Biologic-naive patients who were HLA-C*06:02 positive and PsA negative exhibited a significantly poorer response to adalimumab at 12 months.

HLA-C*06:02 status is a predictive biomarker that influences response to adalimumab and ustekinumab in patients with psoriasis, according to a study published in The Journal of Allergy and Clinical Immunology.

The investigators sought to explore whether HLA-C*06:02, which is the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologic agents — the antitumor necrosis factor alpha adalimumab and the anti-interleukin-12/23 ustekinumab.

The prospective, observational study used information from participants in a national psoriasis registry. All participants were >16 years of age and were enrolled in the Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) study and the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR). BSTOP was conducted across 60 UK dermatology centers that include biologic sample collection.

 BADBIR is a pharmacovigilance register that has recruited >16,000 patients with psoriasis from the United Kingdom and Ireland who are receiving systemic conventional or biologic therapy. Longitudinal treatment and response observations, along with detailed clinical data, are included in BADBIR.

HLA alleles were imputed from genome-wide genotype data for a total of 1326 patients for whom 90% reduction in Psoriasis Area and Severity Index 90 response status was observed following 3, 6, or 12 months of treatment. Regression models of Psoriasis Area and Severity Index 90 response were developed that examined the interaction between HLA-C*06:02 and the type of drug (adalimumab or ustekinumab) administered, taking into consideration any potential confounding variables.

Results of the study demonstrated that those who were negative for HLA-C*06:02 were significantly more likely to respond to adalimumab therapy than to ustekinumab therapy at all time points, with the strongest response at 6 months (odds ratio [OR] 2.95; P =5.85×10^-7). In fact, this difference was greater in patients who were negative for HLA-C*06:02 and had psoriatic arthritis (OR 5.98; P =6.89×10^-5).

Those who had never taken biologic drugs and were positive for HLA-C*06:02 and negative for psoriatic arthritis exhibited a significantly poorer response to adalimumab at 12 months (OR 0.31; P =3.42×10^-4). Results from the HLA-wide analysis were consistent with HLA-C*06:02 itself being the primary effect allele contributing to patients’ biologic responses. This role still warrants exploration in larger samples, however, to fully investigate the possible role played by other alleles.

The researchers concluded that HLA-C*06:02 status might help inform optimal selection of first-line biologic therapy for patients with severe psoriasis.

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Reference

Dand N, Duckworth M, Baudry D, et al; BADBIR study group, the BSTOP study group and the PSORT consortium. HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis [published online December 19, 2018]. J Allergy Clin Immunol. doi: 10.1016/j.jaci.2018.11.038

Obesity is an independent risk factor for development of psoriasis and is associated with a worse prognosis.

Psoriasis and obesity have a complex interrelationship. Obesity is a common comorbidity in patients with psoriasis and observational studies initially pointed to a greater likelihood of obesity in these patients, suggesting it might be a risk factor for the development of psoriasis.

Carrying excess weight both exacerbates the manifestations of psoriasis and interferes with treatment;¹ weight loss is associated with an improvement in symptoms.¹ These factors point to an important link between the two diseases, although they do not necessarily share a common mechanism. As Stephen M. Schleicher, MD, director of the DermDOX Center for Dermatology in Hazleton, Pennsylvania, explained to Dermatology Advisor, psoriasis is an inflammatory process linked to immune dysfunction, while obesity has multiple origins.

Obesity, as measured by body mass index (BMI) [results in an] increased [risk] for developing psoriasis,” Dr Schleicher said, adding that “independent of BMI, there is a higher risk for developing psoriasis with weight gain for both males and females.” Results from the HUNT study, which prospectively examined data from 33,734 people in the general population in Norway, found that long-term increases in body weight of even 1 standard deviation substantially increased the risk for psoriasis and that obesity and large waist circumference doubled the risk.²

Possible Linked Mechanisms

Psoriasis is believed to be caused by a perfect storm of genetics, immune dysfunction, and environmental triggers. While it has been linked to multiple features of metabolic syndrome — including dyslipidemia, insulin resistance, diabetes, and obesity — obesity in particular may influence the development and expression of psoriasis as a direct result of inflammation. Current theory points to an important inflammatory role of visceral fat produced by adipose tissues, in which cytokines ([tumor necrosis factor] TNF-α, [interleukin] IL-6, IL-17) and adipokines (adiponectin, omentin, chemerin) contribute in multiple ways to the development of psoriasis, as well as metabolic syndrome.

Obesity is an independent risk factor for the development of psoriasis and is associated with a worse prognosis.⁴ In a commentary linked to the HUNT study, Gisondi and Girolomoni³ suggested that a disequilibrium of pro- and anti-inflammatory cytokines in obese individuals creates a state of chronic low-grade inflammation, which could create an opportunity for psoriasis to develop de novo or worsen in people who have already been diagnosed with psoriasis. While a number of studies have linked the presence of psoriasis to a greater risk for metabolic syndrome,^4,5 whether or not psoriasis increases the risk for obesity is not as clear. In a 2016 review, Chirocozzi, et al⁴ first mentioned the possibility of a bidirectional mechanism when they suggested that “psoriasis-signature proinflammatory cytokines may alter lipid metabolism, enhancing the risk of adiposity…” Further investigation is needed to confirm this.

The Impact of Obesity on Psoriasis Management

In addition to the effects of increased BMI and waist circumference on the risk for developing psoriasis, actual excess weight also complicates treatment. “Certain therapies for psoriasis (such as cyclosporine and ustekinumab) are dosed based on weight,” Dr Schleicher explained, which may contribute to poor response in some patients. Takeshita, et al⁶ reported in 2017 that responses to fixed-dose biologic therapies such as adalimumab, etanercept, and ustekinumab were reduced in obese patients, while responses to weight-based doses of infliximab were not affected. The investigators suggested that current regimens of fixed-dose biologic agents may be insufficient to adequately treat psoriasis in patients who are overweight or obese, while weight reduction may improve response to the current dose.

Also complicating treatment is a 2-fold higher risk for developing non-alcoholic fatty liver disease (NAFLD) associated with obesity in patients with plaque psoriasis.¹ “Obese individuals are at greater risk for developing cirrhosis when treated with methotrexate,” Dr Schleicher said, noting that the risk was significant enough to warrant avoiding methotrexate therapy in patients who are obese. “Weight loss is also listed as an AE [adverse event] for apremilast,” he pointed out, “although many obese patients with psoriasis view this in a positive light.”

Another important factor in the relationship between psoriasis and obesity is that increased BMI compounds the cardiovascular risks posed by either psoriasis or obesity alone.¹ “Obesity is linked to metabolic syndrome characterized by hypertension, elevated lipids, and insulin resistance. All of these factors contribute to increased morbidity,” Dr Schleicher said, suggesting that clinicians should encourage weight loss in patients who are overweight at clinic visits.

Treatment Strategies

Weight reduction is believed to reduce psoriasis severity and may have indirect benefits through improvement of diseases contributing to metabolic syndrome.⁴ “Excess weight contributes to other comorbidities associated with psoriasis,” Dr Schleicher observed. “Obese patients with psoriasis are urged to achieve and maintain a more ideal body weight,” he said, which is best accomplished by reducing caloric intake and alcohol consumption.

Chirocozzi, el al⁴ also suggested that designing treatment strategies aimed at balancing pro- and anti-inflammatory adipokine levels in patients with psoriasis who are obese could benefit both conditions and reduce further complications of metabolic syndrome.

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References

1. Jensen P, Skov L. Psoriasis and obesity. Dermatology. 2016;232:633-639.

2. Snekvik I, Smith CH, Nilsen TIL, et al. Obesity, waist circumference, weight change, and risk of incident psoriasis: perspective data from the HUNT study. J Invest Dermatol. 2017;137:2484-2490.

3. Gisondi P, Girolomoni G. The multifaceted association between psoriasis and obesity. Br J Dermatol. 2019;180:24.

5. Owczarczyk-Saczonek A, Placek W. Compounds of psoriasis with obesity and overweight. Postepy Hig Med Dosw (Online). 2017;71:761-772.

4. Chiricozzi A, Raimondo A, Lembo S, et al. Crosstalk between skin inflammation and adipose tissue-derived products: pathogenic evidence linking psoriasis to increased adiposity. Expert Rev Clin Immunol. 2016;12:1299-1308.

6. Takeshita J, Grewal S, Langan SM Et al. Psoriasis and comorbid diseases: Implications for management. J Am Acad Dermatol 2017;76:393-403.

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The median total charges submitted to Medicare increased, but there was not a significant increase in the actual amount paid from Medicare.

Trends in Medicare payments to dermatologists may be affecting practice patterns and reducing patient access, according to a retrospective study published in JAMA Dermatology.

Researchers analyzed records from the Medicare Provider Utilization and Payment Data: Physician and Other Supplier data set to assess changes in Medicare utilization by dermatologists from 2012 to 2015. Medicare providers, location of providers, number of services performed, unique treatment beneficiaries, submitted Medicare charges, and actual Medicare payments were characterized by either drug services or medical services.

Results indicated that the number of dermatologists utilizing Medicare increased by 6.2% over the 3-year time frame while the median number of services per clinician (P =.98) and the median number of unique beneficiaries (P =.80) remained the same. The median total charges submitted to Medicare increased (P <.001), but there was not a significant increase in the actual amount paid from Medicare (P =.47).

In regards to drug services, there was a significant increase in the median number of drug services provided, median number of unique beneficiaries, amount of charges submitted to Medicare, and the amount paid from Medicare (P <.001, for all). In regards to medical services, there was only a significant increase in the median number of beneficiaries (P =.01) and amount of submitted charges to Medicare (P <.001). According to the Gini coefficient, there was a moderate and stable level of inequality for the total amount paid by Medicare with urban and metropolitan areas receiving more payments.

The limitations of this study include the limited time frame, the potential of insurance compensation, and possible billing by physician extenders.

In conclusion, these trends may affect patients’ access to dermatologists if providers opt out of Medicare due to lack of payments. “[I]t is important to consider how Medicare payments can be optimized to maintain dermatologist access across the entire Medicare population,” the study authors suggested. 

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Reference

Ya J, Ezaldein HH, Scott JF. Trends in Medicare utilization by dermatologists, 2012-2015 [published online December 19, 2018]. JAMA Dermatol. doi: 10.1001/jamadermatol.2018.4212

Desoximetasone with and without phone reminders was associated with clinical improvement in both psoriasis and atopic dermatitis.

Desoximetasone spray has demonstrated efficacy for treatment-resistant atopic dermatitis and psoriasis, according to a study recently published in the Journal of Cutaneous Medicine and Surgery.

This open-label, single-center study included 24 participants, 12 of whom had treatment-resistant atopic dermatitis and 12 of whom had treatment-resistant psoriasis. In each group, 6 participants were randomly assigned to desoximetasone 0.25% spray with phone reminders twice per day, and 6 were assigned to the spray without phone reminders. Baseline assessments included current medications and medical history. To assess severity of disease, the Pruritus Visual Analog Scale, Investigator’s Global Assessment, Psoriasis Area and Severity Index, Eczema Area and Severity Index, and Total Lesion Severity Score were used. Results from visit to visit were compared using paired t-tests, whereas variances between the 2 treatment groups were assessed using a Wilcoxon 2-sample test.

Desoximetasone with and without phone reminders was associated with clinical improvement in both psoriasis and atopic dermatitis. Statistically significant improvement was achieved among the psoriasis group with phone reminders, the psoriasis group without phone reminders in Total Lesion Severity Score and Pruritus Visual Analog Scale measures, and among those with atopic dermatitis in various assessments.

Limitations to this study included small sample size, a short time period of evaluation, and a lack of patient measures such as self-reported adherence.

The study researchers concluded that “[patients] with ‘treatment-resistant’ [psoriasis] and [atopic dermatitis] generally responded well to the use of desoximetasone spray in the trial setting. This may be due to better adherence in the study environment or patients’ preference for the spray vehicle. Patient reminders contributed to improved clinical outcomes in [psoriasis] and [atopic dermatitis] patients with ‘treatment-resistant’ disease.”

Disclosure: This project was funded by Taro Pharmaceuticals. Author SR Feldman reports financial associations with other pharmaceutical companies. For a full list of author disclosures, visit the reference.

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Reference

Hogue L, CardwellLA, Roach C, et al. Psoriasis and atopic dermatitis “resistant” to topical treatment responds rapidly to topical desoximetasone spray [published online December 17, 2018]. J Cutan Med Surg. doi:10.1177/1203475418818082

The rate of treatment success with tapinarof cream 1% applied twice daily was statistically significantly higher than the rate achieved with vehicle cream.

In adolescent and adult patients with atopic dermatitis (AD), treatment with tapinarof cream is both effective and well-tolerated, according to the results of a double-blind vehicle-controlled randomized phase 2 trial (ClinicalTrials.gov identifier: NCT02564055) conducted at 53 sites in the United States, Canada, and Japan between December 2015 and January 2017. Findings from the study were published in the Journal of the American Academy of Dermatology.

The investigators sought to evaluate the efficacy and safety of topical tapinarof cream (2 concentrations and 2 application frequencies) compared with vehicle in patients with AD. The participants were age 12 to 65, with AD body surface involvement of ≥5% to 35% and an Investigator’s Global Assessment score of ≥3 (ie, moderate or severe) at baseline.

The primary study end points included an Investigator’s Global Assessment score of clear or almost clear (ie, 0 or 1) and a minimum 2-grade improvement (ie, treatment success) at 12 weeks. Secondary end points included a ≥75% improvement in the Eczema Area and Severity Index score and a reduction in the numeric rating scale for itch from baseline.

At 12 weeks, rates of treatment success were 53% for a 1% concentration applied twice daily, 46% for a 1% concentration applied once daily, 37% for a 0.5% concentration applied twice daily, 34% for a 0.5% concentration applied once daily, 24% for twice-daily application of vehicle, and 28% for once-daily application of vehicle.

The rate of treatment success with tapinarof cream 1% applied twice daily was statistically significantly higher than the rate achieved with vehicle cream applied twice daily (53% vs 24%, respectively; 95% CI, 6.5%-48.1%). Treatment success was maintained for 4 weeks following the conclusion of tapinarof therapy.

The rate of treatment-emergent adverse events associated with the use of tapinarof cream was higher than that with vehicle cream (56% vs 41%, respectively), although all of the treatment-emergent adverse events reported were mild to moderate in intensity.

A major limitation of the study was the fact that the study population was relatively small, and thus larger confirmation trials are warranted.

The investigators concluded that tapinarof cream represents an important clinical advance in the development of topical medicine for the treatment of AD, with a unique mechanism of action that distinguishes this product from currently available topical therapies for AD.

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Reference

Peppers J, Paller AS, Maeda-Chubachi T, et al. A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis. J Am Acad Dermatol. 2019;80(1):89-98.e3. doi:10.1016/j.jaad.2018.06.047

Fixed-combination HP/TAZ lotion to manage moderate to severe plaque psoriasis was effective and superior to individual active ingredients.

A fixed-combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion to treat moderate to severe psoriasis is more effective than its individual active ingredients and is associated with rapid and significant changes in disease severity, according to study results published in Journal of Drugs in Dermatology.

The investigators of this study sought to determine the effectiveness of a unique fixed-combination HP/TAZ lotion for treating moderate to severe plaque psoriasis using validated alternative tools for measuring improvement in psoriasis severity.

The study included 212 patients with moderate to severe plaque psoriasis in a post hoc analysis; participants were randomly assigned 2:2:2:1 to receive HP/TAZ lotion, individual active ingredients (HP or TAZ), or vehicle only. Participants applied treatment once daily for 8 weeks and were followed for 4 weeks post-treatment.

The investigators used a composite Investigator Global Assessment and Body Surface Area (IGAxBSA) tool to assess efficacy outcomes, specifically changes in erythema, plaque elevation, and scaling from baseline to week 12. The primary study end point was mean change in IGAxBSA composite scores; additional end points were the time required to achieve 25% and 50% reduction in mean baseline IGAxBSA composite scores and the proportion of patients achieving ≥75% reduction in mean baseline IGAxBSA composite scores.

The study results showed HP/TAZ lotion was significantly superior to HP, TAZ, and vehicle at week 12 for reducing psoriasis symptoms. By week 8, participants treated with HP/TAZ lotion achieved a greater reduction in mean IGAxBSA composite scores vs participants treated with HP (63.5% vs 49.2%; P =.056), TAZ (63.5% vs 15.2%; P <.001) or vehicle alone (63.5% vs 11.9%; P <.001); this was sustained throughout the 4-week post-treatment follow-up period vs TAZ and vehicle (P <.001) and vs HP (P =.003).

Using HP/TAZ lotion, a 25% improvement in mean IGAxBSA composite scores was achieved within 1.9 weeks, and a 50% improvement in scores was achieved within 4.6 weeks. Participants receiving other treatment achieved a 25% reduction in scores within 3 weeks, and did not achieve a 50% reduction in scores over the course of the study. Of the sample treated with HP/TAZ lotion, 47.5% achieved ≥75% reduction in mean baseline IGAxBSA composite scores by week 8, which was sustained for 4 weeks following the treatment period.

Limitations to the study included a small sample size that only included patients with moderate to severe psoriasis with a baseline IGA score of ≥3 and baseline BSA involvement of 3% to 12%.

Fixed-combination HP/TAZ lotion to manage moderate to severe plaque psoriasis was effective and superior to individual active ingredients; HP/TAZ lotion was associated with significant and rapid improvement of psoriasis indicated by a 63.5% reduction in mean baseline IGAxBSA composite scores. The investigators suggest that the addition of tazarotene to the fixed combination importantly helped sustain post-treatment benefit.

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Reference

Stein Gold L, Bagel J, Lebwohl MG, Lin T, Martin G, Pillai R. Halobetasol and tazarotene: further defining the role of a unique fixed combination topical lotion in moderate-to-severe plaque psoriasis. J Drugs Dermatol. 2018;17(12):1290-1296.

For facial assessments, the investigators found a significant improvement in GAIS scores across all time points from baseline to week 12.

According to study results published in the Journal of Drugs in Dermatology, Melaclear® serum used on the face with sun protection can improve skin quality, prevent photoaging, and help fight signs of facial aging.

The investigators of this single-center, observational, open-label study sought to assess the effectiveness and safety of a new generation non-tyrosinase topical agent  to brighten facial skin and improve skin quality, as well as reduce signs of facial aging.

The study sample included 10 healthy women, aged 30 to 70 years, from Barcelona, Spain with moderate photodamage (hyperpigmentation, sunspots) and signs of facial aging. Participants applied topical Melaclear serum twice daily — once in the morning and once in the evening — to the face and neck, along with sun protection, for 12 weeks.

Efficacy and tolerability outcomes were assessed at 4, 8, and 12 weeks using standardized photographs, expert investigator grading, and tolerability assessments. Visual examination of the face and neck assessed skin quality parameters, including radiance, smoothness, pigmentation, erythema, pore size, clarity, brightness, skin tone, luminosity, and complexion. Changes in wrinkle severity, photodamage, and hyperpigmentation, as well as Dermatologic Quality of Life, were further assessed.

The primary study end point was overall improvement in skin quality measured using the Global Aesthetic Improvement Scale (GAIS). Secondary end points evaluated a change in pigmentation via the modified Melasma Area and Severity Index (mMASI) and in Skin Quality Assessments. Treatment-related adverse events were reported throughout the study as safety outcomes, and tolerability was evaluated for the presence of stinging, burning, dryness, scaling, edema, and erythema.

For facial assessments, the investigators found a significant improvement in GAIS scores across all time points from baseline to week 12 (GAIS 1.3±0.6; P =.01), and a significant reduction in mMASI scores from week 8 onward. All investigator assessments of facial skin quality, photoaging, and hyperpigmentation showed significant improvement from baseline to week 12. Evaluated by the participants, GAIS scores and skin quality assessments improved from baseline to end of the study, and quality of life scores improved by 1.7 points; the average patient satisfaction rating for overall treatment efficacy was 2, or “satisfied.”

Investigator and participant assessments for the neck indicated mild improvement in skin quality but were not statistically significant at any time point. No adverse or unexpected events were reported over the course of study, and Melaclear serum was well tolerated.

Limitations to the study included a small sample size and short follow-up period. In addition, the mMASI test was not developed for the neck area and may not be optimal to measure changes in neck pigmentation.

After 3 months of treatment, Melaclear serum used twice daily with sun protection was well-tolerated and effective for improvement of facial skin quality and for the reduction of appearance of photodamage and hyperpigmentation in women with signs of facial aging. Future studies should compare Melaclear serum with traditional therapies in a larger sample of patients.

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Reference

Serra M, Krista B, Narda M, Granger C, Sadick N. Brightening and improvement of facial skin quality in healthy female subjects with moderate hyperpigmentation or dark spots and moderate facial aging. J Drugs Dermatol. 2018;17(12):1310-1315.

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Investigators obtained and evaluated digital dermoscopic images of 136 histopathologically confirmed cases of cutaneous smooth muscle neoplasms.

Dermoscopy may be helpful as an adjuvant diagnostic tool for piloleiomyiomas (PL), according to research published in the Journal of the European Academy of Dermatology and Venereology. Dermoscopic studies associated with angioleiomyomas (AL) and leiomyosarcomas (LS) were more variable and less reliable.

Investigators obtained and evaluated digital dermoscopic images of 136 histopathologically confirmed cases of cutaneous smooth muscle neoplasms (PL, n=114; AL, n=13; LS, n=9) from 10 hospitals in Spain, Austria, and Italy. Data included age and sex of patients, anatomical location of the lesions, the presence of pain, and the clinical diagnosis or differential diagnoses before excision.

Upon dermoscopy, the histologic pattern of a symmetric, total delicate pigment network with the variable presence of multiple hypopigmented areas in a painful lesion most commonly associated with PL was found in 69.3% of PL cases (79 out of 114 lesions) and not observed in any cases of AL and LS. PL was painful in 78.1% of the cases. Patients with PL presented with a delicate pigment network located on the whole lesion. Symmetric, pink-reddish tumors with vascular and white structures were observed in 46.2% of AL, as well as in 3.5% of PL and in 22.2% of LS. Asymmetric, multilobulated tumor with linear-irregular or polymorphic-atypical vessels and white structures were found most commonly in LS (44.4%) and were associated with malignant tumors such as melanoma.

Several limitations of this study exist. It was retrospective in nature, and the histopathologic diagnoses were unconfirmed by a second pathologist. Sensitivity and specificity of dermoscopic structure or pattern for the diagnosis of smooth muscle tumors were not analyzed.

The authors concluded that dermoscopy can help in diagnosing AL and LS, but because they can simulate more serious lesions, they should continue to be studied histopathologically.

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Reference

Zaballos P, del Pozo LJ, Argenziano G, et al. Dermoscopy of cutaneous smooth muscle neoplasms: a morphological study of 136 cases [published online December 6, 2018]. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.15392