Impact of patient ancestry on heterogeneity of Sjögren’s disease

Objectives We aimed to compare disease characteristics between primary Sjögren’s syndrome (pSS) patients of African ancestry (AA) and Caucasian ancestry.Methods We conducted a retrospective, case–control study in a French national and European referral centre for pSS. All patients with pSS of AA were matched with two Caucasians patients having similar follow-up duration. We explored clinical and biological parameters associated with a cumulative EULAR Sjögren’s Syndrome Disease Activity Index (cumESSDAI ≥5) (consisting of individual clinESSDAI domain maximum throughout follow-up).Results We identified 74 patients of AA matched with 148 Caucasian. Median age at pSS diagnosis was younger in AA patients (43 years (IQR 33–51) vs 56 years (44.8–59.2), p<0.001). AA patients presented higher median titre of gammaglobulins (18.5 g/L (IQR 15–22.8) vs 13.4 g/L (9.9–16.9), p<0.001), more frequently positive for anti-SSA (88% vs 72%, p=0.007) and anti-RNP (11% vs 2.7%, p=0.023) antibodies. During the follow-up (median: 6 years (IQR 2–11)), AA patients presented more systemic complications: arthritis, myositis, interstitial lung disease, lymphadenopathy, central nervous system involvement. Median cumESSDAI score was higher in AA patients (7.5 (IQR 3.2–16.0) vs 4.0 (IQR 2.0–9.0), p=0.002). Interestingly, in multivariate analyses, factors associated with disease activity were sub-Saharan AA (OR 2.65 (95% CI 1.06 to 6.94)), rheumatoid factor (OR 2.50 (95% CI 1.28 to 4.96)) and anti-RNP positivity (OR 11.1 (95% CI 1.88 to 212)).Conclusion Patients of AA display higher disease activity with a hallmark of higher B-cell activation. Studies to investigate biological drivers behind such differences are needed

Adherence to treatment in systemic lupus erythematosus patients

International audienceAdherence is defined as "the extent to which a person's behaviour coincides with medical or health advice." Poor adherence to therapeutic regimens is a common and expensive problem in patients with chronic diseases including systemic lupus erythematosus (SLE) and is associated with a higher risk of flares, morbidity, hospitalisations and poor renal outcome. Non-adherence to the treatment is multifactorial for most patients and varies according to unintentional or intentional patterns. The rates of non-adherence in SLE patients range from 3% to 76% depending on the assessment methods, which are all subject to limitations. Indeed, poor adherence to therapeutic regimens is difficult to evaluate. Two studies have shown that undetectable blood hydroxychloroquine (HCQ) concentration may be a simple, objective and reliable marker of non-adherence in SLE patients. The accurate diagnosis of non-adherence may prevent one from incorrectly interpreting disease manifestations as a lack of response. It may then avoid an unnecessary or even dangerous treatment escalation

Is there a seasonal effect on fatigue, pain and dryness in primary Sjögren's syndrome? Data from the prospective assess cohort and from 3 randomized controlled trials.

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Repeat kidney biopsies fail to detect differences between azathioprine and mycophenolate mofetil maintenance therapy for lupus nephritis: data from the MAINTAIN Nephritis Trial

Background. In the MAINTAIN Nephritis Trial, azathioprine (AZA) and mycophenolate mofetil (MMF) were compared as maintenance immunosuppressive treatment of proliferative lupus nephritis (LN) after a short-course of intravenous cyclophosphamide. Here, we compare the pathological findings on repeat kidney biopsies between the two groups. Methods. Per protocol, repeat renal biopsies were obtained in 30 patients (16 AZA and 14 MMF) at 2 years (+/-6 months). Baseline and follow-up biopsies were graded according to the International Society of Nephrology/Renal Pathological Society (ISN/RPS) classification. The activity and chronicity indices (AI, CI) were calculated using two different semiquantitative scoring systems (Morel-Maroger and National Institutes of Health). Statistics were performed by non-parametric tests. Results. The clinical characteristics of the 30 re-biopsied patients only marginally differ from the entire MAINTAIN cohort (105 patients). Clinical baseline and follow-up characteristics of AZA- and MMF-treated re-biopsied patients did not differ. Time (SD) to repeat renal biopsy was 25.0 (2.0) and 26.5 (3.3) months in AZA and MMF patients, respectively. More patients had normal renal biopsies or Classes I/II/V LN at follow-up compared to baseline and conversely, less patients had Class IV LN at follow-up. In both groups, the AI statistically decreased at follow-up compared to baseline, while the CI slightly, but significantly, increased. No differences could be detected between the groups. Conclusion. Centralized pathological analyses, including ISN/RPS classification and comparisons of AI/CI, failed to find differences between MMF and AZA at 2 years, a result well in line with the absence of difference in long-term clinical outcome reported elsewhere

Whole blood versus serum hydroxychloroquine levels for drug monitoring of patients with systemic lupus erythematosus : prehole blood versus serum hydroxychloroquine levels for drug monitoring of patients with systemic lupus erythematosus : preliminary results of a pharmacological study.

International audienceBackground: In order to assess the pharmacokinetic/pharmacodynamic relationship of hydroxychloroquine (HCQ) in patients with systemic lupus erythematosus (SLE), HCQ levels have been measured in whole blood as well as in serum but both methods have never been compared. In addition, cut offs for non-adherence (classically 200ng/ml but also 100 ng/mL) have been established only in whole blood. Objectives: The aims of this study were (1) to compare these two pharmacological approaches, and (2) since it would be very interesting to retrospectively assess severe non-adherence in clinical trials or in large cohort of patients in which only serum samples are usually available, to determine if serum HCQ level cut offs could be established for identification of severe non-adherent patients. Methods: The HCQ and desethylchloroquine (DCQ) levels were measured in serum and whole blood from 573 SLE patients. The risk factors for active SLE (SLEDAI score >4) were identified using multiple logistic regression. HCQ serum level was also measured in 51 non-adherent patients (whole blood HCQ level <200 ng/mL). Results: The mean HCQ and DCQ levels were 916 ± 449 and 116 ± 55 ng/mL in whole blood, respectively; and 469 ± 223 and 63 ± 31 ng/mL in serum, respectively. The mean ratio of serum/whole blood level for HCQ and DCQ were 0.53 ± 0.15 and 0.57 ± 0.21, respectively. A strong positive correlation was found between serum and whole blood levels of HCQ (rho=0.837 [CI95% 0.810-0.860], p<0.0001), and DCQ (rho=0.771 [CI95% 0.736-0.802], p<0.0001). In the multivariate analysis, only corticosteroids (p=0.044), immunosuppressant (p=0.027), HCQ whole blood level (p=0.023) and hemoglobin (p=0.009) were identified as an independent risk factor of active SLE but serum HCQ level was not. Given the mean ratio of serum/whole blood level for HCQ was 0.53, we extrapolated that serum HCQ level cut offs of 106 and 53 ng/mL would correspond to the previously used cut-off of 200 and 100 ng/mL of HCQ in whole blood. Using HCQ serum level cut off of 106 ng/mL, 43 of 51 patients (84%) with blood HCQ levels <200 ng/mL would also have been considered as non-adherent. The positive and negative predictive value of HCQ serum level < 106 ng/ml to detect non-adherence were 96.6% and 63.6%, respectively. Of these 51 patients, 25 patients (49%) exhibited HCQ whole blood concentration below 100 ng/mL. Using HCQ serum level cut off of 53 ng/mL, 23 of 25 patients (92%) with HCQ whole blood level<100 ng/mL, would also have been considered as non-adherent. The positive and negative predictive value of HCQ serum level < 53 ng/ml to detect non-adherence were 82.1% and 90.9%. Conclusion: Our data support the use of whole blood rather than serum as the matrix for drug monitoring of HCQ levels in SLE patients. However, when whole blood is not available, our results support the use of HCQ serum level to assess non-adherence with a cut off of 106 ng/mL corresponding to 200 ng/ml in whole bloo

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

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

Epidemiology of neurological manifestations in Sjögren's syndrome: data from the French ASSESS Cohort

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

International audienceObjectiveAlthough 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.MethodsWe 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.ResultsThe 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.ConclusionIUFD 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

Churg-Strauss syndrome with poor-prognosis factors: A prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients

International audienceObjective. To compare long and short durations of adjunctive cyclophosphamide for the treatment of severe Churg-Strauss syndrome (CSS). Methods. In this prospective multicenter therapeutic trial, 48 patients with CSS with at least 1 poor-prognosis factor at baseline were treated with glucocorticoids and either 12 or 6 intravenous cyclophosphamide pulses. Results. At 8 years, complete remission rates and severe side effects of therapy were comparable for both groups. The overall difference in relapses was not significant between the 12-pulse and the 6-pulse regimens (P = 0.07), but when considering only the number of mild relapses this difference became statistically significant (P < 0.02). Although the total number of inclusions was not reached, the study was stopped prematurely in response to the superiority of the 12-pulse regimen. Conclusion. We concluded that 12 cyclophosphamide pulses were better able to control severe CSS than a 6-pulse regimen. The optimal duration of therapy remains to be determined

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

International audienceObjectiveAlthough 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.MethodsWe 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.ResultsThe 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.ConclusionIUFD 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