Benchmarking Maintenance Therapy Survival in First-Line Platinum-Based Chemotherapy-Treated Patients with Advanced Urothelial Carcinoma Using Simulated Disease Modeling.

Objective: First-line (1L) maintenance avelumab prolonged overall survival (OS) in patients with advanced urothelial carcinoma (aUC) in JAVELIN Bladder 100. OS was measured from maintenance initiation in patients with disease control following 1L platinum-based therapy (PBT). The OS impact of maintenance for the 1L PBT-treated population is unknown since it was not measured from 1L initiation, nor can it be benchmarked with other 1L therapies. To characterize the OS impact of maintenance avelumab, we used an oncology simulation model to estimate the OS of maintenance-eligible and -ineligible patients with aUC from 1L PBT initiation. Methods: We developed a simulated cohort of 1L PBT-treated patients with aUC, including those who did and did not receive maintenance avelumab. Eligibility was assessed at 5.6 months post 1L PBT initiation based on the JAVELIN trial design. Among the 1L-treated population, 58% (95% credible interval [CrI] 49-67%) were projected to be eligible (calculated from contemporary phase 3 trials); of those, 85% were assumed to receive maintenance. The model estimated median OS (mOS) among a maintenance-ineligible simulated cohort which when combined with the maintenance-eligible cohort yielded an estimated OS in the overall maintenance- intended population from 1L PBT initiation. Results: Approximately half of the modeled 1L PBT-treated population received maintenance. Estimated mOS was 10.1 months (95% CrI 7.5-13.5) for the maintenance-ineligible cohort, 29.3 months (95% CrI 24.8-33.9) for the maintenance-eligible, received maintenance cohort, and 15.9 months (95% CrI 13.2-19.1) in the overall maintenance-intended, 1L PBT-treated population, including those eligible and ineligible for maintenance. Conclusion: The model shows that maintenance avelumab has a modest impact on OS in the overall 1L PBT-treated population of patients with aUC. While maintenance avelumab improves OS for eligible patients, a large proportion of the maintenance-intended population may not receive maintenance due to ineligibility or physician/patient choice.

Treatment patterns and unmet needs in adults with classic congenital adrenal hyperplasia: A modified Delphi consensus study.

Background: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare autosomal recessive condition characterized by cortisol deficiency and excess androgen production. The current standard of care is glucocorticoid (GC) therapy, and sometimes mineralocorticoids, to replace endogenous cortisol deficiency; however, supraphysiologic GC doses are usually needed to reduce excess androgen production. Monitoring/titrating GC treatment remains a major challenge, and there is no agreement on assessment of treatment adequacy. This study surveyed expert opinions on current treatment practices and unmet needs in adults with classic CAH. Methods: A modified two-round Delphi process with adult endocrinologists was conducted via online questionnaire. Survey questions were organized into three categories: practice characteristics/CAH experience, GC management, and unmet needs/complications. Anonymized aggregate data from Round 1 were provided as feedback for Round 2. Responses from both rounds were analyzed using descriptive statistics. Consensus was defined a priori as: full consensus (100%, n=9/9); near consensus (78% to <100%, n=7/9 or 8/9); no consensus (<78%, n<7/9). Results: The same nine panelists participated in both survey rounds; five (56%) were based in North America and four (44%) in Europe. Most panelists (78%) used hydrocortisone in the majority of patients, but two (22%) preferred prednisone/prednisolone. Panelists agreed (89%) that adequate control is best evaluated using a balance of clinical presentation and androgen/precursor laboratory values; no consensus was reached on optimal timing of collecting samples for androgen testing or laboratory values indicating good control. Despite lack of consensus on many aspects of CAH management, panelists agreed on the importance of many disease- and GC-related complications, and that there is a large unmet need for new treatments. With currently available treatments, panelists reported that 46% of classic CAH patients did not have optimized androgen levels, regardless of GC dose. Conclusions: The limited areas of consensus obtained in this study reflect the variability in treatment practices for adults with classic CAH, even among clinicians with expertise in treating this population. However, all panelists agreed on the need for new treatments for classic CAH and the importance of many disease- and GC-related complications, which are difficult to manage with currently available treatments.

Patient perspective of tardive dyskinesia: results from a social media listening study.

BACKGROUND: Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to dopamine receptor blocking agents such as antipsychotics. With the expanding use of antipsychotics, research is needed to better understand patient perspectives of TD, which clinical assessments may fail to capture. Social media listening (SML), which is recognized by the US FDA as a method that can advance ongoing efforts for more patient-focused drug development, has been used to understand patient experiences in other disease states. This is the first study to use SML analysis of unsolicited patient and caregiver insights to help clinicians understand how patients describe their symptoms, the emotional distress associated with TD, and the impact on caregivers. METHODS: In this pilot study, a comprehensive search was performed for publicly available, English-language, online content posted between March 2017 and November 2019 on social media platforms, blogs, and forums. An analytics platform (NetBase™) identified posts containing patient or caregiver experiences of assumed TD using predefined search terms. All posts were manually curated and reviewed to ensure quality and validity of the post and to further classify key symptoms, sentiments, and themes. RESULTS: A total of 261 posts from patients/caregivers ("patient insights") were identified using predefined search terms; 107 posts were used for these analyses. Posts were primarily from forums (47%) and Twitter (33%). Analysis of the most common sentiment-related terms (e.g. "feel" [n = 31], "worse" [n = 17], "symptom" [n = 14], "better" [n = 12]) indicated that 64% were negative, 33% were neutral, and 3% were positive. Theme analysis revealed that patients often felt angry about having TD from a medication used to treat a different condition. In addition, patients felt insecure, including feeling unaccepted by society and fear of being judged by others. CONCLUSION: Although this study was limited by inherent methodological constraints (e.g., small sample size, reliance on patient self-report), the perspectives generated from analyzing social media may help convey the unmet needs of patients with TD. This analysis indicated that movement-related symptoms are the most common patient concern, resulting in strong feelings of anger and insecurity.

A global real-world assessment of the impact on health-related quality of life and work productivity of migraine in patients with insufficient versus good response to triptan medication.

BACKGROUND: Migraine is a chronic, disabling neurological disease characterized by moderate-to-severe headache pain with other symptoms, including nausea, vomiting, and photophobia. Triptans, while generally effective, are insufficiently efficacious in 30-40% of patients and poorly tolerated by or contraindicated in others. We assessed the impact of insufficient response to triptans on health-related quality of life (HRQoL) and work productivity in patients currently receiving any prescribed triptan formulation as their only acute migraine medication. METHODS: Data were from the 2017 Adelphi Migraine Disease Specific Programme, a cross-sectional survey of primary care physicians, neurologists, and headache specialists and their consulting patients with migraine in the USA, France, Germany, Italy, Spain, and UK. Triptan insufficient responders (TIRs) achieved freedom from headache pain within 2 h of acute treatment in ≤3/5 migraine attacks; triptan responders (TRs) achieved pain freedom within 2 h in ≥4/5 attacks. Multivariable general linear model examined differences between TIRs and TRs in HRQoL and work productivity. Logistic regression identified factors associated with insufficient response to triptans. RESULTS: The study included 1413 triptan-treated patients (TIRs: n = 483, 34.2%; TRs: n = 930, 65.8%). TIRs were more likely to be female (76% vs. 70% for TIRs vs TRs, respectively; p = 0.011), older (mean age 42.6 vs. 40.5 years; p = 0.003), and had more headache days/month (7.0 vs. 4.4; p < 0.001). TIRs had significantly more disability, with higher Migraine Disability Scores (MIDAS; 13.2 vs. 7.7; p < 0.001), lower Migraine-specific Quality of Life scores, indicating greater impact (Role Function Restrictive: 62.4 vs. 74.5; Role Function Preventive: 70.0 vs. 82.2; Emotional Function: 67.7 vs. 82.1; all p < 0.001), and lower EQ5D utility scores (0.84 vs. 0.91; p = 0.001). Work productivity and activity were impaired (absenteeism, 8.6% vs. 5.1% for TIRs vs. TRs; presenteeism, 34.3% vs. 21.0%; work impairment, 37.1% vs. 23.3%; overall activity impairment, 39.8% vs. 25.3%; all p < 0.05). CONCLUSION: HRQoL and work productivity were significantly impacted in TIRs versus TRs in this real-world analysis of patients with migraine acutely treated with triptans, highlighting the need for more effective treatments for patients with an insufficient triptan response. Further research is needed to establish causal relationships between insufficient response and these outcomes.

The Role of Diet and Nutrition in Migraine Triggers and Treatment: A Systematic Literature Review.

BACKGROUND: Migraine is a disabling primary headache disorder often associated with triggers. Diet-related triggers are a common cause of migraine and certain diets have been reported to decrease the frequency of migraine attacks if dietary triggers or patterns are adjusted. OBJECTIVE: The systematic literature review was conducted to qualitatively summarize evidence from the published literature regarding the role of diet patterns, diet-related triggers, and diet interventions in people with migraine. METHODS: A literature search was carried out on diet patterns, diet-related triggers, and diet interventions used to treat and/or prevent migraine attacks, using an a priori protocol. MEDLINE and EMBASE databases were searched to identify studies assessing the effect of diet, food, and nutrition in people with migraine aged ≥18 years. Only primary literature sources (randomized controlled trials or observational studies) were included and searches were conducted from January 2000 to March 2019. The NICE checklist was used to assess the quality of the included studies of randomized controlled trials and the Downs and Black checklist was used for the assessment of observational studies. RESULTS: A total of 43 studies were included in this review, of which 11 assessed diet patterns, 12 assessed diet interventions, and 20 assessed diet-related triggers. The overall quality of evidence was low, as most of the (68%) studies assessing diet patterns and diet-related triggers were cross-sectional studies or patient surveys. The studies regarding diet interventions assessed a variety of diets, such as ketogenic diet, elimination diets, and low-fat diets. Alcohol and caffeine uses were the most common diet patterns and diet-related triggers associated with increased frequency of migraine attacks. Most of the diet interventions, such as low-fat and elimination diets, were related to a decrease in the frequency of migraine attacks. CONCLUSIONS: There is limited high-quality randomized controlled trial data on diet patterns or diet-related triggers. A few small randomized controlled trials have assessed diet interventions in preventing migraine attacks without strong results. Although many patients already reported avoiding personal diet-related triggers in their migraine management, high-quality research is needed to confirm the effect of diet in people with migraine.

Patient's Perspective on Disease Burden, Remission Definition, and Symptoms Associated With Treatment Seeking: A Qualitative Study in Adult and Adolescent Patients With Crohn's Disease.

Background: Disease burden, a definition of remission, and symptoms that drive treatment seeking were explored in a Crohn's disease (CD) population. Methods: A qualitative semistructured interview guide was developed, informed by published literature. Clinicians identified adolescents and adult patients with CD. Face-to-face interviews were audio-recorded and transcribed. Two rounds of interviews were conducted with patients. Transcripts were analyzed using thematic methods facilitated by ATLAS.ti. Results: Twenty-four patients participated in the first round of interviews (n = 16 adults, mean age 50.3 years; n = 8 adolescents, mean age 15.6 years). Abdominal pain (n = 24), urgent bowel movements (n = 24), diarrhea (n = 23), and frequent bowel movements (n = 21) were the most frequently reported symptoms. CD affected patients' physical functioning, daily activities, emotional wellbeing, social functioning, work/education, and relationships. No major difference in disease burden was observed between adolescents and adults. Twenty-three patients (96%) reported they would seek or had sought medical treatment for at least one symptom including abdominal pain (n = 19), diarrhea (n = 12), and blood in stools/rectal bleeding (n = 9). On a 0-10 scale (0 = no symptom and 10 = symptom at its worst possible), most patients (87%, 20/23) answered they would seek/had sought treatment when the symptom's severity was at least 7. In the second round of interviews (n = 6 adults, mean age 51.5 years), 5/6 patients described that they did not require a complete absence of abdominal pain or loose/watery stools to consider their CD to be in remission. Conclusions: CD is associated with substantial disease burden. Worsening of some symptoms drives treatment seeking. To some patients, remission is not defined as a complete absence of symptoms.