Publications by authors named "Vincent Goëb"

73 Publications

Interleukin-7: a potential factor supporting B-cell maturation in the rheumatoid arthritis synovium.

Clin Exp Rheumatol 2021 Mar-Apr;39(2):253-262. Epub 2021 Mar 21.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.

Objectives: The exact function of interleukin-7 (IL-7) in autoimmune diseases remains unclear although it is a recognised therapeutic target for cytokine blockade. Our objective was to investigate the regulation and downstream effect of IL-7 in diseased tissue from rheumatoid arthritis (RA) patients notably with respect to its function as bone turnover regulator and tissue architecture (TA) organiser.

Methods: Synovial tissues (fresh, frozen or xed) were obtained from our tissue bank and distributed between experiments for live cell cultures, histology, immunohistochemistry or gene expression array by qPCR.

Results: IL-7 expression in synoviocyte cultures was up-regulated by pro-in ammatory cytokines, notably IL-6. Gene expression pro ling segregated synovial biopsies based on the presence of B/plasma cells and ectopic TA. IL-7 gene expression was associated with that of several genes whose function was to support B-cell maturation in tissue with distinct B-cell aggregates (despite the lack of IL-7-Receptor expression on B-cells) as well as with ectopic germinal-like centres. IL-7 was associated with bone turnover regulation in biopsies with diffuse in ltration. A novel relationship between the IL-7 and IL-6 axis was also highlighted in human tissue.

Conclusions: Overall, IL-7 may contribute to the maintenance of the pro-in ammatory cycle perpetuating in ammation in RA synovium. We therefore propose a novel role for IL-7 as an orchestrator of TA with an impact on B-cell maturation in relation with IL-6.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2021

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

Joint Bone Spine 2021 Feb 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2021.105162DOI Listing
February 2021

The association between body mass index class and coronavirus disease 2019 outcomes.

Int J Obes (Lond) 2021 03 21;45(3):700-705. Epub 2020 Nov 21.

Department of Endocrinology, Diabetes Mellitus and Nutrition, Amiens University Hospital, Amiens, France.

Background/objectives: A growing body of data suggests that obesity influences coronavirus disease 2019 (COVID-19). Our study's primary objective was to assess the association between body mass index (BMI) categories and critical forms of COVID-19.

Subjects/methods: Data on consecutive adult patients hospitalized with laboratory-confirmed COVID-19 at Amiens University Hospital (Amiens, France) were extracted retrospectively. The association between BMI categories and the composite primary endpoint (admission to the intensive care unit or death) was probed in a logistic regression analysis.

Results: In total, 433 patients were included, and BMI data were available for 329: 20 were underweight (6.1%), 95 have a normal weight (28.9%), 90 were overweight (27.4%), and 124 were obese (37.7%). The BMI category was associated with the primary endpoint in the fully adjusted model; the odds ratio (OR) [95% confidence interval (CI)] for overweight and obesity were respectively 1.58 [0.77-3.24] and 2.58 [1.28-5.31]. The ORs [95% CI] for ICU admission were similar for overweight (3.16 [1.29-8.06]) and obesity (3.05 [1.25-7.82]) in the fully adjusted model. The unadjusted ORs for death were similar in all BMI categories while obesity only was associated with higher risk after adjustment.

Conclusions: Our results suggest that overweight (and not only obesity) is associated with ICU admission, but overweight is not associated with death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41366-020-00721-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679236PMC
March 2021

Bone Loss, Osteoporosis, and Fractures in Patients with Rheumatoid Arthritis: A Review.

J Clin Med 2020 Oct 20;9(10). Epub 2020 Oct 20.

Department of Rheumatology, Picardie-Jules Verne University, University hospital of Amiens, 80054 Amiens, France.

Rheumatoid arthritis (RA) is often characterized by bone loss and fragility fractures and is a frequent comorbidity. Compared with a matched population, RA patients with fractures have more common risk factors of osteoporosis and fragility fractures but also risk factors resulting from the disease itself such as duration, intensity of the inflammation and disability, and cachexia. The inflammatory reaction in the synovium results in the production of numerous cytokines (interleukin-1, interleukin-6, tumor necrosis factor) that activate osteoclasts and mediate cartilage and bone destruction of the joints, but also have a systemic effect leading to generalized bone loss. Regular bone mineral density (BMD) measurement, fracture risk assessment using tools such as the FRAX algorithm, and vertebral fracture assessment (VFA) should be performed for early detection of osteoporosis and accurate treatment in RA patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9103361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589399PMC
October 2020

Therapeutic Maintenance of Baricitinib and Tofacitinib in Real Life.

J Clin Med 2020 Oct 16;9(10). Epub 2020 Oct 16.

Department of Rheumatology, Amiens University Hospital, 80000 Amiens, France.

Background: Janus kinase inhibitors (JAKis) represent a new alternative to treat rheumatoid arthritis (RA). The objective of this study was to evaluate the effectiveness, tolerance profile, and maintenance of these treatments (tofacitinib and baricitinib) in real life.

Methods: All patients in the rheumatology department of Amiens University Hospital treated by JAKis for RA were included from 1 October 2017 to 20 May 2020. Clinical and biological data were provided retrospectively in this observational and single-center study. We aimed to study the JAKi maintenance rate at 12 months and their clinical and biological safety profiles.

Results: Fifty-five patients were included. Drug maintenance at 12 months was 67.6%. Factors associated with poorer maintenance were a higher Charlson comorbidity index (HR 1.311 (1.089-1.579); = 0.0042), a higher age (HR 1.055 (1.015-1.096); = 0.0067), and corticosteroids therapy at initiation (HR 2.722 (1.006-7.365); = 0.0487). The clinical and biological safety profile was generally good.

Conclusions: Our study found that a higher Charlson index, age, and corticosteroids appeared to be associated with the earlier discontinuation of treatment. JAKis had a response and tolerance profile in real life at least equivalent to that of biological disease-modifying antirheumatic drugs (bDMARDs).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9103319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602842PMC
October 2020

Characteristics and outcomes of COVID-19 in hospitalized patients with and without diabetes.

Diabetes Metab Res Rev 2021 03 18;37(3):e3388. Epub 2020 Aug 18.

Department of Endocrinology, Diabetes Mellitus and Nutrition, Amiens University Hospital, Amiens, France.

Background: Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic, with four million confirmed cases and 280 000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID-19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID-19 patients with vs without diabetes.

Methods: All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID-19 up until April 21st, 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analysed separately in a logistic regression analysis and a Cox proportional hazards model.

Results: A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non-ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66-1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40-1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09-3.92, P = .027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death.

Conclusions: Diabetes was prevalent in a quarter of the patients hospitalized with COVID-19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID-19 severity and diabetes is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dmrr.3388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404605PMC
March 2021

Actual Persistence of Abatacept in Rheumatoid Arthritis: Results of the French-Ric Network.

J Clin Med 2020 May 19;9(5). Epub 2020 May 19.

CHU Lille, Rheumatology Department, F-59000 Lille, France.

Objectives: Data on abatacept (ABA) persistence in routine practice are limited. We aimed to study ABA persistence rates at 12 months, according to the date of initiation, and to analyze the factors associated with persistence at 12 months.

Methods: We performed an observational, ambispective, multi-center study from January 2008 to July 2016, based on the French-RIC Network. We defined three groups of patients followed up for rheumatoid arthritis (RA), according to the date of initiation of ABA therapy: Group 1 (from 2007 to 31 July 2010: ABA indicated after anti-TNF failure); Group 2 (from 1 August 2010 to 31 March 2014: ABA indicated after conventional antirheumatic drugs failure); Group 3 (from 1 April 2014 to 1 July 2016: ABA available by the subcutaneous injection).

Results: Among 517 patients who initiated ABA, drug persistence at 12 months was 68%. The only factor significantly associated with persistence rate at 12 months was C-reactive protein (CRP) < 10 mg/L at ABA initiation (odds ratio (OR) 0.6, 95% confidence interval 0.3-0.9; 0.0016). There was no significant difference in drug persistence according to date of initiation, the line of biological disease-modifying antirheumatic drugs (bDMARD) therapy or the route of administration.

Conclusions: In routine practice, over time, ABA has come to be initiated earlier in the course of therapy for RA in France. Abatacept persistence is similar to that reported in the Orencia Rheumatoid Arthritis (ORA) registry, and does not differ according to the date of initiation. The only factor found to be associated with the persistence rate at 12 months was CRP < 10 mg/L at ABA initiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9051528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290911PMC
May 2020

Premedication as primary prophylaxis does not influence the risk of acute infliximab infusion reactions in immune-mediated inflammatory diseases: A systematic review and meta-analysis.

Dig Liver Dis 2019 04 13;51(4):484-488. Epub 2018 Dec 13.

Department of Biostatistics, Amiens University Hospital, Amiens, France.

Introduction: Up to 25% of patients treated with infliximab experience hypersensitivity reactions. Prophylactic premedication prior to infliximab infusion, comprising corticosteroids and/or antihistamines, is widely used in clinical practice but its efficacy has recently been called into question due to the lack of pathophysiological rationale and validation by controlled trials.

Materials And Methods: We conducted a comprehensive literature search of multiple electronic databases from inception to June 2017 to identify studies reporting the impact of corticosteroid and/or antihistamine premedication on the risk of acute (<24 h) hypersensitivity reaction to infliximab in immune-mediated inflammatory diseases (IMIDs). Random-effects meta-analysis was performed.

Results: Ten studies, eight observational studies and two randomized control trials, were identified including a total of 3892 patients with IMIDs, and 1,385 patients with IBD. Corticosteroid premedication was not associated with a decreased risk of hypersensitivity reaction in either IMIDs (7 studies; OR, 1.07, 95%CI, 0.64-1.78; I = 57.5%) or IBD (3 studies; OR, 1.04, 95% CI, 0.52-2.07; I = 57%). Antihistamine premedication was not associated with a decreased risk of hypersensitivity reaction in IMIDs (3 studies: OR, 1.39, 95% CI, 0.70-2.73; I = 85%). The combination of corticosteroids and antihistamines did not decrease the risk of acute infliximab infusion reaction in IMIDs (6 studies; OR, 2.12, 95% CI, 0.61-7.35; I = 94%), but was associated with an increased risk in IBD (4 studies, OR, 4.17, 95% CI, 1.61-10.78; I = 77%).

Conclusion: Corticosteroid and/or antihistamine premedication is not associated with a decreased risk of acute hypersensitivity reactions to infliximab in patients with IMIDs. We believe that these premedications should no longer be part of standard protocols.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2018.12.002DOI Listing
April 2019

Tocilizumab Effectiveness After Switching from Intravenous to Subcutaneous Route in Patients with Rheumatoid Arthritis: The RoSwitch Study.

Rheumatol Ther 2019 Mar 10;6(1):61-75. Epub 2019 Jan 10.

Rheumatology Department, Hôpital Roger Salengro, University Hospital of Lille, Lille, France.

Introduction: The main objective of this work was to assess the maintenance of effectiveness of subcutaneous tocilizumab 6 months after switching from intravenous to subcutaneous formulation in patients with rheumatoid arthritis (RA) in a real-world setting. Secondary objectives aimed to describe the characteristics of patients and disease, the effectiveness at 12 months after switching, the therapeutic maintenance, and to search for predictive factors of switching.

Methods: We analyzed all the RA patients of the shared medical file "RIC Nord de France", treated with tocilizumab, switching or not from intravenous to subcutaneous tocilizumab, between April 2015 and January 2016. The primary effectiveness endpoint was the proportion of patients remaining in their DAS28-ESR category remission/low disease activity (LDA) or moving to an inferior DAS28-ESR category at 6 months. Since RoSwitch was an observational study, without randomization, a propensity score was built in a sensitivity analysis to balance on RA and patients' characteristics at inclusion between switching and no-switching groups.

Results: An improvement of initial DAS28-ESR category or maintenance in DAS28-ESR remission/LDA at 6 months was shown in 203 of the 285 patients with an evaluation for the primary criterion (71.2%, 95% CI [65.6-76.4%]) without differences between groups (73.3%, 95% CI [63.0-82.1%] vs. 70.3%, 95% CI [63.3-76.6%]). The RoSwitch study showed the maintenance of effectiveness at 6 and 12 months. Similar therapeutic maintenance rates were observed for switch and no-switch patients. No clinical factor was associated with the switch in patients in remission/LDA at inclusion.

Conclusions: The RoSwitch study showed the maintenance of effectiveness at 6 months in RA patients switching from intravenous (IV) to subcutaneous (SC) tocilizumab.

Funding: Roche SAS and Chugai Pharma France.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40744-018-0138-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393270PMC
March 2019

Mobile Phone Text Messages and Effect on Treatment Adherence in Patients Taking Methotrexate for Rheumatoid Arthritis: A Randomized Pilot Study.

Arthritis Care Res (Hoboken) 2019 10;71(10):1344-1352

Picardie Jules Verne University, and EA 4666, Amiens, France.

Objective: To assess the impact of weekly text messages on adherence in patients taking methotrexate (MTX) for rheumatoid arthritis (RA).

Methods: This prospective, randomized pilot, single-site study included patients with RA stabilized using MTX alone or combined with biologics. Participants were randomized to 3 interventions: a standard consultation (controls), a 15-minute pharmacist-led counseling session, or the receipt of text message reminders. The change over time in the Compliance Questionnaire Rheumatology (CQR-19) score between baseline and 6 months was defined as the primary outcome for adherence. Multivariable analyses and final adherence (as a composite outcome of the CQR-19 score, the Girerd score, and the medication possession ratio) were probed in sensitivity tests. Rheumatologic scales, inflammation, and patient satisfaction were also analyzed.

Results: A total of 96 patients (mean ± SD Disease Activity Score in 28 joints 2.42 ± 1.03) were monitored. The change over time in the CQR-19 score was significantly higher in the text message group (mean ± SD 3.32 ± 5.66; P = 0.02) than in the control group (mean ± SD 0.22 ± 6.56) and the pharmacist-led counseling group (mean ± SD -0.14 ± 7.56). Multivariable logistic regression showed that text messages remained associated with an increase in the CQR-19 score, independently of the baseline CQR-19 score (odds ratio 3.63 [95% confidence interval 1.26-10.49]; P = 0.017). In the text message group, the increase in the CQR-19 score was correlated with the Health Assessment Questionnaire score (r = -0.405, P = 0.021), and patient satisfaction was significantly higher (P < 0.01) than in the control group.

Conclusion: Our results showed evidence of a positive impact of text messages on adherence to MTX treatment for RA. The clinical benefit and the ideal target patient remain to be determined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.23750DOI Listing
October 2019

MICA and NKG2D variants as risk factors in spondyloarthritis: a case-control study.

Genes Immun 2019 09 4;20(7):599-605. Epub 2018 Sep 4.

Department of Rheumatology, Amiens University Medical Center, Amiens, France.

The major histocompatibility complex class I polypeptide-related sequence A (MICA) glycoprotein mediates the activation of the natural killer group 2D receptor (NKG2D) expressed on NK and CD8+ T cells. A methionine or valine at position 129 in exon 3 results in strong (MICA129 met) or weak (MICA129 val) binding to NKG2D. The MICA A5.1 allele causes a premature stop codon. Various NKG2D polymorphisms are associated with low (NKC3 C/C and NKC4 C/C) or high (NKC3 G/G and NKC4 T/T) levels of NK cell cytotoxic activity. In 162 patients with spondyloarthritis (115 with ankylosing spondyloarthritis, 46 with psoriatic arthritis and 1 with reactive arthritis) compared to 124 healthy controls, MICA-129 with methionine allele was more frequent in patients with spondyloarthritis (odds ratio (OR) (95% confidence interval) = 4.84 (2.75‒8.67)), whereas MICA-129 val/val, MICA A5.1 and NKC3 C/C variants were less frequent (OR = 0.20 (0.11‒0.37), 0.15 (0.06‒0.36) and 0.24 (0.13‒0.44), respectively). After adjustment for HLA-B*27 status, only NKC3 C/C remained linked to spondyloarthritis (adjusted OR = 0.14 (0.06‒0.33)). Homozygosity for MICA A5.1 is linked to ankylosing spondyloarthritis, and NKC3 C/C and MICA-129 val/val to psoriatic arthritis. MICA and NKC3 polymorphisms (related to a low NK cell cytotoxic activity) constituted a genetic association with spondyloarthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41435-018-0044-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768283PMC
September 2019

Intraosseous venous drainage anomaly at the tibia.

Joint Bone Spine 2018 03 13;85(2):251. Epub 2017 May 13.

Service de rhumatologie, université de Picardie-Jules-Verne, CHU d'Amiens, place Victor-Pauchet, 80054 Amiens, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2017.05.008DOI Listing
March 2018

Are abatacept and tocilizumab intravenous users willing to switch for the subcutaneous route of administration? A questionnaire-based study.

Clin Rheumatol 2017 Jun 2;36(6):1395-1400. Epub 2017 Mar 2.

Department of Rheumatology, Lille University, CHRU Lille, 2 avenue Oscar Lambret, 59000, Lille, France.

Choosing the subcutaneous (SC) route of administration of abatacept and tocilizumab is more cost-effective than the intravenous (IV) route. The objective of this study was to examine patients' reasons for choosing to keep with their IV infusions or to switch to subcutaneous SC injections. This study was based upon a self-administered questionnaire given to consecutive rheumatoid arthritis patients treated with abatacept or tocilizumab. Patients were asked to express their opinions concerning reasons explaining why they chose to keep the IV route or switch to the SC route. A total of 201 questionnaires completed by 127 patients treated by tocilizumab and 74 by abatacept were analysed. Overall, 45.8% of the patients chose to keep the IV route of administration. Another ongoing SC treatment was noted more often in patients choosing the SC route (15.9 versus 4.3%, p < 0.05). Reasons guiding the choice of the SC route were concerns about repeated hospital day-care (72%), greater autonomy with SC injections (38.7%) and economic considerations (21.5%). Reasons associated with choosing to maintain the IV route were worries about a lack of follow-up (72.1%), the absence of medical assistance during the SC injection (61.2%), maintaining social relationships with other patients developed at the hospital (40.5%), lower frequency of injection (32.9%), fear of adverse events (27.7%) and fear of SC injections (17.9%). Patients reject the SC switch from the IV route of tocilizumab and abatacept mainly because of fears about the unknown SC route, while those who accept it find it more convenient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-017-3587-8DOI Listing
June 2017

Th17 and CD24CD27 regulatory B lymphocytes are biomarkers of response to biologics in rheumatoid arthritis.

Arthritis Res Ther 2017 02 10;19(1):33. Epub 2017 Feb 10.

Rheumatology Department & EA 4666, Amiens University Hospital, University of Picardie-Jules Verne, Amiens, France.

Background: The aim was to describe the regulatory B and T cells (Breg and Treg) and T helper 17 (Th17) lymphocytes before and under treatment with biologic drugs, and to assess their potential predictive value as biomarkers of response in rheumatoid arthritis (RA).

Methods: This was a non-randomised, single-centre, prospective study. Patients with active RA (American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010) who required the initiation or switch to any biologic drug except rituximab were included. The main judgement criterion was the frequency and absolute number of CD24CD27 Breg and CD24CD38 T2/Breg cells, CD25CD127 Treg and CD45RACD161CCR6 Th17 cells measured at inclusion in both patients and controls, and after 1, 3 and 6 months of treatment (M1, M3 and M6) in patients with RA, and compared with the M6 response to treatment (EULAR response and Disease Activity Score in 28 joints (DAS28) remission).

Results: Thirty-one patients with RA and 17 controls were included. There was a reduction in T2/Breg frequency at M0 in patients (p < 0.001) and absolute numbers (p = 0.014) and in immunopositive vs. immunonegative RA (p = 0.016). DAS28 remission at M6 was associated with increased frequency of Treg (p = 0.01). A higher level of CD24CD27 Breg at baseline was associated with DAS28 remission at M6 (p = 0.04) and a good EULAR response at M6 for abatacept-treated patients (p = 0.01). A lower M0 level of Th17 was associated with a good EULAR response at M6 (p = 0.007), notably under anti-cytokine drugs (p = 0.048).

Conclusions: Altogether, these data, although preliminary, suggest that phenotyping of T and B cells has potential value for the stratification of biologic drugs, notably with respect to choosing between abatacept and anti-cytokine blockade.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-017-1244-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301325PMC
February 2017

Gait disorders in the elderly and dual task gait analysis: a new approach for identifying motor phenotypes.

J Neuroeng Rehabil 2017 Jan 31;14(1). Epub 2017 Jan 31.

Rheumatology Department, University Hospital, F 80054, Amiens, France.

Background: Gait disorders and gait analysis under single and dual-task conditions are topics of great interest, but very few studies have looked for the relevance of gait analysis under dual-task conditions in elderly people on the basis of a clinical approach.

Methods: An observational study including 103 patients (mean age 76.3 ± 7.2, women 56%) suffering from gait disorders or memory impairment was conducted. Gait analysis under dual-task conditions was carried out for all patients. Brain MRI was performed in the absence of contra-indications. Three main gait variables were measured: walking speed, stride frequency, and stride regularity. For each gait variable, the dual task cost was computed and a quartile analysis was obtained. Nonparametric tests were used for all the comparisons (Wilcoxon, Kruskal-Wallis, Fisher or Chi tests).

Results: Four clinical subgroups were identified: gait instability (45%), recurrent falls (29%), memory impairment (18%), and cautious gait (8%). The biomechanical severity of these subgroups was ordered according to walking speed and stride regularity under both conditions, from least to most serious as follows: memory impairment, gait instability, recurrent falls, cautious gait (p < 0.01 for walking speed, p = 0.05 for stride regularity). According to the established diagnoses of gait disorders, 5 main pathological subgroups were identified (musculoskeletal diseases (n = 11), vestibular diseases (n = 6), mild cognitive impairment (n = 24), central nervous system pathologies, (n = 51), and without diagnosis (n = 8)). The dual task cost for walking speed, stride frequency and stride regularity were different among these subgroups (p < 0.01). The subgroups mild cognitive impairment and central nervous system pathologies both showed together a higher dual task cost for each variable compared to the other subgroups combined (p = 0.01). The quartile analysis of dual task cost for stride frequency and stride regularity allowed the identification of 3 motor phenotypes (p < 0.01), without any difference for white matter hyperintensities, but with an increased Scheltens score from the first to the third motor phenotype (p = 0.05).

Conclusions: Gait analysis under dual-task conditions in elderly people suffering from gait disorders or memory impairment is of great value in assessing the severity of gait disorders, differentiating between peripheral pathologies and central nervous system pathologies, and identifying motor phenotypes. Correlations between motor phenotypes and brain imaging require further studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12984-017-0218-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282774PMC
January 2017

The term "seropositive" to qualify polyarthritis/rheumatoid arthritis should be banned.

Authors:
Vincent Goëb

Joint Bone Spine 2018 01 29;85(1):123. Epub 2016 Dec 29.

Service de Rhumatologie, CHU Amiens, Amiens, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2016.12.006DOI Listing
January 2018

High-Grade Salivary-Gland Involvement, Assessed by Histology or Ultrasonography, Is Associated with a Poor Response to a Single Rituximab Course in Primary Sjögren's Syndrome: Data from the TEARS Randomized Trial.

PLoS One 2016;11(9):e0162787. Epub 2016 Sep 23.

Service de Rhumatologie, Hôpital de la Cavale Blanche, CHRU Brest, Boulevard Tanguy Prigent, 29609 Brest, France.

Purpose: To determine whether the severity of salivary-gland involvement, assessed using salivary gland ultrasonography [SGUS], histological focus score, or the unstimulated whole salivary flow [UWSF], was associated with the response to rituximab in patients with primary Sjögren's syndrome [pSS].

Materials And Methods: Among the 120 patients with pSS enrolled in the randomised TEARS trial of rituximab versus placebo, 35 underwent either centralised minor salivary-gland biopsy or SGUS at inclusion. The echostructure of each parotid and submandibular gland was graded on a scale of 0 to 4. Histologic minor salivary gland involvement was assessed by the focus score. Among rituximab-treated patients with available data (n = 14), half met the Sjögren's Syndrome Responder Index [SSRI]-30 definition of a response at week 24.

Results: The SGUS score correlated positively to the focus score [r = 0.61] and negatively to the UWSF [r = -0.68]. The focus score was not correlated to the UWSF. The median total SGUS grade at inclusion was 9 [6-11] in responders versus 16 [11-16] in non-responders [p = 0.04]. The proportion of SSRI-30 responders was 0% among patients with SGUS grade 4 and 88% among those with SGUS grade ≤3. Low baseline SGUS scores were associated with sicca-related outcomes improvement, but not with fatigue or biological improvement. Median baseline focus score was 0.3 [0.0-1.3] in the responders versus 4.0 [2.7-5.3] in the non-responders [p = 0.02]. Baseline UWSF was not associated with the response rate.

Conclusion: In patients with pSS, the highest SGUS grade or a high histological focus score is associated with absence of a response to a single rituximab course after 6 months. Further studies, including more patients and different treatment strategies, are required to confirm the clinical utility of these potential biomarkers in pSS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035078PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162787PLOS
September 2016

Severe Health-Related Quality of Life Impairment in Active Primary Sjögren's Syndrome and Patient-Reported Outcomes: Data From a Large Therapeutic Trial.

Arthritis Care Res (Hoboken) 2017 04;69(4):528-535

Centre Hospitalier Universitaire de la Cavale Blanche, and EA 2216, INSERM ESPRI, ERI29, Université de Brest, LabEx IGO, Brest, France.

Objective: To identify the principal determinants of health-related quality of life (HRQOL) impairment in patients with active primary Sjögren's syndrome (SS) participating in a large therapeutic trial, Tolerance and Efficacy of Rituximab in Primary Sjögren's Syndrome (TEARS).

Methods: At the inclusion visit for the TEARS trial, 120 patients with active primary SS completed the Short Form 36 health survey (SF-36), a validated HRQOL assessment tool. Univariate then multivariate linear regression analyses were used to assess associations linking SF-36 physical and mental components to demographic data, patient-reported outcomes (symptom intensity assessments for dryness, pain, and fatigue, including the European League Against Rheumatism [EULAR] Sjögren's Syndrome Patient Reported Index [ESSPRI]), objective measures of dryness and autoimmunity, and physician evaluation of systemic activity (using the EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI]).

Results: SF-36 scores indicated marked HRQOL impairments in our population with active primary SS. Approximately one-third of the patients had low, moderate, and high systemic activity according to the ESSDAI. ESSPRI and ESSDAI scores were moderately but significantly correlated. The factors most strongly associated with HRQOL impairment were patient-reported symptoms, best assessed using the ESSPRI, with pain and ocular dryness intensity showing independent associations with HRQOL. Conversely, systemic activity level was not associated with HRQOL impairment in multivariate analyses, even in the patient subset with ESSDAI values indicating moderate-to-high systemic activity.

Conclusion: The cardinal symptoms of primary SS (dryness, pain, and fatigue, best assessed using the ESSPRI) are stronger predictors of HRQOL impairment than systemic involvement (assessed by the ESSDAI) and should be used as end points in future therapeutic trials focusing on patients' well-being. New consensual and data-driven response criteria are needed for primary SS studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.22974DOI Listing
April 2017

Expression of the calcium-sensing receptor in monocytes from synovial fluid is increased in osteoarthritis.

Joint Bone Spine 2017 Mar 23;84(2):175-181. Epub 2016 Jun 23.

Department of Rheumatology, University Hospital Amiens, 1, place Victor-Pauchet, 80000 Amiens, France.

Objectives: We assessed calcium-sensing receptor (CaSR) expression in monocytes isolated from synovial fluid of patients with different types of rheumatisms and explored whether CaSR expression was related to the inflammatory nature of synovial fluid.

Methods: Forty-one patients were included: osteoarthritis (n=10), microcristallin rheumatisms (n=10), rheumatoid arthritis (n=12) and other inflammatory rheumatisms (n=9). Surface and total CaSR expressions in monocytes isolated from synovial fluid and blood were assessed by flow cytometry analysis. U937 cells were cultured during 24hours in presence of cell-free synovial fluids.

Results: Every monocyte population tested express the CaSR intra- and extracellularly. Whereas similar pattern of CaSR expression exist in monocyte isolated from blood or synovial fluids, our results indicate that higher CaSR expression levels can be observed in monocytes from synovial fluids than in circulating monocytes. In both populations of monocytes, surface and total CaSR expressions were found to be significantly increased in patients with osteoarthritis compared to rheumatoid arthritis. Similar data were obtained when U937 cells were incubated with cell-free synovial fluids from osteoarthritis patients. Still present, this effect was significantly lowered when "inflammatory" synovial fluids were introduced in culture.

Conclusions: Our results indicate that CaSR expression in synovial derived monocytes is higher in osteoarthritis than in inflammatory rheumatisms and that CaSR expression is modulated by the nature of the synovial fluid. Given the role played by monocytes in the pathogenesis of chronic rheumatisms, monocytes could be interesting therapeutic targets via the CaSR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2016.03.012DOI Listing
March 2017

Decrease of Tocilizumab Dose in Patients with Rheumatoid Arthritis: A Pilot Study.

Pharmacology 2016 27;98(1-2):73-8. Epub 2016 Apr 27.

Department of Rheumatology, CHU Amiens, Amiens, France.

Background: The efficacy and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) are well demonstrated. Doses of 4 and 8 mg/kg are used intravenously. The objective of our study was to report the efficacy and safety for a set of patients who had an 8 mg/kg doze of TCZ and for another set who had this treatment first at a dose of 8 followed by 4 mg/kg.

Methods: All RA patients treated with TCZ in a University Hospital Centre Department of Rheumatology between January 2010 and December 2014 were included. Sixty-three patients received TCZ at a dose of 8 mg/kg and 19 patients received this treatment first receiving a dose of 8 mg/kg decreased to 4 mg/kg. The demographic characteristics, the clinical response and adverse events were reported.

Results: At the end of follow-up, 48% of patients were in clinical remission defined by disease activity score based on 28 joints with an erythrocyte sedimentation rate <2.6 in the 8 mg/kg group and 74% of patients in the 8-4 mg/kg. The rates of severe infections were 4.8 per 100 patients-years (PY) in the 8 mg/kg group and 2.9 per 100 PY in the 8 then 4 mg/kg. The infections were mainly pulmonary, ENT and skin infections.

Conclusion: Our study reported the efficacy and safety of the TCZ in patients with RA in 'real life' with the dose of 8 mg/kg or 8 then 4 mg/kg.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000445953DOI Listing
March 2017

Paradoxical articular manifestations in patients with inflammatory bowel diseases treated with infliximab.

Eur J Gastroenterol Hepatol 2016 Aug;28(8):876-81

aDepartment of Gastroenterology bEA4666, Department of Rheumatology cEA4666, LNPC, Department of Immunology dLaboratory of Hematology and Histocompatibility eDepartment of Digestive and Oncologic Surgery fClinical Research and Innovation Directorate, Amiens University Hospital, Amiens, France.

Introduction: Articular involvement is the most common extraintestinal manifestation associated with inflammatory bowel diseases (IBDs). Manifestations are 'paradoxical' when they occur during treatment, notably with anti-tumor necrosis factor (anti-TNF) drugs, which are expected to prevent or treat them. The aim of this study was to assess the frequency, characteristics, and associated factors of paradoxical articular manifestations in patients with IBD treated with anti-TNF.

Patients And Methods: In this prospective single-center study, an examination by a rheumatologist was systematically offered to all patients with IBD treated with infliximab (IFX) to assess the prevalence of articular manifestations and distinguish between those related to treatment and those associated with intestinal disease. Paradoxical manifestations were defined as the occurrence of articular manifestations (excluding induced lupus and hypersensitivity reactions) during anti-TNF therapy in patients with intestinal remission. Measures of biological inflammatory, immunological markers, HLA-B27 allele, IFX trough levels, and anti-IFX antibody (Ab) were performed for all patients.

Results: Between May 2013 and April 2014, 65 patients with Crohn's disease and 15 with patients ulcerative colitis treated with IFX were included. The median duration of anti-TNF therapy was 66 months [quartile (Q)1=23 months-Q3=81 months]. Articular manifestations were observed in 50 (62%) patients treated with IFX. Eleven percent (n=9) were considered to be associated with IBD and 16% (n=13) to be associated with anti-TNF therapy. Among articular manifestations associated with anti-TNF therapy, nine (11%) patients were considered paradoxical, two (2%) as drug-induced lupus, and two (2%) as a hypersensitivity reaction. Among the nine patients with paradoxical manifestations, all had Crohn's disease in clinical remission, three patients presented a spondyloarthropathy, and three developed associated paradoxical psoriasis. No patient discontinued anti-TNF because of the articular manifestations. Methotrexate was effective on articular symptoms in two of the three treated patients with paradoxical manifestations. No clinical or biological factors, including IFX trough levels, were associated with the occurrence of paradoxical manifestations.

Conclusion: Paradoxical articular manifestations in IBD patients treated by anti-TNF are common, affecting more than 10% of patients. These events are generally mild and do not need discontinuation of anti-TNF therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000000643DOI Listing
August 2016

Comparison of continuation rates with three TNFα antagonists (adalimumab, infliximab, etanercept) in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: Retrospective 10-year study.

Joint Bone Spine 2016 Oct 23;83(5):607-9. Epub 2016 Feb 23.

Service de rhumatologie, CHU d'Amiens, place Victore-Pauchet, 80054 Amiens cedex 1, France; EA4666, Université de Picardie-Jules-Verne, chemin du Thil, 80000 Amiens, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2016.01.005DOI Listing
October 2016

B-cell and T-cell quantification in minor salivary glands in primary Sjögren's syndrome: development and validation of a pixel-based digital procedure.

Arthritis Res Ther 2016 Jan 20;18:21. Epub 2016 Jan 20.

Rheumatology Department and EA 2216-ESPRI 29, Brest University Hospital, Brest, France.

Background: Evaluating lymphocytic infiltration of minor salivary gland biopsy in primary Sjögren's syndrome is challenging. We developed and evaluated a digital method for quantifying B and T lymphocytes in whole minor salivary gland biopsy slides.

Methods: Minor salivary gland biopsies were immunostained with anti-CD20/anti-CD3 antibodies using red/brown chromogens. Slides were digitised and spliced into mosaics of smaller JPEG format images in which red and brown pixels were counted. ImageJ Cell counter was used for validation. Agreement between the digital and manual methods was evaluated using Bland-Altman plots and the interclass correlation coefficient. External validation relied on the Chisholm-Mason, Tarpley, and focus-score methods.

Results: Of 62 minor salivary gland biopsy slides, 61.3 % had a Chisholm-Mason grade ≥ III or a focus score ≥1. The number of pixels correlated well with manual cell counts (r = 0.95 for red pixels vs. B cell count and r = 0.91 for brown pixels vs. T cell count). Interclass correlation coefficients between digital and manual counts were excellent (0.92 for B/T cells). B-cell proportion showed a significant positive correlation with the focus score (Spearman's coefficient 0.463, p < 0.0001). Median B-cell proportion was lower in minor salivary gland biopsies with Chisholm grades I-II (2.5 % (0.2-13.9)) than III-IV (30.0 % (15.5-45.2)) and increased with Tarpley's class (1, 2.2 % (0.2-6.6); 2, 27.2 % (13.0-38.9); and 3-4, 48.5 % (29.4-56.4); p < 0.001 for all comparisons). Minor salivary gland biopsy B-cell proportion was also significantly correlated with several markers of clinical and biological activity of the disease, especially with markers of systemic B-cell hyperactivation.

Conclusion: The digital procedure proved accurate compared to the reference standard, producing reliable results for whole tissue sections.

Trial Registration: ClinicalTrials.gov [ NCT00740948 ]. Registered 22 August 2008.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-016-0924-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719698PMC
January 2016

Early phase clinical and biological markers associated with subclinical atherosclerosis measured at 7 years of evolution in an early inflammatory arthritis cohort.

Clin Exp Rheumatol 2016 Jan-Feb;34(1):58-67. Epub 2015 Dec 20.

Rheumatology Department, CIC/CRB1404, Rouen University Hospital, and Inserm Unit 905, IRIB, Rouen University, Rouen, France.

Objectives: Accelerated atherosclerosis has emerged as a critical issue in rheumatoid arthritis (RA). There is a need to better understand the link between RA and atherosclerosis. Our aim was to identify parameters associated with the development of subclinical atheroma in a very early arthritis (VErA) cohort.

Methods: VErA-cohort patients were prospectively recruited from 1998 to 2002. Arthritis treatment was standardised from onset. The clinical, biological and radiological parameters of all patients were collected from inclusion. Carotid intima-media thickness (cIMT) was measured 7 years after their first symptoms.

Results: Among 105 patients included, 82 developed RA (mean age at onset: 51.7±12.8 years). Mean carotid artery IMT at year 7 was 0.67±0.12 mm. Larger thickness defined by values above the median (0.66) was associated with inclusion age (p<10-6), swollen joint count (p=0.01), DAS44 (p=0.048) and hypertension (p=0.006). In contrast, anti-CCP positivity (>50 UA/ml) was associated with thinner cIMT (p=0.03). Baseline as well as cumulated values of markers reflecting systemic inflammation, lymphocyte activation, endothelial dysfunction and oxidative stress were not correlated with carotid subclinical atherosclerosis. Major independent atheroma risk factors retained by multivariate analyses were hypertension (OR 4.33 [1.59-11.73]; p=0.004) and swollen joint count at inclusion (OR 3.87 [1.54-9.72]; p=0.004), while methotrexate use was a protective marker (OR 0.27 [0.11-0.71]; p=0.007).

Conclusions: This study conducted from the VErA vascular cohort of community-cases of RA confirm that cIMT is under the influence of classical CV risk (hypertension), disease marker (SJC) and methotrexate intake.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2016

Blood and salivary-gland BAFF-driven B-cell hyperactivity is associated to rituximab inefficacy in primary Sjögren's syndrome.

J Autoimmun 2016 Feb 10;67:102-110. Epub 2015 Dec 10.

EA2216, INSERM ESPRI, ERI29, Laboratoire d'Immunothérapies et Pathologies lymphocytaires B, Université de Brest, and Labex "IGO", Brest, France. Electronic address:

Objectives: To determine whether B-cell markers (blood and minor salivary gland [SG] B-cell depletion [BCD], autoantibodies, B-cell-activating factor [BAFF]) are associated with clinical response to rituximab in patients with primary Sjögren's syndrome (pSS).

Methods: 45 patients with pSS were included: in group I, 14 received low-dose rituximab (two 375-mg/m(2) infusions) in an open-labelled study; in group II, 17 received full-dose rituximab (two 1000-mg infusions) and 14 received a placebo in a randomized, controlled study. The proportion of SG B cells was assessed using pixel-based software analyses of digitized double-immunostained (CD3/CD20) whole SGs. Response was defined at week-24 according to the Sjögren's Syndrome Responder Index (SSRI)-30.

Results: Response rate was 50% in both groups of rituximab-treated patients. Duration of blood BCD was similar in both groups despite the difference in rituximab dosage, and was highly correlated with residual serum-rituximab levels at week-16. SG B-cell dynamics mirrored blood B-cell levels, with a drastic decrease in SG B-cells at week-12 (group I), but an increase in ∼ 50% of patients in group II by week-24, in whom blood B cells had already returned. Duration of BCD was not associated with the clinical response, but responders had lower baseline proportions of SG B cells. Baseline serum BAFF level was correlated with the proportion of SG B-cells and other B-cell-activation markers, and was associated with the clinical response with higher levels in non-responders.

Conclusions: In pSS, half of the patients display an intense BAFF-driven B-cell activation and do not respond to a single course of rituximab.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaut.2015.11.002DOI Listing
February 2016

Human parvovirus B19 and autoimmune diseases. Review of the literature and pathophysiological hypotheses.

J Clin Virol 2015 Nov 26;72:69-74. Epub 2015 Sep 26.

Unité de Virologie UVICEF EA4294, UPJV-CHU, Amiens, France.

A number of arguments support the role played by PVB19 in autoimmunity, in the broad sense of the term essentially derived from numerous clinical case reports and/or small series over the past 20-30 years in the medical literature. PVB19 can induce a very broad spectrum of autoantibody production, especially including: anti-soluble nuclear antigen antibodies, antiphospholipid antibodies anti-native DNA antibodies, antilymphocyte antibody, anticardiolipin antibodies, antinuclear antibodies and rheumatoid factor. Notably acute PVB19 infection can mimic or stimulate autoimmune systemic diseases as rheumatoid arthritis or systemic lupus erythematosus. However, at the present time, there is no formal scientific evidence demonstrating a direct role of PVB19 in autoimmunity, bearing in mind that there are also no formal arguments against it. Further large studies are needed to understand the eventual role of PVB19 in autoimmune diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcv.2015.09.007DOI Listing
November 2015

Which and How Many Patients Should Be Included in Randomised Controlled Trials to Demonstrate the Efficacy of Biologics in Primary Sjögren's Syndrome?

PLoS One 2015 14;10(9):e0133907. Epub 2015 Sep 14.

Rheumatology Department, CHU de la Cavale Blanche, Boulevard Tanguy Prigent, 29609, Brest, France; EA 2216, INSERM ESPRI, ERI29 Université Bretagne Occidentale, 29200, Brest, France.

Objective: The goal of this study was to determine how the choice of the primary endpoint influenced sample size estimates in randomised controlled trials (RCTs) of treatments for primary Sjögren's syndrome (pSS).

Methods: We reviewed all studies evaluating biotechnological therapies in pSS to identify their inclusion criteria and primary endpoints. Then, in a large cohort (ASSESS), we determined the proportion of patients who would be included in RCTs using various inclusion criteria sets. Finally, we used the population of a large randomised therapeutic trial in pSS (TEARS) to assess the impact of various primary objectives and endpoints on estimated sample sizes. These analyses were performed only for the endpoints indicating greater efficacy of rituximab compared to the placebo.

Results: We identified 18 studies. The most common inclusion criteria were short disease duration; systemic involvement; high mean visual analogue scale (VAS) scores for dryness, pain, and fatigue; and biological evidence of activity. In the ASSESS cohort, 35 percent of patients had recent-onset disease (lower than 4 years), 68 percent systemic manifestations, 68 percent high scores on two of three VASs, and 52 percent biological evidence of activity. The primary endpoints associated with the smallest sample sizes (nlower than 200) were a VAS dryness score improvement higher to 20 mm by week 24 or variable improvements (10, 20, or 30 mm) in fatigue VAS by week 6 or 16. For patients with systemic manifestations, the ESSDAI change may be the most logical endpoint, as it reflects all domains of disease activity. However, the ESSDAI did not improve significantly with rituximab therapy in the TEARS study. Ultrasound score improvement produced the smallest sample size estimate in the TEARS study.

Conclusion: This study provides valuable information for designing future RCTs on the basis of previously published studies. Previous RCTs used inclusion criteria that selected a small part of the entire pSS population. The endpoint was usually based on VASs assessing patient complaints. In contrast to VAS dryness cut-offs, VAS fatigue cut-offs did not affect estimated sample sizes. SGUS improvement produced the smallest estimated sample size. Further studies are required to validate standardised SGUS modalities and assessment criteria. Thus, researchers should strive to develop a composite primary endpoint and to determine its best cut-off and assessment time point.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133907PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569343PMC
June 2016

[Arthrosis].

Rev Prat 2015 May;65(5):709-18

View Article and Find Full Text PDF

Download full-text PDF

Source
May 2015

Do not forget the joint involvement of sarcoidosis.

Immunotherapy 2015 22;7(6):599-600. Epub 2015 Jun 22.

Rheumatology Department, Research Unit EA 4666, Amiens University Hospital, University of Picardie Jules-Verne, Amiens, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/imt.15.24DOI Listing
September 2015

Development of the Sjögren's Syndrome Responder Index, a data-driven composite endpoint for assessing treatment efficacy.

Rheumatology (Oxford) 2015 Sep 8;54(9):1699-708. Epub 2015 May 8.

Service de Rhumatologie, CHU de la Cavale Blanche, EA 2216, INSERM ESPRI, ERI29, Université de Brest, LabEx IGO, Brest,

Objectives: To determine which outcome measures detected rituximab efficacy in the Tolerance and Efficacy of Rituximab in Sjögren's Disease (TEARS) trial and to create a composite endpoint for future trials in primary SS (pSS).

Methods: Post hoc analysis of the multicentre randomized placebo-controlled double-blind TEARS trial. The results were validated using data from two other randomized controlled trials in pSS, assessing rituximab (single-centre trial in the Netherlands) and infliximab, respectively.

Results: Five outcome measures were improved by rituximab in the TEARS trial: patient-assessed visual analogue scale scores for fatigue, oral dryness and ocular dryness, unstimulated whole salivary flow and ESR. We combined these measures into a composite endpoint, the SS Responder Index (SSRI), and we defined an SSRI-30 response as a ≥30% improvement in at least two of five outcome measures. In TEARS, the proportions of patients with an SSRI-30 response in the rituximab and placebo groups at 6, 16 and 24 weeks were 47% vs 21%, 50% vs 7% and 55% vs 20%, respectively (P < 0.01 for all comparisons). SSRI-30 response rates after 12 and 24 weeks in the single-centre rituximab trial were 68% (13/19) vs 40% (4/10) and 74% (14/19) vs 40% (4/10), respectively. No significant differences in SSRI-30 response rates were found between infliximab and placebo at any of the time points in the infliximab trial.

Conclusion: A core set of outcome measures used in combination suggests that rituximab could be effective and infliximab ineffective in pSS. The SSRI might prove useful as the primary outcome measure for future therapeutic trials in pSS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/kev114DOI Listing
September 2015