Devick, Katrina L.

Background Erenumab, a calcitonin gene‐related peptide (CGRP) receptor monoclonal antibody, has been well tolerated with good efficacy for the preventive treatment of episodic and chronic migraine in phase 2 and phase 3 clinical trials. Limited post‐market observations are available to validate these findings in a real‐world tertiary headache clinic population with complex comorbidities and refractory migraine. Objective The goal of this study is to demonstrate the real‐world performance of erenumab among patients in a tertiary care headache clinic by describing patient selection, experience, and clinical characteristics after 6 months of erenumab therapy. Methods A retrospective, exploratory, observational study was conducted on patients receiving at least 1 erenumab injection (70 or 140 mg). Baseline data obtained by chart review and telephone calls were compared to 6‐month follow‐up telephone calls. The primary outcome was the reduction in self‐reported headache days per month at baseline compared to 6 months for those with complete 6‐month data. The significance level was set at P < .05. Secondary analyses explored the distribution of headache severity, responder rates, Migraine Disability Assessment scores, adverse effects, ineffective preventives, comorbidities, wearing‐off, and discontinuation. Results Of the 101 patients who consented to participate, 89.1% (90/101) were women, and the mean age of all patients was 49 years (range, 19‐80 years). At baseline, 94.1% (95/101) of patients had chronic migraine, 5.0% (5/101) had episodic migraine, and 18.8% (19/101) had medication overuse headache. The mean (SD) number of baseline headache and migraine days per month for the entire cohort were 24.3 (8.2) and 18.2 (9.3) days, respectively. Participants had numerous comorbidities and had tried a mean of 11.2 unique oral medications and 4.8 unique medication categories before receiving erenumab, including 83.2% (84/101) who had also received onabotulinumtoxinA. Six‐month post‐erenumab follow‐up data were available for 42.6% (43/101) of participants. For these 43 participants, the number of headache days per month decreased significantly by 6.5 days from a baseline mean (SD) of 24.8 (6.47) days to 18.3 (12) days at 6‐month follow‐up ( P < .001); similarly, the monthly migraine days decreased significantly by 8.4 days from a baseline mean of 19.1 (9.3) days to 10.7 days at 6‐month follow‐up ( P < .001). The 50% responder rate was 34.9% (15/43) for monthly headache days and 54.8% (23/43) for monthly migraine days. Of all 101 participants, 28 (27.7%) discontinued erenumab, primarily because it was ineffective (39.3%, 11/28) or because of adverse effects (42.9%, 12/28). Conclusion This post‐market observational study of patient experience describes response to erenumab in a real‐world tertiary headache clinic with a complex patient population. Overall, these complex patients had a significant positive clinical response to erenumab, but with high rates of discontinuation. This study also noted a 1‐week wearing‐off response and high rates of constipation. Further post‐market studies are needed to better characterize patient selection and real‐world response to erenumab.

SummaryThe study of racial/ethnic inequalities in health is important to reduce the uneven burden of disease. In the case of colorectal cancer (CRC), disparities in survival among non-Hispanic Whites and Blacks are well documented, and mechanisms leading to these disparities need to be studied formally. It has also been established that body mass index (BMI) is a risk factor for developing CRC, and recent literature shows BMI at diagnosis of CRC is associated with survival. Since BMI varies by racial/ethnic group, a question that arises is whether differences in BMI are partially responsible for observed racial/ethnic disparities in survival for CRC patients. This article presents new methodology to quantify the impact of the hypothetical intervention that matches the BMI distribution in the Black population to a potentially complex distributional form observed in the White population on racial/ethnic disparities in survival. Our density mediation approach can be utilized to estimate natural direct and indirect effects in the general causal mediation setting under stronger assumptions. We perform a simulation study that shows our proposed Bayesian density regression approach performs as well as or better than current methodology allowing for a shift in the mean of the distribution only, and that standard practice of categorizing BMI leads to large biases when BMI is a mediator variable. When applied to motivating data from the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium, our approach suggests the proposed intervention is potentially beneficial for elderly and low-income Black patients, yet harmful for young or high-income Black populations.