Nirmatrelvir/ritonavir use in pregnant women with SARS-CoV-2 Omicron infection: a target trial emulation
Wong C et al. Nature Medicine (November 2023)
Bottom line: This is a target trial emulation study that evaluated the use of nirmatrelvir/ritonavir in non-hospitalized pregnant persons with symptomatic SARS-CoV-2 Omicron variant infection. The study used one-to-ten propensity-score matching between nirmatrelvir/ritonavir users and nonusers. The intervention group included 211 pregnant persons who received outpatient nirmatrelvir/ritonavir treatment within 5 days of symptom onset or COVID-19 diagnosis. The control group included 1,998 pregnant persons who did not receive antiviral therapy. The study was not blinded. The primary outcomes were maternal morbidity and mortality index (MMMI) and all-cause maternal death and COVID-19-related hospitalization. The secondary outcomes were individual components of the maternal morbidity and mortality index (MMMI), preterm birth, stillbirth, neonatal death, and cesarean section. Nirmatrelvir/ritonavir treatment was associated with reduced 28-day MMMI risk (ARR = 1.47%, 95% confidence interval (CI) = 0.21–2.34%), and reduced risk of cesarean section (ARR = 1.58%, 95% CI = 0.85–2.39%) and preterm birth (ARR = 2.70%, 95% CI = 0.98–5.31%). However, there was no reduction in 28-day COVID-19 related hospitalization. No events of maternal or neonatal death or stillbirth were recorded. The study suggests that nirmatrelvir/ritonavir is an effective treatment in symptomatic pregnant persons with SARS-CoV-2 Omicron variant infection.
RANKL blockade for erosive hand osteoarthritis: a randomized placebo-controlled phase 2a trial
Wittoek R et al. Nature Medicine (February 2024)
Bottom Line: This is a monocentric, placebo-controlled, double-blind, randomized phase 2a clinical trial with denosumab in patients with erosive hand osteoarthritis. The study lasted for 48 weeks and included 100 participants, with 51 in the treatment group receiving 60 mg of denosumab every 3 months and 49 receiving placebo. The primary outcome was the change in total Ghent University Scoring System (GUSS) at week 24. Secondary endpoints were the change in GUSS at week 48 and the number of new erosive joints by the anatomical phase scoring system within the same time frame. Baseline mean GUSS (standard deviation) of target joints was 155.9 (69.3) in the denosumab group and 158.7 (46.8) in the placebo group. At week 48, baseline adjusted GUSS for denosumab and placebo were 163.5 and 149.2 respectively, with an estimated difference between groups of 14.3 (odds ratio 0.24 (95% CI 0.08 to 0.72); P = 0.009). Additionally, denosumab showed a greater effect in preventing new erosive joints (odds ratio 0.24 (95% CI 0.08 to 0.72); P = 0.009). The safety outcomes also favoured denosumab, with fewer adverse events reported (97 events in 31 patients versus 125 events in 44 patients in the placebo group). This study demonstrates that denosumab has structure-modifying effects in erosive hand OA and may be a promising treatment option for this condition.
LINK TO ARTICLE (Wittoek et al.)
Clopidogrel vs Aspirin Monotherapy Beyond 1 Year After Percutaneous Coronary Intervention
Watanabe H et al. JACC (January 2024)
Bottom Line: This randomized clinical trial conducted in Japan compared clopidogrel monotherapy following 1 month of DAPT with aspirin monotherapy following 12 months of DAPT for a period of five years after PCI. The study included 3005 patients who underwent PCI with cobalt-chromium everolimus-eluting stents. The primary endpoint was a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis) or major bleeding. Results showed that clopidogrel was non-inferior but not superior to aspirin for the primary endpoint (11.75% and 13.57%, respectively; HR: 0.85; 95% CI: 0.70-1.05; Pnoninferiority < 0.001; Psuperiority = 0.13), but was superior for cardiovascular outcomes (8.61% and 11.05%, respectively; HR: 0.77; 95% CI: 0.61-0.97; P = 0.03). The clopidogrel group was not superior for major bleeding (4.44% and 4.92%, respectively; HR: 0.89; 95% CI: 0.64-1.25; P = 0.51). By the 1-year landmark analysis, clopidogrel showed a borderline benefit for cardiovascular events without a difference in major bleeding. The study concluded that clopidogrel may be a more attractive alternative to aspirin for long-term antiplatelet therapy following DAPT after PCI.
LINK TO ARTICLE (Watanabe et al.)
