Abrocitinib Provides Rapid and Sustained Improvement in Skin Pain and Is Associated with Improved Quality of Life Outcomes in Adult and Adolescent Patients with Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Skin pain in atopic dermatitis (AD) increases with disease severity and is associated with substantial quality of life (QoL) burden. OBJECTIVES: The aim of the study was to evaluate abrocitinib efficacy on skin pain and QoL in adults and adolescents with moderate-to-severe AD. METHODS: This post hoc analysis included data with abrocitinib administered as monotherapy (pooled phase 2b [NCT02780167] and phase 3 JADE MONO-1 [NCT03349060] and JADE MONO-2 [NCT03575871]) or in combination with topical therapy (phase 3 JADE COMPARE [NCT03720470] and JADE TEEN [NCT03796676]). Patients received oral, once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 or 16 weeks (JADE COMPARE). Skin pain was rated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) skin pain Numerical Rating Scale (NRS) item ("How painful was your skin over the past 24 h?") on a scale from 0 (not painful) to 10 (extremely painful). Itch (Peak Pruritus NRS) and QoL (Dermatology Life Quality Index or Children's Dermatology Life Quality Index) were assessed. Least squares mean (LSM) change from baseline was analyzed using mixed-effects repeated measures modeling. RESULTS: A total of 1,822 patients (monotherapy pool, n = 942; JADE COMPARE, n = 595; and JADE TEEN, n = 285) were analyzed. LSM change from baseline in PSAAD skin pain score was significantly greater with abrocitinib versus placebo from week 2 through week 12 or 16 across all 3 study populations and occurred in a dose-dependent manner. A greater proportion of patients achieved a ≥4-point improvement from baseline in PSAAD skin pain score with abrocitinib (200 mg and 100 mg) versus placebo in the monotherapy pool (56% and 38% vs. 12%; week 12), JADE COMPARE (72% and 52% vs. 26%; week 16), and JADE TEEN (51% and 60% vs. 31%; week 12). Additionally, a greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score <2) with abrocitinib versus placebo. Adults and adolescents who achieved a ≥4-point improvement in skin pain reported greater QoL improvement than those who did not achieve a ≥4-point improvement. A positive correlation (≥0.3) was observed between skin pain and QoL and separately between skin pain and itch across the 3 study populations. CONCLUSION: Abrocitinib as monotherapy or in combination with topical therapy improved skin pain and was associated with improved QoL in both adults and adolescents with moderate-to-severe AD across all evaluated studies.

Americans' Awareness of Access Changes and Utilization of Telehealth During COVID-19: A Survey in the United States.

Background: We examine how and why Americans have experienced interrupted health care during the COVID-19 pandemic and measure awareness and usage of expanded benefits offered by health insurers and employers. We use an expanded concept of health literacy to include knowledge of access conditions and consider if patients' knowledge of the health system may relate to utilization of care. Methods: We conducted an online survey of 451 U.S. adults in September 2020, asking respondents about their health care experiences since March 1, 2020. This survey measured usage of medical care and awareness of the efforts made by government, private insurers, and employers to increase access to benefits such as telehealth services, well-being and mental health programs, and new prescription options. Results: The most common reasons cited for postponing or skipping medical appointments included fears over COVID-19 exposure, following local restrictions, or wanting to preserve resources for those with COVID-19. Our survey also finds that many Americans are largely unaware of whether they have access to expanded benefits implemented during the pandemic. Critically, respondents who recalled telehealth and prescription medication benefits being promoted were more likely to report using such benefits. Conclusion: This research suggests that greater attention to health literacy can help promote participation in the system by patients and has the potential to lead to improved health outcomes and greater adherence to treatment plans. Telehealth may offer patients increased opportunities to consult with their physicians for ailments that they might otherwise have delayed seeking care.

Americans' Health Priorities During the COVID-19 Pandemic.

OBJECTIVES: This study aimed to examine how Americans' opinions of the seriousness of various health-related problems have changed over time and to quantify the public's preferences for research prioritization. METHODS: We conducted a survey that asked respondents to rate the seriousness of 80 health-related problems on a 4-point Likert scale ("very serious problem," "somewhat serious problem," "not too serious of a problem," or "not a problem at all"). Results were compared with past surveys from 2001 and 2013 that examined the same set of health-related problems (with the exception of COVID-19). The survey also included best-worst scaling questions that asked respondents to select, from 20 health problems, those they considered most and least important for research funding. Respondents were recruited from the KnowledgePanel, a nationally representative sample of American households. RESULTS: A total of 768 adults completed the survey between September 3, 2020, and September 14, 2020. The health-related problems that Americans consider to be "very serious" generally align with the leading causes of death and noncommunicable diseases such as heart disease, diabetes, and mental health; nevertheless, several social determinants of health are also identified. COVID-19 was an unsurprising top priority, whereas cancer remains the highest and a persistent priority for research funding. CONCLUSIONS: Americans consider a diverse set of health-related problems to be "very serious," with recognition of social determinants of health rising. Our findings offer guidance as to the disease areas for which the public would value further public and private investment in treatment innovations.

Understanding authorized generics-A review of the published clinical data.

WHAT IS KNOWN AND OBJECTIVES: Despite the large body of evidence demonstrating equivalent efficacy and safety for branded drugs and their generic counterparts, some patients and providers have the perception that generics may be less safe and effective than branded agents. Authorized generics (AGs) are a category of generic drugs defined by the United States Food and Drug Administration (FDA) as being the same as the brand-name drug without the brand's name on the label and which may have minor differences, such as tablet or capsule markings for identification. Studies in which AGs are considered along with other generics may increase our understanding of factors that may influence perceptions about generics and shed light on areas where education may be impactful. The objectives of this paper are to provide information about AGs, review studies in which they have been evaluated and explore the role that AGs may fill in the individualized treatment of patients. METHODS: A literature review was conducted on 30 September 2019 with follow-up search on 4 March 2020. The search was focussed on published papers and meeting abstracts that provided information on AGs with respect to medical and health outcomes of therapy as well as switching in individuals receiving branded, AG, or other generic agents. Information about patients' perceptions of generic medications and adherence to therapy was also included. Additional information, including relevant government sources, such as the FDA website and the Federal Trade Commission Report, was included as appropriate. RESULTS: The literature specific to AGs is limited, but available data clearly highlight the importance of patient perception of generics as well as medication appearance as factors that may affect adherence and potentially more frequent switchbacks to branded agents from generics or AGs. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first narrative review to provide a summary of the published evidence about AGs with respect to clinical and health outcomes and switching. There is a need for more research and education regarding the use of AGs in clinical practice if they are to become more recognized as a potential treatment choice for patients. Generic medications play an important role in the healthcare system, and AGs may be able to provide an option to meet the specific needs of individual patients.

A review of the immunogenicity, safety and current recommendations for the meningococcal serogroup B vaccine, MenB-FHbp.

WHAT IS KNOWN AND OBJECTIVE: This review describes invasive meningococcal disease (IMD) epidemiology in the United States, provides a brief overview of available meningococcal vaccines and discusses meningococcal serogroup B (MenB) vaccine development. Particular focus is given to the recombinant protein MenB vaccine, MenB-FHbp (Trumenba® , bivalent rLP2086) in light of recent publication of phase 3 data; the other MenB vaccine (Bexsero® , MenB-4C) has been recently reviewed. Current recommendations of the US Advisory Committee on Immunization Practices (ACIP) for MenB vaccination and potential barriers to immunization are also discussed. METHODS: Using the published literature, this article reviews the development and use of MenB-FHbp to date, with a focus on the United States. RESULTS AND DISCUSSION: Despite the availability of medical treatment, IMD is associated with significant mortality and frequently occurring serious permanent sequelae in surviving individuals. Worldwide, most IMD is caused by six serogroups (A, B, C, W, X and Y). MenB is the most common disease-causing meningococcal serogroup in the United States and has caused several recent university-based IMD outbreaks. MenB vaccines, including MenB-FHbp, are available in the United States. ACIP recommends that all individuals ≥10 years of age at increased risk for meningococcal disease receive MenB vaccination; healthy individuals 16-23 years of age are recommended MenB vaccines based on individual clinical decision-making. MenB-FHbp is used on a 2-dose schedule (0, 6 months) when vaccinating healthy individuals and on a tailored 3-dose schedule (0, 1-2, 6 months) in cases of increased risk. WHAT IS NEW AND CONCLUSION: Because vaccination provides the most effective protection against IMD, pharmacists are in an excellent position to offer evidence-based vaccine information, as well as to encourage and provide meningococcal immunizations to adolescents and young adults.

Integrated Safety Update of Abrocitinib in 3802 Patients with Moderate-to-Severe Atopic Dermatitis: Data from More than 5200 Patient-Years with Up to 4 Years of Exposure.

BACKGROUND: Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile. OBJECTIVE: We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program. METHODS: Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed. RESULTS: Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 103/mm3 before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1]). CONCLUSIONS: This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.] CLINICAL TRIAL REGISTRATION: NCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026).

Abrocitinib is an approved treatment for people with moderate or severe atopic dermatitis, also known as AD or atopic eczema. Abrocitinib is a tablet that is taken by mouth once a day. This safety analysis looked at the side effects of treatment in a large group of adults and adolescents with moderate or severe AD who took abrocitinib up to a maximum of almost 4 years. This analysis also looked at which people were more likely to have certain side effects after taking abrocitinib. The results from this analysis were similar to those of previous safety analyses with abrocitinib, with no new side effects. Infections such as shingles, pneumonia, or herpes simplex can occur during treatment with abrocitinib. Shingles was more likely to occur in people who previously had shingles before taking abrocitinib, or who took the higher dose of abrocitinib (200 mg), or were 65 years of age or older, or had certain blood test results, or lived in Asia. People who are 65 years of age or older and took abrocitinib were more likely to develop some types of cancer, have certain abnormal blood test results, or develop blood clots in the veins than people with AD who were younger and took abrocitinib. Current or former smokers with AD who took abrocitinib were more likely to develop skin cancer (but not melanoma) than people with AD who took abrocitinib but have never smoked. This analysis further shows that abrocitinib had manageable safety in patients with moderate-to-severe AD. Video abstract: Integrated safety update of abrocitinib in 3802 patients with moderate-to-severe atopic dermatitis: data from more than 5200 patient-years with up to 4 years of exposure (MP4 63720 KB).

Understanding treatment patterns and patient-reported outcomes associated with the use of authorized generics and corresponding independent generics across multiple therapeutic areas.

OBJECTIVES: To assess patient characteristics, treatment patterns, and patient-reported outcomes (PROs) associated with authorized generics (AGs) and independent generics (IGs) use. METHODS: Prescription claims and National Health and Wellness Survey (NHWS) data were linked. Adults with billable national drug code (AG or IG), NHWS completion from June 2015 to July 2019, AG or IG on-hand at NHWS completion, and continuous insurance eligibility in 12 months pre- and post-NHWS completion were included. To be included, all unique medication formulations had to have at least one AG and one IG observation. PRO index date was NHWS completion; claims index date was defined as the first prescription claim identified during the 180-day period prior to NHWS completion for the same active ingredient and formulation type that was on-hand at NHWS completion. RESULTS: Patients (N = 20,229; 17.2% AG users) in six therapeutic areas (attention deficit-hyperactivity disorder [ADHD], antidepressants, beta blockers [BBs], calcium channel blockers [CCBs], statins, and thyroid) were included. Generally, AG (vs. IG) users were younger and differed in regional access and insurance type (all, p < .05). In multivariable analysis, significant differences were observed for presenteeism and overall work impairment (BBs), healthcare provider visits (BBs), and indirect costs (thyroid) (all, p < .05). AG and IG users differed in persistence (ADHD and statins; both, p < .05) and switch (BBs and CCBs; both, p < .01) rates. CONCLUSIONS: PRO differences were often small in magnitude and varied by therapeutic area. The impact of switching should consider observed PRO differences, patient preferences, and market availability of AG and IG alternatives.

Retrospective Database Analysis to Explore Patterns and Economic Burden of Switchback to Brand After Generic or Authorized Generic Utilization.

Background: Despite demonstration of bioequivalence of generics to brands and the potential for reduced costs, some patients switch back from a generic to the brand. A prior retrospective analysis suggested that this switchback rate may be lower among patients that had initially switched to authorized generics (AG), often both produced and marketed by the brand company, compared to those initially switched to another generic. Objective: Explore switching patterns of brands, AGs, and generics, switchback rates, and the potential impact of switchbacks on healthcare costs. Methods: An analysis of the Pharmetrics Plus™ database (2007-2019), a United States (US) payer administrative database, was conducted to examine the use of Upjohn medications available as AGs across multiple therapeutic areas. Patients initiating treatment with brand medication in the 6 months prior to generic market entry were identified and switch rates to generics and AGs, as well as switchback rates, were evaluated. Costs were descriptively compared between patients who switched back to brand and those who remained on any generic. Results: Across 14 brand medications, more than half of the patients initiating treatment with the brand medication were switched to a generic. Generally, switching to AG, which ranged from 0.5 to 39.6%, was lower than switching to non-AG generics (16.7-79.9%). The comparison of switchback rates from AGs to brand and non-AGs to brand showed similar results (AG:1.3-7.5%; non-AG:1.4-12.9%); however, the most substantial differences were observed where non-AG switchbacks were higher. Patients that switched back to brand remained on AG or generic for an average of 1-3 months (32-88 days). The analysis showed a tendency towards increased medical costs in the period immediately preceding switchback for all medications except sildenafil in both indications (erectile dysfunction and pulmonary arterial hypertension). For the remaining medications, medical costs ranged from $63 to $1544 higher for the switchback population. Pharmacy costs similarly tended to be higher for patients who had a switchback, with the exception of sildenafil for pulmonary arterial hypertension and sirolimus. Conclusion: Patients receiving a brand medication are likely to be switched to a generic upon market availability. Some patients switch back to the brand medication, usually within 1-3 months; this may be associated with increased medical costs. Additional research is needed to understand switching, its potential disruption to patients, and the role of brands, generics, and AGs.

Lessons from mass vaccination response to meningococcal B outbreaks at US universities.

College students in the United States are at an increased risk for meningococcal serogroup B disease or MenB, which causes the majority of invasive meningococcal disease in the country among adolescents and young adults (62%) and also across all age groups (36%) as of 2018. Approximately one-third of MenB cases among college students occur during campus outbreaks, which trigger substantial public health concern and costs associated with conducting rapid mass vaccination campaigns in an emergency setting. Eleven US college outbreaks of MenB disease have occurred since the initial licensure and recommendation of two MenB vaccines in 2014/2015; both vaccines have been used as part of outbreak responses on campuses, but vaccine coverage and multidose series completion among the general adolescent population are very low (approximately 17% of 17-year-olds in the United States received ≥1 dose in 2018). This review recounts shifts in US meningococcal outbreak epidemiology, lessons from immunogenicity evaluations of MenB vaccines with outbreak strains, and recent college outbreak experiences and mass vaccination responses. The challenges of reactive MenB outbreak containment and potential benefits of preventive immunization of US adolescents are also considered.

Meningococcal vaccination: a discussion with all adolescents, whether college-bound or not.

Introduction: Adolescents and young adults are the primary reservoirs and transmitters of meningococci. In the US, meningococcal serogroup B (MenB) disease predominates over A, C, W, and Y; ACIP-recommended MenACWY and MenB vaccines are available. We investigated invasive meningococcal disease (IMD) burden and vaccination among non-college adolescents.Methods: IMD incidence by college attendance status and vaccination rates were analyzed using publicly available surveillance data.Results: 64/158 IMD cases occurred in non-college 18-24-year-olds during 2015-2017. Among non-college cases, the MenACWY vaccination rates were 38%-57% vs 90%-100% among college cases when vaccination status was known; MenB vaccination was 0% vs 0%-7%, respectively. In 2018, 17.2% of all 17-year-olds received ≥1 dose of multidose MenB vaccines; ≤50% completed the series.Conclusion: Meningococcal vaccination is emphasized for college-bound adolescents, but non-college adolescents bear much of the disease burden. Low vaccine receipt preserves their risk, underscoring the need to protect all adolescents through vaccination.

Concomitant administration of meningococcal vaccines with other vaccines in adolescents and adults: a review of available evidence.

Invasive meningococcal disease (IMD), a rapidly progressing and potentially fatal illness, disproportionately affects adolescents and young adults. While IMD is best prevented by vaccination, vaccine uptake in these groups is low. An evidence-based understanding of the safety and effectiveness of concomitant vaccination of meningococcal vaccines, including the newer MenB protein vaccines and the more established MenACWY conjugate vaccines, with other vaccines recommended for adolescents and young adults may help maximize vaccination opportunities. We identified 21 studies assessing concomitant administration of meningococcal vaccines with other vaccines in adolescents and adults. Although studies varied in methodology, concomitant administration generally did not affect immunogenicity of the meningococcal or coadministered vaccines. In some cases, reactogenicity increased following concomitant administration, but no definitive safety concerns were raised. In general, data suggest that meningococcal vaccines can be safely and effectively coadministered with other vaccines.