Drug Utilization Studies in Pregnant Women for Newly Licensed Medicinal Products: A Contribution from IMI ConcePTION.

Purpose: Studies focusing on safety outcomes typically require large populations to comprehensively characterise the patient groups exposed to the medicines under investigation. However, there is often less information for subpopulations, such as pregnant or breastfeeding women, particularly when new medicines are considered. It is important to understand what information can be obtained from drug utilization studies (DUS) involving pregnant women in the early years postmarketing to provide supportive information for safety studies. The aims of this literature review are to (1) identify and review DUS for new medicines in pregnancy and breastfeeding and (2) list and summarise key information items to be reported in a DUS for new medicines in pregnancy. Methods: To identify postmarketing DUS of new prescription medicines or enantiomers in pregnancy, a systematic literature review was undertaken in PubMed and Embase between January 2015 and June 2022. In addition, the complete database of the ENCePP EU PAS Register was systematically searched to June 2022. Results: We identified 11 published DUS on new medicines in pregnancy from the ENCePP EU PAS Register and none from other sources. No studies on breastfeeding were identified. The 11 identified publications reported the medicine's use for the first 3 to 5 years after marketing approval. No reports assessed utilization in the first 3 years of approval. It was usual to issue interim reports annually (7 studies). All studies concerned conditions managed in ambulatory care (primary care and outpatient facilities) and included some primary care prescribing. Most (n = 8) only had prescribing/dispensing data available at individual level for ambulatory care; outpatient prescribing was included in three of these studies Three studies held a limited amount of in-hospital prescribing data. A DUS can confirm at an early stage whether there are sufficient exposed pregnancies in available data sources to ensure a safety study is powered to detect a difference in the prevalence of adverse pregnancy or infant outcomes or if additional data from other databases are needed. A DUS may also help address methodological considerations such as selection of comparators. DUS can be performed embedded in a DUS in the general population, in a cohort of women of childbearing age, or in a cohort of pregnant women. Conclusion: This review summarises key aspects of a DUS for new medicines in pregnancy. DUS for new medicines in pregnancy should be planned before marketing, scheduled for the first 3 to 5 years after release, with annual interim/progress reports, and reported in peer-reviewed journals. By offering detailed information on data sources, exposure timing, prevalence and location, coprescribing, comorbidities, coexposures, and demographics, a DUS will offer a firm foundation for safety studies and will help to contextualize spontaneous reporting of serious adverse events.

Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study.

BACKGROUND: Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies. METHODS: IMAGE was a multinational, prospective, observational study assessing adult patients with advanced melanoma treated with ipilimumab or non-ipilimumab systemic therapies between June 2012 and March 2015 with ≥3 years of follow-up. Adjusted OS curves based on multivariate Cox regression models included covariate effects. Safety and patient-reported outcomes were assessed. RESULTS: Among 1356 patients, 1094 (81%) received ipilimumab and 262 (19%) received non-ipilimumab index therapy (systemic therapy [chemotherapy, anti-programmed death 1 antibodies, or BRAF ± MEK inhibitors], radiotherapy, and radiosurgery). In the overall population, median age was 64 years, 60% were male, 78% were from Europe, and 78% had received previous treatment for advanced melanoma. In the ipilimumab-treated cohort, 780 (71%) patients did not receive subsequent therapy (IPI-noOther) and 314 (29%) received subsequent non-ipilimumab therapy (IPI-Other) on study. In the non-ipilimumab-treated cohort, 205 (78%) patients remained on or received other subsequent non-ipilimumab therapy (Other-Other) and 57 (22%) received subsequent ipilimumab therapy (Other-IPI) on study. Among 1151 patients who received ipilimumab at any time during the study (IPI-noOther, IPI-Other, and Other-IPI), 296 (26%) reported CTCAE grade ≥ 3 treatment-related adverse events, most occurring in year 1. Ipilimumab-treated and non-ipilimumab-treated patients who switched therapy (IPI-Other and Other-IPI) had longer OS than those who did not switch (IPI-noOther and Other-Other). Patients with prior therapy who did not switch therapy (IPI-noOther and Other-Other) showed similar OS. In treatment-naive patients, those in the IPI-noOther group tended to have longer OS than those in the Other-Other group. Patient-reported outcomes were similar between treatment cohorts. CONCLUSIONS: With long-term follow-up (≥ 3 years), safety and OS in this real-world population of patients treated with ipilimumab 3 mg/kg were consistent with those reported in clinical trials. Patient-reported quality of life was maintained over the study period. OS analysis across both pretreated and treatment-naive patients suggested a beneficial role of ipilimumab early in treatment. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01511913. Registered January 19, 2012 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01511913.