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The aim of this study was to assess the prevalence and the burden of difficult-to-treat primary ITP (pITP), defined by the need for another ITP treatment after romiplostim and eltrombopag. Adult patients were selected in the prospective, real-world CARMEN-France registry up to December 2021. Out of 821 adult patients with pITP, 29 had difficult-to-treat ITP (3.5%; 95% confidence interval [CI]: 2.3%-4.8% in total; 7.6%; 95% CI: 4.9%-10.2% of patients needing ≥2nd line treatment). The 3-year cumulative incidence of bleeding, infection and thrombosis was 100%, 24.1% and 13.8% respectively. The median cumulative duration of hospital stays was 31 days (median follow-up: 30.3 months)., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Objectives: An increased risk of haematological malignancies (HM) has been reported in GCA patients. Our study aimed to investigate the incidence and the type of HM occurring in GCA., Methods: All patients with GCA and HM living in Côte d'Or (France) were identified by crossing data from the RHEMCO (Registre des Hémopathies Malignes de Côte d'Or) and those having a positive temporal artery biopsy between 1 January 2001 and 31 December 2018., Results: Among 276 biopsy-proven GCA patients, 14 HM were identified in 12 patients (4.3%). In comparison with the general population aged >50 y, the incidence of myeloid HM and myeloproliferative syndromes were increased in GCA patients [standardized incidence ratios (SIR) = 2.71 and 5.16, respectively], with a specific increase in men with GCA (SIR = 4.82 and 9.04, respectively) but not in women. In addition, the study of SIR depending on the chronology between GCA and HM diagnoses suggests that there was an increased risk of developing GCA in men but not in women, after a diagnosis of myeloid HM (SIR = 9.56), especially if it was a MPS (SIR = 17.56)., Conclusions: Our study shows a particular epidemiology of HM in GCA patients, which is characterized by an increased incidence of myeloid HM, especially MPS, in male GCA patients. The chronology of the diagnoses of GCA and HM raises the hypothesis that clonal hematopoiesis may be implicated in some cases of GCA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Cardiovascular risk is increased in giant cell arteritis (GCA). We aimed to characterize myocardial infarction (MI) in a GCA cohort, and to compare the GCA and non-GCA population affected by MI., Methods: In patients with a biopsy-proven diagnosis of GCA between 1 January 2001 and 31 December 2016 in Côte D'Or (France), we identified patients with MI by crossing data from the territorial myocardial infarction registry (Observatoire des Infarctus de Côte d'Or) database. Five controls (non-GCA + MI) were paired with one case (GCA + MI) after matching for age, sex, cardiovascular risk factors and prior cardiovascular disease. MI were characterized as type 1 MI (T1MI), resulting from thrombus formation due to atherothrombotic disease, or type 2 MI (T2MI), due to a myocardial supply/demand mismatch. GCA-related MI was defined as MI occurring within 3 months of a GCA flare (before or after)., Results: Among 251 biopsy-proven GCA patients, 13 MI cases were identified and paired with 65 controls. MI was GCA-related in 6/13 cases, accounting for 2.4% (6/251) of our cohort. T2MI was more frequently GCA-related than GCA-unrelated (80% vs. 16.7%, p = 0.080), and GCA diagnosis was the only identified triggering factor in 75% of GCA-related T2MI. GCA-unrelated MI were more frequently T1MI and occurred in patients who had received a higher cumulative dose of prednisone (p = 0.032). GCA was not associated with poorer one-year survival., Conclusions: GCA-related MI are mainly T2MI probably caused by systemic inflammation rather than coronaritis. GCA-unrelated MI are predominantly T1MI associated with atherothrombotic coronary artery disease., (Copyright © 2021. Published by Elsevier B.V.)

Rituximab is a second-line option in adults with immune thrombocytopenia (ITP), but the estimated 5-year response rate, only based on pooled retrospective data, is about 20%, and no studies have focused on long-term safety. We conducted a prospective multicenter registry of 248 adults with ITP treated with rituximab with 5 years of follow-up to assess its long-term safety and efficacy. The median follow-up was 68.4 [53.7-78.5] months. The incidence of severe infections was only 2/100 patient-years. Profound hypogammaglobulinemia (<5 g/L) developed in five patients at 15 to 31 months after the last rituximab infusion. In total, 25 patients died at a median age of 80 [69.5-83.9] years, corresponding to a mortality rate of 2.3/100 patient-years. Only three deaths related to infection that occurred 12 to 14 months after rituximab infusions could be due in part to rituximab. At 60 months of follow-up, 73 (29.4%) patients had a sustained response. On univariate and multivariate analysis, the only factor significantly associated with sustained response was a previous transient response to corticosteroids (P = .022). Overall, 24 patients with an initial response and then relapse received retreatment with rituximab, which gave a response in 92%, with a higher duration of response in 54%. As a result of its safety profile and its sustained response rate, rituximab remains an important option in the current therapeutic armamentarium for adult ITP. Retreatment could be an effective and safe option., (© 2019 Wiley Periodicals, Inc.)

Background: An increased risk of thrombosis has been reported in immune thrombocytopenic purpura (ITP), but the characteristics, risk factors of occurrence, recurrence and management of venous thromboembolic events (VTE) have been poorly investigated., Aims: To describe VTE and ITP characteristics, distribution of VTE risk factors and their impact on VTE features and recurrence., Methods: A retrospective study of patients with ITP and VTE registered in databases of three reference French centres of ITP., Results: Among 49 patients, 66 VTE were recorded. The platelet count at the time of the first VTE was <100 × 10 9 /L for 28/43 (65%) patients. In total, 19/48 (40%) patients had at least one positive antiphospholipid test result. For the 10 VTE occurring in eight patients with platelet count <50 × 10 9 /L, ITP treatment was efficient in 7. One haemorrhagic complication associated with anticoagulant (AC) therapy was recorded. For 31/49 (63%) patients, long-term AC therapy could have been discussed after the first VTE, but only 13 received it. A second VTE occurred in 13 (27%) patients. The risk of recurrence was increased in patients with unprovoked VTE before ITP diagnosis or active cancer., Conclusion: VTE in ITP mainly occurred in the presence of multiple risk factors of TE. A low platelet count does not protect against VTE. Management with AC therapy despite persistently low platelet count seems possible. Risk of VTE recurrence is high, particularly with a history of unprovoked VTE or active cancer. In this setting, indefinite AC therapy could be discussed., (© 2019 Royal Australasian College of Physicians.)

Background: The aim of this study was to evaluate tocilizumab (TCZ) as an add-on therapy to glucocorticoids (GC) during the first 3 months of treatment of giant cell arteritis (GCA)., Methods: GCA patients, as defined by ≥3/5 ACR criteria and positive temporal artery biopsy (TAB) or angio-CT-scan or PET-scan-proven aortitis, were included in this prospective open-label study. Prednisone was started at 0.7 mg/kg/day and then tapered according to a standardized protocol. All patients received four infusions of TCZ (8 mg/kg/4 weeks) after inclusion. The primary endpoint was the percentage of patients in remission with ≤0.1 mg/kg/day of prednisone at week 26 (W26). Patients were followed for 52 weeks and data prospectively recorded., Results: Twenty patients with a median (IQR) age of 72 (69-78) years were included. TAB were positive in 17/19 (90%) patients and 7/16 (44%) had aortitis. Remission was obtained in all cases. At W26, 15 (75%) patients met the primary endpoint. Ten patients experienced relapse during follow-up, mainly patients with aortitis (P = 0.048), or CRP >70 mg/L (P = 0.036) or hemoglobin ≤10 g/dL (P = 0.015) at diagnosis. Among 64 adverse events (AE) reported in 18 patients, three were severe and 30, mostly non-severe infections (n = 15) and hypercholesterolemia (n = 8), were imputable to the study., Conclusion: This study shows that an alternative strategy using a short-term treatment with TCZ can be proposed to spare GC for the treatment of GCA. However, 50% of patients experienced relapse during the 9 months following TCZ discontinuation, especially patients with aortitis, or CRP > 70 mg/L or Hb ≤ 10 g/dL at diagnosis., Trial Registration: ClinicalTrials.gov (NCT01910038)., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: To report efficacy and tolerance of interleukin 1 blockade in adult patients with mevalonate kinase deficiency (MKD)., Methods: We retrospectively collected data on 13 patients with MKD who had received anakinra (n = 10) and canakinumab (n = 7)., Results: Anakinra resulted in complete or partial remission in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to canakinumab led to partial remission. Canakinumab resulted in complete or partial remission in 3/7 and 4/7 patients, respectively., Conclusion: These data support frequent partial responses, showing a better response with canakinumab. The genotype and therapeutic outcomes correlation should help in the personalization of treatment.

The aim of this study was to describe the clinical and biological features of Mevalonate kinase deficiency (MKD) in patients diagnosed in adulthood. This is a French and Belgian observational retrospective study from 2000 to 2014. To constitute the cohort, we cross-check the genetic and biochemical databases. The clinical, enzymatic, and genetic data were gathered from medical records. Twenty-three patients were analyzed. The mean age at diagnosis was 40 years, with a mean age at onset of symptoms of 3 years. All symptomatic patients had fever. Febrile attacks were mostly associated with arthralgia (90.9%); lymphadenopathy, abdominal pain, and skin lesions (86.4%); pharyngitis (63.6%); cough (59.1%); diarrhea, and hepatosplenomegaly (50.0%). Seven patients had psychiatric symptoms (31.8%). One patient developed recurrent seizures. Three patients experienced renal involvement (13.6%). Two patients had angiomyolipoma (9.1%). All but one tested patients had elevated serum immunoglobulin (Ig) D level. Twenty-one patients had genetic diagnosis; most of them were compound heterozygote (76.2%). p.Val377Ile was the most prevalent mutation. Structural articular damages and systemic AA amyloidosis were the 2 most serious complications. More than 65% of patients displayed decrease in severity and frequency of attacks with increasing age, but only 35% achieved remission. MKD diagnosed in adulthood shared clinical and genetic features with classical pediatric disease. An elevated IgD concentration is a good marker for MKD in adults. Despite a decrease of severity and frequency of attacks with age, only one-third of patients achieved spontaneous remission.

Background: Giant cell arteritis (GCA) is the most common vasculitis in people ≥50 years and can be associated with stroke. We aimed to evaluate the epidemiology and characteristics of stroke in patients with GCA., Methods: All patients with a biopsy-proven diagnosis of GCA were identified among residents of the city of Dijon, France (152 000 inhabitants), between 2001 and 2012 using a prospective database. Among these, patients who suffered from stroke were retrieved by crossing data from the population-based Dijon Stroke Registry. Demographics and clinical features were recorded. We considered that the stroke was GCA-related if the stroke revealed GCA or occurred between the onset of symptoms and 4 weeks after the start of treatment., Results: Among the 57 biopsy-proven patients with GCA (incidence rate 10.9/100 000/year in individuals ≥50 years), 4 (7.0%) experienced a GCA-related stroke. Three were men and all had ≥2 vascular risk factors and were ≥80 years. The stroke was vertebrobasilar for 3/4 patients and undetermined for the remaining one. The incidence rate of GCA-related stroke in patients ≥50 years was 0.76/100 000/year (95% CI 0 to 2.47), 1.36/100 000/year in men (95% CI 0 to 3.63) and 0.33/100 000/year (95% CI 0 to 1.45) in women., Conclusions: This population-based study demonstrated that GCA-related stroke essentially affects the vertebrobasilar territory and mainly occurs in old men with associated vascular risk factors. Although rare, GCA symptoms must be searched for in elderly patients with stroke, and optimal vascular prevention must be conducted carefully in patients with GCA with a high vascular risk before initiating GCA treatment., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)