Progression-free survival as a surrogate endpoint for overall survival in patients with relapsed or refractory multiple myeloma.

OBJECTIVES: The goal of the research was to assess the quantitative relationship between median progression-free survival (PFS) and median overall survival (OS) specifically among patients with relapsed/refractory multiple myeloma (RRMM) based on published randomized controlled trials (RCTs). METHODS: Two bibliographic databases (PubMed and Embase, 1970-2017) were systematically searched for RCTs in RRMM that reported OS and PFS, followed by an updated search of studies published between 2010 and 2022 in 3 databases (Embase, MEDLINE, and EBM Reviews, 2010-2022). The association between median PFS and median OS was assessed using the nonparametric Spearman rank and parametric Pearson correlation coefficients. Subsequently, the quantitative relationship between PFS and OS was assessed using weighted least-squares regression adjusted for covariates including age, sex, and publication year. Study arms were weighted by the number of patients in each arm. RESULTS: A total of 31 RCTs (56 treatment arms, 10,450 patients with RRMM) were included in the analysis. The average median PFS and median OS were 7.1 months (SD 5.5) and 28.1 months (SD 11.8), respectively. The Spearman and Pearson correlation coefficients between median PFS and median OS were 0.80 (P < 0.0001) and 0.79 (P < 0.0001), respectively. In individual treatment arms of RRMM trials, each 1-month increase in median PFS was associated with a 1.72-month (95% CI 1.26-2.17) increase in median OS. CONCLUSION: Analysis of the relationship between PFS and OS incorporating more recent studies in RRMM further substantiates the use of PFS to predict OS in RRMM.

Real-World Persistence of Ustekinumab in the Treatment of Inflammatory Bowel Disease.

INTRODUCTION: There is an urgent need to understand the long-term real-world effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD), fistulizing CD (FCD), and ulcerative colitis (UC). Persistence on treatment is commonly used as a surrogate measure of real-world treatment response. This study aims to estimate the long-term real-world persistence of UST in adult patients with CD, FCD, and UC. METHODS: A retrospective study was conducted in patients with CD, FCD, and UC treated with UST through a national patient support program in Canada. Treatment persistence was described using the Kaplan-Meier method, and the impact of patient characteristics on persistence was explored through stratified analyses and multivariable Cox proportional hazards models. RESULTS: Persistence rates for 8724 patients with CD were 82.9%, 71.4%, 64.1%, and 59.7% at 1, 2, 3, and 4 years, respectively. Similarly, persistence rates for 276 patients with FCD were 84.1%, 70.9%, 64.9%, and 63.1% at 1, 2, 3, and 4 years, respectively. Persistence rates for 1291 patients with UC were 76.5% at 1 year and 69.5% at 1.5 years. When stratified by prior IBD-indicated biologic experience, persistence was numerically higher in biologic-naïve patients across all disease cohorts. A Cox proportional hazards model confirmed that this difference was significant in patients with CD (hazard ratio: 0.72; confidence interval: [0.65-0.79]). CONCLUSIONS: This study estimated long-term persistence in a large population of patients with IBD. At 1 year, over three-fourths of patients remained on UST treatment in all disease cohorts, and over half of patients remained on treatment at 4 years in CD and FCD patients. Biologic-naïve status was significantly associated with higher persistence in patients with CD.

Inflammatory bowel disease is a term that refers to a group of disorders where the tissues of the gastrointestinal tract are chronically inflamed and may become damaged; it includes Crohn's disease and ulcerative colitis. While there is no cure, treatments are available to help patients manage their disease. Patients must typically continue treatment to ensure ongoing control. As such, the length of time a patient continues using a specific treatment can be suggestive of its success in the real-world. Ustekinumab is a biologic therapy that is used to treat both Crohn's disease and ulcerative colitis. Although ustekinumab has been evaluated in clinical trials, understanding how patients respond to treatment in the real world is valuable to physicians. This study was able to look at patients with inflammatory bowel disease who received treatment with ustekinumab through a patient support program in Canada and assess the length of time they continued treatment. After 1 year, over three-fourths of all patients with inflammatory bowel disease were still using ustekinumab; and after 4 years, more than half of patients with Crohn's disease were still using ustekinumab. This study was also able to look at whether certain factors affected the likelihood of a patient continuing treatment with ustekinumab. Patients that had never received a biologic therapy before were more likely to continue ustekinumab treatment than those who had received a different biologic therapy beforehand.