What is this summary about? Atopic dermatitis (AD) is a chronic (long-lasting) skin disease that leads to dry, itchy, and swollen red spots, which can also be painful and flare up at any time. Some people with AD have a high number of eosinophils, a type of white blood cell, which are associated with worse disease. Medicated creams and lotions, prescribed by health care providers, are meant to reduce the symptoms of AD. For some people, these creams and lotions do not work. Benralizumab injection is a medication that reduces and removes eosinophils. A clinical trial called HILLER tested benralizumab to see if there was a difference in symptoms of AD after reducing or removing eosinophils. This article explains how benralizumab reduced eosinophils and the effect it had on AD symptoms in the HILLIER study. What were the main conclusions reported by the researchers? Benralizumab reduced blood eosinophil numbers. However, benralizumab showed no evidence of treatment benefit on signs, symptoms, or severity of AD, as measured by three skin assessments compared with placebo. Benralizumab was well tolerated and had a safety profile that was consistent with previous studies. The five most commonly reported side effects were COVID-19 infection, upper respiratory tract infection, headache, swelling of the lymph nodes, and pink eye (conjunctivitis) in patients who received either benralizumab or placebo What are the key takeaways? Benralizumab lowered the number of blood eosinophils without improving AD symptoms and was well tolerated.

BACKGROUND:Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear. METHODS:In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24. RESULTS:A total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, -1.4 to 7.4; P = 0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events. CONCLUSIONS:In this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.).

Background Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor-alpha monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils.Objectives To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment.Methods The 24-week, randomized, double-blind, placebo-controlled, phase IIb portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomized to one of five treatment groups according to benralizumab dose and regimen for a 24-week treatment period. The primary endpoint was change from baseline in Itch Severity Score (ISS)7 at week 12. The key secondary endpoint was change from baseline in Urticaria Activity Score (UAS)7 at week 12. Additional secondary endpoints included other metrics to assess CSU at week 24, blood eosinophil levels, and pharmacokinetics and immunogenicity assessments. Exploratory subgroup analyses were conducted to explore responses according to demographics, clinical features and biomarkers. Safety was assessed in all treatment groups.Results Of 155 patients, 59 were randomized to benralizumab 30 mg, 56 to benralizumab 60 mg and 40 to placebo. Baseline and disease characteristics were consistent with what was expected for patients with CSU. There were no significant differences in change from baseline in ISS7 score at week 12 between benralizumab and placebo [benralizumab 30 mg vs. placebo, least-squares mean difference -1.01, 95% confidence interval (CI) -3.28 to 1.26; benralizumab 60 mg vs. placebo, least-squares mean difference -1.79, 95% CI -4.09 to 0.50] nor in change from baseline in UAS7 score at week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, P = 0.407; benralizumab 60 mg vs. placebo, P = 0.082). Depletion of blood eosinophil levels was observed at week 24 in patients treated with benralizumab. All other secondary endpoints and exploratory/subgroup analyses indicated no significant differences between benralizumab and placebo. Safety results were consistent with the known profile of benralizumab.Conclusions Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo. Eosinophils play a role in the pathogenesis of chronic spontaneous urticaria (CSU). ARROYO was a 24-week randomized placebo-controlled phase IIb clinical study that compared benralizumab treatment with a placebo in adult patients who had CSU and were currently taking antihistamines. Benralizumab depleted eosinophil levels, but there was no clinical benefit over placebo. Graphical Abstract Chronic spontaneous urticaria (CSU) is a common disease characterized by hives, itching and inflammation (swelling) of the skin. CSU is mainly driven by what we call 'mast cells'. 'Eosinophils' are a type of white blood cell that protect the body from infections and allergens. These cells are abundant in skin biopsy samples of people with CSU, especially in the hives that contribute to swelling. Therefore, we thought that reducing eosinophils would be beneficial for treating CSU. Benralizumab is a drug that has been shown to reduce eosinophils in other diseases.This study, called 'ARROYO', was a 24-week clinical trial that compared benralizumab treatment with a placebo (inactive medicine) in adults with CSU who were taking antihistamines. We aimed to determine whether benralizumab would improve symptoms of CSU over time. Several assessments were used to measure changes in CSU symptoms, including hives, severity of itchiness, swelling of the skin, and other aspects related to overall psychological and physical wellbeing. The characteristics of the 155 people who took part in this study were consistent with what was expected for patients with CSU.We found that while benralizumab reduced eosinophil levels in people with CSU, there were no differences in symptoms in people receiving benralizumab compared with those receiving placebo. There were no new safety concerns related to benralizumab and no deaths.Overall, although benralizumab is effective at reducing the number of eosinophils, it is not effective at treating the symptoms of CSU. More studies are needed to uncover potential treatment targets in CSU.

Background: Real -world data describing the impact of incident bullous pemphigoid (BP) on patients and health care resource utilization (HCRU) are limited. Objective: To examine characteristics, treatment patterns, HCRU, and costs for incident BP. Methods: Retrospective analysis of 2015 to 2019 US health insurance claims for patients $ 18 years with an incident BP diagnosis. Patients with BP were matched to those without on demographic and clinical characteristics. Statistics were descriptive. Results: The mean Charlson Comorbidity Index score was higher for patients with BP ( n = 1108) than without ( n = 4621) at baseline (mean [SD]: 3.3 [2.7] vs 2.8 [2.4]) and during follow-up (5.0 [4.9] vs 3.7 [3.0]). Hypertension, diabetes, skin ulcers, chronic pulmonary disease, dyslipidemia, sleep disorders, and congestive heart failure were higher with BP. Most patients with BP received antibiotics ( > 80%) and/or corticosteroids ( > 90%). Hospitalizations were more common (44.0% vs 17.1%) and monthly all -cause health care costs more than double ($3214 vs $1353) in patients with BP than without. Limitations: Diagnoses were based on billing codes. HCRU claims data may not reflect the true number of encounters. Conclusion: Incident BP is associated with considerable morbidity, HCRU, and costs. More effective, targeted treatments are needed to improve quality of life, while minimizing exposure to systemic corticosteroids.

Atopic dermatitis (AD) is a common, chronic inflammatory skin disease characterized by itchy skin lesions.1-4 Some patients with AD present with elevated peripheral eosinophilia. Evidence suggests a role of eosinophils in the pathophysiology of AD; therefore, an eosinophil-depleting treatment, such as benralizumab, could prove beneficial, particularly in patients with increased eosinophil counts.5, 6 HILLIER (NCT04605094) was a 52-week, randomized, double-blind, placebo-controlled, phase 2 clinical trial in patients with moderate-to-severe AD who remained symptomatic despite background topical therapy. Patients were 12 years or older with an investigator global assessment (IGA) ≥3, Eczema Area and Severity Index (EASI) ≥16, ≥10% Body Surface Area of Involvement (BSA), Peak Pruritus Numerical Rating Scale (PPNRS) ≥4, and inadequate response to treatment with topical medications. Patients were randomized 1:1 to benralizumab 30 mg every 4 weeks or placebo groups and stratified by blood eosinophil (bEOS) counts (<300 cells/μL vs. ≥300 cells/μL) and age groups (≥12 to <18 years and ≥18 years). The 16-week placebo-controlled period was followed by a 36-week open-label extension. Results are described for the 16-week placebo-controlled period. The trial was terminated early due to a lack of efficacy. The primary endpoint was an IGA response defined by the proportion of patients with an IGA 0/1 (clear/almost clear) and a decrease in IGA score of ≥2 points at Week 16 relative to baseline. Secondary endpoints were assessed at Week 16 relative to baseline and included the proportion of patients with skin clearance based on EASI-75 and EASI-90, and itch response, defined as the proportion of patients with an improvement of ≥4 points in the PPNRS score. Ninety-six patients (including 26 adolescents) and 98 patients (27 adolescents) were randomized into the benralizumab and placebo groups, respectively. Patient demographics and clinical characteristics were comparable between the two groups and consistent with moderate-to-severe AD (Table 1). There were no differences between the groups on the primary endpoint, IGA 0/1 response rate absolute difference (benralizumab–placebo rates, −8.62% [95% CI, −17.94 to 0.71]; p = 0.080; Table 2). There were no differences between groups on any secondary endpoints, including EASI-75, EASI-90 and itch improvement, as well as other endpoints that measured signs, symptoms and health-related quality-of-life. Despite the lack of improvement, benralizumab therapy resulted in substantial reductions in mean (SD) bEOS at Week 16, 40.0 (77.19) cells/μL versus baseline, 482.3 (394.63) cells/μL, which were not observed in the placebo group (Week 16: 354.9 [242.21] cells/μL; baseline: 464.4 [443.74] cells/μL). The benralizumab group also saw greater mean (SD) reductions in serum EDN (12.20 [5.43] mg/L at Week 16 compared to 79.67 [68.37] mg/L at baseline) versus placebo at Week 16, (64.47 [47.38] mg/L vs. baseline, 76.10 [55.01] mg/L). The proportion of patients experiencing any adverse event (AE) was similar between the benralizumab (n = 39 [40.6%]) and placebo (40 [40.8%]) groups. Three benralizumab patients (3.1%) experienced serious AEs, none of which were considered by the investigator to be related to the study drug. No serious AEs occurred in the placebo group and no deaths in any group. The most common AEs were COVID-19 (9.4%) and upper respiratory tract infections (5.2%) in the benralizumab group and headaches (5.1%), lymphadenopathy (4.1%), conjunctivitis (4.1%) and COVID-19 (4.1%) in the placebo group. Safety and tolerability findings were consistent with the known profile of benralizumab.7-10 In conclusion, despite bEOS depletion, this phase 2 study showed that treatment with benralizumab did not provide clinical benefit for AD, suggesting that solely targeting eosinophils may not be sufficient to treat such a heterogeneous disease. Future research is needed to understand better the role of eosinophils in AD, which may provide further insights into the pathophysiology of the disease and guide future treatment approaches. Medical writing support was provided by Lea Anne Gardner, PhD, and Dan Jackson, PhD, CMPP (CiTRUS Health Group), which was in accordance with Good Publication Practice (GPP 2022) guidelines. We thank the patients and their caregivers, as well as the study investigators and site staff, for participating in this study. This study and medical writing support were funded by AstraZeneca (Cambridge, UK). Emma Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, AstraZeneca, Boehringer Ingelheim, Cara Therapeutics, Celgene, Eli Lilly, Galderma, Glenmark/Ichnos Sciences, Innovaderm, Janssen, KAO, Kiniksa, Kyowa Kirin, Leo Pharma, Novan, Novartis, Pfizer, Ralexar, Regeneron Pharmaceuticals and UCB and is a consultant for AbbVie, Almirall, Amgen, Arena, Asana Biosciences, Aslan Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol-Meyers Squibb, Cara Therapeutics, Celgene, Connect Pharma, Eli Lilly, EMD Serono, Evidera, Galderma, Ichnos Sciences, Incyte, Janssen Biotech, Kyowa Kirin, Leo Pharma, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Sanofi, SATO Pharmaceutical, Siolta Therapeutics, Target Pharma Solutions, UCB and Ventyx Biosciences. Lila Bahadori, Laura Brooks, Ken L. Clark, Hanna Grindebacke, Calvin N. Ho, Rohit Katial, Tuyet-Hang Pham, Claire Walton and Catherine J. Datto are or were employees of AstraZeneca at the time of the study and may own stock or stock options. This trial was conducted in accordance with the principles of the Declaration of Helsinki and guidelines from the International Council for Harmonisation and Good Clinical Practice. The clinical study protocol was reviewed and approved by institutional review boards or independent ethics committees prior to study initiation and the data and safety monitoring board oversight. All patients provided written informed consent prior to enrolment. HILLIER study group: Emma Guttman-Yassky, Pedro Jesús Gómez Arias, Ricardo Alpizar, Sady Alpizar, Petr Asrenberger, Selma Azib, Anais Badia, Lisa Beck, Eduardo Lopez Bran, Debra Breneman, Petyo Brezoev, Antonio Martorell Calatayud, Yendrys Calderin, Hoon Choi, Myoung Eun Choi, Cezary Chwała, Esther Roe Crespo, Rafal Czajkowski, Frédéric Dezoteux, Nadezda Fiserova, Viviana Fonseca, Francisco José Gómez García, Loyd Godwin, Diana Grigoryan, Violeta Hernandez, Anna Hofman, Teresa Hofman, Anthony Honigman, Yong Hyun Jang, Abel Jarell, Barbara Kaczmarek, Zuzana Kaščáková, Johannes Kern, Ryan Klein, Hyun Chang Ko, Joo Yeon Ko, Otakar Komarek, Klaudie Komárková, Leah Laageide, Yaohan Lam, Yang Won Lee, Jeffrey Leflein, Bark-Lynn Lew, Lon D. Lynn, Mariana Mandazhieva-Pepelanova, Laurent Misery, Dedee Murrell, Kamila Musiał, Chan Ho Na, Jung Im Na, Sarah O’Connor, Hnin Pwint Oo, Witold Owczarek, Chun Wook Park, Young Min Park, Jonathon Peek, Karolina Pełka, Grazyna Pulka, Álvaro Iglesias Puzas, Juan Alberto Ruano Ruiz, Zach Sabaday, Juan Francisco Silvestre Salvador, Virgnia Sanz-Motilva, Stephen Schleicher, Robert Scott, Seong Jun Seo, Hyung Seok Son, Sang Wook Son, Priscel Sosa, Lynda Spelman, Delphine Staumont-Salle, Marion Stefanski, Madeleine Supranowicz, Ricardo Tan, Jaroslava Vaneckova, Yvetta Vantuchova, Ivaylo Vasilev, Irida Vasileva, Kamelia Vekovska, Chong-Hyun Won, and Sylva Zajicova. Sarah Aldridge, Eileen Babcock, Peter Barker, Zuzanna Betlińska, Marnie Duncan, Rama Empati, Maria Jison, Justin Kwiatek, Emmanuelle Maho, Allen McAlexander, Christopher McCrae, Margaret Melville, Urszula Natkańska, Apollo Ndamira, Yasa Reddy, Scott Regan, Eva Rodríguez-Suárez, Anna Rusiecka, David Shen, Magnus Bergman Svärd, and Urszula Zaborowska. Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca's data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

We conducted a systematic literature review of treatment patterns of eosinophilic esophagitis (EoE) to understand patients who may benefit from novel treatment approaches. The search included the Embase, MEDLINE, Cochrane and Web of Science databases, and relevant observational studies (articles published 1 January 2015 to 20 April 2022) were included. Results were screened against predetermined criteria by two independent reviewers and adjudicated by a third per PRISMA guidelines. Of 311 articles screened, 45 met inclusion criteria; among these, study designs varied. Based on included studies, 16%-100% (median: 74%) of all EoE patients initiate pharmacotherapy; most commonly with PPIs (0%-67%), topical steroids (16%-56%) or combination therapy (0%-20%). Between 6% and 27% go on to receive second-line therapy. Between 72% and 94% (median: 80%) of all EoE patients are reported to be on pharmacotherapy (37%-61% PPIs; 14%-40% topical steroids; 16%-48% combination therapy) at any time. A proportion of patients do not achieve a response to treatment and 30%-67% relapse to active eosinophilia (≥15 eos/hpf). Stricture is reported in up to 30% of EoE patients at initial presentation and in 4%-49% during clinical follow-up. Among patients on treatment, up to 23% undergo ≥1 esophageal dilation procedure; up to 37% experience a food impaction, with higher rates among those undergoing ≥1 dilation; and up to 29% experience a food impaction requiring urgent medical intervention. Treatment patterns indicate a proportion of patients experiences manifestations of more severe disease, despite treatment, pointing to an unmet need in this subgroup that may benefit from novel treatment approaches.

Background and Significance: Hypereosinophilic syndrome (HES) is a rare, heterogeneous disorder defined by blood eosinophilia (absolute eosinophil count [AEC] >1500 cells/μL) on 2 examinations ≥1 month apart and eosinophil-mediated end-organ involvement, including dermatologic, pulmonary, gastrointestinal, and/or cardiovascular manifestations. Symptoms and health-related quality of life vary depending on the organ systems involved. HES is often treated with corticosteroids and other immunosuppressants. However, long-term use of these agents is associated with decreased efficacy and significant toxicity. Whereas anti-IL-5 antibody mepolizumab was recently approved for the treatment of HES (Roufosse, et al. J Allergy Clin Immunol. 2020;146(6):1397-1405), response is not universal and additional targeted agents are clearly warranted. Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor α monoclonal antibody that induces rapid, near-complete depletion of eosinophils through antibody-dependent, cell-mediated cytotoxicity. It is currently approved for use in patients with severe eosinophilic asthma and has demonstrated AEC-reducing effects in patients with HES (Kuang, et al. N Engl J Med. 2019;380(14):1336-46). Study Design and Methods:This phase 3, multicenter, randomized, double-blind (DB), placebo-controlled study (NATRON; NCT04191304) evaluating the efficacy of benralizumab versus placebo will enroll ~120 patients with documented HES (Figure 1A). Recruitment will stop after approximately 38 patients have had their first HES worsening/flare during the DB period, at which point the data cutoff for the primary analysis will occur. Eligible patients are ≥12 years of age with an AEC ≥1000 cells/mL at screening, have active signs/symptoms of an HES worsening/flare or a history of ≥2 HES worsening/flares within 12 months before enrollment, and have a stable treatment regimen (≥4 weeks). Patients must be FIP1L1-PDGFRA-negative and corticosteroid-responsive, defined as an AEC of <1000 cells/μL after 2 days of corticosteroid treatment. The primary endpoint is time to first HES worsening/flare during the DB period. Key secondary endpoints during the DB period include the proportion of patients who experience HES worsening/flare events, the number of HES worsening/flare events (annualized rate/year), time to first hematologic relapse, and change from baseline in fatigue at week 24 as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a. Patients who complete the 24-week DB treatment period will continue with active treatment in a ≥52-week open-label extension. We present the study design and interim baseline characteristics of patients recruited to date. Results:As of the June 6, 2023, cutoff date, 87 patients were enrolled in the full analysis set (Figure 1B). Among these patients, the mean (SD) age was 48.4 (17.79) years, 64.4% were female, and 84.3% were White. The mean (SD) time since the first appearance of HES symptoms and since HES diagnosis was 8.14 (8.12) and 4.87 (6.54) years, respectively. The proportion of patients with the lymphocytic variant HES was 14.9%. The most common primary organs involved were the lungs (35.6%), followed by the skin (25.3%) and the gastrointestinal tract (21.8%). Thirty-four (39.1%) and 32 (36.8%) patients experienced 2 and ≥3 HES worsening/flare events in the previous 12 months, respectively. The mean (SD) PROMIS Fatigue T-score was 55.0 (9.42). Mean (SD) baseline eosinophil levels were 1960 (2610) cells/µL, with median (interquartile range) levels of 1120 (60, 20910) cells/µL. Conclusions: Results from the NATRON study will provide insight into whether benralizumab is beneficial in addition to background therapy in patients with FIP1L1-PDGFRA-negative steroid-responsive HES. Funding: This study is funded by AstraZeneca (Gothenburg, Sweden). This work is funded in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Acknowledgments:Vivian H. Shih, Dianne Griffis, Himanshu Parikh, Ron A. Chen, Ying Fan, Gaëll Mayer, Rohit Katial, and Ioannis Psallidas.

To evaluate the impact of bullous pemphigoid (BP) on healthcare resource utilization (HCRU) and costs in a retrospective analysis of 2015–2019 US administrative health insurance claims data (MarketScan).

Background A patient reported outcome (PRO) instrument with evidence of validity and reliability for assessing symptoms of eosinophilic gastritis (EG) and eosinophilic gastroenteritis (EGE) is needed to measure treatment benefit in clinical trials. The aim of this research is to develop an EG/EGE symptom PRO instrument for patients aged 12 and above. Methods The Symptom Assessment for Gastrointestinal Eosinophilic Diseases (SAGED) was developed through a literature review, discussions with expert clinicians, and concept elicitation and cognitive debriefing interviews with patients. Patients (n = 28) were recruited based on confirmed diagnosis and self-reported symptoms. The final instrument was translated and linguistically validated with additional cognitive debriefing interviews (n = 105). Results SAGED is a 24-h recall questionnaire consisting of eight items evaluating the core symptoms of EG and EGE (abdominal pain, nausea, bloating, early satiety, loss of appetite, vomiting, and diarrhea). Seven of the eight items are evaluated on an 11-point numerical rating scale ranging from ‘none’ to ‘worst imaginable’. Cognitive debriefing interviews showed that adults and adolescents understand the content and are able to select a response that reflects their experience. The linguistic validation process produced 21 translations that are understandable to patients and conceptually equivalent to the source version. Conclusions SAGED is suitable for measuring symptom improvement in adult and adolescent patients with EG and/or EGE. The content validity of SAGED has been established through best practices in qualitative research for PRO instrument development. The psychometric properties of SAGED will be evaluated in a future study.

Aim: To evaluate analgesic use and associated conditions in postmenopausal women who had undergone curative breast cancer treatment. Materials & methods: This post hoc analysis used the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial database, which included patient reports of concomitant medications and associated indications during follow-up. Results: Of 3434 women with eligible concomitant medication data, 71.8% reported oral analgesic use. Of 2321 patients using analgesics ≥30 days, 47.9% reported opioid use. Musculoskeletal pain was the most common indication for oral analgesic use. Of patients using opioids, 28.1% reported concomitant laxative use. Conclusion: Approximately half of the patients reported opioid use, most commonly for noncancer (musculoskeletal) pain, suggesting that breast cancer survivors experience chronic pain that should be appropriately managed.

Brenner, Darren M. MD1; Hu, Yiqun MD, PhD2; Datto, Catherine MD, MS2; Creanga, Dana PhD2; Camilleri, Michael MD3 Author Information

OBJECTIVE:Opioid pain medication continues to be an important treatment option for patients with moderate to severe cancer and non-cancer pain; however, limited evidence is available regarding differences in opioid use between these two populations. The objective of this analysis was to compare real-world opioid use patterns over time in these two populations.DESIGN:Retrospective analysis of administrative claims data.SETTING:HealthCore Integrated Research Environment database.PATIENTS:Adults with ≥1 opioid pharmacy claim (and a confirmed cancer diagnosis for the cancer pain cohort).MAIN OUTCOME MEASURES:Opioid doses and dose changes following the initial prescribed (index) dose were determined.RESULTS:In the cancer pain (n = 9,209) and non-cancer pain (n = 409,703) cohorts, median index opioid doses were 51.7 and 45.0 morphine-equivalent units (MEU), respectively, and median post-index opioid doses were 55.8 and 45.1 MEU for the cancer pain and non-cancer pain cohorts, respectively. The most common dose escalation in both groups was up to a dose doubling (cancer pain, 31.8 percent; non-cancer pain, 28.3 percent). The proportions of patients with dose increases exceeding two times the index dose were low and clinically comparable between cohorts (cancer pain, 9.9 percent; non-cancer pain, 7.4 percent).CONCLUSIONS:Opioid use was consistent between patients with cancer pain and non-cancer pain, including clinically comparable total daily opioid doses and consistent rates of dose escalations and chronic utilization. Opioid medications are an important element of cancer and non-cancer pain management; thus, access to appropriate therapies, use patterns, and risk assessment and management are important for both patient populations.

Objectives: To determine patient preference for treating opioid-induced constipation (OIC) using naloxegol or polyethylene glycol (PEG) 3350 in patients receiving opioids for noncancer pain. Methods: This crossover study included two 2-week active treatment periods, each preceded by a 1-week washout period (NCT03060512). Individuals with baseline Bowel Function Index scores ≥30 were randomized to 1 of 2 treatment sequences (naloxegol/PEG 3350 or PEG 3350/naloxegol). Patient preference (primary end point) was measured at the end of the second treatment period. Results: Of 276 patients randomized, 246 completed both treatment periods and reported preference (per protocol). Similar proportions of patients reported overall preference for naloxegol (50.4%) or PEG 3350 (48.0%; P = 0.92); 1.6% reported no preference. Medication characteristics influencing preference were similar for both treatments, except convenience and working quickly, which were strong influences of preference for higher proportions of patients preferring naloxegol (69.9% and 39.0%, respectively) vs those preferring PEG 3350 (29.9% and 27.4%, respectively). Patients aged <50 years or receiving laxatives within the previous 2 weeks generally preferred naloxegol. Changes from baseline in overall Bowel Function Index and Patient Global Impression of Change scores were similar between treatments, but analyses according to treatment preference revealed clinical improvement aligned with reported preference. Safety profiles were generally consistent with known medication profiles. Conclusions: Almost equal proportions of patients with OIC reported similar preference for daily naloxegol or PEG 3350 treatment, and their preference was generally supported by clinically relevant and measurable improvements in OIC symptoms.

OBJECTIVE:This analysis of patient-health care provider discussions of opioid-induced constipation (OIC) evaluated the dynamics of interactions, identified communication gaps, and assessed the functional burden of opioid-induced constipation on patients' lives.DESIGN:Retrospective analysis of a Health Insurance Portability and Accountability Act-compliant database of >120,000 patient-provider conversations.SETTING:Outpatient offices in the United States.METHODS:Conversations between providers and patients prescribed opioids that occurred in the United States (January 2014-May 2016) and included a discussion of opioid-induced constipation were identified. Demographics and prespecified opioid-induced constipation conversation characteristics were evaluated for these conversations.RESULTS:This analysis included 216 patient-provider discussions. Most patients (76.4% [165/216]) were ≥50 years old. Most conversations were with pain management specialists (39.8% [86/216]) or primary care physicians (36.6% [79/216]). Overall, 64.4% (139/216) of patients reported experiencing symptoms of constipation. Health care providers indicated that symptoms of constipation could be caused by opioid use for 75.5% (105/139) of patients with constipation. In most cases (82.4% [178/216]), providers did not probe about specific constipation symptoms. Few patients (11.5% [16/139]) with OIC discussed the burden of OIC with their providers; burdens reported by patients with OIC included emergency room visits and reduced food or fluid intake. No specific action was recommended for 33.8% (47/139) of patients with constipation.CONCLUSIONS:In this analysis, when opioid-induced constipation was discussed, health care providers did not inquire about specific symptoms for most patients, opioids were not cited as a cause of constipation in approximately one-quarter of patients with opioid-induced constipation, and no clear treatment plan or guidance was recommended for one-third of patients. Results of this analysis suggest that more education may be needed to improve patient-provider communication about opioid-induced constipation.

Aims Constipation associated with opioid therapy for chronic pain may negatively impact colonoscopy success. This retrospective, observational study using administrative data and electronic medical records evaluated the impact of opioid use on colonoscopy outcomes. Methods and Results Procedural codes were used to identify patients who had a screening colonoscopy at two Henry Ford Health System centers (January 2015–December 2016). All patients had completed a standard uniform bowel preparation protocol. Medication orders and filled prescriptions were used to identify patients with a history of opioid use during the 28 days preprocedure (exposed) and a matched random sample of presumptive opioid nonusers (unexposed). Electronic medical records were reviewed for colonoscopy procedure data and outcomes. The exposed and unexposed groups included 964 and 1054 patients, respectively. Inadequate bowel preparation was significantly more common in the exposed versus unexposed group (18.5% vs 12.7%; P < 0.001). In the exposed and unexposed groups, 97.1 and 98.0% of colonoscopy procedures were completed, respectively ( P = nonsignificant). Total procedure time was slightly increased for the exposed versus unexposed group (23.8 vs 22.5 min; P = 0.039). Polyp identification and cancer diagnosis were similar between groups. Prolonged sedation occurred in three patients in the exposed group and none in the unexposed group. Procedural complications were rare, but the incidence was significantly greater in the exposed versus unexposed group (1.3% vs 0.2%; P < 0.01). Conclusions Opioid exposure was associated with significant reductions in the quality of preprocedure bowel preparation and an increased risk of complications in patients undergoing colonoscopy.

Background Patients are often unable to recall post procedure discussions regarding findings and recommendations.The optimal time of physician-patient discussion has not been studied.Cognition is impaired immediately after an endoscopic procedure and critical information may be forgotten which could have clinical and legal implications.Patients undergoing outpatient esophagogastroduodenoscopy (EGD) and/or colonoscopy were prospectively enrolled and time of patient-physician (P-P) discussion was noted.Anxiety and alertness was assessed before the P-P discussion.Patients were contacted by phone 24 hours and 72-96 hours after the procedure to assess patient recall.Patients were given copy of reports in sealed envelope, to be opened after the second phone call.134 patients were included.45% of patients who had the P-P discussion less than 10mins after the procedure did not remember talking to the physician vs. 16% after 10mins(9 vs. 18 p=0.004).29% of patients who had the P-P discussion less than 15mins after the procedure did not remember talking to the physician vs. 16% after 15mins(14 vs. 13 p=0.077).76% remembered the P-P discussion performed 20mins after the procedure clearly and there was no significant difference between less than 20mins and more than 20mins group.Patients who could not clearly recall the PP discussion had less knowledge at 72 hours about the indication for the endoscopy(p= 0.015), findings of the endoscopy at 24(p<0.001) and 72 hours(p<0.001),number of polyps found on colonoscopy at 24 hours(p<0.001)and 72 hours(p<0.001),recommendations provided at 24 hours(p==0.006)and 72 hours(p=0.004),recall timing of next recommended procedure at 24 hours(p=0.027)and 72 hours(p=0.049).Patients who could not remember the P-P discussion clearly also felt like the results were not communicated to them adequately(p<0.001)and they could not reiterate the next steps in management (p<0.001)compared to those who remembered the P-P discussion.Patients with higher BMI(mean 31.1) were significantly likely to remember P-P discussion compared to those with BMI mean of 29.1 p=0.031Modified Observer's Assessment of Alertness(MOAA) score in patients who could not remember the P-P discussion was significantly lower(mean rank 50 vs.63, p=0.029) compared to those who could remember the P-P discussion.Patients who were not able to recall the P-P discussion clearly had much lower patient satisfaction(mean rank 45 vs. 73, p=<0.001).Patient satisfaction was also lower if the P-P discussion was < 15mins after the procedure(mean rank 58 vs. 69, p = 0.041).Conclusion PP discussion should not be planned less than 15 minutes after an endoscopic procedure or until MOAA score exceeds 4 as it has a significantly negative impact on patient recall of findings of the procedure, provider recommendations and next steps after the procedure Tu1720

e22200 Background: Literature reports that cancer-related pain is experienced by 17-30% of patients with non-metastatic disease and 56-85% with advanced cancer. The characterization of pain following curative breast cancer treatment is the subject of this analysis. Methods: This post hoc analysis utilized the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial database. This study enrolled over 9000 postmenopausal women with invasive, operable, nonmetastatic breast cancer who had completed primary breast cancer therapy (surgery and chemotherapy if given) and were eligible to receive adjuvant hormonal therapy. Median follow-up was 120 months and the database included patient reports of pain types and pain treatments. The data assessed was a portion of those enrolled who had informed consent that allowed for post hoc analysis of the data. This analysis of pain and pain treatment was conducted without respect to the randomized treatment. Pain was considered cancer-related when the investigator specifically identified the pain as related to cancer or its treatment; all others were considered non-cancer pain. Results: Of the 3434 women whose data were available for analysis, 2466 (71.8%) reported any pain medication exposure during the study period; 1633 (47.6%) reported any opioid use and 25.5% of these patients reported any concomitant laxative use. Non-cancer related pain was more commonly reported regardless of the duration of pain medication use: 7-30 days (n = 83): 67.5% non-cancer only and 8.4% cancer-related pain only; ≥30 days (n = 2321): 77.4% non-cancer only and 2.0% cancer-related pain only. Most common conditions associated with opioid pain medications taken for ≥30 days were musculoskeletal pain (35.3%), headache (10.1%), cancer-related pain (6.9%), and use related to non-cancer surgeries (3.9%). Conclusions: In this study of cancer survivors, almost half reported the need for opioid pain management over the follow-up period. The incidence of non-cancer pain was consistently higher than cancer-related pain regardless of opioid therapy duration. Laxative use concomitant with opioid therapy was limited. Consequently, practitioners caring for these patients should be aware of the current pain guidelines to appropriately manage these patients.