February 14, 2019

The 2007 and 2008 shingles and varicella vaccination recommendations may have contributed to the declining herpes zoster hospitalization rates in some groups.

The 2007 and 2008 herpes zoster and varicella vaccination recommendations may have affected the declining herpes zoster hospitalization rates in targeted age groups, according to a study published in Vaccine.

The Centers for Disease Control and Prevention officially endorsed the 2005 recommendation from the Advisory Committee on Immunization Practices for the addition of a second booster dose at age 4 to 6 years in the varicella vaccine schedule, and the herpes zoster single-dose vaccine for people aged ³60 years, in 2007 and 2008, respectively. Currently, there are limited published data on the effect of the 2-dose varicella and single-dose herpes zoster vaccine recommendations on herpes zoster incidence in the United States. Therefore, this study examined trends in herpes zoster hospitalization rates and assessed the effect of both policy recommendations, using hospital discharge data.

Discharge data (2001-2015) were extracted to identify primary and secondary herpes zoster diagnoses from the Nationwide Inpatient Sample, which contains annual discharge data for a 20% sample of US hospitals and is the largest publicly available all-payer inpatient care database in the United States, containing roughly 8 million hospitalizations annually. Herpes zoster-associated hospitalization was defined by a first or second discharge diagnosis, indicated with specific International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), or ICD-10-CM codes. 

Annual total and age-specific herpes zoster hospitalization rates and average length of stay trends were examined. The average annual rates for the pre- and postzoster vaccination policy eras were compared (2001-2005 and 2012-2015, respectively). Researchers noted that the 2006 to 2011 period was treated as a transition period because of a vaccine supply shortage resulting from manufacturing issues. In addition, absolute change in herpes zoster hospitalizations was calculated.

Results suggested that the 2-dose varicella vaccination recommendation may have contributed to declining herpes zoster hospitalization rates among children (£14 years), and the 2008 herpes zoster vaccine may have also contributed to declining hospitalization rates for adults aged ³60 years. From 2001 to 2015, there were 400,651 herpes zoster hospitalizations, which accounted for 0.07% of all US hospitalizations during the study period. 

The number of herpes zoster hospitalizations increased in direct proportion with age: 0.07% in those aged 7 to 14 years, 0.06% in those aged 40 to 49 years, 0.07% in those aged 60 to 69 years, 0.12% in those aged 70 to 79 years, 0.16% among those aged 80+ years, and less than 0.05% in all other groups. In 2001, the annual incidence rate of herpes zoster hospitalizations was 8.6 per 100,000 population in the US and decreased to 6.8 per 100,000 population in 2015. Although there were steady increases in the overall rate of herpes zoster hospitalizations from 2001 to 2008, this significantly decreased between 2001 and 2015. 

Further, the largest decreases in herpes zoster hospitalization rates between 2001 and 2015 occurred in groups that were directly targeted by the 2007/2008 recommendations. The age-adjusted average annual change in hospital rates from pre- vs post-herpes zoster vaccine period was 1.9 fewer hospitalizations per 100,000 population (P <.001).

Overall, the study authors concluded, “The recent licensure of a new 2-dose recombinant sub-unit herpes zoster vaccine and expansion of the recommended age of herpes zoster vaccination to ³50 years should have significant [effect] in the [US] on vaccination coverage and herpes zoster hospitalizations over time, and continued surveillance will be necessary to measure this [effect].”

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Reference

Pham MA, Bednarczyk RA, Becker ER, Orenstein WA, Omer SB. Trends in U.S. community hospitalizations due to herpes zoster: 2001-2015. Vaccine. 2019;37:882-888.

February 14, 2019

Nuzyra is designed to overcome tetracycline resistance and has broad-spectrum activity against Gram-positive, Gram-negative and atypical bacteria, and other drug-resistant strains.

Paratek announced the launch of Nuzyra (omadacycline) for the treatment of adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). It is the first once-daily antibiotic approved to treat CABP and ABSSSI that is available in both an intravenous (IV) and oral formulation.

Nuzyra, an aminomethylcycline (related to tetracycline antibiotics), is designed to overcome tetracycline resistance and has broad-spectrum activity against Gram-positive, Gram-negative and atypical bacteria, and other drug-resistant strains. Specifically, it is indicated for CABP caused by Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae and ABSSSI caused by S. aureus (methicillin-susceptible and -resistant isolates), S. lugdunensis, S. pyogenes, S. anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Enterococcus faecalis, Enterobacter cloacae, and K. pneumoniae.

Concurrently, Paratek announced the availability of 3 FDA-approved antimicrobial susceptibility tests (Hardy Diagnostics’ Omadacycline Susceptibility Disk [HardyDisk], Liofilchem Omadacycline MIC Test Strip, and Thermo Scientific Sensititre MIC Plate) to help guide clinicians toward the appropriate use of Nuzyra, and the KEYSTONE Surveillance Program, which provides access to current antimicrobial surveillance susceptibility data.

Nuzyra is available as 150mg strength tablets in 6-, 14-, and 16-count blisters, and as a 100mg lyophilized powder for IV infusion (after reconstitution and dilution) in single-dose vials.

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For more information call (833) 727-2835 or visit Nuzyra.com.

February 13, 2019

Omadacycline is noninferior to moxifloxacin for community-acquired bacterial pneumonia and noninferior to linezolid for acute bacterial skin infections.

HealthDay News — Omadacycline is noninferior to moxifloxacin for community-acquired bacterial pneumonia and noninferior to linezolid for acute bacterial skin infections, according to two studies published in the Feb. 7 issue of the New England Journal of Medicine.

Roman Stets, M.D., Ph.D., from the City Clinical Hospital in Zaporizhzhia, Ukraine, and colleagues randomly assigned adults with community-acquired bacterial pneumonia to receive omadacycline (386 patients) or moxifloxacin (388 patients), with a total treatment duration of seven to 14 days. The researchers found that omadacycline was noninferior to moxifloxacin for early clinical response (81.1 and 82.7 percent, respectively; difference, −1.6 percentage points; 95 percent confidence interval, −7.1 to 3.8). Omadacycline was also noninferior for the posttreatment evaluation rates of investigator-assessed clinical response (87.6 and 85.1 percent, respectively; difference, 2.5 percentage points; 95 percent confidence interval, −2.4 to 7.4).

William O’Riordan, M.D., from eStudySite in San Diego, and colleagues randomly assigned adults with acute bacterial skin and skin-structure infections to omadacycline (316 patients) or linezolid (311 patients), with total treatment duration of seven to 14 days. The researchers found that omadacycline was noninferior to linezolid in the modified intention-to-treat analysis with respect to early clinical response (84.8 and 85.5 percent, respectively; difference, −0.7 percentage points; 95 percent confidence interval, −6.3 to 4.9). With respect to investigator-assessed clinical response at the posttreatment evaluation, omadacycline was also noninferior to linezolid (86.1 and 83.6 percent, respectively; difference, 2.5 percentage points; 95 percent confidence interval, −3.2 to 8.2).

“Well designed clinical trials of omadacycline for the treatment of infections caused by multiple-drug-resistant gram-negative pathogens are needed to determine its real value as an antibacterial agent,” write the authors of an accompanying editorial.

Both studies were funded by Paratek, the manufacturer of omadacycline.

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Abstract/Full Text – Stets (subscription or payment may be required)
Abstract/Full Text – O’Riordan (subscription or payment may be required)
Editorial (subscription or payment may be required)

February 13, 2019

These findings indicate age-specific treatment approaches would likely benefit patients with atopic dermatitis.

Age-specific treatment modalities may be more beneficial for patients with atopic dermatitis (AD) across the life span, according to research that explored changes in the molecular profiles of people with moderate to severe AD. The findings were published in the Journal of Allergy and Clinical Immunology.

Researchers examined age-specific changes in blood and lesional/non-lesional tissues from patients with moderate to severe AD (n=246) and age-matched, healthy controls (n=72) via Singulex, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry. Participants were categorized into 18-40, 41-60, and 61+ age groups for analysis.

Although disease severity, as measured by SCORing Atopic Dermatitis (SCORAD), was similar across the age groups with AD (mean: ∼60; P =.873), dendritic cell infiltrates (CD1b+, FcεRI+; P <.05) decreased with age. Measures of T_H2 (IL-5, IL-13, CCL13, CCL18, CCL26) decreased significantly with age in participants with AD, but increased with age in controls. T_H22-secreted IL-22 also decreased with age in participants with AD only (P <.05), while T_H1- (IFN-γ, IL-12/23p40, STAT1, CXCL9; P <.05 for CXCL9) and T_H17-related markers (IL-17A, IL-20; P <.05 for IL-20) increased with age in both controls and patients with AD. 

Significant increases in terminal differentiation measures were observed in older participants with AD (LOR, FLG; P <.05), while decreases were observed in hyperplasia markers (epidermal thickness, K16, Ki67; P <.05 for K16) and S100As (S100A8; P <.01). Serum trends among participants with AD mimicked skin findings, with age-related T_H2 downregulation (CCL26; r=-0.32, P <.1) and T_H1 upregulation (IFN-γ; r=0.48, P <.01).

Study investigators concluded that these findings indicate age-specific treatment approaches would likely benefit patients with AD. “Therapeutic targeting with T_H2-, T_H22-, and T_H17/T_H1-specific antagonists are needed in order to understand the varying pathogenic roles of these axes in [atopic dermatitis]. Elucidating the differential patterns of immune skewing and barrier abnormalities among different [atopic dermatitis] phenotypes may be useful for developing personalized treatment approaches, especially in patients with recalcitrant [atopic dermatitis].”

Disclosures: Study authors disclose consulting fees and research funds received from Abbvie, Amgen, Anacor, AnaptysBio, Asana, Aventis, Baxter, BiogenIdec, Boehringer, Celgene, Dermira, Eli Lilly, Glenmark, Galderma, Innovaderm, Janssen, Kadmon, Kyowa, Leo Pharma, Mitsubishi Tanabe, Medimmune/Astra Zeneca, Novartis, Paraxel, Pfizer, Promius, Regeneron, Sanofi, Serono, Stiefel/GlaxoSmithKline, UCB, Vitae, and Xenoport.

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Reference

Zhou L, Leonard A, Pavel AB, et al. Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis [published online January 24, 2019]. J Allergy Clin Immunol. doi: 10.1016/j.jaci.2019.01.015

February 13, 2019

Data collection included socio-demographic variables, comorbidities, treatment-related clinical events, immunosuppressant usage, concomitant treatment, and more.

Patients with moderate to severe atopic dermatitis using immunosuppressant treatment experience unsatisfactory outcomes, frequently need systemic steroid rescue therapy, and report many associated adverse events, according to a study published in PLoS One.

Researchers in this retrospective cohort study used data from the Truven Health MarketScan database to analyze the impact immunosuppressant treatment has on patients with atopic dermatitis. All patients included in this study had a pre-index baseline period that lasted 6 months and a post-index follow-up period that lasted 12 months. All patients were categorized into either the immunosuppressant arm that included treatments of cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil or a control arm that excluded treatments of systemic immunosuppressants, systemic corticosteroids, or phototherapy. Data collection included socio-demographic variables, comorbidities, treatment-related clinical events, immunosuppressant usage, concomitant treatment, and adjustments in dose or type of immunosuppressant.

The study included 4204 patients using an immunosuppressant to treat atopic dermatitis who were matched with 4201 controls using another form of treatment. During the post-index follow-up period for patients in the immunosuppressant arm, 68.5% were non-persistent, 84.6% received concomitant treatment, 36.3% required dose escalation, 7.6% required additional immunosuppressants, and 2.8% switched immunosuppressants. Significantly more patients in the immunosuppressant arm had immunosuppressant-related clinical events, required hospitalization (P <.0001), required immunosuppressant-related monitoring tests (P <.001), and had higher levels of healthcare resource utilization and associated costs.

Limitations of this study include using medical claim codes as a basis for diagnosis, which could lead to misclassification of patients. Also, using retrospective data means a direct causal relationship cannot be proven.

The researchers concluded that their study “highlights the unmet need for more effective long-term therapies for atopic dermatitis with improved safety profiles and reduced monitoring requirements.”

Disclosures: This study was supported by Sanofi and Regeneron Pharmaceuticals, Inc. Please refer to the reference for a complete list of authors’ disclosures.

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Reference

Armstrong AW, Huang A, Wang L, et al. Real-world utilization patterns of systemic immunosuppressants among US adult patients with atopic dermatitis. PLoS One. 2019; 14(1):e0210517.

February 13, 2019

The FDA has announced a new plan to significantly modernize the regulation and oversight of dietary supplements.

The Food and Drug Administration (FDA) has announced a new plan to significantly modernize the regulation and oversight of dietary supplements, according to a statement released today. The new document will be the first update in over 25 years.

“I’ve personally benefited from the use of dietary supplements and, as a physician, recognize the benefits of certain supplements as a part of a comprehensive care plan,” said FDA Commissioner Scott Gottlieb, MD, in the statement. 

“It’s clear that the US Food and Drug Administration plays an important role in helping consumers make use of safe, high-quality dietary supplements while also protecting Americans from the potential dangers of products that don’t meet the agency’s standards for marketing.”

The dietary supplement industry is worth more than $40 billion; more than 50,000 supplement products are available to consumers. In contrast, when the original Dietary Supplement Health and Education Act (DSHEA) was passed, the industry was worth only $4 billion.

While DSHEA stipulates a number of requirements for the manufacture and label of dietary supplements, there are numerous loopholes through which so-called bad actors can “exploit the halo created by quality work of legitimate manufactures to…distribute and sell dangerous products that put consumers at risk.”

Dr Gottlieb added that one of the top goals of the new regulation is to ensure that consumers still have access to safe, well-manufactured, appropriately labeled products, while holding accountable those who do not comply with the laws.

“Legitimate industry benefits from a framework that inspires the confidence of consumers and providers. Patients benefit from products that meet high standards for quality,” Dr Gottlieb concluded.

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Reference

Statement from FDA Commissioner Scott Gottlieb, MD, on the agency’s new efforts to strengthen regulation of dietary supplements by modernizing and reforming FDA’s oversight [news release]. Silver Springs, MD: US Food and Drug Administration. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/UCM631065.htm. Published February 11, 2019. Accessed February 11, 2019.

February 12, 2019

Primary study outcomes were the development of alopecia areata in the cohort exposed to depression and the development of major depressive disorder in the cohort exposed to alopecia.

Major depressive disorder and alopecia areata have a strong bidirectional association, according to a study published in JAMA Dermatology.

The investigators of this population-based retrospective study sought to assess the bidirectional relationship of major depressive disorder and alopecia areata by establishing clinical temporality between these diseases.

The study investigators extracted data on approximately 12 million patients, aged 10 to 90 years, from a registry of general practices in the United Kingdom between January 1986 to May 2012. Risk for alopecia areata was assessed in a cohort of patients with incident major depressive disorder (n=405,339) and in a reference general population cohort (n=5,738,596). Risk for major depressive disorder was assessed in a cohort of patients with incident alopecia areata (n=6861) and in a reference general population cohort (n=6,137,342).

Primary study outcomes were the development of alopecia areata in the cohort exposed to depression and the development of major depressive disorder in the cohort exposed to alopecia.

Analyzing for risk of alopecia areata, 662 patients (0.2%) in the major depressive disorder cohort developed alopecia vs 6356 patients (0.1%) in the reference cohort. After adjusting for variables, a diagnosis of major depressive disorder was associated with increased risk of subsequently developing alopecia areata by 90% (hazard ratio [HR] 1.90; 95% CI, 1.67-2.15; P <.001). Demonstrated by lower incident ratios in both cohorts, antidepressant use showed a protective effect on the risk for alopecia areata (HR 0.57; 95% CI, 0.53-0.62; P <.001). Analyzing for risk of major depressive disorder, 513 patients (7.5%) in the alopecia areata cohort developed depression vs 405,102 patients (6.6%) in the reference cohort. After adjusting for variables, incident alopecia areata was associated with the risk of subsequently developing major depressive disorder by 34% (HR 1.34; 95% CI, 1.23-1.46; P <.001).

Limitations to study included the possible misclassification of major depressive disorder or alopecia areata and potential confounding factors not considered in the study.

Through reciprocal analysis of major depressive disorder and alopecia areata, the investigators discovered a bidirectional association between the 2 diseases in which the incidence of major depression imposed a significant risk for the subsequent development of alopecia areata. Additional evidence of these findings was supported by the association of antidepressant use with reduced alopecia risk compared with not taking antidepressants.

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Reference

Vallerand IA, Lewinson RT, Parsons LM, et al. Assessment of a bidirectional association between major depressive disorder and alopecia areata [published online January 16, 2019]. JAMA Dermatol. doi: 10.1001/jamadermatol.2018.4398

February 12, 2019

This systematic review was limited by literature that was lacking in survival analyses and inconsistent definitions of drug discontinuation across the literature.

A systematic review of the persistence and effectiveness of systemic therapies for psoriasis was limited by lack of evidence and incomplete reporting in clinical practice, according to research published in the British Journal of Dermatology.

Researchers utilized a literature search using Embase, MEDLINE, PubMed, and the Cochrane Library to identify studies that investigated persistence of therapy survival probabilities, mean or median time to therapy discontinuation, or the proportion of patients discontinuing treatment with acitretin, ciclosporin, fumaric acid esters (FAE), or methotrexate. The observational studies reporting on persistence (therapy duration or the proportion of patients discontinuing therapy during follow-up) or effectiveness (improvements in Psoriasis Area and Severity Index [PASI] or Physician Global Assessment [PGA]) were published between January 1, 2007, and November 1, 2017. Eight studies involving patients with moderate to severe psoriasis (N=4624) were included for analysis.

The probability of drug survival at 1 year was 23% for ciclosporin, 42% for acitretin, and 50% for methotrexate. Discontinuations due to adverse events were more common for FAE than for methotrexate (42-46% FAE vs 22% methotrexate). For discontinuations due to ineffectiveness, results were mixed (44% acitretin, 21% ciclosporin, and 33% methotrexate vs 22% FAE).

This systematic review was limited by literature that was lacking in survival analyses and inconsistent definitions of drug discontinuation across the literature.

Further research is needed to fully elucidate the persistence and effectiveness of acitretin, ciclosporin, FAE, and methotrexate; reviews should include a more robust definition to minimize risk of excluding studies that used different but relevant outcome definitions.

Disclosures: Multiple authors declare affiliations with the pharmaceutical industry. Please see original reference for authors’ disclosures.

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Reference

Mason KJ, Williams S, Yiu ZZN, et al. Persistence and effectiveness of non-biologic systemic therapies for moderate-severe psoriasis in adults: a systematic review [published online January 10, 2019]. Br J Dermatol. doi:10.1111/bjd.17625

February 11, 2019

Hidradenitis suppurativa has a significant negative impact on patient quality of life, which has been reported to be greater than that of atopic eczema and psoriasis.

The HIDRAdisk, a validated, visual, interactive electronic instrument completed together by patients and dermatologists, is an easy-to-use quality of life tool that could improve the management of hidradenitis suppurativa while also strengthening patient-clinician relationships, according to a study published in Journal of the European Academy of Dermatology and Venerology.

The chronic relapsing inflammatory skin disease hidradenitis suppurativa has a significant negative impact on patient quality of life, which has been reported to be greater than that of atopic eczema and psoriasis. This multicenter, longitudinal, observational study was designed to demonstrate the reliability, responsiveness, and overall validity of HIDRAdisk, a new tool designed to rapidly assess hidradenitis suppurativa burden with an intuitive graphic visual of the measurement outcome. Study authors compared HIDRAdisk with the following validated questionnaires: Work Productivity and Activity Impairment-General Health (WPAI:GH), Dermatology Life Quality Index (DLQI), and Skindex-16. They evaluated HIDRAdisk’s correlation with disease severity as measured by Hurley stage and Hidradenitis Suppurativa Physician Global Assessment (HS-PGA).

Participants were identified from 27 Italian dermatologic centers (N=140; mean age 34.9±11.0 years, 59% women). HIDRAdisk showed a statistically significant correlation with both Hurley stage (P =.0002) and HS-PGA (P =.0041), a good correlation with WPAI:GH (correlation coefficient: 0.5947), and a strong correlation with Skindex-16 (correlation coefficient: 0.7568) and DLQI (correlation coefficient: 0.6651). Very good internal consistency was demonstrated, with raw and standardized Cronbach coefficient values greater than >0.80 (0.894 and 0.898, respectively), correlation between the 10 items ranging between 0.308 and 0.673, good test-retest reliability (Spearman correlation coefficient, 0.8331; P <0.0001), and statistically significant responsiveness to changes.

Study investigators concluded that “the HIDRAdisk is a validated visual instrument administered on electronic devices, completed by patient and dermatologist together, making it an easy-to-use [quality of life] tool that, in our wishes, should be implemented soon in routine clinical practice to improve the management of [hidradenitis suppurativa], as well as strengthen the patient–physician relationship.”

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Reference

Peris K, Lo Schiavo A, Fabbrocini G, et al. HIDRAdisk: validation of an innovative visual tool to assess the burden of hidradenitis suppurativa [published online January 11, 2019]. J Eur Acad Dermatol Venereol. doi: 10.1111/jdv.15425

February 11, 2019

After 16 weeks of treatment with dupilumab, the median SCORAD score decreased 55%.

After 16 weeks of dupilumab usage, patients with atopic dermatitis saw improvements in quality of life, pruritus, and sleep, according to a study published in The British Journal of Dermatology.

Researchers of this prospective, observational study evaluated the efficacy of dupilumab on atopic comorbidities, symptoms, and immunoglobulin E levels in a real-life practice setting. Patients with moderate to severe atopic dermatitis completed ophthalmologic and ear nose and throat examinations, respiratory tests, SCOring Atopic Dermatitis (SCORAD) evaluations, visual analogue scales for sleep and pruritus, Investigator’s Global Assessment, Dermatology Life Quality Index, and immunoglobulin E concentration laboratory work.

Of the 19 patients included, 79% were men, and the mean age was 38 years old. Follow-up data were available for 18 patients. At baseline, 10 patients had >2 atopic comorbidities, including asthma, allergic rhinitis, allergic conjunctivitis, or food allergy. All but 1 patient had above normal immunoglobulin E levels; 10 patients had abnormal ophthalmologic evaluations; and 15 patients had seasonal rhinitis, perennial rhinitis, or rhinosinusitis. The median SCORAD was 49, the median visual analogue scale for pruritus was 5, and the median visual analogue for sleep loss was 3.

After 16 weeks of treatment with dupilumab, the median SCORAD score decreased 55% (P <.001), the median visual analogue scale for pruritus decreased significantly, the median visual analogue for sleep loss decreased significantly, and there was a significant decrease in median total immunoglobulin E levels (P =.001). Ophthalmologic examinations showed a worsening of conjunctivitis in 5 of the 10 patients. Ear nose and throat examinations indicated 10 patients showed stability and 4 showed improvements, and no significant changes were found in asthma control.

Limitations of this study included small sample size, short-term follow-ups, and the observational nature of the study.

In conclusion, “[d]upilumab reduces global severity, pruritus, sleep loss and improves quality of life in [atopic dermatitis] in real-life clinical practice.”

Disclosure: One author declared affiliation with Sanofi-Regeneron.

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Reference

Tauber M, Apoil PA, Richet C, et al. Effect of dupilumab on atopic manifestations in patients treated for atopic dermatitis in real life practice [published online January 11, 2019]. Br J Dermatol. doi: 10.1111/bjd.17629