Nicolas Martin Silva

Background: Biannual rituximab infusions over 18 months effectively maintain remission after a “standard” remission induction regimen for patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Objective: 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. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT02433522) Setting: 39 clinical centers in France. Patients: 68 patients with GPA and 29 with MPA who achieved complete remission after the first phase of maintenance therapy. Intervention: Rituximab or placebo infusion every 6 months for 18 months (4 infusions). Measurements: 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. Results: 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) (P = 0.008). Major relapse–free survival estimates at month 28 were 100% (CI, 93% to 100%) versus 87% (CI, 78% to 97%) (P = 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. Limitation: Potential selection bias based on previous rituximab response and tolerance. Conclusion: Extended therapy with biannual rituximab infusions over 18 months was associated with a lower incidence of AAV relapse compared with standard maintenance therapy. Primary Funding Source: French Ministry of Health and Hoffmann–La Roche.

Erdheim-Chester disease (ECD) pathophysiology remains largely unknown. Its treatment is not codified and usually disappointing. Interferon (IFN)-α therapy lacks efficacy for some life-threatening manifestations and has a poor tolerance profile. Because interleukin (IL)-1Ra synthesis is naturally induced after stimulation by IFN-α, we hypothesized that recombinant IL-1Ra (anakinra) might have some efficacy in ECD. We treated 2 patients who had poor tolerance or contraindication to IFN-α with anakinra as a rescue therapy and measured their serum C-reactive protein, IL-1β, IL-6, and monocytic membranous IL-1α (mIL-1α) levels before, under, and after therapy. Another untreated ECD patient and 5 healthy subjects were enrolled as controls. After treatment, fever and bone pains rapidly disappeared in both patients, as well as eyelid involvement in one patient. In addition, retroperitoneal fibrosis completely or partially regressed, and C-reactive protein, IL-6, and mIL-1α levels decreased to within the normal and control range. Beside injection-site reactions, no adverse event was reported. Therefore, our results support a central role of the IL-1 network, which seemed to be overstimulated in ECD. Its specific blockade using anakinra thereby opens new pathophysiology and therapeutic perspectives in ECD.

OBJECTIVE: Our aim was to describe patients with giant cell arteritis (GCA)-related stroke and to compare them with a control group of GCA patients without stroke. METHODS: We created a retrospective multicenter cohort of patients with (1) GCA diagnosed according to the American College of Rheumatology criteria between 1995 and 2015, and (2) stroke occurring at the time of GCA diagnosis or occurring within 4 weeks of starting GCA therapy. The control group consisted of GCA patients without stroke. RESULTS: Forty patients [21 women (53%), median age 78 (60-91) yrs] with GCA-related stroke were included and were compared with 200 control patients. Stroke occurred at GCA diagnosis in 29 patients (73%), whereas it occurred after diagnosis in 11 patients. Vertebrobasilar territory was involved in 29 patients (73%). Seven patients died within a few hours or days following stroke. Compared with the control group, stroke patients had more ophthalmic ischemic symptoms [25 (63%) vs 50 (25%), p < 0.001]. Conversely, they demonstrated lower biological inflammatory variables [C-reactive protein: 61 (28-185) mg/l vs 99 (6-400) mg/l, p = 0.04] and less anemia [22/37 (59%) vs 137/167 (79%), p = 0.03] than patients without stroke. Multivariate logistic regression revealed that the best predictors for the occurrence of stroke were the presence of ophthalmic ischemic symptoms at diagnosis (OR 5, 95% CI 2.14-12.33, p = 0.0002) and the absence of anemia (OR 0.39, 95% CI 0.16-0.99, p = 0.04). CONCLUSION: Stroke, especially in the vertebrobasilar territory, is more likely to occur in patients with GCA who experience recent ophthalmic ischemic symptoms and who exhibit low inflammatory variables.