FDA Approval Summary: Ruxolitinib for Treatment of Chronic Graft-Versus-Host Disease after Failure of One or Two Lines of Systemic Therapy

On September 22, 2021, the Food and Drug Administration approved ruxolitinib for the treatment of chronic graft-versus-host disease (cGVHD) after the failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424-365 (REACH-3; CINC424D2301; {"type":"clinical-trial","attrs":{"text":"NCT03112603","term_id":"NCT03112603"}}NCT03112603), a randomized, open-label, multicenter trial of ruxolitinib in comparison to best available therapy (BAT) for the treatment of corticosteroid-refractory cGVHD occurring after the allogeneic hematopoietic stem cell transplantation. A total of 329 patients were randomized 1:1 to receive either ruxolitinib 10 mg twice daily (n = 165) or BAT (n = 164). BAT was selected by the investigator prior to randomization. The overall response rate through Cycle 7 Day 1 was 70% (95% CI, 63-77) in the ruxolitinib arm, and 57% (95% CI, 49-65) in the BAT arm. The median duration of response, calculated from first response to progression, death, or initiation of new systemic therapies for cGVHD, was 4.2 months (95% CI, 3.2-6.7) for the ruxolitinib arm and 2.1 months (95% CI, 1.6-3.2) for the BAT arm; and the median time from first response to death or initiation of new systemic therapies for cGVHD was 25 months (95% CI, 16.8-not estimable) for the ruxolitinib arm and 5.6 months (95% CI, 4.1-7.8) for the BAT arm. Common adverse reactions included anemia, thrombocytopenia, and infections. Given the observed response rate with durability, the clinical benefit of ruxolitinib appears to outweigh the risks of treatment for cGVHD after the failure of one or two lines of systemic therapy.     

Prostaglandin E1 treatment of NZB/NZW mice

NZB/NZW F₁ hybrid mice were treated with pharmacologic doses of prostaglandin E₁ (PGE₁) (200 μg subcutaneously either once or twice daily) from 6 through 52 weeks of age. PGE₁-treated mice were protected against development of anemia, clinical nephritis, and death. At 52 weeks, 18 of 19 treated mice were alive, whereas only 2 of 19 untreated control mice were alive. None of the 10 mice treated with PGE₁ twice daily exhibited significant (>2+) proteinuria at 1 year of age. PGE₁ treatment did not prevent development of antibodies to nuclear antigens. The data also suggest that survival of NZB/NZW mice is prolonged when treatment with PGE₁ is begun at 24 weeks, an age at which mice already show evidence of nephritis. Thus all 6 mice treated with PGE₁ (200 μg sc twice daily) from 24 weeks were alive at 52 weeks, whereas only 2 of 6 untreated control mice were alive. The mechanisms whereby PGE₁ treatment influences the course of disease in NZB/NZW mice are not known.     

Exploratory data analysis of hyperlipidemia on the Macintosh: Software tools for analysis of biochemical,clinical, and genetic variables in 1677 consecutive lipid clinic patients

Exploratory data analysis (EDA) software facilitates unstructured, iterative open exploration of complex datasets with the aid of multiple linked graphical displays. We are investigating relationships between plasma lipoproteins and coronary artery disease by retrospective analysis of 1677 consecutive UCSF Lipid Clinic patients. Our preliminary experience is with Data Deck 3.0 although several additional software programs (JMP 2.0, Systat 5.1, Minitab 8.0, StatView 4.0) are mentioned. Lipid diagnosis (751 women and 925 men) was 22% primary hypercholesterolemia, 19% combined hyperlipidemia, 3% dysbetalipoproteinemia, 15% endogenous lipemia, 4% mixed lipemia, 5% elevated Lp(a) and 32% with no major lipid abnormality. We found the Macintosh platform (68030) to be flexible and powerful for analysis of moderate size (less than 1 Mb) clinical datasets. High resolution color monitors (1024 MX 768 pixels), fast hard disks (<18 msec) and moderate amounts of system memory (8 + Mb) facilitate exploratory analysis.