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.

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

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

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

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

Although associations were consistent, a key limitation of this meta-analysis was that included studies were heterogeneous in several aspects.

Psoriasis is associated with elevated rates of all-cause mortality in a dose-response manner with disease severity, as well as with cause-specific mortality, according to the results published in the Journal of the American Academy of Dermatology.

With the recognition that an overview of the mortality risk associated with psoriasis is lacking, investigators conducted a meta-analysis and systematic review of risk for mortality among individuals with psoriasis. Included in the review were studies that reported all-cause or cause-specific mortality risk estimates in persons with psoriasis compared with the general population or with individuals free of psoriasis. A total of 12 studies were included in the analysis.

Among 6 studies of 299,374 patients with psoriasis, the pooled risk ratio (RR) for all-cause mortality was 1.21 (95% CI, 1.14-1.28; P <.001). Among 4 studies of 265,292 individuals with mild psoriasis, the pooled RR for all-cause mortality was 1.13 (95% CI, 1.09-1.16; P =.048). Among 6 studies of 36,428 patients with severe psoriasis, the pooled RR for all-cause mortality was 1.52 (95% CI, 1.35-1.72; P <.001).

Among 5 studies of 285,675 patients with psoriasis, the pooled RR for cardiovascular (CV) mortality was 1.15 (95% CI, 1.09-1.21; P =.02). Among 3 studies of 188,223 individuals with mild psoriasis, the pooled RR for CV mortality was 1.05 (95% CI, 0.92-1.20; P <.001). Among 4 studies of 17,317 patients with severe psoriasis, the pooled RR for CV mortality was 1.38 (95% CI, 1.09-1.74; P <.001).

With respect to non-CV causes of death, the risk for mortality from kidney and liver disease was highest. The RRs for mortality from kidney disease was 2.16 (95% CI, 1.37-3.40) among all patients with psoriasis, 2.20 (95% CI, 1.36-3.56) among individuals with mild psoriasis, and 3.54 (95% CI, 1.73-7.26) among those with severe psoriasis. In addition, the RRs for mortality from liver disease were 2.00 (95% CI, 1.34-2.99) among all patients with psoriasis, 4.26 (95% CI, 1.87-9.73) among individuals with mild psoriasis, and 3.97 (95% CI, 2.87-5.50) among those with severe psoriasis.

Moreover, the RRs for mortality from infections was 1.24 (95% CI, 1.14-1.31) among all patients with psoriasis, 1.41 (95% CI, 1.11-1.79) among individuals with mild psoriasis, and 1.58 (95% CI, 1.22-2.05) among those with severe psoriasis. Significantly increased mortality risk from neoplasms was also reported among patients with severe psoriasis, as well as from chronic lower respiratory disease in all individuals with psoriasis and in those with mild psoriasis.

The investigators concluded that on the basis of the findings from this study, patients with psoriasis, and in particular those with risk factors and severe disease, should receive appropriate screening and preventive interventions. Additional research is warranted to evaluate the effect of psoriasis on mortality independent of mortality risk factors, to elucidate cause-specific mortality among patients with psoriasis, and to establish the mechanisms that induce excess mortality.

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Reference

Dhana A, Yen H, Yen H, Cho E. All-cause and cause-specific mortality in psoriasis: a systematic review and meta-analysis [published online December 24, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.12.037

There was no correlation between itch visual analogue scale score and modified Psoriasis Area and Severity Index at baseline,

The use of calcipotriol 50 µg/g plus betamethasone dipropionate 0.5 mg/g cutaneous (Cal/BD) foam in patients with psoriasis provides quicker, more effective relief of itch compared with foam vehicle, with significant improvements in sleep and Dermatology Life Quality Index (DLQI) scores, according to a study published in the Journal of the European Academy of Dermatology and Venereology.

Investigators pooled data from 3 multicenter, randomized, parallel-group, blinded trials (ClinicalTrials.gov identifiers: NCT01536886 [phase 2], NCT01866163 [phase3], and NCT02132936 [phase 3]) and sought to assess the efficacy of topical fixed-dose combination therapy with Cal/BD on itch, itch-associated loss of sleep, and health-related quality of life vs foam vehicle among adults with mild to severe psoriasis.

Patients with visual analogue scale (VAS) scores >40 (range, 1-100) were evaluated. Study outcomes included the following: itch VAS score reduction >40, ≥70% improvement in itch (Itch70) or itch-related loss of sleep, 75% improvement in modified Psoriasis Area and Severity Index (excluding the head; mPASI75), and DLQI scores 0/1 through 4 weeks.

Among a total of 837 patients with itch measurements available, 37 had baseline itch VAS=0 and were excluded from the analysis. Of the remaining 800 patients (Cal/BD foam: n=610; foam vehicle: n=190), 484 had baseline itch VAS >40. No association was reported between itch VAS score and mPASI at baseline. In patients with baseline itch VAS >40, significantly more individuals attained itch VAS reduction >40 in the active treatment vs vehicle treatment group from day 5 on (day 5: 57.5% vs 40.2% [P <.05]; and week 4: 83.0% vs 45.8% [P <.001]).

Furthermore, significantly more Cal/BD foam-treated patients compared with foam vehicle-treated patients achieved Itch70 at day 3 (34.2% vs 22.5%; P <.05) through week 4 (79.3% vs 38.1%; P <.001). Among patients with baseline itch VAS >40 and sleep loss >20, improvements in itch-associated sleep loss were seen at week 1 and continued through 4 weeks, with itch-related improvements occurring before mPASI75 improvements.

Moreover, significant differences were observed in the proportion of Cal/BD foam-treated patients vs foam vehicle-treated patients with baseline DLQI >10 (n=172 vs n=50) attaining DLQI ≤1 (25.0% vs 4.0%; P =.001) and DLQI 0 (17.4% vs 2.0%, respectively; P =.006) at week 4.

Limitations of the current study include the lack of validated itch-related sleep loss measurement tools, as well as the need for different patient pools, the lower patient numbers available for the earlier times (ie, days 3 and 5), and the lack of pooled efficacy data that compared Cal/BD foam and its monocomponents.

The investigators concluded that this pooled analysis of patients with psoriasis demonstrated that Cal/BD foam provides more rapid, effective relief from itch than foam vehicle, and is linked to significant improvements in DLQI and sleep among this population.

Disclosures: LEO Pharma sponsored this study. Multiple authors disclosed affiliations with pharmaceutical companies. See the reference for complete disclosure information.

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Reference

Jalili A, Lebwohl M, Gold LS, et al. Itch relief in patients with psoriasis: effectiveness of calcipotriol plus betamethasone dipropionate foam [published December 6, 2018]. J Eur Acad Dermatol Venereol. doi: 10.1111/jdv.15393

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Your use of this website constitutes acceptance of Haymarket Media’s Privacy Policy and Terms & Conditions.

At week 4 of treatment, there was a common decrease in 2645 genes expressed in lesioned skin between risankizumab vs ustekinumab.

In patients with psoriasis, treatment with risankizumab is associated with changes in the molecular and histopathologic profiles of lesional skin after 4 weeks compared with ustekinumab, according to study results published in The Journal of Allergy and Clinical Immunology.

The investigators used the results of 2 studies – a phase 1 single-rising-dose study of risankizumab therapy (ClinicalTrials.gov identifier: NCT01577550) and a phase 2 study of risankizumab vs ustekinumab (ClinicalTrials.gov identifier: NCT02054481) –  to explore the similarities and differences in the histopathologic and molecular profiles of skin lesions from patients with psoriasis who had been treated with risankizumab or ustekinumab. Lesional skin biopsies obtained from patients with moderate to severe plaque psoriasis who had participated in the phase 1 (n=39) and phase 2 (n=60) studies were analyzed by histopathology, RNA-sequencing, and immunochemistry.

Results showed that treatment with risankizumab generated a rapid decrease in protein and transcriptomic biomarkers associated with the interleukin-23 (IL-23) pathway, with these reductions maintained through 8 weeks. At week 4, risankizumab decreased histopathologic biomarker expression, including K16, Ki67, CD3, CD11c, DC-LAMP, lipocalin-2, β-defensin 2, and S100A7.

Based on global histopathology scoring, 54% and 69% of patients who were treated with risankizumab 90 mg or risankizumab 180 mg, respectively, were graded as “excellent improvement,” compared with 29% of patients treated with ustekinumab. At 4 weeks, a common decrease in 2645 genes expressed in lesional skin was reported between risankizumab and ustekinumab, with a significant reduction observed in 2682 genes that are unique to risankizumab therapy.

Cytokine-induced transcriptome changes in key cell lines linked to psoriatic skin lesions— epidermal cells, keratinocytes, and monocytes—demonstrated a greater reduction in expression with risankizumab treatment compared with ustekinumab therapy.

The investigators concluded that the key pathways and types of cells identified in this study may help build hypotheses for the observed differences in efficacy reported according to biologic agent. Additional studies are warranted in order to further characterize the profile of risankizumab and compare the agent with ustekinumab and other biologics, thus enabling an improved understanding of the relationship of these agents to longer-term efficacy and the potential remission of psoriasis.

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Reference

Visvanathan S, Baum P, Vinisko R, et al. Psoriatic skin molecular and histopathological profiles following treatment with risankizumab versus ustekinumab [published online December 19, 2018]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2018.11.042