BackgroundSystemic lupus erythematosus (SLE) is a complex autoimmune disease, characterized by unpredictable organ and tissue involvement. Immunosuppressive drugs and corticosteroids (CS) are central to control serious SLE flares, but long-term use is associated with significant morbidity and may obscure distinctions between investigational treatments and placebo. BMS-986165 is an oral, selective TYK2 inhibitor that blocks cytokine signaling pathways key to SLE pathophysiology. A phase 2 trial of this agent is underway, designed to address some of these issues seen in lupus trials.MethodsIn this randomized, double-blind, placebo-controlled, global study (ClinicalTrials.gov: NCT03252587), adults diagnosed with SLE at least 24 weeks before screening, and with antinuclear antibody titer of 1:80 or who were positive for anti-double-stranded DNA or anti-Smith antibodies, are being randomized (1:1:1:1) to placebo or 1 of 3 doses of BMS-986165 (figure 1). The primary endpoint is the SLE Responder Index 4 (SRI-4) response rate at Week 32. Secondary endpoints include Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) response rate, British Isles Lupus Assessment Group-based Composite Lupus Assessment response rate, both at Week 32, and safety. Key inclusion criteria include SLE Disease Activity Index 2000 (SLEDAI-2K) of 6 points, with active joint and/or skin involvement. Eligible patients must have received standard of care background immune modulators for 12 weeks. CS are permitted. Trial designs that encourage CS tapering or other limitations to background treatments have been associated with increased discrimination between treatments and placebo by lowering relative rates of placebo responses. In the current study, CS tapering is required for all patients whose disease has not worsened.Abstract 5 Figure 1PAISLEY study designResultsPlanned enrollment is 360 patients (90 per cohort) at approximately 170 sites in 15 countries. A monitored review of medically appropriate disease activity scoring and tapering of CS is a part of the administration of this trial. Accrual into the PAISLEY study is ongoing.ConclusionsThis study will characterize the efficacy and safety of BMS-986165, which works by a novel mechanism of TYK2 inhibition, in patients with moderate to severe manifestations of SLE.Funding Source(s):Bristol-Myers Squibb
Background: Patients affected by several forms of malignant neoplasms receive chemotherapy (CT) or radiation therapy (RT). These treatments can cause many side effects, such as oral mucositis (OM). Mucositis is the most frequently occurring early side effect of conservative treatment of patients with malignant tumors in the head and neck, and it is registered in more than 60% of cases. It occurs due to the effect of chemotherapeutic drugs on the cells of the mucous membrane, which causes their death, and to a greater extent, due to the effect of ionizing radiation on the endothelium of the blood vessels and the basal cells of the mucous membrane the submucosa. Objectives: To assess the correlation between the indicators of hemomicrocirculation of the oral mucosa and the intensity of the clinical manifestations of oral mucositis. Results: It was found that, in all the subgroups, the severity index of mucositis National Cancer Institute (NCI) clearly correlated with the indicators of the flow of microcirculation through the study area at point A (r = -0.85, -0.99 and -0.77). At point A, blood perfusion in the study of hemomicrocirculation in all the subgroups 18–44 g in Ia, 45–59 g and 60–74 g in Ic was the opposite of the value of the severity of mucositis. A strong negative correlation was found between the severity of mucositis and the perfusion index at point B in subgroup Ia : (r = -0.99) along with, a moderate inverse correlation in subgroups Ib (r = -0.69) and Ic (r = -0.36). At point B, a strong inverse correlation was found in subgroups Ib and Ic (r = -0.72 and -0.65, respectively), and a moderate inverse correlation was found in subgroup Ia — NCI where r = -0.32. Conclusions: There is a negative correlation between the indicators of hemomicrocirculation of the oral mucosa and the severity of oral mucositis. It was found that the higher the lesions of the microvasculature, the lower the intensity of mucositis. These data have important prognostic value and make it possible to recommend the determination of hemomicrocirculation as a screening test.
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