C. Lavigne

Tocilizumab in refractory Takayasu arteritis: A case series and updated literature review

BACKGROUND/PURPOSEnThe aim of this study is to analyze the efficacy and tolerance of tocilizumab in patients with Takayasu arteritis (TA).nnnMETHODSnWe retrospectively studied patients with TA (ACR and/or Ishikawas criteria): 5 French multicenter cases and 39 from the literature. Clinical, biological, radiological disease activity and treatment were analyzed before tocilizumab, during the follow-up and at the last available visit.nnnRESULTSnForty-four patients (median age 26years [3-65];) were included in the present study: 5 patients from the 3 French university hospitals and 39 cases from the literature review. Median follow-up after initiation of tocilizumab was 15months [8-33]. Clinical and biological activities significantly decreased within 3months, similarly to steroid amount (from 15mg/day [5-75] at baseline to 10mg/day [2-30] at 6months; p<0.05) and steroid-dependence rate. Even radiological activity did not significantly decrease at 6months, significant decrease of arterial FDG uptake was noted at 6months. Median duration of tocilizumab treatment was 9months [3-180]. At the last visit, tocilizumab was continued in 17/32 patients (53%), and was discontinued in the 15 remaining cases because of the remission (n=5), relapse (n=3), persistent radiological activity (n=3), cutaneous rash (n=2), severe infection (n=1) and lacking of care welfare system (n=1). No death related to tocilizumab treatment was noted.nnnCONCLUSIONnThis study show the efficacy of tocilizumab in terms of clinical, biological and radiological response, as well as steroid-sparing agent. Only well-designed studies could definitely address the efficacy of tocilizumab in TA.

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

Background— The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-&agr; 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-&agr; 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-&agr; 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.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.nnMethods 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.nnConclusion— This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile.nn# CLINICAL PERSPECTIVE {#article-title-34}

Systemic and immune manifestations in myelodysplasia: A multicenter retrospective study

The presence of systemic and/or immune manifestations in myelodysplasia has been currently reported. The influence of these manifestations on the natural outcome of myelodysplastic syndrome has to be considered. We present a multicenter retrospective study (2002–2009) of patients with myelodysplastic syndrome disclosing systemic and/or immune manifestations.

The Clinical Spectrum and Therapeutic Management of Hypocomplementemic Urticarial Vasculitis: Data From a French Nationwide Study of Fifty‐Seven Patients

Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology that is rarely described in the literature. We undertook this study to analyze the clinical spectrum and the therapeutic management of patients with HUV.

ASXL1 but Not TET2 Mutations Adversely Impact Overall Survival of Patients Suffering Systemic Mastocytosis with Associated Clonal Hematologic Non-Mast-Cell Diseases

Systemic mastocytosis with associated hematologic clonal non-mast cell disease (SM-AHNMD) is a rare and heterogeneous subtype of SM and few studies on this specific entity have been reported. Sixty two patients with Systemic mastocytosis with associated hematologic clonal non-mast cell disease (SM-AHNMD) were presented. Myeloid AHNMD was the most frequent (82%) cases. This subset of patients were older, had more cutaneous lesions, splenomegaly, liver enlargement, ascites; lower bone mineral density and hemoglobin levels and higher tryptase level than lymphoid AHNMD. Defects in KIT, TET2, ASXL1 and CBL were positive in 87%, 27%, 14%, and 11% of cases respectively. The overall survival of patients with SM-AHNMD was 85.2 months. Within the myeloid group, SM-MPN fared better than SM-MDS or SM-AML (pu200a=u200a0.044,). In univariate analysis, the presence of C-findings, the AHNMD subtypes (SM-MDS/CMML/AML versus SM-MPN/hypereosinophilia) (pu200a=u200a0.044), Neutropenia (pu200a=u200a0.015), high monocyte level (pu200a=u200a0.015) and the presence of ASXL1 mutation had detrimental effects on OS (pu200a=u200a0.007). In multivariate analysis and penalized Cox model, only the presence of ASXL1 mutation remained an independent prognostic factor that negatively affected OS (pu200a=u200a0.035). SM-AHNMD is heterogeneous with variable prognosis according to the type of the AHNMD. ASXL1 is mutated in a subset of myeloid AHNMD and adversely impact on OS.

Anti-Ku antibodies: Clinical, genetic and diagnostic insights

Anti-Ku antibodies are reported in various connective tissue diseases and the Ku complex can be responsible for a very strong autoimmune answer in autoimmune disease. Nowadays, anti-Ku antibodies are detected by ELISA, counterimmunoelectrophoresis (CIE), immunoblot (IB) and new highly performant techniques. Although the prevalence of anti-Ku antibodies is not homogenous, depending on several features such as disease type, genetic and geographical clustering, and also method of detection, they could be found in 55% overlap PM/systemic sclerosis patients. Moreover, anti-Ku antibodies are not associated with a particular clinical outcome, and especially with cancer related to myositis.

Psychiatric adult-onset of urea cycle disorders: A case-series

Adult onset urea cycle disorders (UCD) may present with psychiatric symptoms, occasionally as the initial presentation. We aimed to describe the characteristics of patients presenting with a psychiatric adult-onset of UCDs, to discuss which signs could suggest this diagnosis in such a situation, and to determine which tests should be conducted. A survey of psychiatric symptoms occurring in teenagers or adults with UCD was conducted in 2010 among clinicians involved in the French society for the study of inborn errors of metabolism (SFEIM). Fourteen patients from 14 to 57 years old were reported. Agitation was reported in 10 cases, perseveration in 5, delirium in 4, and disinhibition in 3 cases. Three patients had pre-existing psychiatric symptoms. All patients had neurological symptoms associated with psychiatric symptoms, such as ataxia or dysmetria, psychomotor slowing, seizures, or hallucinations. Fluctuations of consciousness and coma were reported in 9 cases. Digestive symptoms were reported in 7 cases. 9 patients had a personal history suggestive of UCD. The differential diagnoses most frequently considered were exogenous intoxication, non-convulsive status epilepticus, and meningoencephalitis. Hyperammonemia (180–600 μmol/L) was found in all patients. The outcome was severe: mechanical ventilation was required in 10 patients, 5 patients died, and only 4 patients survived without sequelae. Adult onset UCDs can present with predominant psychiatric symptoms, associated with neurological involvement. These patients, as well as patients presenting with a suspicion of intoxication, must have UCD considered and ammonia measured without delay.

Cogan syndrome: Characteristics, outcome and treatment in a French nationwide retrospective study and literature review

BACKGROUNDnCogan syndrome is mainly treated with steroids. We aimed to determine the place of DMARDs and biologic-targeted treatments.nnnPATIENTS AND METHODSnWe conducted a French nationwide retrospective study of patients with Cogan syndrome (n=40) and a literature review of cases (n=22) and analyzed the efficacy of disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor α (TNF-α) antagonists.nnnRESULTSnWe included 62 patients (31 females) (median age 37years [range 2-76]. At diagnosis, 61 patients (98%) had vestibulo-auditory symptoms, particularly bilateral hearing loss in 41% and deafness in 31%. Ocular signs were present in 57 patients (92%), with interstitial keratitis in 31 (51%). The first-line treatment consisted of steroids alone (n=43; 70%) or associated with other immunosuppressive drugs (n=18; 30%). Overall, 13/43 (30%) and 4/18 (22%) patients with steroids alone and with associated immunosuppressive drugs, respectively (p=0.8), showed vestibulo-auditory response; 32/39 (82%) and 15/19 (79%) ocular response; and 23/28 (82%) and 10/14 (71%) general response. Overall 61 patients had used a total of 126 lines of treatment, consisting of steroids alone (n=51 lines), steroids with DMARDs (n=65) and infliximab (n=10). Vestibulo-auditory response was significantly more frequent with infliximab than DMARDs or steroids alone (80% vs 39% and 35%, respectively), whereas ocular, systemic and acute-phase reactant response rates were similar. Infliximab was the only significant predictor of vestibulo-auditory improvement (odds ratio 20.7 [95% confidence interval 1.65; 260], p=0.019).nnnCONCLUSIONnInfliximab could lead to vestibulo-auditory response in DMARDS and steroid-refractory Cogan syndrome, but prospective studies are necessary.

Mastocytosis among elderly patients: A multicenter retrospective French study on 53 patients.

AbstractMastocytosis is a heterogeneous group of diseases with a young median age at diagnosis. Usually indolent and self-limited in childhood, the disease can exhibit aggressive progression in mid-adulthood. Our objectives were to describe the characteristics of the disease when diagnosed among elderly patients, for which rare data are available.The French Reference Center conducted a retrospective multicenter study on 53 patients with mastocytosis >69 years of age, to describe their clinical, biological, and genetic features.The median age of our cohort of patients was 75 years. Mastocytosis variants included were cutaneous (n = 1), indolent systemic (n = 5), aggressive systemic (n = 11), associated with a hematological non-mast cell disease (n = 34), and mast cell leukemia (n = 2). Clinical manifestations were predominantly mast cell activation symptoms (75.5%), poor performance status (50.9%), hepatosplenomegaly (50.9%), skin involvement (49.1%), osteoporosis (47.2%), and portal hypertension and ascites (26.4%). The main biological features were anemia (79.2%), thrombocytopenia (50.9%), leucopenia (20.8%), and liver enzyme abnormalities (32.1%). Of the 40 patients tested, 34 (85%), 2 (5%), and 4 (10%) exhibited the KIT D816V mutant, other KIT mutations and the wild-type form of the KIT gene, respectively. Additional sequencing detected significant genetic defects in 17 of 26 (65.3%) of the patients with associated hematological non-mast cell disease, including TET2, SRSF2, IDH2, and ASLX1 mutations. Death occurred in 19 (35.8%) patients, within a median delay of 9 months, despite the different treatment options available.Mastocytosis among elderly patients has a challenging early detection, rare skin involvement, and/or limited skin disease; it is heterogeneous and has often an aggressive presentation with nonfortuitous associated myeloid lineage malignant clones, and thus a poor overall prognosis.

Efficacy of tocilizumab in Takayasu arteritis: Multicenter retrospective study of 46 patients

OBJECTIVESnTo assess the efficacy of tocilizumab in patients with Takayasu arteritis (TA).nnnMETHODSnWe conducted a retrospective multicenter study in 46u202fTA patients treated with tocilizumab. We analyzed factors associated with response to tocilizumab (assessed using NIH score).nnnRESULTSnForty-six patients with TA were included, with a median age of 43 years [29-54], and 35 (76%) females. We observed a decrease in the median NIH scale (from 3 [2-3] at baseline to 0 [0-1] and 0u202fat 3 and 6 months, respectively; pu202f<u202f0.0001). The daily prednisone dose also decreased from 15u202fmg [8-19] at baseline to 4u202fmg [5-21] and 5u202fmg [4.5-9] at 3 and 6 months, respectively (pu202f<u202f0.0001) under tocilizumab. The overall tocilizumab failure free survival was 81% [CI 95%; 0.7-0.95], 72% [CI 95%; 0.55-0.95] and 48% [CI 95%; 0.2-0.1] at 12, 24 and 48 months, respectively. The presence of constitutional symptoms (HR 5.6 [CI 95%; 1.08-29], pu202f=u202f0.041), and C-reactive protein level (HR 1.16 [CI 95%; 1.01-1.31], Pu202f=u202f0.003) at the time of tocilizumab initiation were significantly associated with tocilizumab event-free survival. The event-free survival was significantly better under tocilizumab therapy in comparison to DMARDs (pu202f=u202f0.02).nnnCONCLUSIONnThis large multicenter study shows that tocilizumab is efficient and may reduce the incidence of relapses in TA.