Publications by authors named "Miguel Hie"

37 Publications

Differential Expression of Interferon-Alpha Protein Provides Clues to Tissue Specificity Across Type I Interferonopathies.

J Clin Immunol 2021 Apr 7;41(3):603-609. Epub 2021 Jan 7.

Université de Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, 24 boulevard du Montparnasse, 75015, Paris, France.

Whilst upregulation of type I interferon (IFN) signaling is common across the type I interferonopathies (T1Is), central nervous system (CNS) involvement varies between these disorders, the basis of which remains unclear. We collected cerebrospinal fluid (CSF) and serum from patients with Aicardi-Goutières syndrome (AGS), STING-associated vasculopathy with onset in infancy (SAVI), presumed monogenic T1Is (pT1I), childhood systemic lupus erythematosus with neuropsychiatric features (nSLE), non-IFN-related autoinflammation (AI) and non-inflammatory hydrocephalus (as controls). We measured IFN-alpha protein using digital ELISA. Eighty-two and 63 measurements were recorded respectively in CSF and serum of 42 patients and 6 controls. In an intergroup comparison (taking one sample per individual), median CSF IFN-alpha levels were elevated in AGS, SAVI, pT1I, and nSLE compared to AI and controls, with levels highest in AGS compared to all other groups. In AGS, CSF IFN-alpha concentrations were higher than in paired serum samples. In contrast, serum IFN was consistently higher compared to CSF levels in SAVI, pT1I, and nSLE. Whilst IFN-alpha is present in the CSF and serum of all IFN-related diseases studied here, our data suggest the primary sites of IFN production in the monogenic T1I AGS and SAVI are, respectively, the CNS and the periphery. These results inform the diagnosis of, and future therapeutic approaches to, monogenic and multifactorial T1Is.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10875-020-00952-xDOI Listing
April 2021

A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP.

Blood 2021 Feb;137(6):733-742

Centre de Référence des Microangiopathies Thrombotiques, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2020008021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986049PMC
February 2021

Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine.

Ann Rheum Dis 2020 06 24;79(6):837-839. Epub 2020 Apr 24.

Sorbonne Université, Assistance Publique - Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Inserm UMRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2020-217566DOI Listing
June 2020

Correction to: Adrenocortical carcinoma complicated by renal thrombotic microangiopathy, a case-series.

BMC Nephrol 2020 Feb 10;21(1):44. Epub 2020 Feb 10.

Department of Medical Critical Care, Rouen University Hospital, Rouen, France.

Following publication of the original article [1], we have been notified that the name of one author was spelled incorrectly as Julien Haddoux, when the correct spelling is Julien Hadoux.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-020-1712-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008570PMC
February 2020

Adrenocortical carcinoma complicated by renal thrombotic microangiopathy, a case-series.

BMC Nephrol 2020 01 30;21(1):35. Epub 2020 Jan 30.

Department of Medical Critical Care, Rouen University Hospital, Rouen, France.

Background: Cancer-related thrombotic microangiopathy (CR-TMA) is a rare entity associated with a dismal prognosis. Usually, CR-TMA is associated with mucin-producing carcinomas among which stomach, breast, prostate, lung and pancreas tumours are the most frequent.

Cases Presentation: We describe for the first time three cases of CR-TMA due to adrenocortical carcinoma (ACC). All of them had mechanical hemolytic anemia and thrombocytopenia without any other identifiable cause. Bicytopenia was diagnosed either simultaneously with ACC or at the time of metastatic evolution. Two patients had acute kidney injury (AKI) with severe pathological findings on kidney biopsy. Despite total adrenalectomy, chemotherapy, and specific treatment of TMA with plasma-exchanges, renal failure and hemolytic anemia remained. The only manifestation of CR-TMA in the third patient was hemolytic anemia, which resolved after surgical removal of ACC. The evolutions in these patients suggests ACC-related TMA may be related to a circulating factor.

Conclusions: CR-TMAs are rare. Here we describe the first case series of ACC-related TMA, among which two had renal involvement. This entity is associated with dismal renal prognosis despite specific treatment of TMA. According to patients' evolution, the persistence of TMA may reflect an uncontrolled malignancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-020-1703-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993319PMC
January 2020

Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial.

Ann Rheum Dis 2020 03 18;79(3):339-346. Epub 2019 Dec 18.

Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Inserm UMRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France

Objectives: To compare the efficacy to prevent flares of maintenance versus withdrawal of 5 mg/day prednisone in systemic lupus erythematosus (SLE) patients with clinically quiescent disease.

Methods: A monocentric, 12-month, superiority, open-label, randomised (1:1) controlled trial was conducted with 61 patients continuing 5 mg/day prednisone and 63 stopping it. Eligibility criteria were SLE patients who, during the year preceding the inclusion, had a clinically inactive disease and a stable SLE treatment including 5 mg/day prednisone. The primary endpoint was the proportion of patient experiencing a flare defined with the SELENA-SLEDAI flare index (SFI) at 52 weeks. Secondary endpoints included time to flare, flare severity according to SFI and British Isles Lupus Assessment Group (BILAG) index and increase in the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI).

Results: Proportion of patients experiencing a flare was significantly lower in the maintenance group as compared with the withdrawal group (4 patients vs 17; RR 0.2 (95% CI 0.1 to 0.7), p=0.003). Maintenance of 5 mg prednisone was superior with respect to time to first flare (HR 0.2; 95% CI 0.1 to 0.6, p=0.002), occurrence of mild/moderate flares using the SFI (3 patients vs 12; RR 0.2 (95% CI 0.1 to 0.8), p=0.012) and occurrence of moderate/severe flares using the BILAG index (1 patient vs 8; RR 0.1 (95% CI 0.1 to 0.9), p=0.013). SDI increase and adverse events were similar in the two treatment groups. Subgroup analyses of the primary endpoint by predefined baseline characteristics did not show evidence of a different clinical response.

Conclusion: Maintenance of long term 5 mg prednisone in SLE patients with inactive disease prevents relapse.

Trial Registration Number: NCT02558517; Results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2019-216303DOI Listing
March 2020

Ultrasensitive serum interferon-α quantification during SLE remission identifies patients at risk for relapse.

Ann Rheum Dis 2019 12 30;78(12):1669-1676. Epub 2019 Sep 30.

Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Inserm UMRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.

Objectives: Maintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, its expression in remission has been poorly studied as yet. To study its expression in remission and its prognostic value in the prediction of a disease relapse, serum IFN-α levels were determined using an ultrasensitive single-molecule array digital immunoassay which enables the measurement of cytokines at physiological concentrations.

Methods: A total of 254 SLE patients in remission, according to the Definition of Remission in SLE classification, were included in the study. Serum IFN-α concentrations were determined at baseline and patients were followed up for 1 year. Lupus flares were defined according to the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index Flare Index, whereas the Kaplan-Meier analysis and Cox regression analysis were used to estimate the time to relapse and to identify baseline factors associated with time to relapse, respectively.

Results: Of all patients in remission, 26% displayed abnormally high IFN-α serum levels that were associated with the presence of antibodies specific for ribonucleoprotein (RNP), double stranded (ds)DNA and Ro/SSA60, as well as young age. Importantly, elevated-baseline IFN-α serum levels and remission duration were associated in an independent fashion, with shorter time to relapse, while low serum levels of complement component 3 and anti-dsDNA Abs were not.

Conclusion: Direct serum IFN-α assessment with highly sensitive digital immunoassay permits clinicians to identify a subgroup of SLE patients, clinically in remission, but at higher risk of relapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2019-215571DOI Listing
December 2019

Achieving lupus low-disease activity and remission states under belimumab in refractory systemic lupus erythematosus: time and organ involvement matter.

Ann Rheum Dis 2020 11 8;79(11):e148. Epub 2019 Jul 8.

French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, AssistancePublique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2019-215732DOI Listing
November 2020

Safety and effectiveness of transjugular renal biopsy for systemic lupus erythematosus and antiphospholipid antibody syndrome patients taking antithrombotics.

Nephrol Dial Transplant 2020 10;35(10):1721-1729

Assistance Publique-Hôpitaux de Paris (APHP), Groupe Hospitalier Pitié-Salpêtrière (GHPS), French National Referral Center for Systemic Lupus Erythematosus and Antiphospholipid Antibody Syndrome, Service de Médecine Interne 2, Institut E3M, Paris, France.

Background: Renal biopsy is the cornerstone of systemic lupus erythematosus (SLE) nephritis and antiphospholipid syndrome (APS) nephropathy management. However, transcutaneous renal biopsy (TCRB) is hampered by the antithrombotic treatment frequently prescribed for those diseases. Transjugular renal biopsy (TJRB) offers an attractive alternative for patients at increased risk of bleeding. The primary objective of the study was to describe the safety profile and diagnostic performance of TJRB in SLE and APS patients.

Methods: All SLE and/or APS patients who underwent a renal biopsy in our department (between January 2004 and October 2016) were retrospectively reviewed. Major complications were death, haemostasis nephrectomy, renal artery embolization, red blood cell transfusion, sepsis and vascular thrombosis; macroscopic haematuria, symptomatic perirenal/retroperitoneal bleeding and renal arteriovenous fistula without artery embolization were considered as minor complications.

Results: Two hundred and fifty-six TJRBs-119 without antithrombotics (untreated), 69 under aspirin and 68 on anticoagulants and 54 TCRBs without antithrombotics-were analysed. Their major and minor complication rates, respectively, did not differ significantly for the four groups: 0 and 8% for untreated TJRBs, 1 and 6% for aspirin-treated, 6 and 10% for anticoagulant-treated and 2 and 2% for TCRBs. The number of glomeruli sampled and the biopsy contribution to establishing a histological diagnosis was similar for the four groups.

Conclusions: TJRBs obtained from SLE and APS patients taking antithrombotics had diagnostic yields and safety profiles similar to those of untreated TCRBs. Thus, TJRB should be considered for SLE and APS patients at risk of bleeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfz085DOI Listing
October 2020

Infliximab biosimilar for treating neurosarcoidosis: tolerance and efficacy in a retrospective study including switch from the originator and initiation of treatment.

J Neurol 2019 May 9;266(5):1073-1078. Epub 2019 Feb 9.

Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service de Médecine Interne 2, Centre National de Référence Maladies Systémiques Rares, Hôpital Pitié-Salpêtrière, 47-83 Boulevard de l'hôpital, 75651, Paris Cedex 13, France.

Objectives: Infliximab is increasingly used to treat neurosarcoidosis. We aimed to determine the efficacy and tolerance of an infliximab biosimilar for treating neurosarcoidosis.

Methods: We conducted a retrospective single-center study to describe the efficacy, safety and immunogenicity of an infliximab biosimilar in neurosarcoidosis patients. We compared the survival time without relapse while receiving the biosimilar or previous originator-infliximab treatment.

Results: Twenty patients with histologically documented neurosarcoidosis were treated with an infliximab biosimilar (initiation of treatment in 12 and switch from the originator drug in 8) between February 2016 and August 2018. All patients presenting with neurological involvement of one or more areas, including meningeal (n = 15), cerebral (n = 10), spinal cord (n = 9), and/or cranial nerves (n = 5); epilepsy (n = 3); and/or intracranial hypertension (n = 3) were enrolled. Eighteen patients received glucocorticoids during infliximab treatment, and 16 had methotrexate or azathioprine concomitant treatment. The median duration of follow-up was 25 months (19-28). Six patients relapsed during biosimilar treatment. Relapse rates and time-to-relapse did not differ between the infliximab originator previously received and biosimilar treatment groups (p = 0.40 and 0.51, respectively). Nine patients experienced 11 adverse events with the infliximab biosimilar, including infections (n = 5), urticaria (n = 4), headache (n = 1), and diarrhea (n = 1). All side effects were grade 2 or less using the WHO classification.

Conclusions: In this retrospective study, the infliximab biosimilar was efficacious and safe for treating neurosarcoidosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-019-09234-yDOI Listing
May 2019

IgG4-related diseases: state of the art on clinical practice guidelines.

RMD Open 2018 19;4(Suppl 1):e000787. Epub 2019 Jan 19.

Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany.

Immunoglobulin G4-related diseases (IgG4-RD) are a group of chronic relapsing-remitting inflammatory conditions, characterised by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, fibrosis and a usually favourable response to steroids. In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the European Reference Network ReCONNET, aimed at evaluating existing clinical practice guidelines (CPGs) and recommendations in IgG4-RD. From 167 publications initially obtained from a systematic literature search, only one was identified as a systematic multispecialist, evidence-based, consensus guidance statement on diagnosis and treatment of IgG4-RD, which may be recommended for use as CPG in IgG4-RD. With the recognition of a limited evidence based in this increasingly recognised disease, the group discussion has identified the following unmet needs: lack of shared classification criteria, absence of formal guidelines on diagnosis, no evidence-based therapeutic recommendations and lack of activity and damage indices. Areas of unmet needs include the difficulties in diagnosis, management and monitoring and the scarcity of expert centres.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/rmdopen-2018-000787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341179PMC
January 2019

Monitoring Disease Activity in Systemic Lupus Erythematosus With Single-Molecule Array Digital Enzyme-Linked Immunosorbent Assay Quantification of Serum Interferon-α.

Arthritis Rheumatol 2019 05;71(5):756-765

Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Inserm UMRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.

Objective: No simple or standardized assay is available to quantify interferon-α (IFNα) in routine clinical practice. Single-molecule array (Simoa) digital enzyme-linked immunosorbent assay (ELISA) technology enables direct IFNα quantification at attomolar (femtogram per milliliter [fg/ml]) concentrations. This study was undertaken to assess IFNα digital ELISA diagnostic performances to monitor systemic lupus erythematosus (SLE) activity.

Methods: IFNα concentrations in serum samples from 150 consecutive SLE patients in a cross-sectional study were determined with digital ELISA and a functional biologic activity assay (bioassay). According to their Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) flare composite scores, patients were divided into groups with inactive SLE (SLEDAI score of <4 or clinical SLEDAI score of 0) or active SLE (SLEDAI score of ≥4 or clinical SLEDAI score of >0), and into groups with no flare or mild/moderate flare or severe flare.

Results: Based on serum samples from healthy blood donors, the abnormal serum IFNα level threshold value was 136 fg/ml. Next, using receiver operating characteristic curves for an SLE patient series that was widely heterogeneous in terms of disease activity and organ involvement, the threshold IFNα value associated with active disease was determined to be 266 fg/ml. The digital ELISA-assessed serum IFNα level was a better biomarker of disease activity than the Farr assay because its specificity, likelihood ratio for positive results, and positive predictive value better discerned active SLE or flare from inactive disease. The digital ELISA was more sensitive than the bioassay for detecting low-abnormal serum IFNα concentrations and identifying patients with low disease activity.

Conclusion: Direct serum IFNα determination with a highly sensitive assay might improve monitoring of clinical SLE activity and selection of the best candidates for anti-IFNα treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.40792DOI Listing
May 2019

Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura.

Blood 2018 11 10;132(20):2143-2153. Epub 2018 Sep 10.

Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.

Preemptive rituximab infusions prevent relapses in immune thrombotic thrombocytopenic purpura (iTTP) by maintaining normal ADAMTS13 activity. However, the long-term outcome of these patients and the potential adverse events of this strategy need to be determined. We report the long-term outcome of 92 patients with iTTP in clinical remission who received preemptive rituximab after identification of severe ADAMTS13 deficiency (activity <10%) during the follow-up. Thirty-seven patients had >1 iTTP episode, and the median cumulative relapse incidence before preemptive rituximab was 0.33 episode per year (interquartile range [IQR], 0.23-0.66). After preemptive rituximab, the median cumulative relapse incidence in the whole population decreased to 0 episodes per year (IQR, 0-1.32; < .001). After preemptive rituximab, ADAMTS13 activity recovery was sustained in 34 patients (37%) during a follow-up of 31.5 months (IQR, 18-65), and severe ADAMTS13 deficiency recurred in 45 patients (49%) after the initial improvement. ADAMTS13 activity usually improved with additional courses of preemptive rituximab. In 13 patients (14%), ADAMTS13 activity remained undetectable after the first rituximab course, but retreatment was efficient in 6 of 10 cases. In total, 14 patients (15%) clinically relapsed, and 19 patients (20.7%) experienced benign adverse effects. Preemptive rituximab treatment was associated with a change in ADAMTS13 conformation in respondent patients. Finally, in the group of 23 historical patients with iTTP and persistently undetectable ADAMTS13 activity, 74% clinically relapsed after a 7-year follow-up (IQR, 5-11). In conclusion, persistently undetectable ADAMTS13 activity in iTTP during remission is associated with a higher relapse rate. Preemptive rituximab reduces clinical relapses by maintaining a detectable ADAMTS13 activity with an advantageous risk-benefit balance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2018-04-840090DOI Listing
November 2018

Risk of thrombosis with anti-phospholipid syndrome in systemic lupus erythematosus treated with thrombopoietin-receptor agonists.

Rheumatology (Oxford) 2018 Aug;57(8):1432-1438

Internal Medicine, French Referral Centre for Adult Immune Cytopenia, Henri Mondor Hospital, AP-HP, UPEC University, Créteil, France.

Objectives: The use of thrombopoietin-receptor agonists (TPO-RAs) has increased as a second-line therapy in ITP, but the efficacy and safety of such drugs has not been evaluated in SLE-associated ITP.

Methods: This was a multicentre retrospective cohort study from 2009 to 2016. Participating centres (n = 11) were secondary- or tertiary-care hospitals belonging to the French national network for adult ITP.

Results: We included 18 patients with SLE-ITP treated with TPO-RAs; 10 (55%) had aPL, 5 (27%) showing definite APS. Except for one patient, all (94%) achieved response with TPO-RAs overall. After a median follow-up of 14.7 months with TPO-RAs, four arterial thrombosis events (including one catastrophic APS) occurred in four patients. Two venous thrombosis events occurred in a patient without APS or aPLs.

Conclusion: Our results suggest that aPLs should be systematically screened before TPO-RA initiation in patients with SLE. With aPL positivity, alternative therapy should be discussed (if possible), especially in patients with definite APS or suboptimal adherence to anti-coagulation therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/key119DOI Listing
August 2018

Efficacy and safety of rituximab for systemic lupus erythematosus-associated immune cytopenias: A multicenter retrospective cohort study of 71 adults.

Am J Hematol 2018 03 25;93(3):424-429. Epub 2018 Jan 25.

AP-HP, Department of Internal Medicine, national referral center for adult's immune cytopenia, Henri-Mondor University Hospital, Université Paris-Est Créteil (UPEC), Créteil, France.

The aim of the study was to assess the efficacy and safety of rituximab (RTX) for treating systemic lupus erythematosus (SLE)-associated immune cytopenias. This multicenter retrospective cohort study of adults from French referral centers and networks for adult immune cytopenias and SLE involved patients ≥18 years old with a definite diagnosis of SLE treated with RTX specifically for SLE-associated immune cytopenia from 2005 to 2015. Response assessment was based on standard definitions. In total, 71 patients, 61 women (85.9%), with median age 36 years [interquartile range 31-48], were included. The median duration of SLE at the time of the first RTX administration was 6.1 years [2.6-11.6] and the reason for using RTX was immune thrombocytopenia (ITP) for 44 patients (62.0%), autoimmune hemolytic anemia (AIHA) for 16 (22.5%), Evans syndrome for 10 (14.1%), and pure red cell aplasia for one patient. Before receiving RTX, patients had received a mean of 3.1 ± 1.3 treatments that included corticosteroids (100%), and hydroxychloroquine (88.5%). The overall initial response rate to RTX was 86% (91% with ITP, 87.5% with AIHA, and 60% with Evans syndrome), including 60.5% with complete response. Median follow-up after the first injection of RTX was 26.4 months [14.3-71.2]. Among 61 initial responders, relapse occurred in 24 (39.3%); for 18, RTX retreatment was successful in 16 (88.8%). Severe infections occurred after RTX in three patients, with no fatal outcome. No cases of RTX-induced neutropenia were observed. In conclusion, RTX seems effective and relatively safe for treating SLE-associated immune cytopenias.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.24999DOI Listing
March 2018

Clinical, histological, immunological presentations and outcomes of bullous systemic lupus erythematosus: 10 New cases and a literature review of 118 cases.

Semin Arthritis Rheum 2018 08 4;48(1):83-89. Epub 2017 Nov 4.

AP-HP, Service de Médecine Interne 2, Centre National de Référence des Maladies Systémiques Rares, Lupus et Syndrome des Anticorps antiphospholipides, Institut e3m, Groupe Hospitalier Pitié-Salpêtrière, Paris 75013, France; Université Paris VI Pierre et Marie Curie, Sorbonnes Universités, Paris 75013, France.

Background: Bullous systemic lupus erythematosus (BSLE) is a rare blistering condition associated with systemic lupus erythematosus (SLE).

Patients And Methods: We conducted a multi-center retrospective study and literature review in order to describe the clinical, immunological, and histological presentations and outcomes of BSLE. The skin biopsies were centrally reviewed, and sera obtained during a flare of BSLE were analyzed for identification of circulating anti-basement membrane zone antibodies.

Results: Ten patients (all women, median age at SLE diagnosis of 22 years) were included, as well as 118 cases from a systematic review of the literature. Lupus nephritis was associated in 50% of the cases. BSLE presented as tensed bullae on normal or erythematous skin, predominantly localized on the trunk, arms, head, and neck. Urticarial lesions were associated in 31% of the cases, and mucous membrane involvement was seen in 51%. Histological analyses displayed subepidermal detachment, dermal infiltration of polynuclear neutrophils, alignment of these cells at the basal membrane zone and leukocytoclasis. The direct immunofluorescence was polymorphic, showing linear and/or granular deposits of IgG, IgA, IgM, and/or C3. Anti-type VII collagen antibodies were detected in 69% of cases. Dapsone was efficacious in 90% of cases.

Conclusion: BSLE is rather an autoimmune neutrophilic blistering disease associated with SLE than a cutaneous manifestation and may be associated with active extra-cutaneous manifestations of SLE. Dapsone is the first-choice option.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semarthrit.2017.11.003DOI Listing
August 2018

Clinicopathological features of multiple mononeuropathy associated with systemic lupus erythematosus: a multicenter study.

J Neurol 2017 Jun 23;264(6):1218-1226. Epub 2017 May 23.

AP-HP, Service de Médecine Interne 2, Institut e3 m, Hôpital de la Pitié-Salpêtrière, 75013, Paris, France.

Multiple mononeuropathy (MM) occurs rarely during systemic lupus erythematosus (SLE) but may lead to major disability. The aim of this study was to investigate the clinic-pathological presentations of MM during SLE, as well as long-term outcomes. We conducted a multicentric retrospective study that included patients receiving a diagnosis of MM during SLE. Ten patients were included (8 women and 2 men, median age at MM diagnosis: 40.4 years). SLE was diagnosed before MM in 9/10 patients (median time 8.2 years). When MM occurred, the SLEDAI score was ≥6 for 6/9 patients. Presenting symptoms consisted of sensory deficits (n = 10), neuropathic pain (n = 9), and/or motor deficits (n = 9), sometimes symmetrical, affecting the lower limbs (10/10) and occasionally the upper limbs (5/10). All patients presented with uni- or bilateral damage of the common fibular nerve, with less frequent involvement of the tibial nerve. Serum cryoglobulinemia was positive in 5/9 patients. Electrophysiological studies confirmed the non-symmetrical involvement of multiple nerve trunks in all patients. Neuromuscular biopsy (performed in five patients) showed histological signs of vasculitis in two patients and perivascular lymphocytic inflammatory infiltrates in two others. All patients were treated with glucocorticosteroids combined with cyclophosphamide (n = 6), rituximab (n = 3), or mycophénolate-mofétil (n = 1). The median follow-up was 5 years. Two patients relapsed during follow-up. All patients had motor and/or sensory sequelae upon follow-up. MM associated with SLE is frequently caused by a vasculitis mechanism. Patients improve with steroids and immunosuppressive drugs. Long-term outcomes include frequent clinical sequelae and possible relapses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-017-8519-7DOI Listing
June 2017

Long-term outcomes of refractory neurosarcoidosis treated with infliximab.

J Neurol 2017 May 4;264(5):891-897. Epub 2017 Mar 4.

AP-HP, Service de Médecine Interne 2, Institut e3m, Centre National de Référence Maladies Auto-immunes Systémiques Rares, Groupe Hospitalier Pitié-Salpétrière, 47-83 Boulevard de l'hôpital, 75013, Paris Cedex 13, France.

Central nervous system localizations of sarcoidosis may be refractory to conventional treatment such as steroids and immunosuppressive drugs. Infliximab, a TNF-α antagonist chimeric antibody, has been shown to be effective for treatment of these localizations. The aim of this study was to evaluate the efficacy and safety, in particular the long-term outcomes, of the use of infliximab for the treatment of neurosarcoidosis. We retrospectively reviewed medical records of patients with neurosarcoidosis who had been treated with infliximab between 2009 and 2015. All patients had histologically proven non-caseating granulomas. Eighteen patients with histologically proven sarcoidosis were included in this study. All had neurological involvement consisting of meningeal (n = 16), cerebral (n = 10), spinal cord (n = 6), and/or optic nerve (n = 5) involvement. Sixteen patients had previously received at least one immunosuppressive drug in addition to corticosteroids, including cyclophosphamide in 11 patients. All patients received treatment with infliximab (3-7.5 mg/kg) associated with corticosteroids (n = 18), low-dose methotrexate (n = 15), azathioprine (n = 2), or mycophenolate (n = 1). Sixteen out of 18 patients improved clinically (initial median modified Rankin scale score of 3, final median score of 1; p < 0.0001). At 6 months after initiation of infliximab, six patients obtained complete remission (33%), ten attained partial remission (56%), and two had stable disease (11%). The median follow-up time was 20 months (range 6-93). Nine patients relapsed during follow-up (50%). Eight patients developed toxic side effects and seven of these side effects were infectious events. Infliximab is an efficacious treatment of refractory neurosarcoidosis. However, relapses frequently occurred during follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-017-8444-9DOI Listing
May 2017

Lupus Myocarditis: Initial Presentation and Longterm Outcomes in a Multicentric Series of 29 Patients.

J Rheumatol 2017 01 15;44(1):24-32. Epub 2016 Nov 15.

From the APHP, Service de Médecine Interne, Institut E3M, Hôpital de la Pitié-Salpêtrière and Sorbonnes Universités, UPMC Université Paris VI, Paris; Service de Réanimation, and Service de Médecine Interne, Hôpital Européen, Marseille; Centre National de Référence pour les Maladies systémiques rares, Lupus et Syndrome des Anticorps antiphospholipides, Hôpital de la Pitié-Salpêtrière, Paris; APHP, Service de Médecine Interne, Centre de référence maladies auto-immunes et systémiques rares, Paris; Université Paris Descartes-Sorbonne Paris Cité, Paris; Assistance Publique-Hôpitaux de Marseille (APHM), Service de Médecine interne, Hôpital de la Conception, Marseille; APHM, Service de Médecine interne, Hôpital de la Timone, Marseille; APHP, Service de Radiologie, Pitié-Salpêtrière, Paris; Unité de Dermatologie-Médecine Interne, EA4546, CHU Pointe à Pitre, Guadeloupe; Département de Néphrologie et Transplantation, CHU de Toulouse, Toulouse; APHP, Service de Réanimation, INSERM, UMRS-1166, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.

Objective: Cardiac involvement during systemic lupus erythematosus (SLE) may include the pericardium, myocardium, valvular tissue, and coronary arteries. The aim of this study was to describe the clinical, biological, and radiological presentation of lupus myocarditis (LM) as well as the treatment response and longterm outcomes.

Methods: We conducted a multicentric retrospective study of LM from January 2000 to May 2014.

Results: Twenty-nine patients (3 men and 26 women) fulfilled the inclusion criteria (median age at the diagnosis of SLE: 30 yrs, range 16-57). Myocarditis was the first sign of SLE in 17/29 cases (58.6%). Troponin was elevated in 20/25 cases. Electrocardiogram results were abnormal in 25/28 cases. Echocardiography revealed low (≤ 45%) left ventricular ejection fraction (LVEF; 19/29, 66%) and pericardium effusion (20/29, 69%). Cardiac magnetic resonance imaging revealed delayed gadolinium enhancement in 9/13 patients (69%). Patients were treated with corticosteroids (n = 28), cyclophosphamide (CYC; n = 16), intravenous immunoglobulins (n = 8), and/or mycophenolate mofetil (n = 2). The median followup was 37 months. One month after the beginning of the treatment, 10/23 patients (43%) who had undergone echocardiography had an LVEF ≥ 55%. At the end of followup, 21/26 patients (81%) exhibited an LVEF ≥ 55%. Three patients died during followup, and 2 died from LM.

Conclusion: LM is a severe manifestation of SLE. It can be the first manifestation of the disease or it can occur during followup, in particular in untreated patients. However, the longterm prognosis is typically positive. Patients with less severe disease exhibited good LVEF recovery without CYC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.160493DOI Listing
January 2017

Relapsing polychondritis: A 2016 update on clinical features, diagnostic tools, treatment and biological drug use.

Best Pract Res Clin Rheumatol 2016 04 1;30(2):316-333. Epub 2016 Oct 1.

Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière (GHPS), French National Reference Center for Rare Systemic Auto-immune Diseases, Service de Médecine interne 2, Paris, France; Inserm, U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France; Université Pierre et Marie Curie, Univ Paris 06, Paris, France.

Relapsing polychondritis (RP) is a very rare autoimmune disease characterised by a relapsing inflammation of the cartilaginous tissues (joints, ears, nose, intervertebral discs, larynx, trachea and cartilaginous bronchi), which may progress to long-lasting atrophy and/or deformity of the cartilages. Non-cartilaginous tissues may also be affected, such as the eyes, heart, aorta, inner ear and skin. RP has a long and unpredictable course. Because no randomised therapeutic trials are available, the treatment of RP remains mainly empirical. Minor forms of the disease can be treated with non-steroidal anti-inflammatory drugs, whereas more severe forms are treated with systemic corticosteroids. Life-threatening diseases and corticosteroid-dependent or resistant diseases are an indication for immunosuppressant therapy such as methotrexate, azathioprine, mycophenolate mofetil and cyclophosphamide. Biologics could be given as second-line treatment in patients with an active disease despite the use of steroids and immunosuppressive drugs. Although the biologics represent new potential treatment for RP, very scarce information is available to draw any firm conclusion on their use in RP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.berh.2016.08.001DOI Listing
April 2016

Treatment of neurosarcoidosis: A comparative study of methotrexate and mycophenolate mofetil.

Neurology 2016 Dec 16;87(24):2517-2521. Epub 2016 Nov 16.

From AP-HP, Service de Médecine Interne 2, Institut e3m, Centre National de Référence Maladies Systémiques Rares, Lupus, Syndrome des Anticorps Antiphospholipides (S.B., J.H., A.M., M.H., D.L.T.H.B., Z.A., F.C.A.), and AP-HP, Service de Neurologie 1 (D.P.), Hôpital de la Pitié-Salpêtrière, Paris; AP-HP, Service de Pneumologie (D.B., D.V., H.N.), Hôpital Avicenne, Bobigny; AP-HP, Services de Pneumologie (R.B.) and Médecine Interne (K.S., T.P.), Hôpital Bichat, Paris; AP-HP, Service de Médecine Interne (M.M., B.G.), Hôpital Henri Mondor, Créteil; Université Paris VI, UPMC (J.H., A.M., M.H., D.L.T.H.B., Z.A., C.A.), Sorbonnes Universités, Paris; and Service de Neurologie (C.P.), Centre Hospitalier René Dubos, Pontoise, France.

Objective: To compare the efficacy of methotrexate (MTX) and mycophenolate mofetil (MMF) in the prevention of relapses in neurosarcoidosis.

Methods: We conducted a retrospective multicenter study including patients who received MTX or MMF for the treatment of histologically proven neurosarcoidosis. The efficacy of the immunosuppressive drug was assessed by determining the time to relapse.

Results: Forty patients with a diagnosis of neurosarcoidosis (24 men, 16 women, median age at diagnosis 43.5 years) who received at least 3 months of MTX (n = 32) or MMF (n = 14) were included. The immunosuppressive drug was always associated with steroids. The rate of relapse was 47% in the MTX group (0.2 relapses per year of exposure) and 79% in the MMF group (0.6 relapses per year of exposure) (p = 0.058). The median time to relapse was significantly shorter in the MMF group (11 months) compared with the MTX group (28 months) (p = 0.049). Adverse events occurred in 11 patients during MTX therapy and in 1 patient during MMF therapy (p = 0.12).

Conclusions: Relapses of neurosarcoidosis occur frequently, despite the use of an immunosuppressive drug in addition to corticosteroids. MTX significantly increases the survival time without relapse compared to MMF and should be preferred over MMF for the treatment of neurosarcoidosis. This study provides Class IV evidence that for patients with neurosarcoidosis taking steroids, MTX is superior to MMF in reducing the risk of relapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000003431DOI Listing
December 2016

Management of a Thoracic Aortic Aneurysm during Pregnancy Leading to the Diagnosis of Takayasu Arteritis.

Ann Vasc Surg 2016 Oct 6;36:291.e1-291.e4. Epub 2016 Jul 6.

Interne des hôpitaux de Paris, Hôpital La Pitié Salpétriêre, Paris, France.

Takayasu arteritis is a chronic inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. We report the case of a patient presenting with the rapid growth of a thoracic aortic aneurysm during pregnancy leading to the diagnosis of Takayasu disease and treated by a rapid delivery by cesarean section followed by an open aortic repair. One year after the operation the patient and her baby are alive and well.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.avsg.2016.02.040DOI Listing
October 2016

Sjögren Sensory Neuronopathy (Sjögren Ganglionopathy): Long-Term Outcome and Treatment Response in a Series of 13 Cases.

Medicine (Baltimore) 2016 May;95(19):e3632

From the Internal Medicine Department (PRP, JH, AM, MH, ZA, FCA), AP-HP, Pitié-Salpêtrière Hospital, Institut E3 M, French National Reference Center for Rare Systemic diseases, Paris, France; Internal Medicine Department (PRP), ULS Matosinhos, Portugal; Neurophysiology Department (KV, TM), AP-HP, Pitié-Salpêtrière Hospital; Neuropathology Department (TM), AP-HP, Pitié-Salpêtrière Hospital; and Sorbonnes Universités (JH, AM, ZA, FC), Paris VI University, UPMC, Paris, France.

Primary Sjögren syndrome (SS) is an autoimmune disease mainly affecting the exocrine glands causing a sicca syndrome. Neurological manifestations are rarely seen in SS although they are debilitating. Peripheral neuropathies namely sensory axonal neuropathy and painful small fiber neuropathy are the most frequent neurological manifestations. Sensory neuronopathy (SN) is less frequently seen although leading to more severe handicap.The aim of the study was to analyze the clinical presentation and treatment efficacy in a series of SS-related SN.We retrospectively studied patients with SS fulfilling the American-European Classification Criteria and SN according to recent criteria. Studied variables were neurological findings, associated autoimmune diseases, biological profiles, nerve conduction and sensory/motor amplitudes study, treatments received, and outcomes. Handicap scores were studied at beginning and end of each treatment using the modified Rankin Scale (mRS).Thirteen patients were included (12 women, 1 man; median age 55 years at SN diagnosis) presenting with SN with a median follow-up of 3 years (range 2-17). In 11 patients, SN preceded or coincided with SS diagnosis. Most common neurological findings were ataxia and areflexia followed by paresthesia and pain. Lower limbs were more affected than upper limbs, neurological deficits were often symmetric and cranial nerves were affected in 3 patients. Seven patients were treated with corticosteroids, 7 with mycophenolate mofetil, 6 with hydroxychloroquine, 5 with intravenous immunoglobulins, 4 with cyclophosphamide, and 2 patients received other immunosuppressive drugs. At the beginning and at the end of follow-up, average mRS was 2.15 (median 2) and 2.38 (median 2), respectively.SS-related SN progression is heterogeneous but tends to be chronic, insidious, and debilitating despite treatment. From these data concerning a small number of patients, treatment strategies with corticosteroids in association with immunosuppressive drugs, namely mycophenolate mofetil, had positive results. In contrast, intravenous immunoglobulins had disappointing results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000003632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902517PMC
May 2016

Dermatomyositis With or Without Anti-Melanoma Differentiation-Associated Gene 5 Antibodies: Common Interferon Signature but Distinct NOS2 Expression.

Am J Pathol 2016 Mar 21;186(3):691-700. Epub 2016 Jan 21.

Department of Neuropathology, Charité-Universitätsmedizin, Berlin, Germany.

The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti-MDA5(+)-patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti-MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti-MDA5-positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed in anti-MDA5 DM and not in classic DM patients. Only anti-MDA5 DM showed numerous nitric oxide synthase 2-positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti-MDA5-positive patients demonstrate a morphological pattern distinct from classic DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajpath.2015.11.010DOI Listing
March 2016

Efficacy of Biological-Targeted Treatments in Takayasu Arteritis: Multicenter, Retrospective Study of 49 Patients.

Circulation 2015 Nov 9;132(18):1693-700. Epub 2015 Sep 9.

From AP-HP, Hôpital Saint Antoine, Service de Médecine Interne et Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France (A.M., O.F.); Service de Médecine Interne, Hôpital Pitié Salpetrière, Université Paris 6, Paris, France (C.C., P. Cacoub, D.S.); Unité Epidémiologie et Biostatistiques, INSERM, Hôpital Saint Louis, Paris, France (M.R.-R.); Service de Médecine Vasculaire, Hôpital Européen Georges-Pompidou, Assistance Publique Hôpitaux de Paris-APHP, Université Paris Descartes, Sorbonne Paris Cité, PARCC, Inserm U970, Centre de Référence National Maladies Vasculaires Rares, Paris, France (T.M., E.M.); Service de Médecine Interne, Hôpital Foch, Université Versailles Saint Quentin en Yvelines, Versailles, France (J.E.K.); Service de Médecine Interne, CHU Lille, Université Lille II, Lille, France (M.L.); Inserm UMR_1109, Fédération de Médecine Translationnelle, Université de Strasbourg, Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France (J.S.); Service de Médecine Interne, CHU Hôtel-Dieu, Nantes, France (A.N., M. Hamidou); Université Paris Descartes, AP-HP, Hôpital Cochin, Centre de Référence Maladies Auto-Immunes et Systémiques Rares, Service de Médecine Interne, Paris, France (P. Cohen, L.G.); Service de Médecine Interne, Hôpital Pitié Salpetrière, Department of Internal Medicine and Clinical Immunology Groupe Hospitalier Pitié-Salpetrière, Université Pierre et Marie Curie, UPMC, Paris, France (M. Hie, Z.A.); Service de Médecine Interne et Immunologie Clinique, Hôpital le Bocage, Dijon, France (S.B.); Service de Médecine Interne, Université Rouen, Rouen, France (I.M.); Service de Médecine Interne et Maladies Vasculaires, Centre de Compétence de Maladies Rares, CHU Angers, Université Angers, Angers, France (C.L.); Service de Médecine Interne, Université Bordeaux, CHU Bordeaux, Bordeaux, France (M.A.V.); Service de Médecine Interne et Immunologie Clinique, Universi

Background: The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-α antagonists and tocilizumab) in patients with Takayasu arteritis.

Methods And Results: This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20-55 years] treated by tumor necrosis factor-α antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1-5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10-46 mg/L] versus 58 mg/L [26-76 mg/L]; P=0.006) and a trend toward fewer immunosuppressants drugs used before biologics (P=0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C-reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [P<0.05] and 15 versus 7.5 mg [P<0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%-99%) over the biological treatment period compared with 58.7% (43.3%-79.7%; P=0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-α antagonists and tocilizumab. After a median follow-up of 24 months (2-95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases.

Conclusion: This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.114.014321DOI Listing
November 2015

Rituximab in autoimmune thrombotic thrombocytopenic purpura: A success story.

Eur J Intern Med 2015 Nov 17;26(9):659-65. Epub 2015 Aug 17.

Centre de Référence des Microangiopathies Thrombotiques, AP-HP, Paris, France; Service d'hématologie, Hôpital Saint Antoine, Paris, France; Inserm U1009, Institut Gustave Roussy, Villejuif, France. Electronic address:

Despite a significant improvement of thrombotic thrombocytopenic purpura (TTP) prognosis since the use of plasma exchange, morbidity and mortality remained significant because of poor response to standard treatment or exacerbations and relapses. Rituximab, a chimeric monoclonal antibody directed against the B-lymphocyte CD20 antigen, has shown a particular interest in this indication. Recent studies also reported strong evidence for its efficiency in the prevention of relapses. This review addresses these recent progresses and still opened questions in this topic: should rituximab be proposed in all patients at the acute phase? Should all patients benefit from a preemptive treatment? Is the infectious risk acceptable in this context?
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejim.2015.07.021DOI Listing
November 2015

Targeting interferons in systemic lupus erythematosus: current and future prospects.

Drugs 2015 May;75(8):835-46

AP-HP, Groupement Hospitalier Pitié-Salpêtrière, Service de médecine interne 2, Institut E3M, Centre de Référence National pour le Lupus et le Syndrome des Antiphospholipides, 83 boulevard de l'hôpital, 75013, Paris, France.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown aetiology that can be debilitating and life threatening. As new insights are gained into the underlying pathology of SLE, there have been an unprecedented number of new agents under development to treat the disease via a diverse range of targets. One such class of emerging agents target interferon (IFN) signalling. In this article, we review the preclinical evidence that the inhibition of the secretion and downstream effectors of both IFN-α and IFN-γ may be effective for the treatment of SLE. The primary agents that are currently in clinical development to treat SLE via the targeting of interferon pathways are monoclonal neutralising antibodies (Mab) that bind to and neutralise IFN-γ (AMG 811), IFN-α (sifalimumab, rontalizumab and AGS-009) or its receptor (anifrolumab), and IFN-α kinoid, which is a drug composed of inactivated IFN-α molecules coupled to the keyhole limpet haemocyanin protein. Phase I and II trials have demonstrated acceptable short-term safety with no increase in severe viral infections or reactivation, favourable pharmacokinetic profiles and an inhibition of IFN-associated gene overexpression; however, the impact of these drugs on disease activity must still be assessed in phase III clinical trials. This review concludes with a summary of the challenges that are inherent to this approach to managing SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40265-015-0394-xDOI Listing
May 2015