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2 Minute Medicine Rewind November 25, 2024
Estimated Effectiveness of Influenza Vaccines in Preventing Secondary Infections in Households
1. Influenza vaccination was associated with a reduced risk of secondary influenza infections among household contacts, with an estimated effectiveness of 21%.
Evidence Rating Level: 2 (Good)
Influenza vaccinations are recommended for all individuals aged 6 months and older in the United States for the prevention of influenza infection. However, while the effectiveness of influenza vaccines in preventing serious disease and hospitalization has been investigated, the effectiveness of influenza vaccines in preventing any influenza infection regardless of symptoms as well as secondary infections has not been well characterized. This cohort study therefore sought to investigate the effectiveness of influenza vaccines in preventing secondary infections following influenza introduction into a household. Between 2017 and 2020, individuals with laboratory-confirmed influenza infection from Tennessee and Wisconsin were enrolled as primary cases if they were the first known person in their household to become ill. In total, 699 primary or co-primary cases (median[IQR] age, 13[7-38] years) and 1581 household contacts (median[IQR] age, 31[10-41] years) were included in the study. The estimated vaccine effectiveness (VE) of influenza vaccines in preventing laboratory-confirmed influenza infections among household contacts was 21.0% (95% CI, 1.4% to 36.7%). The estimated VE of influenza vaccines in preventing influenza B was 56.4% (95% CI, 30.1% to 72.8%), while no detectable VE was observed in preventing influenza A infection (5.0%; 95% CI, −22.3% to 26.3%). Overall, this study found that influenza vaccination was associated with a reduction in risk of influenza infection among household contacts of the vaccinated individual. However, this association existed only for influenza B infections and not for influenza A.
Use of Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drugs and Cancer Risk
1. The use of rituximab, abatacept and Janus kinase inhibitors (JAKis) in individuals with rheumatoid arthritis (RA) was associated with a statistically significant higher risk of cancer incidence compared to the use of tumour necrosis factor inhibitors (TNFis).
Evidence Rating Level: 2 (Good)
In recent years, safety concerns have been raised over the continued use of JAKis in patients with RA, as one trial reported a higher incidence of cancer associatd with the use of tofacitinib compared to TNFis. Similar studies were conducted since then, but are limited in their generalizability to patients in the United States. This retrospective cohort study therefore sought to investigate the comparative safety of TNFis, non-TNFis and JAKis in RA patients living in the United States. Between November 2012 and December 2021, patients aged 18 to 64 with RA were identified using the Merative Marketscan Research Databases. The primary outcome of interest was any incident cancer, which was attributed to the most recent biologic or synthetic DMARD exposure. A total of 25,305 patients (median age[IQR], 50[42-56] years; 79% female) were included in the study. Rituximab exposure was associated with the highest incidence rate of any cancer compared to all other groups (171 [95% CI, 94-285] cancer diagnoses per 10 000 person-years), while TNFis were associated with the lowest incidence rate (78 [95% CI, 66-91] diagnoses per 10 000 person-years). Based on multiavariate Cox proportional hazards regression analysis, rituximab was associated with a higher risk of incident cancer compared with TNFis (HR, 1.91; 95% CI, 1.17-3.14), followed by abatacept (HR, 1.47; 95% CI, 1.03-2.11) and JAKis (HR, 1.36; 95% CI, 0.94-1.96). Overall, this study found that the use of rituximab, abatacept and JAKis in RA patients living in the United States was associated with an increased risk of any incident cancer compared to the use of TNFis.
Endometriosis and uterine fibroids and risk of premature mortality: prospective cohort study
1. A history of endometriosis and uterine fibroids in women was associated with a greater risk of premature mortality and mortality due to gynecological cancers.
2. A history of endometriosis in women was associated with a greater risk of non-cancer mortality.
Evidence Rating Level: 2 (Good)
Endometriosis and uterine fibroids are common disorders among women of reproductive age which have previously been shown to be associated with increased risks of cardiovascular disease, hypertension and cancer. However, the associations between endometriosis and uterine fibroids and subsequent mortality risk as well as the impact of co-occurrence of the two disorders have not been well characterized. This prospective cohort study therefore sought to investigate the effect of endometriosis and uterine fibroids on the long-term risk of premature mortality in women living in the United States. Female nurses living in the United States between the ages of 25-42 were identified as part of the Nurses’ Health Study II ongoing prospective cohort. Women were excluded if they had a prior history of cardiovascular disease or cancer before enrollment or had a hysterectomy prior to diagnosis of endometriosis or uterine fibroids. Overall, 110,091 women (mean age in 1989, 34.7±4.7 years; mean age in 2019, 64.4±4.7 years) were enrolled in the study and received questionnaires until death or end of follow-up in June 2019, with deaths under the age of 70 years being defined as premature deaths. When adjusted for potential confounders, laparoscopically-confirmed endometriosis was associated with a hazard ratio (HR) of 1.31 (95% confidence interval (CI) 1.20 to 1.44) for premature death, with an HR for cancer of 1.22 (95% CI, 1.04 to 1.44) and an HR for respiratory diseases of 1.95 (95% CI, 1.11 to 3.41). Uterine fibroids were not associated with all-cause premature mortality (HR, 1.03; 95% CI, 0.95 to 1.11). When jointly categorizing participants based on occurrence of endometriosis and uterine fibroids, an increased risk of total mortality was observed in women reporting endometriosis only (HR, 1.32; 1.19 to 1.47) as well as women reporting endometriosis and uterine fibroids (HR, 1.31; 95% CI, 1.12 to 1.53). Overall, this study found a history of endometriosis and uterine fibroids was associated with a greater risk of premature mortality and that endometriosis was associated with a greater risk of non-malignant mortality.
The Risk of Venous Thromboembolism in Children With Inflammatory Bowel Disease
1. Children living with inflammatory bowel disease (IBD) are at greater risk of venous thromboembolism (VTE) compared to children without VTE, with the highest risk occurring around time of diagnosis.
Evidence Rating Level: 2 (Good)
Evidence from recent studies suggest that children living with IBD are at greater risk of VTE compared to children without IBD. However, due to the rarity of VTE in IBD patients in spite of this increased risk, studies have been limited to a lower number of events, making it difficult to characterize VTE risk in children beyond incidence rates. This study therefore sought to characterize children with IBD who develop VTE and to calculate absolute and relative risks compared to the general population. Patients under the age of 18 with IBD between 2001 and 2019 were identified via HES, a nationwide administrative database of all hospitals in England. A comparator cohort was constructed using data from children without IBD from the Office for National Statistics as well as HES data. The absolute risk of VTE in the general pediatric population was 0.18 (95% confidence interval [CI], 0.18-0.19) per 10,000 patient-years, while it was 9.42 (95% CI, 7.4-11.4) per 10 000 patient-years for pediatric patients living with IBD. Among children living with IBD, there was an overall relative risk increase of 51.8 (95% CI, 41.8-64.3) compared to children without IBD. When analyzing based on demographic factors, children with ulcerative colitis were at a higher risk for VTE compared to children with Crohn’s disease (incidence rate 12.4 vs 5.6 per 10 000 patient-years). Among children with IBD and VTE, 65 (76.5%) developed a VTE either within the first year following IBD diagnosis or 6 months prior to IBD diagnosis. Overall, this study found that children living with IBD are at increased risks of developing a VTE, with the greatest risk occurring around the time of diagnosis.
1. An intermittent strategy with fluorouracil, leucovorin and irinotecan (FOLFIRI) plus panitumumab (PAN) following induction was feasible, showed reduced toxicity and allowed patients more time off treatment.
Evidence Rating Level: 1 (Excellent)
The combination of chemotherapy along with panitumumab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has been an important treatment available for patients with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC). However, some limitations to the use of anti-EGFR therapy in these patients revolve around the development of drug resistance as well as significant toxicities. This multicentre, open-label, randomized phase II trial therefore sought to investigate the effectiveness of an intermittent strategy after induction with first-line FOLFIRI plus PAN in the prevention of resistance as well as in reducing toxicities. Patients over the age of 18 with RAS/BRAF wt mCRC with no previous systemic chemotherapy exposure were randomized to receive either continuous FOLFIRI plus PAN until disease progression, or induction treatment for eight cycles with the same regimen followed by a treatment-free interval until disease progression, after which another eight cycles of FOLFIRI plus PAN would be initiated. The primary endpoint was progression-free survival on treatment (PFSot) at 12 months, with secondary endpoints including overall survival (OS) and safety profile and adverse events (AEs). A total of 69 patients were randomized to arm A, receiving FOLFIRI + PAN (median[IQR] age, 62[55-71] years), and 67 patients were randomized to arm B, receiving intermittent FOLFIRI + PAN (median[IQR] age, 66[61-73] years). The median duration of treatment was 7.4 months (range, 0.7-32.3 months) in arm A and 11.0 months (range, 0.5-56.7 months) in arm B. The 12-month PFSot rate in arm A was 45.7% (95% CI, 33.9 to 57.5), while for arm B the 12-month PFSot rate was 58.5% (95% CI, 46.5 to 70.5). The median PFSot in arm A was 11.2 months (95% CI, 9.2 to 13.3) while the median PFSot in arm B was 17.5 months (95% CI, 4.8 to 30.4). Discontinuation due to toxicity or refusal occurred in 13 patients in arm A (25.0%) and 5 patients (10.0%) in arm B. The incidence of grade 3/4 skin AEs was 30.3% in arm A and 17.9% in arm B. Overall, this study found that an intermittent strategy with FOLFIRI plus PAN is feasible and shows reduced toxicity while allowing patients more time off treatment.
Image: PD
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