Br J Haematol

Immune thrombocytopenia (ITP) is defined by a low platelet count that can trigger potentially life-threatening haemorrhages. Three-quarters of adult patients exhibit persistent or chronic disease and require second-line treatments. Among these, rituximab, an anti-CD20 antibody, has yielded valuable results, with global responses in 60% of patients at 6 months and complete responses in 30% at 5 years. Factors predictive of response to ITP therapy would help physicians choose optimal treatments. We retrospectively analysed clinical courses, biological markers and blood lymphocyte subset numbers of 72 patients on rituximab to treat persistent/chronic ITP followed-up in our department between 2007 and 2021, divided into three groups according to the platelet count at 6 months: complete, partial or no response. Among all studied parameters, a low number of CD3 CD16 CD56 circulating NK cells was associated with the complete response to rituximab. We also found that, after rituximab therapy, complete responders exhibited increased NK and decreased activated CD8 T cell percentages. These results emphasize that the role played by NK cells in ITP remains incompletely known but that factors predictive of response to rituximab can be easily derived using blood lymphocyte subset data

J Rheumatol

OBJECTIVE: Tocilizumab (TCZ), an IL-6 receptor antagonist, is approved for giant cell arteritis (GCA) as a cortisone-sparing strategy and in refractory patients. This study assessed the real-world efficacy, safety, and long-term outcomes of GCA patients treated with TCZ. METHODS: We conducted a multicenter retrospective observational study at three French centers. All patients ≥ 50 years, meeting the American College of Rheumatology (ACR) criteria, and had received at least one dose of TCZ were included. Relapse was defined by therapeutic escalation, such as increased doses of CS, resumption of CS after weaning, or introduction or intensification of adjuvant therapy. RESULTS: Between 2013 and 2019, 43 patients were included. Patients were followed-up in median 511 days between GCA diagnosis and inclusion with 34/43 (72%) patients experiencing relapses. At inclusion, median age was 77 years and median dose of corticosteroid (CS) was 15 mg/day. After inclusion, the mean cumulative dose of CS was 2.1g/year versus 9.4g/year before inclusion (p\textbackslashtextless2.10(7)) with 12/43 (28%) patients experiencing relapses on TCZ. Among 29 patients undergoing TCZ discontinuation, 18 (62%) experienced relapse. Factors associated with relapse after inclusion were introduction of TCZ \textbackslashtextgreater 6 months after diagnosis (p=0,005), absence of ischemic signs at diagnosis (p=0,006), relapse rate \textbackslashtextgreater0.8/year (p=0.03) and absence of CS tapering ≤ 5 mg/day (p=0,03) before inclusion. Serious adverse events occurred in 18/43 patients (42%), including four deaths. CONCLUSION: Our results confirm the effectiveness of TCZ for CS-sparing, but after discontinuation of treatment, TCZ allows for a prolonged remission in less than 50% of patients. Attention must be paid to the tolerance of this long-term treatment in this elderly and heavily treated population

A summertime pause in immunoglobulin replacement therapy: a prospective real-world analysis

Aim: To describe the effects of a summertime pause (SP) in immunoglobulin replacement therapy (IgRT). Patients & methods: We conducted a prospective single-center observational study, including 44 patients undergoing intravenous IgRT between May and June 2019 in a French teaching hospital. Results: IgRT was interrupted in 23 patients from June to October. Patients who underwent an SP were older, more likely to have secondary immunodeficiency (SID) and received lower doses of immunoglobulin and more antibiotics during winter. Most patients who did not undergo an SP had severe primary immunodeficiency. The SP did not increase the risk of infection, improved the quality of life and reduced treatment costs. Conclusion: SP in IgRT is a safe practice and should be considered for patients with mild SID. Lay abstract Immunoglobulin replacement therapy (IgRT) is an expensive treatment used to prevent infections in patients with immunodeficiency. Becauase most of the infections occur during winter, it is sometimes possible to interrupt IgRT during summer. In our study between May and October 2019, the 23 patients who underwent a summertime pause (SP) did not have more infections than the 21 who did not; the former also described an improvement in their quality of life. However, the physicians proposed SP to patients with a specific type of immunodeficiency, with fewer infections during winter and lower doses of IgRT. We report here for the first time the safety and benefits of a summertime pause in IgRT, for selected patients with less severe immunodeficiency. en

Safety and efficacy of low-dose intravenous arsenic trioxide in systemic lupus erythematosus: an open-label phase IIa trial (Lupsenic)

International audienceBackground: Lupus animal model has shown that arsenic trioxide (ATO), a treatment of acute promyelocytic leukaemia, could be effective in SLE. This is the first clinical study to determine the safety and efficacy of a short course of intravenous ATO in patients with active SLE.Methods: This phase IIa, open-label, dose-escalating study enrolled 11 adult SLE patients with a non-organ threatening disease, clinically active despite conventional therapy. Patients received 10 IV infusions of ATO within 24 days. The first group received 0.10 mg/kg per injection, with dose-escalating to 0.15 mg/kg in a second group, and to 0.20 mg/kg in a third group. The primary endpoint was the occurrence of adverse events (AEs) and secondary endpoints were the number of SLE Responder Index 4 (SRI-4) responders at week 24 and reduction of corticosteroid dosage. In an exploratory analysis, we collected long-term data for safety and attainment of lupus low disease activity state (LLDAS).Results: Four serious AEs occurred (grade 3 neutropenia, osteitis, neuropathy), 2 of which were attributable to ATO (neutropenia in the 2 patients treated with mycophenolate). Two patients suffered a severe flare during the last 4 weeks of the trial. At W24, five patients among 10 were SRI-4 responders. Overall, mean corticosteroid dosage decreased from 11.25 mg/day at baseline to 6 mg/day at W24 (P < 0.01). In the long term, 6 patients attained LLDAS at W52, which continued at last follow-up (median LLDAS duration 3 years, range 2-4).Conclusions: A short course of ATO has an acceptable safety profile in SLE patients and encouraging efficacy

Eur J Intern Med

Antisynthetase syndrome (ASyS) is a rare autoimmune disease. We aimed to determine clinical, biological, radiological, and evolutive profiles of ASyS patients with anti-PL7 or anti-PL12 autoantibodies. We performed a retrospective study that included adults with overt positivity for anti-PL7/anti-PL12 autoantibodies and at least one Connors' criterion. Among 72 patients, 69% were women, 29 had anti-PL7 and 43 anti-PL12 autoantibodies, median age was 60.3 years, and median follow-up period was 52.2 months. At diagnosis, 76% of patients had interstitial lung disease, 61% had arthritis, 39% myositis, 25% Raynaud's phenomenon, 18% mechanic's hands, and 17% had fever. The most frequent pattern on initial chest computed tomography was non-specific interstitial pneumonia and 67% had fibrosis at last follow-up. During follow-up, 12 patients had pericardial effusion (18%), 19 had pulmonary hypertension (29%), 9 (12.5%) had neoplasms, and 14 (19%) died. Sixty-seven patients (93%) received at least one steroid or immunosuppressive drug. Patients with anti-PL12 autoantibodies were younger (p=0.01) and more frequently exhibited anti-SSA autoantibodies (p=0.01); patients with anti-PL7 autoantibodies had more severe weakness and higher maximum creatine kinase levels (p=0.03 and 0.04, respectively). Initial severe dyspnoea was more common in patients from the West Indies (p=0.009), with lower predicted values of forced vital capacity, forced expiratory volume in 1s, and total lung capacity (p=0.01, p=0.02, p=0.01, respectively) contributing to a more severe 'respiratory' initial presentation. The high mortality and significant numbers of cardiovascular events, neoplasms and lung fibrosis in anti-PL7/12 patients justify close monitoring and question addition of antifibrotic drugs

Efficacy and safety of two rituximab biosimilars for treating immune thrombocytopenia: a reference-product matched study

The emergence of rituximab biosimilars offers the prospect of significant savings to the healthcare system. However, these drugs have never been evaluated for treating immune thrombocytopenia (ITP). This was an observational, matched study. We included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from the historic ITP-ritux registry. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product. Response status was defined according to international criteria. We included 107 patients; 55 receiving Rixathon™ and 52 Truxima™. Three months after the first infusion of rituximab biosimilars, the overall response rate was 47/74 (63.5%) versus 76/142 (53.5%) for the matched controls receiving the reference product (p = .13). The 3-month overall response rate was 76.5% for Rixathon™ versus 51.5% for the matched control group (p = .01) and 21/40 (52.5%) for Truxima™ versus 41/74 (55.4%) for the matched controls (p = .81). For non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product. Rituximab biosimilars seemed safe and effective for ITP treatment

A French cohort for assessing COVID-19 vaccine responses in specific populations

International audienc