Objective
Earlier studies of eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA), with limited patient numbers and followup durations, demonstrated that clinical presentation at ...diagnosis, but not outcome, differed according to antineutrophil cytoplasmic antibody (ANCA) status. This study was undertaken to describe the main characteristics of a larger patient cohort and their long‐term outcomes.
Methods
A retrospective study of EGPA patients in the French Vasculitis Study Group cohort who satisfied the American College of Rheumatology criteria and/or Chapel Hill definitions was conducted. Patient characteristics and outcomes were compared according to ANCA status and year of diagnosis.
Results
We identified 383 patients diagnosed between 1957 and June 2009 (128 33.4% before 1997 or earlier) and followed up for a mean ± SD of 66.8 ± 62.5 months. At diagnosis, their mean ± SD age was 50.3 ± 15.7 years, and 91.1% had asthma (duration 9.3 ± 10.8 years). Main manifestations included peripheral neuropathy (51.4%); ear, nose, and throat (ENT) signs (48.0%); skin lesions (39.7%); lung infiltrates (38.6%); and cardiomyopathy (16.4%). Among the 348 patients tested at diagnosis for ANCA, the 108 ANCA‐positive patients (31.0%) had significantly more frequent ENT manifestations, peripheral neuropathy, and/or renal involvement, but less frequent cardiac manifestations, than the ANCA‐negative patients. Vasculitis relapses occurred in 35.2% of the ANCA‐positive versus 22.5% of the ANCA‐negative patients (P = 0.01), and 5.6% versus 12.5%, respectively, died (P < 0.05). The 5‐year relapse‐free survival rate was 58.1% (95% confidence interval 95% CI 45.6–68.6) for ANCA‐positive and 67.8% (95% CI 59.8–74.5) for ANCA‐negative patients (P = 0.35). Multivariable analysis identified cardiomyopathy, older age, and diagnosis during or prior to 1996 as independent risk factors for death and lower eosinophil count at diagnosis as predictive of relapse.
Conclusion
The characteristics and long‐term outcomes of EGPA patients differ according to their ANCA status. Although EGPA relapses remain frequent, mortality has declined, at least since 1996.
Summary
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).
Summary
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.
Graphical showing the modifications of the lymphocyte subsets from blood of 72 ITP patients compared to controls (left) and according to the response to rituximab (right).
To compare individually tailored, based on trimestrial biological parameter monitoring, to fixed-schedule rituximab reinfusion for remission maintenance of antineutrophil cytoplasm antibody ...(ANCA)-associated vasculitides (AAVs).
Patients with newly diagnosed or relapsing granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in complete remission after induction therapy were included in an open-label, multicentre, randomised controlled trial. All tailored-arm patients received a 500 mg rituximab infusion at randomisation, with rituximab reinfusion only when CD19+B lymphocytes or ANCA had reappeared or ANCA titre rose markedly based on trimestrial testing until month 18. Controls received a fixed 500 mg rituximab infusion on days 0 and 14 postrandomisation, then 6, 12 and 18 months after the first infusion. The primary endpoint was the number of relapses (new or reappearing symptom(s) or worsening disease with Birmingham Vasculitis Activity Score (BVAS)>0) at month 28 evaluated by an independent Adjudication Committee blinded to treatment group.
Among the 162 patients (mean age: 60 years; 42% women) included, 117 (72.2%) had GPA and 45 (27.8%) had MPA. Preinclusion induction therapy included cyclophosphamide for 100 (61.7%), rituximab for 61 (37.6%) and methotrexate for 1 (0.6%). At month 28, 21 patients had suffered 22 relapses: 14/81 (17.3%) in 13 tailored-infusion recipients and 8/81 (9.9%) in 8 fixed-schedule patients (p=0.22). The tailored-infusion versus fixed-schedule group, respectively, received 248 vs 381 infusions, with medians (IQR) of 3 (2-4) vs 5 (5-5) administrations.
AAV relapse rates did not differ significantly between individually tailored and fixed-schedule rituximab regimens. Individually tailored-arm patients received fewer rituximab infusions.
NCT01731561; Results.
Biannual rituximab infusions over 18 months effectively maintain remission after a "standard" remission induction regimen for patients with antineutrophil cytoplasmic antibody-associated vasculitis ...(AAV).
To evaluate the efficacy of prolonged rituximab therapy in preventing AAV relapses in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who have achieved complete remission after completing an 18-month maintenance regimen.
Randomized controlled trial. (ClinicalTrials.gov: NCT02433522).
39 clinical centers in France.
68 patients with GPA and 29 with MPA who achieved complete remission after the first phase of maintenance therapy.
Rituximab or placebo infusion every 6 months for 18 months (4 infusions).
The primary end point was relapse-free survival at month 28. Relapse was defined as new or reappearing symptoms or worsening disease, with a Birmingham Vasculitis Activity Score greater than 0.
From March 2015 to April 2016, 97 patients (mean age, 63.9 years; 35% women) were randomly assigned, 50 to the rituximab and 47 to the placebo group. Relapse-free survival estimates at month 28 were 96% (95% CI, 91% to 100%) and 74% (CI, 63% to 88%) in the rituximab and placebo groups, respectively, an absolute difference of 22% (CI, 9% to 36%) with a hazard ratio of 7.5 (CI, 1.67 to 33.7) (
= 0.008). Major relapse-free survival estimates at month 28 were 100% (CI, 93% to 100%) versus 87% (CI, 78% to 97%) (
= 0.009), respectively. At least 1 serious adverse event developed in 12 patients (24%) in the rituximab group (with 9 infectious serious adverse events occurring among 6 patients 12%) versus 14 patients (30%) in the placebo group (with 6 infectious serious adverse events developing among 4 patients 9%). No deaths occurred in either group.
Potential selection bias based on previous rituximab response and tolerance.
Extended therapy with biannual rituximab infusions over 18 months was associated with a lower incidence of AAV relapse compared with standard maintenance therapy.
French Ministry of Health and Hoffmann-La Roche.
Although splenectomy is still considered the most effective curative treatment for immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the approval ...of thrombopoietin receptor agonists (TPO‐RAs). The main objective of the study was to determine whether splenectomy was still as effective nowadays, particularly for patients with failure to respond to TPO‐RAs. Our secondary objective was to assess, among patients who relapsed after splenectomy, the pattern of response to treatments used before splenectomy. This multicenter retrospective study involved adults who underwent splenectomy for ITP in France from 2011 to 2020. Response status was defined according to international criteria. We included 185 patients, 100 (54.1%) and 135 (73.0%) patients had received TPO‐RAs and/or rituximab before the splenectomy. The median follow‐up after splenectomy was 39.2 months 16.5–63.0. Overall, 144 (77.8%) patients had an initial response and 23 (12.4%) experienced relapse during follow‐up, for an overall sustained response of 65.4%, similar to that observed in the pre‐TPO‐RA era. Among patients who received at least one TPO‐RA or rituximab before splenectomy, 92/151 (60.9%) had a sustained response. Six of 13 (46%) patients with previous lack of response to both TPO‐RAs and rituximab had a sustained response to splenectomy. Among patients with relapse after splenectomy, 13/21 (61.2%) patients responded to one TPO‐RAs that failed before splenectomy. In conclusion, splenectomy is still a relevant option for treating adult primary ITP not responding to TPO‐RAs and rituximab. Patients with lack of response or with relapse after splenectomy should be re‐challenged with TPO‐RAs.
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.
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