Meta-analysis of pazopanib and trabectedin effectiveness in previously treated metastatic synovial sarcoma (second-line setting and beyond).

Background: This study examined the efficacy/effectiveness of pazopanib and trabectedin in previously treated metastatic synovial sarcoma (mSS). Materials & methods: A literature search identified studies (2002-2019) reporting outcomes of pazopanib and trabectedin in previously treated mSS, including median overall survival (mOS) and overall response rate (ORR). A meta-analysis was conducted and sensitivity analyses examined outcomes by agent (pazopanib/trabectedin), study type (clinical trial [CT] or real-world [RW]) and sample size. Results: Sixteen studies were included (pazopanib: n = 7; trabectedin: n = 9). Pooled mOS was 10.4 months and was consistent across agents and in RW and CT (pazopanib: 10.3; trabectedin: 10.4; CT: 10.8; RW: 9.9). ORR results were more variable (pooled ORR: 14.7%). ORR was consistently higher for RW (17.7%) than for CT (9.5%) and for pazopanib (18.9%) compared with trabectedin (12.3%). Conclusion: Poor outcomes across agents and settings highlight a need for novel treatments with improved efficacy. This study serves as a benchmark for efficacy estimates in this rare disease.

Synovial sarcoma (SS) is a rare and aggressive type of soft tissue sarcoma. SS frequently spreads to other locations, referred to as metastatic SS (mSS) and is associated with a high death rate. Patients treated with first-line chemotherapy (1L setting), may need further lines of treatment (≥2L setting), which commonly involve the drugs pazopanib and trabectedin. This study assessed how well pazopanib and trabectedin work in people with ≥2L mSS, by examining both clinical trial (CT) and real-world (RW) studies. Overall, findings across 16 studies showed that mSS patients lived approximately 10 months after treatment with pazopanib or trabectedin in the ≥2L setting, and this was similar across both agents (10.3 months for pazopanib; 10.4 months for trabectedin) and between the CT (10.8 months) and the RW (9.9 months) settings. In terms of response to treatment, a higher percentage of people appeared to respond in RW settings (17.7%) than in CTs (9.5%), and to pazopanib (18.9%) compared with trabectedin (12.3%). These results show there is a need for better treatments for patients with previously treated mSS. These findings are useful benchmarks for the development of future treatment approaches for this rare disease.

Burden of vaccine-preventable disease in adult Medicaid and commercially insured populations: analysis of claims-based databases, 2006­2010.

Vaccination rates among United States (US) adults are suboptimal, resulting in morbidity, mortality, and financial burden attributable to potentially vaccine-preventable diseases (VPDs). Unadjusted annual incidence proportions of VPDs were estimated for Medicaid and commercially insured adults aged 19-64 years using 2006-2010 claims, along with age/gender-adjusted incidence proportions for 2010. In 2010, 1.6 million Medicaid adults (mean age 34 ± 12 years; 73.4% female) and 33 million commercially insured (mean age 42 ± 13 years; 52.2% female) were included. Age/gender-adjusted incidence proportions (per 100 000) in 2010 among Medicaid vs commercially insured adults for meningococcal disease were 26.2 (95% CI 22.9-29.8) vs 2.0 (1.9-2.2) (P < 0.001); hepatitis B 88.9 (82.6-95.6) vs 17.5 (17.0-17.9) (P < 0.001); pneumococcal disease 98.2 (91.7-105.1) vs 21.1 (20.7-21.6) (P < 0.001); hepatitis A 19.8 (16.9-23.1) vs 4.5 (4.3-4.7) (P < 0.001); mumps 2.1 (1.3-3.3) vs 1.4 (1.3-1.6) (P = 0.14); measles 0.3 (0.1-1.0) vs 0.3 (0.2-0.3) (P = 0.38); herpes zoster (60- to 64-year-olds only) 459 (408-515) vs 473 (466-481) (P = 0.35); varicella (19- to 39-year-olds only) 6.5 (4.8-8.5) vs 8.0 (7.5-8.5) (P = 0.12); influenza 586 (573-598) vs 633 (631-636) (P < 0.001); and pertussis 1.8 (1.1-2.8) vs 3.2 (3.0-3.4) (P < 0.001). Research is needed to fully understand the causes of the disparity of the coded incidence of some VPDs in adult Medicaid population than commercially insured adults in the US.

Patterns of 6-mercaptopurine and azathioprine maintenance therapy among a cohort of commercially insured individuals diagnosed with Crohn's disease in the United States.

BACKGROUND AND AIMS: Thiopurines, including 6-mercaptopurine (6-MP) and azathioprine (AZA), are the mainstay of maintenance therapy for Crohn's disease (CD). However, studies examining their effectiveness in routine practice among diverse patient populations are lacking. Among a cohort of new users of 6MP/AZA, we described treatment patterns and changes in subsequent therapy. METHODS: Using the Truven Health Analytics databases, we identified all individuals diagnosed with CD and initiating 6-MP/AZA monotherapy from 2001-2008 (n=3,657). We estimated the proportion of CD patients remaining on 6-MP/AZA monotherapy, using Kaplan-Meier methods, and identified predictors of treatment noncontinuation, using multivariable Cox regression. Among the "noncontinuers," we described subsequent patterns of maintenance therapy and summarized the diagnosis and procedure codes and prescription drug claims preceding treatment discontinuation. RESULTS: The 1-year 6-MP/AZA treatment continuation rate was 42%. Children (age ≤18 years) and individuals with no prior anti-tumor necrosis factor (TNF) use were more likely to continue 6-MP/AZA, while those dispensed more (>4) outpatient prescriptions for any drug before initiation of 6-MP/AZA were less likely to continue maintenance treatment. Overall, 1,128 (39%) and 105 (4%) individuals experienced a clinical event potentially indicating active disease or 6-MP/AZA-intolerance prior to discontinuation, respectively. Most patients discontinued therapy; among the remaining patients who failed to continue 6-MP/AZA, most augmented with an anti-TNF. CONCLUSION: Most patients initiating 6-MP/AZA monotherapy did not continue beyond 1 year. In contrast to trial evidence showing 1-year remission rates of 40%-80%, this study observed a lower effectiveness of 6-MP/AZA treatment, possibly due to differences in disease severity, patient demographics, comorbidity, adherence, and health care utilization.

International variation in medication prescription rates among elderly patients with inflammatory bowel disease.

BACKGROUND AND AIMS: The elderly represent a growing demographic of patients with IBD. No study has previously described variations in care or medication prescriptions in senior patients with IBD. We compared prescription rates among elderly patients with IBD in four countries using health administrative data. METHODS: Databases from the United States (US), United Kingdom (UK), Denmark and Canada were queried. Variation in prescription rates between countries was assessed in patients ≥65y with prevalent IBD who had ≥1 prescription for an IBD-related medication in a given quarter between 2004 and 2009. Patients were identified using previously-reported, validated algorithms. Country-specific rates were compared in each quarter using Fisher's exact test. RESULTS: In patients with Crohn's disease, Canada and US had higher prescription rates for oral 5-ASA (P<0.0001 in all quarters) and infliximab (P<0.05 in 22/24 quarters), while the US had higher rates of thiopurine usage (P<0.05 in 23/24 quarters). Canada had greater rates of methotrexate prescriptions (P<0.05 in 21/24 quarters analyzed). In patients with ulcerative colitis (UC), rates of oral steroid usage was lowest in the US (P<0.05 in 22/24 quarters) and oral 5-ASA use was highest in the US and Canada (P<0.0001 in all quarters). Canada and Denmark used more rectal therapy than the US. Infliximab usage in UC was significantly higher in the US and Canada after 2006. CONCLUSIONS: Significant variation in medication prescription rates exists among countries. Future research should assess whether these differences were associated with disparities in outcomes and health care costs.

Burden of gastrointestinal disease in the United States: 2012 update.

BACKGROUND & AIMS: Gastrointestinal (GI) diseases account for substantial morbidity, mortality, and cost. Statistical analyses of the most recent data are necessary to guide GI research, education, and clinical practice. We estimate the burden of GI disease in the United States. METHODS: We collected information on the epidemiology of GI diseases (including cancers) and symptoms, along with data on resource utilization, quality of life, impairments to work and activity, morbidity, and mortality. These data were obtained from the National Ambulatory Medical Care Survey; National Health and Wellness Survey; Nationwide Inpatient Sample; Surveillance, Epidemiology, and End Results Program; National Vital Statistics System; Thompson Reuters MarketScan; Medicare; Medicaid; and the Clinical Outcomes Research Initiative's National Endoscopic Database. We estimated endoscopic use and costs and examined trends in endoscopic procedure. RESULTS: Abdominal pain was the most common GI symptom that prompted a clinic visit (15.9 million visits). Gastroesophageal reflux was the most common GI diagnosis (8.9 million visits). Hospitalizations and mortality from Clostridium difficile infection have doubled in the last 10 years. Acute pancreatitis was the most common reason for hospitalization (274,119 discharges). Colorectal cancer accounted for more than half of all GI cancers and was the leading cause of GI-related mortality (52,394 deaths). There were 6.9 million upper, 11.5 million lower, and 228,000 biliary endoscopies performed in 2009. The total cost for outpatient GI endoscopy examinations was $32.4 billion. CONCLUSIONS: GI diseases are a source of substantial morbidity, mortality, and cost in the United States.