecutive early miscarriages.

Conclusion: IUFD was most often the inaugural sign of APS. Of the APS classification criteria, IUFD, preeclampsia, and thromboses were common in this cohort, while the "3 consecutive early miscarriages" criterion was met only once. With treatment, most of the women successfully had at least one live birth.
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http://dx.doi.org/10.1186/s13075-018-1745-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235231PMC
November 2018

A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires.

Clin Pharmacol Ther 2019 08 2;106(2):374-382. Epub 2018 Sep 2.

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ < 200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI < 80%). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 23.4% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.).
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http://dx.doi.org/10.1002/cpt.1194DOI Listing
August 2019

Reply to the comment of Fayet et al. Obstacles and motivations to influenza and pneumococcal vaccination in patients with rheumatoid arthritis. A qualitative study.

Joint Bone Spine 2019 01 24;86(1):119. Epub 2018 Jul 24.

Inserm CIC 1417, Paris Descartes university, Sorbonne Paris Cité, Paris, France; Antimicrobial Stewardship Team, Assistance publique-Hôpitaux de Paris, hôpitaux universitaires Paris Centre-Cochin, 75014 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.jbspin.2018.06.015DOI Listing
January 2019

Classification of primary antiphospholipid syndrome as systemic lupus erythematosus: Analysis of a cohort of 214 patients.

Autoimmun Rev 2018 Sep 10;17(9):866-872. Epub 2018 Jul 10.

Université Paris Descartes-Sorbonne Paris Cité, France; AP-HP, Centre de référence maladies auto-immunes et systémiques rares de l'île de France, Service de médecine interne Pôle médecine, Hôpital Cochin, 27 rue du Faubourg Saint Jacques, 75679 Paris cedex 14, France; INSERM U 1153, Center for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France. Electronic address:

Objectives: To assess the limitations of the SLICC (Systemic Lupus International Collaborating Clinics) classification criteria for systemic lupus erythematosus (SLE), in patients with primary antiphospholipid syndrome (PAPS).

Methods: Retrospective study of a cohort of APS patients (Sydney criteria). We successively excluded patients with (1) at least one "SLE-specific" manifestation (biopsy-proven SLE nephropathy, arthritis, cutaneous, or neurologic SLE manifestations, pericarditis, autoimmune haemolytic anaemia, oral and nasal ulcers, non-scarring alopecia, anti-dsDNA, and anti-Sm antibodies), (2) any other autoimmune connective tissue disease, and/or (3) antinuclear antibodies >1/320. Careful file review confirmed PAPS among the remaining patients. We then assessed the number of SLICC criteria each patient met.

Results: Among these 214 APS patients, we excluded 85 with at least one SLE-specific manifestation, 8 with another connective tissue disease, and 21 with antinuclear antibodies >1/320, leaving 100 patients with primary APS. Among them, 28% met at least 4 SLICC classification criteria including one clinical and one immunological criterion (antiphospholipid antibodies, aPL, by definition) and could thus theoretically be classified with SLE. Fourteen had an arterial phenotype (50%), 9 a history of catastrophic APS (32%), and 18 a triple-positive profile for aPL (64%). None had developed SLE during a median follow-up of 12 [6.5-17] years.

Conclusion: Because 28% of our patients with longstanding and strictly defined PAPS could be mistakenly classified as SLE, they were at risk of deleterious therapeutic management. We therefore suggest that any future classification for SLE should specifically require at least one SLE-specific criterion for patients with aPL.
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http://dx.doi.org/10.1016/j.autrev.2018.03.011DOI Listing
September 2018

Risk Factors for Adverse Maternal and Fetal Outcomes in Women With Confirmed aPL Positivity: Results From a Multicenter Study of 283 Pregnancies.

Front Immunol 2018 7;9:864. Epub 2018 May 7.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili di Brescia, Brescia, Italy.

Objective: Antiphospholipid antibodies positivity (aPL) is considered as a risk factor for adverse pregnancy outcome (APO). The aim of this study was to determine the risk factors for APO in patients with confirmed aPL positivity, isolated (aPL carriers) or associated with a definite primary antiphospholipid syndrome (PAPS).

Methods: The clinical and laboratory features of 283 pregnancies occurring between 2000 and 2014 in 200 women were collected in three institutions.

Results: The rate of live birth was 87.9% and APO was observed in 50 cases (17.7%). Multivariate analysis showed that the independent variables related to APO were the concomitant diagnosis of an organ-specific autoimmune disease ( = 0.012, odds ratio (OR) 3.29, confidence interval (CI) 95% 1.29-8.38) and the presence of low complement levels during the first trimester ( = 0.02, OR 2.3, CI 95% 1.17-9.15). No statistical differences were found in APO occurrence among patients treated with low-dose aspirin (LDA) versus those treated with LDA plus heparin (LMWH), but LDA + LMWH was more frequently administered in patients with triple aPL positivity ( = 0.001, OR 3.21, CI 95% 1.48-7.11) and with PAPS ( < 0.001, OR 8.08, CI 95% 4.3-15.4). Based on clinical history, the patients were divided into four groups: obstetric, thrombotic, non-criteria antiphospholipid syndrome (clinical non-criteria), and aPL carriers. APOs were more frequent in the thrombotic group (24%). Seven patients had a thrombotic event during pregnancy or puerperium (2.4%).

Conclusion: Maternal and fetal complications were observed in some aPL-positive patients despite their efficient management according to the current recommendations. A higher risk of APO was observed in patients with a previous thrombosis and/or more complex autoimmune phenotype.
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http://dx.doi.org/10.3389/fimmu.2018.00864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949611PMC
July 2019

A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires.

Clin Pharmacol Ther 2018 06 9;103(6):1074-1082. Epub 2017 Nov 9.

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ <200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI <80% or MMAS-8 <6). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 39.9% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.).
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http://dx.doi.org/10.1002/cpt.885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858989PMC
June 2018

Role of the IL-12/IL-35 balance in patients with Sjögren syndrome.

J Allergy Clin Immunol 2018 07 12;142(1):258-268.e5. Epub 2017 Sep 12.

Université Paris-Sud, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris-Sud, Paris, and the Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, France. Electronic address:

Background: An interferon signature is involved in the pathogenesis of primary Sjögren syndrome (pSS), but whether the signature is type 1 or type 2 remains controversial. Mouse models and genetic studies suggest the involvement of T1 and type 2 interferon pathways. Likewise, polymorphisms of the IL-12A gene (IL12A), which encodes for IL-12p35, have been associated with pSS. The IL-12p35 subunit is shared by 2 heterodimers: IL-12 and IL-35.

Objective: We sought to confirm genetic association of the IL12A polymorphism and pSS and elucidate involvement of the IL-12/IL-35 balance in patients with pSS by using functional studies.

Methods: The genetic study involved 673 patients with pSS from 2 French pSS cohorts and 585 healthy French control subjects. Functional studies were performed on sorted monocytes, irrespective of whether they were stimulated. IL12A mRNA expression and IL-12 and IL-35 protein levels were assessed by using quantitative RT-PCR and ELISA and a multiplex kit for IL-35 and IL-12, respectively.

Results: We confirmed association of the IL12A rs485497 polymorphism and pSS and found an increased serum protein level of IL-12p70 in patients with pSS carrying the risk allele (P = .016). Serum levels of IL-12p70 were greater in patients than control subjects (P = .0001), especially in patients with more active disease (P = .05); conversely, IL-35 levels were decreased in patients (P = .0001), especially in patients with more active disease (P = .05). In blood cellular subsets both IL12p35 and EBV-induced gene protein 3 (EBI3) mRNAs were detected only in B cells, with a trend toward a lower level among patients with pSS.

Conclusion: Our findings emphasize involvement of the IL-12/IL-35 balance in the pathogenesis of pSS. Serum IL-35 levels were associated with low disease activity, in contrast with serum IL-12p70 levels, which were associated with more active disease.
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http://dx.doi.org/10.1016/j.jaci.2017.07.041DOI Listing
July 2018

Pulmonary Arterial Hypertension Associated With Systemic Lupus Erythematosus: Results From the French Pulmonary Hypertension Registry.

Chest 2018 01 26;153(1):143-151. Epub 2017 Aug 26.

Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre; AP-HP, Centre de reference de l'Hypertension Pulmonaire, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre; INSERM UMR_S999, LabEx LERMIT, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson, France.

Background: Pulmonary arterial hypertension (PAH) is a rare complication of systemic lupus erythematosus (SLE).

Methods: We identified all patients with SLE and PAH (SLE-PAH) who were enrolled in the French Pulmonary Hypertension Registry with a diagnosis confirmed by right heart catheterization (RHC). A control group of 101 patients with SLE without known PAH was selected from SLE expert centers participating in the Pulmonary Hypertension Registry. Survival was estimated by the Kaplan-Meier method. Hazard ratios associated with potential predictors of death were estimated using Cox proportional hazard models.

Results: Of the 69 patients with SLE-PAH identified in the French Pulmonary Hypertension Registry, 51 were included in the study. They did not differ from the control group regarding age, sex, or duration of SLE at the time of the analysis but had a higher frequency of anti-SSA and anti-SSB antibodies. The delay between SLE diagnosis and PAH diagnosis was 4.9 years (range, 2.8-12.9) years. The 3- and 5-year overall survival rates were 89.4% (95% CI, 76.2%-96.5%) and 83.9% (95% CI, 68.8%-92.1%), respectively. The survival rate was significantly better in patients with anti-U1-RNP antibodies (P = .04).

Conclusions: Patients with SLE-PAH have an overall 5-year survival rate of 83.9% after the PAH diagnosis. Anti-SSA/SSB antibodies may be a risk factor for PAH, and the presence of anti-U1-RNP antibodies appears to be a protective factor regarding survival.
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http://dx.doi.org/10.1016/j.chest.2017.08.014DOI Listing
January 2018

Pneumococcal vaccination in patients with systemic lupus erythematosus: A multicenter placebo-controlled randomized double-blind study.

Vaccine 2017 09 4;35(37):4877-4885. Epub 2017 Aug 4.

Inserm, CIC 1417, Paris, France; Université Paris Descartes, Sorbonne Paris Cité AP-HP, Groupe Hospitalier Cochin Broca Hôtel-Dieu, Fédération d'Infectiologie, Paris, France; Inserm, F-CRIN I-REIVAC, France. Electronic address:

Background: Invasive pneumococcal disease and respiratory tract infections are both frequent and severe in patients with systemic lupus erythematosus (SLE). This study aimed to compare the immunological efficacy and safety of pneumococcal vaccination with the 23-valent polysaccharide (PPS) vaccine alone to a sequential immunization with the 7-valent pneumococcal conjugate (PnCj) vaccine followed by PPS in patients with SLE and stable diseaase.

Methods: Multicenter randomized placebo-controlled double-blind trial: PPS vaccine alone (placebo-PPS group) or PnCj vaccine followed by PPS vaccine (PnCj-PPS group) 24weeks later. The primary endpoint was the rate of responders at week 28 to at least 5 of the 7 serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) shared by both PPS and PnCj. Pneumococcal IgG antibodies' opsonophagocytic activity (OPA) were also assessed.

Results: Twenty-five patients in the placebo-PPS group and 17 in the PnCj-PPS group were included in a modified intention-to-treat analysis. The primary endpoint was reached in 72% (18/25) in the placebo-PPS and 76% (13/17) in the PnCj-PPS group (p=0.75). There was no difference in the rates of responders with OPA. At week 52, 13/18 (72%) patients in the placebo-PPS group and 10/13 (77%) patients in the PnCj-PPS group (p=0.77) that met the primary endpoint at week 28 were still responders to ≥5/7 serotypes shared by both PPS and PnCj vaccines. Nine SLE flares were reported in 6 patients (4 in the placebo-PPS and 2 in the PnCj-PPS groups respectively, p=0.70).

Conclusion: Sequential administration of PnCj vaccine followed by PPS vaccine is safe and shows short-term immunological efficacy in patients with SLE but was not superior to the PPS vaccine alone.

Trial Registration: www.clinicaltrials.gov, NCT NCT00611663.
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http://dx.doi.org/10.1016/j.vaccine.2017.07.094DOI Listing
September 2017

Rituximab alone as induction therapy for membranous lupus nephritis: A multicenter retrospective study.

Medicine (Baltimore) 2017 Jul;96(27):e7429

Department of Nephrology, Hôpital Bichat, AP-HP, Université Paris Diderot, DHU FIRE, INSERM U1149, Paris Department of Nephrology, Hôpital Henri Duffaut, Avignon Department of Nephrology, Centre Hospitalier Sud Francilien, Corbeil-Essonnes Department of Nephrology, Hôpital de la Pitié Salpêtrière, AP-HP, Paris, France; INSERM CESP team 5, Villejuif Department of Medicine, Hôpital François Quesnay, Mantes-la-Jolie Department of Nephrology, CHU de Point-à Pitre, Guadeloupe Department of Internal Medicine,Hôpital Cochin, APHP Department of Nephrology, Hôpital Européen Georges-Pompidou, APHP, Paris, France.

The optimal treatment for pure membranous lupus nephritis (MLN) remains undetermined. Rituximab constitutes a promising therapeutic option for lupus nephritis and is currently being evaluated for use in idiopathic membranous nephritis. We retrospectively analysed the efficacy and tolerance of rituximab as a monotherapy in the induction treatment of pure MLN.We retrospectively investigated SLE patients with biopsy-proven pure class V lupus nephritis presenting with a protein-to-creatinine ratio of at least 2 g/g and treated with rituximab as monotherapy. A background low dose of corticosteroids (≤20 mg/day) was allowed, as was hydroxychloroquine; higher doses of steroids and/or immunosuppressive drugs fell under the exclusion criteria. Remission status was evaluated at baseline and 6, 12, and 24 months after rituximab.The study included 15 patients (13 women, median age 37 years, 27% with extra-renal manifestations, median SLE duration 1.5 years). The median protein-to-creatinine ratio was 4.9 g/g, 80% of the patients had nephrotic-range proteinuria, the median serum albumin was 24 g/L, the median serum creatinine was 0.7 mg/dL, and the median eGFR was 122 mL/min/1.73 m. The median follow-up was 29 months (6-112 months). Treatment failure occurred in 2 patients. However, remission was recorded in the remaining 13 (87%, complete remission in 8 patients) with a median time to remission of 5 months. Median proteinuria decreased from 4.9 g/g to 0.16 g/g at month 12 and to 0.11 g/g at month 24. Median serum albumin increased to 36.5 g/L at month 24, and all patients had serum albumin levels greater than 30 g/L at month 12. Renal function remained stable in all patients. Relapse of proteinuria was recorded in 3 patients (at 12, 29, and 34 months). No patients experienced serious adverse events.Rituximab as monotherapy may represent an effective treatment for pure MLN with an excellent tolerance profile.
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http://dx.doi.org/10.1097/MD.0000000000007429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502178PMC
July 2017

Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors: A Randomized, Controlled Trial.

Arthritis Rheumatol 2017 11 15;69(11):2175-2186. Epub 2017 Oct 15.

National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France.

Objective: In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN).

Methods: All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24.

Results: Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms.

Conclusion: Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.
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http://dx.doi.org/10.1002/art.40205DOI Listing
November 2017

Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: A study of 103 episodes in 89 adult patients.

Autoimmun Rev 2017 Jul 5;16(7):743-749. Epub 2017 May 5.

Service d'immunologie Clinique et médecine interne, CHU de Strasbourg, France.

Objectives: Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory syndrome that can occur during systemic lupus erythematosus (SLE). Data on MAS in adult SLE patients are very limited. The aim of this study is to describe the clinical characteristics, laboratory findings, treatments, and outcomes of a large series of SLE-associated MAS.

Methods: We conducted a retrospective study that included 103 episodes of MAS in 89 adult patients with SLE.

Results: 103 episodes in 89 adult patients were analyzed. Median age at first MAS episode was 32 (18-80) years. MAS was inaugural in 41 patients (46%).Thirteen patients relapsed. Patients had the following features: fever (100% episodes), increased serum levels of AST (94.7%), LDH (92.3%), CRP (84.5%), ferritin (96%), procalcitonin (41/49 cases). Complications included myocarditis (n=22), acute lung injury (n=15) and seizures (n=11). In 33 episodes, patients required hospitalization in an ICU and 5 died. Thrombocytopenia and high CRP levels were associated independently with an increased risk for ICU admission. High dose steroids alone as first line therapy induced remission in 37/57 cases (65%). Additional medications as first or second line therapies included IV immunoglobulins (n=22), cyclophosphamide (n=23), etoposide (n=11), rituximab (n=3). Etoposide and cyclophosphamide-based regimens had the best efficacy.

Conclusion: MAS is a severe complication and is often inaugural. High fever and high levels of AST, LDH, CRP, ferritin and PCT should be considered as red flags for early diagnosis. High dose steroids lead to remission in two third of cases. Cyclophosphamide or etoposide should be considered for uncontrolled/severe forms.
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http://dx.doi.org/10.1016/j.autrev.2017.05.010DOI Listing
July 2017

International and multidisciplinary expert recommendations for the use of biologics in systemic lupus erythematosus.

Autoimmun Rev 2017 Jun 18;16(6):650-657. Epub 2017 Apr 18.

Internal Medicine Department, Lille University Hospital, University of Lille, Lille, France.

Background/purpose: Despite conventional immunosuppressants, active and steroid-dependent systemic lupus erythematosus (SLE) represents a therapeutic challenge. Only one biologic, belimumab, has been approved, but other biologics are sometimes used off-label. Given the lack of evidence-based data in some clinical situations encountered in real life, we developed expert recommendations for the use of biologics for SLE.

Methods: The recommendations were developed by a formal consensus method. This method aims to formalize the degree of agreement among experts by identifying, through iterative ratings with feedback, the points on which experts agree, disagree or are undecided. Hence, the recommendations are based on the agreed-upon points. We gathered the opinion of 59 French-speaking SLE experts from 3 clinical networks dedicated to systemic autoimmune diseases (FLEUR, IMIDIATE, FAI2R) from Algeria, Belgium, France, Italy, Morocco, Switzerland and Tunisia. Represented medical specialities were internal medicine (49%), rheumatology (34%), nephrology (7%), dermatology (5%), pediatrics (3%) and cardiology (2%). Two methodologists and 3 strictly independent SLE expert groups contributed to developing these recommendations: a steering group (SG) (n=9), an evaluation group (EG) (n=28) and a reading group (RG) (n=22). Preliminary recommendations were drafted by the SG, then proposed to the EG. Each EG member rated the degree of agreement from 1 to 9 (1: lowest; 9: strongest) for each recommendation. After 2 rating rounds, the SG submitted a new version of the recommendations to the RG. With comments from the RG, the SG finalised the recommendations.

Results: A total of 17 final recommendations were formulated by the SG, considering all agreement scores and comments by the EG and RG members and the two methodologists. These recommendations define the subset of patients who require a biologic; the type of biologics to use (belimumab, rituximab, etc.) depending on the organ involvement and associated co-treatments; what information should be given to patients; and how to evaluate treatment efficacy and when to consider discontinuation.

Conclusion: Overall, 17 recommendations for the good use of biologics in SLE were formulated by a large panel of SLE experts to provide guidance for clinicians in daily practice. These recommendations will be regularly updated according to the results of new randomized trials and increasing real life experience.
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http://dx.doi.org/10.1016/j.autrev.2017.04.011DOI Listing
June 2017