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The New England Journal of Medicine Jun 2023Mirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Mirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial.
METHODS
We conducted two phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab in adults with moderately to severely active ulcerative colitis. In the induction trial, patients were randomly assigned in a 3:1 ratio to receive mirikizumab (300 mg) or placebo, administered intravenously, every 4 weeks for 12 weeks. In the maintenance trial, patients with a response to mirikizumab induction therapy were randomly assigned in a 2:1 ratio to receive mirikizumab (200 mg) or placebo, administered subcutaneously, every 4 weeks for 40 weeks. The primary end points were clinical remission at week 12 in the induction trial and at week 40 (at 52 weeks overall) in the maintenance trial. Major secondary end points included clinical response, endoscopic remission, and improvement in bowel-movement urgency. Patients who did not have a response in the induction trial were allowed to receive open-label mirikizumab during the first 12 weeks of the maintenance trial as extended induction. Safety was also assessed.
RESULTS
A total of 1281 patients underwent randomization in the induction trial, and 544 patients with a response to mirikizumab underwent randomization again in the maintenance trial. Significantly higher percentages of patients in the mirikizumab group than in the placebo group had clinical remission at week 12 of the induction trial (24.2% vs. 13.3%, P<0.001) and at week 40 of the maintenance trial (49.9% vs. 25.1%, P<0.001). The criteria for all the major secondary end points were met in both trials. Adverse events of nasopharyngitis and arthralgia were reported more frequently with mirikizumab than with placebo. Among the 1217 patients treated with mirikizumab during the controlled and uncontrolled periods (including the open-label extension and maintenance periods) in the two trials, 15 had an opportunistic infection (including 6 with herpes zoster infection) and 8 had cancer (including 3 with colorectal cancer). Among the patients who received placebo in the induction trial, 1 had herpes zoster infection and none had cancer.
CONCLUSIONS
Mirikizumab was more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis. Opportunistic infection or cancer occurred in a small number of patients treated with mirikizumab. (Funded by Eli Lilly; LUCENT-1 and LUCENT-2 ClinicalTrials.gov numbers, NCT03518086 and NCT03524092, respectively.).
Topics: Adult; Humans; Colitis, Ulcerative; Double-Blind Method; Herpes Zoster; Induction Chemotherapy; Maintenance Chemotherapy; Opportunistic Infections; Remission Induction; Anti-Inflammatory Agents, Non-Steroidal; Administration, Intravenous; Subcutaneous Absorption
PubMed: 37379135
DOI: 10.1056/NEJMoa2207940 -
Frontiers in Cardiovascular Medicine 2023Cardiovascular disease (CVD) is currently one of the prevalent causes of human death. Iron is one of the essential trace elements in the human body and a vital component... (Review)
Review
Cardiovascular disease (CVD) is currently one of the prevalent causes of human death. Iron is one of the essential trace elements in the human body and a vital component of living tissues. All organ systems require iron for various metabolic processes, including myocardial and skeletal muscle metabolism, erythropoiesis, mitochondrial function, and oxygen transport. Its deficiency or excess in the human body remains one of the nutritional problems worldwide. The total amount of iron in a normal human body is about 3-5 g. Iron deficiency may cause symptoms such as general fatigue, pica, and nerve deafness, while excessive iron plays a crucial role in the pathophysiological processes of the heart through ferroptosis triggered by the Fenton reaction. It differs from other cell death modes based on its dependence on the accumulation of lipid peroxides and REDOX imbalance, opening a new pathway underlying the pathogenesis and mechanism of CVDs. In this review, we describe the latest research progress on the mechanism of ferroptosis and report its crucial role and association with miRNA in various CVDs. Finally, we summarise the potential therapeutic value of ferroptosis-related drugs or ferroptosis inhibitors in CVDs.
PubMed: 37731525
DOI: 10.3389/fcvm.2023.1241282 -
Nursing Jul 2023
Topics: Humans; Pica
PubMed: 37343253
DOI: 10.1097/01.NURSE.0000936780.65756.90 -
Journal of Clinical Oncology : Official... Jul 2023Rituximab improves progression-free survival (PFS) and time to next treatment (TTNT) when compared with the watch and wait strategy for patients with low-tumor burden... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Rituximab improves progression-free survival (PFS) and time to next treatment (TTNT) when compared with the watch and wait strategy for patients with low-tumor burden follicular lymphoma (FL). Prolonged rituximab maintenance did not prolong TTNT, whereas it raises concerns about resources use and patient adhesion. Our aim was then to investigate the use of short rituximab maintenance using the subcutaneous (SC) route in patients with low-tumor burden FL.
METHODS
Patients with histologically confirmed CD20 low-tumor burden FL were randomly assigned to receive either rituximab, 375 mg/m once daily on D1, D8, D15, and D22, intravenous route (IV, control arm), or rituximab, 375 mg/m, on day 1 (D1), IV followed by rituximab 1,400 mg total dose, SC once daily on D8, D15, and D22, with maintenance at months 3 (M3), M5, M7, and M9 (experimental arm). The primary end point was PFS. Secondary end points included safety, overall response rates, TTNT, and overall survival (OS).
RESULTS
Two hundred two patients with low-tumor burden FL were randomly assigned to the experimental (n = 100) or control arm (n = 102). The primary end point was met: the 4-year PFS was 58.1% (95% CI, 47.5 to 67.4) and 41.2% (95% CI, 30.6 to 51.6) in experimental and control arms, respectively (hazard ratio, 0.585 [0.393 to 0.871]; = .0076). Complete response (CR) rates were 59.0% (95% CI, 48.7 to 68.7) in the experimental arm and 36.3% (95% CI, 27.0 to 46.4) in the control arm ( = .001). TTNT and OS were not significantly different. CR was associated with longer PFS and TTNT. High rituximab exposure during the first three months was independently associated with higher CR, PFS, and TTNT.
CONCLUSION
SC rituximab improves PFS for patients with low-tumor burden FL when used in induction followed by short maintenance. High rituximab exposure during the first 3 months after treatment initiation is, however, the only parameter influencing patient outcomes.
Topics: Humans; Rituximab; Lymphoma, Follicular; Tumor Burden; Antineoplastic Combined Chemotherapy Protocols; Progression-Free Survival
PubMed: 37071836
DOI: 10.1200/JCO.22.02327