Safety and efficacy of filgotinib, lanraplenib and tirabrutinib in Sjogren's syndrome: a randomized, phase 2, double-blind, placebo-controlled study

OBJECTIVE: The aim of this study was to characterize the safety and efficacy of filgotinib, lanraplenib and tirabrutinib in patients with active SS. METHODS: This multicentre, double-blind study randomized patients with active primary or secondary SS [EULAR SS disease activity index (ESSDAI) ≥5) to receive filgotinib 200 mg (Janus kinase-1 inhibitor), lanraplenib 30 mg (spleen tyrosine kinase inhibitor), tirabrutinib 40 mg (Bruton’s tyrosine kinase inhibitor), or placebo. The composite primary end point was the week-12 proportion of patients fulfilling protocol-specified improvement criteria (based on CRP and SS-related symptoms). The EULAR SS patient-reported index (ESSPRI) and the ESSDAI change from baseline (CFB) were secondary end points. Exploratory end points included disease-related biomarkers. Treatment-emergent adverse events (AEs) represented safety outcomes. RESULTS: The mean of the baseline ESSDAI was 10.1, and of ESSPRI was 6.2 in the 150 patients who were treated; 125 completed the 24-week placebo-controlled treatment period. At week 12, 43.3% of the filgotinib group achieved the primary end point (P = 0.17 vs placebo) vs 42.3% (P = 0.16), 34.7% (P = 0.33), and 26.7% of lanraplenib, tirabrutinib, and placebo groups, respectively. Neither secondary end point was met. Biomarker reductions included immunoglobulins classically associated with SS disease activity. Filgotinib ESSDAI CFB appeared more pronounced in subgroups with baseline ESSDAI ≥14 or without DMARDs/CSs. Most AEs were Grade 1 or 2. CONCLUSION: Three drugs with disparate mechanisms were tested, but no significant differences vs placebo in primary or secondary end points were observed. These results may be considered hypothesis-generating, given the drug tolerability, subgroup analysis, and biomarker findings. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03100942

No increased bleeding events in patients with relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma treated with idelalisib

The advent of novel B-cell receptor pathway targeting agents like ibrutinib dramatically changed management of B-cell malignancies. However, with concomitant anticoagulation (AC) and antiplatelet (AP) therapy, ibrutinib is associated with increased bleeding. This post hoc analysis aimed to determine the role of AC/AP therapy in patients with idelalisib-treated B-cell malignancies and to establish if it contributes to increased bleeding events. Data from two idelalisib trials (rituximab ± idelalisib in chronic lymphocytic leukemia [CLL] and idelalisib monotherapy in indolent non-Hodgkin lymphoma [iNHL]) were analyzed. Antithrombotic therapy was common (36%–63%), with comparable bleeding incidence across treatment groups (14%–19%; p = 0.56). Bleeding events of grade ≥3 occurred in 0.9% and 3.2% of the idelalisib-treated CLL and iNHL cohorts, respectively. Our findings demonstrate no increase in bleeding events with simultaneous AC/AP treatment and idelalisib use. Hemorrhagic risk is prevalent in these patients and an important consideration when evaluating available treatment options

CARDIAC LESION IN CHURG - STRAUSS SYNDROME

Cardiac involvement is the most important prognostic factor in eosinophilic granulomatosis with polyangiitis (Churg - Strauss syndrome). We report a case of Churg - Strauss syndrome in 65-year-old women masquerading as a non-ST elevation myocardial infarction. She had chest discomfort, dyspnea and ST depression, high troponin level and so myocardial infarction was diagnosed. She had had asthma for 4 years but had no eosinophilia in peripheral blood and lesions in the lungs at the time of the first hospitalization. Her skin was clean without rashes. 3 months later she was hospitalized again having pulmonary infiltrates. Laboratory tests revealed that eosinophil was significantly increased. Cardiac involvement in a pathological process led to death. Histological examination of heart and lungs showed necrotic coronary vasculitis, granulomas and perivascular eosinophilic infiltrates in myocardium, endocardium, pericardium and pulmonary eosinophilic infiltrates