Cutis

Click here to view the articles published in March 2018.

Read more about A Peek at Our March 2018 Issue

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel

Click here to view the articles published in March 2018.

Publications

Publications

Article Type

Display Headline

A Peek at Our March 2018 Issue

Display Headline

A Peek at Our March 2018 Issue

Disallow All Ads

Content Gating

No Gating (article Unlocked/Free)

Alternative CME

Disqus Comments

Default

Gate On Date

Mon, 03/12/2018 - 09:30

Un-Gate On Date

Mon, 03/12/2018 - 09:30

Teaser Media

Product News: 03 2018

Article Type

Changed

Thu, 01/10/2019 - 13:49

Avène TriXera

Pierre Fabre Dermo-Cosmetique launches the Avène TriXera line consisting of 3 products. The TriXera Nutrition Nutri-fluid Cleanser gently cleanses and nourishes dry to very dry, sensitive skin. TriXera Nutrition Nutri-fluid Lotion offers 48-hour hydration for dry, sensitive skin. These nourishing effects last up to 6 hours after application. TriXera Nutrition Nutri-fluid Balm has a fluidlike texture and also offers 48-hour hydration. All 3 products contain Avène Thermal Spring Water to soothe and soften as it restores the skin’s balance, as well as evening primrose oil and soy extract to rebuild the skin barrier and prevent moisture loss. For more information, visit www.aveneusa.com.

CoolSculpting

Allergan plc announces US Food and Drug Administration clearance for the CoolSculpting treatment, a nonsurgical fat reduction technology for improved appearance of lax tissue in conjunction with submental fat. CoolSculpting works by gently cooling targeted fat cells in the body to induce natural, controlled elimination of fat cells without affecting surrounding tissue. For more information, visit www.coolsculpting.com.

Discoloration Defense

SkinCeuticals introduces Discoloration Defense, a high-potency treatment serum that prevents and corrects multiple types of discoloration. This product contains tranexamic acid and niacinamide for pigmentation, hepes for hydration, and kojic acid to brighten skin and help to reduce the amount of melanin produced. These ingredients work together to help break up existing melanin clusters, inhibit the formation of melanocytes, and deactivate inflammatory mediators. The serum provides a reduction in visible and stubborn pigmentation for a revitalized and even complexion with refined texture and clarity. For more information, visit www.skinceuticals.com.

Eskata

Aclaris Therapeutics, Inc, announces US Food and Drug Administration approval of Eskata (hydrogen peroxide) topical solution 40% for the treatment of raised seborrheic keratoses. This product is a targeted, in-office treatment applied directly to raised seborrheic keratoses using a penlike applicator. Clinical studies showed clearing of seborrheic keratoses after 2 treatments. Eskata is expected to be commercially available in the spring of 2018. For more information, visit www.eskata.com.

Ixifi

Pfizer Inc announces US Food and Drug Administration approval of Ixifi (infliximab-qbtx), a chimeric human-murine monoclonal antibody against tumor necrosis factor, as a biosimilar to Remicade (infliximab) for all eligible indications of the reference product. Ixifi has been approved in the United States as a treatment for rheumatoid arthritis, Crohn disease, ulcerative colitis, psoriatic arthritis, and plaque psoriasis. For more information, visit www.pfizer.com.

Jemdel

Ortho Dermatologics announces US Food and Drug Administration acceptance of the New Drug Application for Jemdel (halobetasol propionate 0.01%), a high-potency topical steroid for the treatment of plaque psoriasis with dosing for as long as 8 weeks. Jemdel has a Prescription Drug User Fee Act action date of October 5, 2018. For more information, visit www.ortho-dermatologics.com.

Retin-A Micro

Ortho Dermatologics announces that Retin-A Micro (tretinoin) gel microsphere 0.06%, a topical treatment for acne vulgaris, will be available commercially to health care professionals. The US Food and Drug Administration previously approved the Supplemental New Drug Application for this product in October 2017. Retin-A Micro features a microsponge delivery system technology that helps control the release of tretinoin and improves photostability, even when used in conjunction with benzoyl peroxide. This product also features a pump delivery system for controlled dispensing and consistent dosing. Caution should be exercised when prescribing to eczema patients and nursing mothers. For more information, visit www.retinamicro.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@frontlinemedcom.com.

Article PDF

Issue

Cutis - 101(3)

Publications

Page Number

228

Read more about Product News: 03 2018

Sections

Product Review

Article PDF

Article PDF

Avène TriXera

CoolSculpting

Discoloration Defense

Eskata

Ixifi

Jemdel

Retin-A Micro

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@frontlinemedcom.com.

Avène TriXera

CoolSculpting

Discoloration Defense

Eskata

Ixifi

Jemdel

Retin-A Micro

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@frontlinemedcom.com.

Issue

Cutis - 101(3)

Issue

Cutis - 101(3)

Page Number

228

Page Number

228

Publications

Publications

Article Type

Sections

Disallow All Ads

Content Gating

No Gating (article Unlocked/Free)

Alternative CME

Disqus Comments

Default

Gate On Date

Fri, 03/09/2018 - 08:45

Un-Gate On Date

Fri, 03/09/2018 - 08:45

Consolidated Pubs: Do Not Show Source Publication Logo

Use ProPublica

Teaser Media

Article PDF Media

Teambase ID

18000DFD.SIG

Cutis - 101(3S)

Read more about Cutis - 101(3S)

Pediatric Psoriasis: An Interview With Nanette B. Silverberg, MD

Article Type

Changed

Thu, 12/15/2022 - 14:51

Display Headline

Pediatric Psoriasis: An Interview With Nanette B. Silverberg, MD

What causes psoriasis in children?

Psoriasis is a chronic immune-mediated inflammatory skin disease with a genetic predisposition (Eichenfield et al). Similar to many inflammatory skin diseases, school-aged children have a greater predisposition before or in early adolescence. As with adult disease, pediatric psoriasis has a complex pathogenesis largely related to aberrant immune response to triggers such as infections (eg, streptococcal pharyngitis, perianal streptococcal dermatitis, upper respiratory viral infections), trauma (ie, Koebner phenomenon), stress, and obesity.

What are the emerging data and recommendations on screening for comorbidities in children with psoriasis?

Similar to psoriasis in adults, obesity and the metabolic syndrome are a true association with pediatric psoriasis that has been discussed in the literature (Eichenfield et al). Although many children with psoriasis have obesity as a potential comorbidity, the risk of cardiovascular comorbidities independent of obesity is high in pediatric psoriasis including elevated lipids, hypertension, polycystic ovaries, nonalcoholic liver disease, and elevated liver enzymes (Tollefson et al). Children with psoriasis have greater central obesity and adiposity, often accompanied by a family history of obesity. Interventions in this direction may be needed for long-term disease control and general health (Mercy and Paller). One target population is hospitalized children with psoriasis, particularly black and Hispanic children aged 0 to 9 years. This population has been identified to have a greater risk for obesity, diabetes mellitus, hypertension, arrhythmia, and valvular heart disease (Kwa et al). Therefore, it can be said that dermatologists can help to improve the overall health and lifestyle long-term in children with psoriasis.

Early-onset disease also is associated with greater risk for lifetime quality-of-life impairments including poor lifetime dermatology life quality index scores, depression and psoriasis-induced depression, social discrimination, sleep problems, and recreational drug usage (Kim et al).

How does psoriasis in children differ from adults?

Children have a variety of features that differ from adult disease. First, they are more likely to have an infectious trigger and therefore may have an identifiable treatable source. Second, they are more likely to have a family history of disease, with one-third having a relative with psoriasis, therefore, identifying the child at risk for long-standing disease. Third, children have far more visible head and neck disease, especially facial involvement including eyelids (Raychaudhuri and Gross), which increases the risk of bullying, social stigma, and negative effects on self-image. Of course, site is affected by age, and in infancy diaper dermatitis and inverse disease with maceration and overlying candidal diaper dermatitis can occur. Although children have less joint disease, it can be dramatic and crippling to the developing child.

What treatments are available for children?

In childhood, identification of precipitating infections such as streptococcal infection is ideal with appropriate intervention thereafter. Topical therapies are appropriate for limited disease with minimal disability; however, phototherapy and systemic agents can be used in pediatric psoriasis in extensive cases. Topical therapies can include corticosteroids, calcineurin inhibitors often used in sensitive skin such as the face and intertriginous areas, and calcipotriene (Eichenfield et al). Additional agents such as tar and salicylic acid can be used, with limitations on the latter due to risk for absorption in smaller children. Systemic interventions often are introduced after years of disease. A recent study identified practitioners with special interest in pediatric psoriasis and determined that systemic interventions were on average introduced 3 years after psoriasis was diagnosed and most commonly included methotrexate followed by etanercept, the latter having fewer gastrointestinal tract side effects. The panel found that usage of folic acid 6 days weekly minimized gastrointestinal tract side effects with methotrexate. Acitretin and cyclosporine were alternatives (Bronckers et al; Psoriasis Investigator Group [PsIG] of the Pediatric Dermatology Research Alliance and the European Working Group on Pediatric Psoriasis [EWGPP]).

Recently, dermatologists have become aware of the dramatic benefits of immune response modifiers and some biologics on pediatric psoriasis. In the setting of joint and skin involvement, I allow the rheumatologist to make the choice of agents for the child's best outcome. However, for pediatric and adolescent psoriasis, we now have 2 US Food and Drug Administration-approved agents and more rapid and thorough testing of adult-approved agents in children, with a hope of greater ability to modify disease course at a younger age, both now and in the future.

Which biologics are approved for the pediatric patient population?

Currently, in the United States 2 biologics have been approved: (1) etanercept, a fusion protein of tumor necrosis factor receptor extracellular domain linked to the Fc portion of human IgG, for moderate to severe plaque psoriasis in patients 4 years and older, and (2) ustekinumab, a human IgG1κ monoclonal antibody against the shared p40 subunit of the IL-12 and IL-23 cytokines, for moderate to severe plaque psoriasis in patients 12 years and older based on the encouraging data of the CADMUS trial (Kellen et al; Landells et al). In Europe, adalimumab has been approved as a first-line therapy in pediatric psoriasis (age ≥4 years), and etanercept (age ≥6 years) and ustekinumab (age ≥12 years) have been approved as second-line agents, all with grade A evidence, according to a recent Italian panel (Fortina et al). (A thorough review of the guidelines on screening, administration, and vaccination is available from Eichenfield et al.)

What treatments are in the pipeline?

In the United States we have clinical trials ongoing of adult-approved topical and immune response-modifying agents such as apremilast. These agents, as they become available and the data are gathered, will be added to what I refer to as our "pharmamentarium" of agents we can use to combat a difficult and disabling illness.

What gaps are there in the pediatric psoriasis research?

Currently, there is poor awareness that there is research for pediatric psoriasis, and there is a need for pediatric groups and the National Psoriasis Foundation to allow children, adolescents, and their families to know that clinical trials are available looking into newer, more targeted, and less immunosuppressive agents. There is new hope on the horizon!

What causes psoriasis in children?

What are the emerging data and recommendations on screening for comorbidities in children with psoriasis?

How does psoriasis in children differ from adults?

What treatments are available for children?

Which biologics are approved for the pediatric patient population?

What treatments are in the pipeline?

What gaps are there in the pediatric psoriasis research?

What causes psoriasis in children?

What are the emerging data and recommendations on screening for comorbidities in children with psoriasis?

How does psoriasis in children differ from adults?

What treatments are available for children?

Which biologics are approved for the pediatric patient population?

What treatments are in the pipeline?

What gaps are there in the pediatric psoriasis research?

Biologics and Systemic Therapies for Psoriasis: Treat the Patient, Not the Disease

Article Type

Changed

Thu, 12/15/2022 - 14:51

Display Headline

Biologics and Systemic Therapies for Psoriasis: Treat the Patient, Not the Disease

Author(s)

George Han, MD, PhD

What do patients need to know initially about psoriasis treatment?

It is important to set expectations with the patient based on the treatment selected, not only for patient satisfaction but to forge an enduring bond with the patient so he/she will trust you to guide the treatment plan if the first therapy does not work as well as anticipated. Because psoriasis is a longitudinal disease process, the patient-physician relationship should be, too. Certainly, these principles generally apply among all patient groups and demographics; however, one may take into account a few special circumstances when dealing with psoriasis. In a pediatric patient, I may try to see if topical therapy including calcipotriene can adequately treat the skin disease before pursuing systemic treatment. The rationale is 2-fold: (1) this patient would be committed to an extended period on immunomodulatory therapy if he/she truly requires it, and (2) some of the forms of psoriasis in children, such as guttate psoriasis, may be self-limited, so it is reasonable to see if it will persist before forging ahead with a long-term systemic medication. In patients with a recent history of cancer, I would likely choose an oral medication such as apremilast before a biologic; even though there are no real data to suggest biologics are associated with higher rates of solid-organ malignancy, most practitioners would err on the side of being more conservative. For patients with human immunodeficiency virus, the tendency is to use the agents with more data (eg, tumor necrosis factor α inhibitors) due to safety concerns with an immunomodulatory medication.

What are your go-to treatments?

I tend to be as aggressive as the patient wants to be with therapy. I regularly see patients in whom multiple systemic treatments have failed and a more creative regimen is needed, such as combining a biologic medication with an oral antipsoriatic treatment (eg, apremilast, acitretin). However, I do have patients with moderate to severe psoriasis who have not seen a dermatologist before. I do not find it necessary to have topical treatments fail before starting a biologic; after all, the sequelae of long-term topical steroid use are notable.

With the newer biologics on the market, such as the IL-17 and IL-23 inhibitors, the sky's the limit for psoriasis area and severity index clearance, but the true benefit is that these medications are much more targeted toward the pathogenesis of psoriasis. Unfortunately, we have to be mindful of insurance and formulary restrictions, but when faced with choosing a broad-acting immunomodulatory agent or a more specific/targeted immunomodulatory agent for an inflammatory disease, most dermatologists would choose the more targeted medication. The data support that the newer agents have better psoriasis area and severity index responses and a much greater proportion of clearance, but there is something to be said about biologics such as etanercept, adalimumab, and ustekinumab, which have been on the market for much longer and have shown durable response with a longer track record of safety and efficacy. Recent head-to-head comparisons can help guide treatment. For instance, patients who achieved suboptimal clearance on ustekinumab can safely and reasonably be switched to guselkumab based on the findings of the NAVIGATE study, which looked at this exact situation. More of these studies looking at specific prior treatment failures and improvement upon switching to a newer agent are needed to underscore the efficacy of these drugs and also to help argue for their placement on insurance formularies.

For a new patient with psoriasis, I will screen for psoriatic arthritis, look at involvement (eg, body surface area, individual plaque severity/thickness, locations such as scalp and extremities), and assess patient attitudes toward different treatments. Two patients with the exact same clinical appearance might have completely different strategies, one wanting to be as aggressive as possible to get rid of the psoriasis and the other not believing in systemic treatments and wanting to be as "natural" as possible.

For patients with only cutaneous involvement, the dosing frequency and efficacy of the newer IL-17 and IL-23 classes of medications are hard to beat. If a patient has notable psoriatic arthritis, I still tend to reach for a tumor necrosis factor α inhibitor first. For patients with limited involvement, especially those with scalp and/or palmoplantar psoriasis, I have found that apremilast works quite well. Apremilast, in general, would be a good first-step medication for patients wary of systemic therapy, and with its relatively benign side-effect profile, it has almost completely supplanted methotrexate in my practice. We also have a few newer topical medicines such as a calcipotriene 0.005%-betamethasone dipropionate 0.064% foam and a betamethasone dipropionate spray 0.05% that have proven useful, with more products in the pipeline.

How do you keep patients compliant with treatment?

Setting expectations is most important, and letting patients know what to expect from their first visit really helps to keep them satisfied with the plan and progress. Giving the patient a say in guiding the treatment and perhaps coming up with a rough treatment plan with a defined timeline also helps, such as starting with a topical regimen but moving on to an oral medicine if the topical does not work within 2 to 3 months, and then a biologic if oral therapy does not work well within 3 to 6 months. It is important not to push the patient to pursue a more aggressive therapy unless he/she wants to, otherwise the patient might not be compliant or may stop altogether.

What do you do if they refuse treatment?

If the patient is in your office, clearly he/she does want some help. Try to figure out what is at the root of the treatment refusal. Is the patient refusing topical steroids because he/she is afraid of them? Is the patient unable to stomach having to inject himself/herself? Finding the basis of their reticence may take more time, but we usually can find a mutually agreeable plan of action. Even if the first step is to watch and wait, you want the patient leaving your office knowing that if things do not progress as expected or get worse, they can have faith in you to come back and get more help.

What resources do you recommend to patients for more information?

The National Psoriasis Foundation is a great resource for patients. They have numerous outreach programs and a wealth of patient information. Also, the American Academy of Dermatology is a good resource, not just for patients but for providers; for example, the academy offers appeals letters that can be sent to insurance companies to try to advocate for a specific medication for patients.

What do patients need to know initially about psoriasis treatment?

What are your go-to treatments?

How do you keep patients compliant with treatment?

What do you do if they refuse treatment?

What resources do you recommend to patients for more information?

What do patients need to know initially about psoriasis treatment?

What are your go-to treatments?

How do you keep patients compliant with treatment?

What do you do if they refuse treatment?

What resources do you recommend to patients for more information?

Current Guidelines for Psoriasis Treatment: A Work in Progress

Article Type

Alexa B. Kimball, MD, MPH

Changed

Thu, 12/15/2022 - 14:51

Display Headline

Current Guidelines for Psoriasis Treatment: A Work in Progress

Author(s)

Nicole M. Golbari, BA

Martina L. Porter, MD

Psoriasis is a chronic autoinflammatory disorder affecting approximately 2% to 4% of the Western population.¹ While there is no absolute cure for psoriasis, novel therapies allow for substantial reduction in symptoms and considerable improvement in quality of life (QoL). In the past few years, multiple treatment guidelines (recommendations based on evidence-based literature reviews) and consensus statements (a set of declarations determined and voted on by a panel of experts in the field) have been developed to guide physicians worldwide in treating psoriasis in the clinical setting (eTable).^2-10

Because psoriasis is a complex disease with multiple comorbidities, applicability of these guidelines may be limited. Although some basic treatment algorithms exist, patient preference, disease severity, and other variables including comorbidities (eg, psoriatic arthritis [PsA], risk of major cardiac events, inflammatory bowel disease [IBD]), history of nonmelanoma skin cancer (NMSC), pregnancy and lactation, and specific contraindications to therapy (eg, renal failure, liver disease, active malignancy) should be considered. In this article, we summarize common themes across existing guidelines and consensus statements for the treatment of psoriasis and highlight areas where there is consistent agreement or lack of sufficient information.

Disease Severity and Treatment Outcomes

There currently are no consensus definitions for mild, moderate, and severe psoriasis, but several consensus statements have attempted to standardize grading systems based on objective values, such as body surface area (BSA) and psoriasis area and severity index (PASI)(a scoring system used to grade the degree of redness, thickness, and scaling of psoriasis plaques), as well as subjective QoL measures.^2,6 Although classification of disease severity varies, mild psoriasis generally is characterized as disease that can be managed with local and topical therapy, and moderate to severe psoriasis typically warrants consideration for escalated treatment with phototherapy or systemic agents.

Most definitions of disease severity in psoriasis reference 5% to 10% BSA involvement as a cutoff that should trigger consideration of systemic treatment; however, these criteria could result in undertreatment of patients with substantial disease. For example, patients who have limited BSA involvement but whose disease has a considerable impact on QoL, as well as those who have debilitating disease in localized areas (eg, palms, soles, scalp, nails) or substantial joint involvement may also be appropriate candidates for systemic treatment.^5,8

Once therapy is initiated, patients should be evaluated for appropriate treatment response at dedicated intervals. While the time to maximum therapeutic benefit depends on the agent of choice, European guidelines recommend that patients be evaluated after an induction phase (typically 16–24 weeks) and define treatment success as either (1) at least 75% improvement in PASI or (2) at least 50% improvement in PASI and a Dermatology Quality of Life Index (DLQI) score of 5 or lower.⁶

Alternatively, the National Psoriasis Foundation (NPF) recommended BSA as the preferred outcome measure in a recent consensus statement and concluded that an outcome of 3% or less BSA involvement or improvement in BSA of 75% or more is considered a desirable treatment response.⁹ Additionally, the Medicare Merit-based Incentive Payment System (MIPS) guidelines for successful systemic treatment response include at least 1 of the following: (1) physician global assessment score of 2 or lower, (2) BSA involvement of less than 3%, (3) PASI score lower than 3, or (4) DLQI score of 5 or lower.¹⁰

Although an array of outcome measures have been utilized in clinical trials and proposed in psoriasis guidelines and consensus statements, BSA is typically a manageable measure of treatment response in a clinical setting; however, DLQI should also be assessed if possible, particularly in patients with debilitating localized disease.⁹

Treatment Options

Because topical treatment regimens can be arduous and typically do not result in sustained clearance, patient expectations should be ascertained prior to initiation of therapy. Topical corticosteroids often can be used as monotherapy in patients with mild psoriasis.³ Topical vitamin D analogues and retinoids also can be effective; however, combined use of these agents with topical steroids should be considered to increase efficacy, and combination formulations can be prescribed to simplify application and improve adherence.

Treatment with UVB or psoralen plus UVA phototherapy is recommended for patients with moderate to severe psoriasis as well as in those who have had minimal response to topical therapy.⁴ Targeted phototherapy with an excimer laser can be used in patients with BSA involvement of less than 10%.

Methotrexate (MTX), cyclosporine, and acitretin are the most commonly prescribed systemic medications for severe psoriasis in the United States.⁵ Despite the risk for hepatotoxicity, MTX appears to have the best combined safety and efficacy profile in terms of serious adverse events compared to other systemic agents.¹¹ Guidelines for MTX monitoring, especially with regard to when to do a liver biopsy, have been substantially liberalized over time, and the recommended interval for biopsy has been extended by years; biopsy was previously recommended after a cumulative MTX dose of 1 to 1.5 g, but guidelines now suggest biopsy after 3.5 to 4 g in low-risk patients.⁵ While abnormally elevated liver function tests during treatment with MTX may necessitate liver biopsy, the use of transient elastography and a panel of serum biomarkers for liver function also can be used to monitor noninvasively for hepatotoxicity before biopsy is considered; these recommendations are likely to be incorporated into newer guidelines in development.¹² Methotrexate has demonstrated safety and increased efficacy when used in combination with biologic agents such as adalimumab, etanercept, infliximab, and secukinumab⁷ and has been studied in combination with many biologics indicated for PsA.¹³

Due to a considerable risk of glomerulosclerosis, cyclosporine is approved for a maximum of 1 year of continuous treatment of psoriasis in the United States and2 years in Europe.^5,7Cyclosporine is best used as induction therapy in psoriasis patients with severe disease who are seeking faster abatement of symptoms.

Acitretin is another systemic treatment option, although efficacy of this agent is dose dependent. Higher dosing often is limited due to lower tolerability.⁵

Given that many insurance formularies primarily cover traditional systemic therapies and that MTX and phototherapy are generally well tolerated and cost effective, patients may need to be treated with traditional agents before escalating to biologics. Prior to starting treatment with any biologic, patients should typically be screened for tuberculosis (TB), human immunodeficiency virus infection, and immunization for, exposure to, and/or infection with hepatitis B and C virus, and any other active infections. In patients who do not demonstrate hepatitis immunity, the hepatitis B vaccine should be administered prior to starting treatment with a biologic.¹⁴ In psoriasis patients with latent TB, 2 months of treatment should be completed before initiating biologic therapy⁸; once a biologic has been initiated, all patients should be screened annually for TB.

European guidelines for biologic treatment recommend that complete blood count and liver and renal function be evaluated at baseline, at months 1 and 3 of treatment, and then every 3 to 6 months thereafter while on the biologic agent.⁷These recommendations are more stringent than those indicated in regulatory labeling and, based on the continual accumulation of data regarding the safety of these agents, some investigators have argued that laboratory testing might not be necessary at all.¹⁵

Treatment in Special Populations

Psoriasis patients often present with comorbidities or a complicated medical history, which can make it challenging to decide which therapy is most suitable. Patients with comorbid diseases (eg, PsA, risk of major cardiac event, IBD) or a history of NMSC and those who are pregnant or are lactating require special considerations to ensure treatment safety and efficacy.

Tumor necrosis factor α (TNF-α) and IL-17 inhibitors are used in the treatment of joint disorders and should be considered in patients with PsA. IL-23/IL-12 inhibition appears to have less benefit in patients with PsA, but studies on IL-23 inhibition (p19 antibodies) alone are ongoing.¹⁶ It has been reported that TNF-α inhibition may be beneficial in patients at risk for major cardiac events.^8,17 In patients with IBD, IL-17 inhibitors should be avoided because they may exacerbate the condition; however, TNF-α and IL-23/IL-12 inhibition have shown to be safe in patients with IBD and many agents in these classes are approved by the US Food and Drug Administration for use in this population.^18,19

Although biologics may increase the risk of developing NMSC²⁰ and should generally be avoided in patients with any active malignancy, specific guidelines for screening and initiation of treatment in patients with a history of cancer are not clearly outlined. Prior to initiating systemic therapy in any patient, a careful medical history should be obtained. These agents often are not prescribed in patients with a history of cancer until remission has been established for at least 5 years, with the exception of patients with a history of treated NMSC.⁸ Annual skin monitoring for NMSC should be undertaken for psoriasis patients on most immunomodulating systemic therapies.

Recommendations for biologic treatment in psoriasis patients who are pregnant or lactating also are limited. European guidelines have noted pregnancy as an absolute contraindication to treatment with biologics,⁷but the regulatory guidance has recently changed for some agents, so this recommendation also may evolve.²¹ British⁸ and US⁵ guidelines do not consider pregnancy a contraindication for treatment with biologics.

Information on the safety of TNF-α antagonists during pregnancy comes primarily from use in patients with IBD and rheumatologic disease. To date, reports on the incidence of congenital malformations have been generally reassuring. Because IgG antibodies are actively transferred across the placenta in the late-second or the third trimesters, neonates born to mothers on biologic treatments may have high levels of some biologic drugs at birth. As a result, live vaccination should be avoided in neonates whose mothers were treated with IgG-based biologics.

Changing Treatment Agents

Patients may need to stop and change treatment agents due to ineffectiveness, personal preference, or worsening disease. When transitioning from any systemic or biologic agent to another (other than MTX), the British Association of Dermatologists recommends a washout period of at least 1 month before initiating a new therapy.⁸ Most guidelines do not define parameters for therapy escalation when patients fail multiple systemic agents, so physicians should use clinical judgment along with consideration of patient preference and comorbidity profile to ascertain which agent is most appropriate.

Conclusion

Keeping psoriasis treatment guidelines updated can be difficult, especially as new therapeutic options for psoriasis and treatment regimens rapidly evolve. Regulatory recommendations also vary worldwide, but most guidelines are reasonably consistent without being overly prescriptive, appropriately allowing for flexibility for application in clinical practice. Nonetheless, physicians should keep in mind new or changing guidelines while tailoring psoriasis treatment recommendations to best suit their individual patients.

References

Parisi R, Symmons DP, Griffiths CE, et al; Identification and Management of Psoriasis and Associated ComorbidiTty (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence [published online September 27, 2012]. J Invest Dermatol. 2013;133:377-385.
Pariser DM, Bagel J, Gelfand JM, et al. National Psoriasis Foundation clinical consensus on disease severity. Arch Dermatol. 2007;143:239-242.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. section 3. guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009;60:643-659.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 5. guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol. 2010;62:114-135.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61:451-485.
Mrowietz U, Kragballe K, Reich K, et al. Definition of treatment goals for moderate to severe psoriasis: a European consensus. Arch Dermatol Res. 2011;303:1-10.
Nast A, Gisondi P, Ormerod AD, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris—update 2015—short version—EDF in cooperation with EADV and IPC [published online October 9, 2015]. J Eur Acad Dermatol Venereol. 2015;29:2277-2294.
Smith CH, Jabbar-Lopez ZK, Yiu ZZ, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. Br J Dermatol. 2017;177:628-636.
Armstrong AW, Siegel MP, Bagel J, et al. From the medical board of the National Psoriasis Foundation: treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017;76:290-298.
Quality ID #410: psoriasis: clinical response to oral systemic or biologic medications—national quality strategy domain: person and caregiver-centered experience and outcomes. Centers for Medicare and Medicaid Services website. https://www.cms.gov/Medicare/Quality-Payment-Program/Resource-Library/2018-Resources.html. Accessed February 27, 2018.
Sbidian E, Chaimani A, Garcia-Doval I, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database of Syst Rev. 2017;12:CD011535.
Lynch M, Higgins E, McCormick PA, et al. The use of transient elastography and FibroTest for monitoring hepatotoxicity in patients receiving methotrexate for psoriasis. JAMA Dermatol. 2014;150:856-862.
Behrens F, Canete J, Olivieri I, et al. Tumor necrosis factor inhibitor monotherapy versus combination with MTX in the treatment of PsA: a systemic review of the literature. Rheumatology. 2015;54:915-926.
Karadağ Ö, Kaşifoğlu T, Özer B, et al. Viral hepatitis screening guideline before biological drug use in rheumatic patients. Eur J Rheumatol. 2016;3:25-28.
Ahn CS, Dothard EH, Garner ML, et al. To test or not to test? an updated evidence-based assessment of the value of screening and monitoring tests when using systemic biologic agents to treat psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2015;73:420-428.
Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator–controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76:418-431.
Wu JJ, Guérin A, Sundaram M, et al. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76:81-90.
Humira [package insert]. North Chicago, IL: Abbott Laboratories; 2011.
Stelara [package insert]. Bloomington, IN: Janssen Biotech, Inc; 2016.
Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum. 2007;56:2886-2895.
Cimzia [package insert]. UCB, Inc: Smyrna, GA; 2016.

Article PDF

The eTable is available in the PDF.

Author and Disclosure Information

Ms. Golbari is from the School of Medicine, Stony Brook University, New York. Drs. Porter and Kimball are from the Clinical Laboratory for Epidemiology and Applied Research in Skin, Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Ms. Golbari reports no conflict of interest. Dr. Porter has received fellowship funding from the National Psoriasis Foundation. Dr. Kimball is a consultant for Abbvie Inc; Eli Lilly and Company; Janssen Pharmaceuticals, Inc; Novartis; and UCB, Inc and is an investigator for AbbVie Inc, and UCB, Inc. She also has received fellowship funding from AbbVie Inc and Janssen Pharmaceuticals, Inc.

Correspondence: Alexa B. Kimball, MD, MPH, Beth Israel Deaconess Medical Center, 375 Longwood Ave, Boston, MA 02215 (clears@bidmc.harvard.edu).

Issue

Cutis - 101(3S)

Publications

Topics

Page Number

10-12

Read more about Current Guidelines for Psoriasis Treatment: A Work in Progress

Sections

Alexa B. Kimball, MD, MPH

Author(s)

Nicole M. Golbari, BA

Martina L. Porter, MD

Author(s)

Nicole M. Golbari, BA

Martina L. Porter, MD

Alexa B. Kimball, MD, MPH

Author and Disclosure Information

The eTable is available in the PDF.

Correspondence: Alexa B. Kimball, MD, MPH, Beth Israel Deaconess Medical Center, 375 Longwood Ave, Boston, MA 02215 (clears@bidmc.harvard.edu).

Author and Disclosure Information

The eTable is available in the PDF.

Correspondence: Alexa B. Kimball, MD, MPH, Beth Israel Deaconess Medical Center, 375 Longwood Ave, Boston, MA 02215 (clears@bidmc.harvard.edu).

Article PDF

Article PDF

Disease Severity and Treatment Outcomes

Treatment Options

Acitretin is another systemic treatment option, although efficacy of this agent is dose dependent. Higher dosing often is limited due to lower tolerability.⁵

Treatment in Special Populations

Changing Treatment Agents

Conclusion

Disease Severity and Treatment Outcomes

Treatment Options

Acitretin is another systemic treatment option, although efficacy of this agent is dose dependent. Higher dosing often is limited due to lower tolerability.⁵

Treatment in Special Populations

Changing Treatment Agents

Conclusion

References

Parisi R, Symmons DP, Griffiths CE, et al; Identification and Management of Psoriasis and Associated ComorbidiTty (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence [published online September 27, 2012]. J Invest Dermatol. 2013;133:377-385.
Pariser DM, Bagel J, Gelfand JM, et al. National Psoriasis Foundation clinical consensus on disease severity. Arch Dermatol. 2007;143:239-242.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. section 3. guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009;60:643-659.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 5. guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol. 2010;62:114-135.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61:451-485.
Mrowietz U, Kragballe K, Reich K, et al. Definition of treatment goals for moderate to severe psoriasis: a European consensus. Arch Dermatol Res. 2011;303:1-10.
Nast A, Gisondi P, Ormerod AD, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris—update 2015—short version—EDF in cooperation with EADV and IPC [published online October 9, 2015]. J Eur Acad Dermatol Venereol. 2015;29:2277-2294.
Smith CH, Jabbar-Lopez ZK, Yiu ZZ, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. Br J Dermatol. 2017;177:628-636.
Armstrong AW, Siegel MP, Bagel J, et al. From the medical board of the National Psoriasis Foundation: treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017;76:290-298.
Quality ID #410: psoriasis: clinical response to oral systemic or biologic medications—national quality strategy domain: person and caregiver-centered experience and outcomes. Centers for Medicare and Medicaid Services website. https://www.cms.gov/Medicare/Quality-Payment-Program/Resource-Library/2018-Resources.html. Accessed February 27, 2018.
Sbidian E, Chaimani A, Garcia-Doval I, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database of Syst Rev. 2017;12:CD011535.
Lynch M, Higgins E, McCormick PA, et al. The use of transient elastography and FibroTest for monitoring hepatotoxicity in patients receiving methotrexate for psoriasis. JAMA Dermatol. 2014;150:856-862.
Behrens F, Canete J, Olivieri I, et al. Tumor necrosis factor inhibitor monotherapy versus combination with MTX in the treatment of PsA: a systemic review of the literature. Rheumatology. 2015;54:915-926.
Karadağ Ö, Kaşifoğlu T, Özer B, et al. Viral hepatitis screening guideline before biological drug use in rheumatic patients. Eur J Rheumatol. 2016;3:25-28.
Ahn CS, Dothard EH, Garner ML, et al. To test or not to test? an updated evidence-based assessment of the value of screening and monitoring tests when using systemic biologic agents to treat psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2015;73:420-428.
Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator–controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76:418-431.
Wu JJ, Guérin A, Sundaram M, et al. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76:81-90.
Humira [package insert]. North Chicago, IL: Abbott Laboratories; 2011.
Stelara [package insert]. Bloomington, IN: Janssen Biotech, Inc; 2016.
Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum. 2007;56:2886-2895.
Cimzia [package insert]. UCB, Inc: Smyrna, GA; 2016.

References

Parisi R, Symmons DP, Griffiths CE, et al; Identification and Management of Psoriasis and Associated ComorbidiTty (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence [published online September 27, 2012]. J Invest Dermatol. 2013;133:377-385.
Pariser DM, Bagel J, Gelfand JM, et al. National Psoriasis Foundation clinical consensus on disease severity. Arch Dermatol. 2007;143:239-242.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. section 3. guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009;60:643-659.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 5. guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol. 2010;62:114-135.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61:451-485.
Mrowietz U, Kragballe K, Reich K, et al. Definition of treatment goals for moderate to severe psoriasis: a European consensus. Arch Dermatol Res. 2011;303:1-10.
Nast A, Gisondi P, Ormerod AD, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris—update 2015—short version—EDF in cooperation with EADV and IPC [published online October 9, 2015]. J Eur Acad Dermatol Venereol. 2015;29:2277-2294.
Smith CH, Jabbar-Lopez ZK, Yiu ZZ, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. Br J Dermatol. 2017;177:628-636.
Armstrong AW, Siegel MP, Bagel J, et al. From the medical board of the National Psoriasis Foundation: treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017;76:290-298.
Quality ID #410: psoriasis: clinical response to oral systemic or biologic medications—national quality strategy domain: person and caregiver-centered experience and outcomes. Centers for Medicare and Medicaid Services website. https://www.cms.gov/Medicare/Quality-Payment-Program/Resource-Library/2018-Resources.html. Accessed February 27, 2018.
Sbidian E, Chaimani A, Garcia-Doval I, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database of Syst Rev. 2017;12:CD011535.
Lynch M, Higgins E, McCormick PA, et al. The use of transient elastography and FibroTest for monitoring hepatotoxicity in patients receiving methotrexate for psoriasis. JAMA Dermatol. 2014;150:856-862.
Behrens F, Canete J, Olivieri I, et al. Tumor necrosis factor inhibitor monotherapy versus combination with MTX in the treatment of PsA: a systemic review of the literature. Rheumatology. 2015;54:915-926.
Karadağ Ö, Kaşifoğlu T, Özer B, et al. Viral hepatitis screening guideline before biological drug use in rheumatic patients. Eur J Rheumatol. 2016;3:25-28.
Ahn CS, Dothard EH, Garner ML, et al. To test or not to test? an updated evidence-based assessment of the value of screening and monitoring tests when using systemic biologic agents to treat psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2015;73:420-428.
Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator–controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76:418-431.
Wu JJ, Guérin A, Sundaram M, et al. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76:81-90.
Humira [package insert]. North Chicago, IL: Abbott Laboratories; 2011.
Stelara [package insert]. Bloomington, IN: Janssen Biotech, Inc; 2016.
Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum. 2007;56:2886-2895.
Cimzia [package insert]. UCB, Inc: Smyrna, GA; 2016.

Issue

Cutis - 101(3S)

Issue

Cutis - 101(3S)

Page Number

10-12

Page Number

10-12

Publications

Publications

Topics

Article Type

Display Headline

Current Guidelines for Psoriasis Treatment: A Work in Progress

Display Headline

Current Guidelines for Psoriasis Treatment: A Work in Progress

Sections

Citation Override

Cutis. 2018 March;101(3S):10-12

Inside the Article

Practice Points

Guidelines and consensus statements for psoriasis treatment are generally but not always consistent.
As guidelines evolve, individual patient preferences, disease severity, and comorbid conditions remain important considerations when selecting treatment agents for psoriasis.
More frequent updates to psoriasis treatment guidelines are becoming increasingly important given the rapid changes in the field.

Disallow All Ads

Content Gating

No Gating (article Unlocked/Free)

Alternative CME

Disqus Comments

Default

Article PDF Media

Teambase ID

18000E00.SIG

Emerging Therapies In Psoriasis: A Systematic Review

Article Type

Changed

Thu, 12/15/2022 - 14:51

Display Headline

Emerging Therapies In Psoriasis: A Systematic Review

Author(s)

Psoriasis is a chronic, autoimmune-mediated disease estimated to affect 2.8% of the US population.¹ The pathogenesis of psoriasis is thought to involve a complex process triggered by a combination of genetic and environmental factors that induce tumor necrosis factor (TNF) α secretion by keratinocytes, which in turn activates dendritic cells. Activated dendritic cells produce IL-23, leading to helper T cell (T_H17) differentiation.^2,3 T_H17 cells secrete IL-17A, which has been shown to promote psoriatic skin changes.⁴ Therefore, TNF-α, IL-23, and IL-17A have been recognized as key targets for psoriasis therapy.

The newest biologic agents targeting IL-17–mediated pathways include ixekizumab, brodalumab, and bimekizumab. Secukinumab, the first US Food and Drug Administration (FDA)–approved IL-17 inhibitor, has been available since 2015 and therefore is not included in this review. IL-23 inhibitors that are FDA approved or being evaluated in clinical trials include guselkumab, tildrakizumab, and risankizumab. In addition, certolizumab pegol, a TNF-α inhibitor, is being studied for use in psoriasis.

METHODS

We reviewed the published results of phase 3 clinical trials for ixekizumab, brodalumab, bimekizumab, guselkumab, tildrakizumab, risankizumab, and certolizumab pegol. We performed an English-language literature search (January 1, 2012 to October 15, 2017) of articles indexed for PubMed/MEDLINE using the following combinations of keywords: IL-23 and psoriasis; IL-17 and psoriasis; tumor necrosis factor and psoriasis; [drug name] and psoriasis. If data from phase 3 clinical trials were not yet available, data from phase 2 clinical trials were incorporated in our analysis. We also reviewed citations within articles to identify relevant sources.

RESULTS

Phase 3 clinical trial design, efficacy, and adverse events (AEs) for ixekizumab and brodalumab are reported in eTable 1^5-10 and for guselkumab and tildrakizumab in eTable 2.^11-14 Phase 2 clinical trial design, efficacy, and AEs are presented for risankizumab in eTable 3^15-18 and for certolizumab pegol in eTable 4.^17,19 No published clinical trial data were found for bimekizumab.

IL-17 Inhibitors

Ixekizumab
This recombinant, high-affinity IgG4κ antibody selectively binds and neutralizes IL-17A.^5,6 Three phase 3 clinical trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—evaluated ixekizumab for moderate to severe plaque psoriasis.⁷

The 3 UNCOVER trials were randomized, double-blind, phase 3 trials of 1296, 1224, and 1346 patients, respectively, assigned to a placebo group; a group treated with ixekizumab 80 mg every 2 weeks; and a group treated with ixekizumab 80 mg every 4 weeks. Both ixekizumab groups received a loading dose of 160 mg at week 0.^5,6 UNCOVER-2 and UNCOVER-3 also included a comparator group of patients on etanercept 50 mg.⁵ Co-primary end points included the percentage of patients reaching a psoriasis area and severity index (PASI) of 75 and with a static physician global assessment (PGA) score of clear (0) or almost clear (1) at week 12.^5,6

Ixekizumab achieved greater efficacy than placebo: 89.1%, 89.7%, and 87.3% of patients achieved PASI 75 in the every 2-week dosing group, and 82.6%, 77.5% and 84.2% achieved PASI 75 in the every 4-week dosing group in UNCOVER-1, UNCOVER-2, and UNCOVER-3, respectively (P<.001 for both treatment arms compared to placebo in all trials). The percentage of patients achieving a static PGA score of 0 or 1 also was higher in the ixekizumab groups in the 2-week and 4-week dosing groups in all UNCOVER trials—81.8% and 76.4% in UNCOVER-1, 83.2% and 72.9% in UNCOVER-2, and 80.5% and 75.4% in UNCOVER-3—compared to 3.2%, 2.4%, and 6.7% in the placebo groups of the 3 trials (P<.001 for both ixekizumab groups compared to placebo in all trials).^5,6 Ixekizumab also was found to be more effective than etanercept for both co-primary end points in both UNCOVER-2 and UNCOVER-3 (eTable 1).⁵

Safety data for all UNCOVER trials were pooled and reported.⁶ At week 12 the rate of at least 1 AE was 58.4% in patients on ixekizumab every 2 weeks and 58.8% in patients on ixekizumab every 4 weeks compared to 54.0% in the etanercept group in UNCOVER-2 and UNCOVER-3 and 46.8% in the placebo group. At week 12, 72 nonfatal serious AEs were reported: 12 in the placebo group, 14 in the etanercept group, 20 in the ixekizumab every 2 weeks group, and 26 in the ixekizumab every 4 weeks group.⁶

The most common AE across all groups was nasopharyngitis. Overall, infections were more frequent in patients treated with ixekizumab than in patients treated with placebo or etanercept. Specifically, oral candidiasis occurred more frequently in the ixekizumab groups, with a higher rate in the 2-week dosing group than in the 4-week dosing group.⁶ Two myocardial infarctions (MIs) occurred: 1 in the etanercept group and 1 in the placebo group.⁵

Brodalumab
This human monoclonal antibody binds to IL-17ra.^8,9 Three double-blind, placebo-controlled, phase 3 trials—AMAGINE-1, AMAGINE-2, and AMAGINE-3—evaluated its use for plaque psoriasis.¹⁰

In AMAGINE-1 (N=661), patients were randomized to receive brodalumab 140 mg or 210 mg (every 2 weeks for 12 weeks), or placebo.⁸ In AMAGINE-2 (N=1831) and AMAGINE-3 (N=1881), patients were randomized to receive brodalumab 140 mg or 210 mg (every 2 weeks for 12 weeks), ustekinumab 45 mg or 90 mg by weight (at weeks 0 and 4, then every 12 weeks thereafter), or placebo. In all trials, patients on brodalumab received a dose at week 0 and week 1. Co-primary end points were PASI 75 and a static PGA score of 0 or 1 at 12 weeks compared to placebo and to ustekinumab (in AMAGINE-2 and AMAGINE-3 only).⁸

At week 12, 83.3%, 86.3%, and 85.1% of patients on brodalumab 210 mg, and 60.3%, 66.6%, and 69.2% of patients on brodalumab 140 mg, achieved PASI 75 in AMAGINE-1, AMAGINE-2, and AMAGINE-3, respectively, compared to 2.7%, 8.1%, and 6.0% in the placebo groups (P<.001 between both brodalumab groups and placebo in all trials).⁸ Both brodalumab groups were noninferior but not significantly superior to ustekinumab, which achieved a PASI 75 of 70.0% in AMAGINE-2 and 69.3% in AMAGINE-3. The PASI 90 rate was higher, however, in both brodalumab groups compared to ustekinumab but significance was not reported (eTable 1).⁹ For both brodalumab groups, significantly more patients achieved a static PGA value of 0 or 1 compared to placebo (P<.001 across all trials). However, only the brodalumab 210-mg group achieved a significantly higher rate of static PGA 0 or 1 compared to ustekinumab in AMAGINE-2 and AMAGINE-3 (P<.001).⁹

After 12 weeks, the percentage of patients reporting at least 1 AE was 59.0%, 57.8%, and 56.8% in the brodalumab 210-mg group in AMAGINE-1, AMAGINE-2, and AMAGINE-3, respectively; 58.0%, 60.1%, and 52.6% in the brodalumab 140-mg group; and 51.0%, 53.4%, and 48.6% in the placebo group. Patients taking ustekinumab had an AE rate of 59.0% in AMAGINE-2 and 53.7% in AMAGINE-3. The most common AE was nasopharyngitis, followed by upper respiratory infection (URI) and headache across all trials.^8,9 Serious AEs were rare: 10 in AMAGINE-1, 31 in AMAGINE-2, and 24 in AMAGINE-3 across all groups. One death occurred from stroke in the brodalumab 210-mg group in AMAGINE-2.⁹

IL-23 Inhibitors

Guselkumab
This drug is a human IgG1κ antibody that binds to the p19 subunit of IL-23, thereby inhibiting IL-23 signaling.^11,12 Guselkumab was approved by the FDA in July 2017 for moderate to severe plaque psoriasis.¹³

VOYAGE 1 and VOYAGE 2 were phase 3, double-blind, placebo- and active comparator–controlled trials of 837 and 992 patients, respectively, randomized to receive adalimumab (80 mg at week 0 and 40 mg at week 1, then at 40 mg every 2 weeks thereafter), guselkumab 100 mg at weeks 0, 4, and 12, or placebo.¹¹ Co-primary end points for both trials were the percentage of patients reaching PASI 90 and an investigator global assessment (IGA) score of cleared (0) or minimal (1) at week 16.¹¹

By week 16 of both trials, PASI 90 values were statistically superior for guselkumab (VOYAGE 1, 73.3%; VOYAGE 2, 70.0%) compared to adalimumab (VOYAGE 1, 49.7%; VOYAGE 2, 46.8%) and placebo (VOYAGE 1, 2.9%; VOYAGE 2, 2.4%)(P<.001). Moreover, patients on guselkumab achieved a higher rate of IGA values of 0 and 1 at week 12 (85.1% in VOYAGE 1 and 84.1% in VOYAGE 2) than patients on adalimumab (65.9% in VOYAGE 1 and 67.7% in VOYAGE 2) and placebo (6.9% in VOYAGE 1 and 8.5% in VOYAGE 2)(P<.001).^11,12

The frequency of AEs was comparable across all groups in both trials.^11,12 During the 16-week treatment period, 51.7% and 47.6% of the guselkumab groups in VOYAGE 1 and VOYAGE 2, respectively; 51.1% and 48.4% of the adalimumab groups; and 49.4% and 44.8% of the placebo groups reported at least 1 AE. The most common AEs in all groups were nasopharyngitis, headache, and URI.^11,12

Serious AEs also occurred at similar rates: 2.4% and 1.6% in the guselkumab group in VOYAGE 1 and VOYAGE 2, respectively; 2.4% and 1.8% in the adalimumab group; and 1.7% and 1.2% in the placebo group.^11,12 One case of malignancy occurred in the VOYAGE 1 trial: basal cell carcinoma in the guselkumab group.¹¹ Three major cardiovascular events occurred across both trials: 1 MI in the guselkumab group in each trial and 1 MI in the adalimumab group in VOYAGE 1.^11,12

Tildrakizumab
A high-affinity, humanized IgG1κ antibody, tildrakizumab targets the p19 subunit of IL-23. As of February 2018, 2 double-blind, randomized phase 3 trials have studied tildrakizumab with published results: reSURFACE 1 and reSURFACE 2.¹⁴

reSURFACE 1 (N=772) and reSURFACE 2 (N=1090) randomized patients to receive tildrakizumab 100 or 200 mg (at weeks 0 and 4), etanercept 50 mg (twice weekly) for 12 weeks (reSURFACE 2 only), or placebo. Co-primary end points were the percentage of patients achieving PASI 75 and the percentage of patients achieving a PGA score of 0 or 1 at week 12.¹⁴

In reSURFACE 1, significantly more patients receiving tildrakizumab attained PASI 75 at week 12 compared to placebo: 200 mg, 62.0%; 100 mg, 64.0%; and placebo, 6.0% (P<.001 for tildrakizumab groups compared to placebo). Moreover, significantly proportionally more patients received a PGA score of 0 or 1 compared to placebo: 100 mg, 59%; 200 mg, 58.0%; placebo, 7.0% (P<.001 for both tildrakizumab groups compared to placebo).¹⁴

In reSURFACE 2, significantly more patients receiving tildrakizumab achieved PASI 75 compared to etanercept and placebo at week 12: 200 mg, 66.0%; 100mg, 61.0%; etanercept, 48.0%; placebo, 6.0% (P<.001 for both tildrakizumab groups compared to placebo; P<.05 for both tildrakizumab groups compared to etanercept). Additionally, significantly more patients in the tildrakizumab groups experienced a PGA score of 0 or 1 at week 12 compared to placebo: 200 mg, 59%; 100 mg, 55.0%; placebo, 5% (P<.001 for both tildrakizumab groups compared to placebo).¹⁴

Adverse events were reported at a similar rate across all groups. For reSURFACE 1 and reSURFACE 2, at least 1 AE by week 12 was reported by 42.2% and 45.2% of patients in the 200-mg group; 47.2% and 45.9% in the 100-mg group; and 48.1% and 55.1% in the placebo groups.¹⁴The most common AEs were nasopharyngitis, URI (reSURFACE 1), and erythema at the injection site (reSURFACE 2). One case of serious infection was reported in each of the tildrakizumab groups: 1 case of drug-related hypersensitivity reaction in the 200-mg group, and 1 major cardiovascular event in the 100-mg group of reSURFACE 1. There was 1 serious AE in reSURFACE 2 that led to death in which the cause was undetermined.¹⁴

Risankizumab
This humanized IgG1 antibody binds the p19 unit of IL-23.^15,16 The drug is undergoing 3 phase 3 trials—ultIMMa-1, ultIMMa-2, and IMMvent—for which only preliminary data have been published and are reported here.^16,17 There is 1 phase 2 randomized, dose-ranging trial with published data.¹⁵

ultIMMa-1 and ultIMMa-2 comprised 506 and 491 patients, respectively, randomized to receive risankizumab (150 mg at weeks 0, 4, and 16), ustekinumab (45 mg or 90 mg, by weight, at weeks 0, 4, and 16), or placebo. Co-primary end points were PASI 90 and a PGA score of 0 or 1 at week 16.¹⁷

In ultIMMa-1 and ultIMMa-2, 75.0% and 75.0% of patients on risankizumab 150 mg achieved PASI 90 compared to 42.0% and 48.0% on ustekinumab and 5.0% and 2.0% on placebo at 16 weeks (P<.001 between both placebo and ustekinumab in both trials).¹⁷ In both trials, patients receiving risankizumab achieved higher rates of a static PGA score of 0 or 1 (88.0% and 84.0%) compared to ustekinumab (63.0% and 62.0%) and placebo (8.0% and 5.0%) at 16 weeks (P<.001 for both trials).¹⁸

At week 16, 2.0% of patients on risankizumab reported a serious AE in both trials, compared to 8.0% and 3.0% of patients on ustekinumab and 3.0% and 1.0% on placebo. No new safety concerns were noted.¹⁷

In the phase 3 IMMvent trial, 605 patients were randomized to receive risankizumab (150 mg at weeks 0, 4, and 16) or adalimumab (80 mg at week 0, 40 mg at week 1, then 40 mg every 2 weeks). Co-primary end points were PASI 90 and a static PGA score of 0 or 1 at week 16.¹⁷

In IMMvent, risankizumab was significantly more effective than adalimumab for PASI 75 (risankizumab, 72.0%; adalimumab, 47.0%) and a static PGA score of 0 or 1 (risankizumab 84.0%; adalimumab, 60.0%) (P<.001 risankizumab compared to adalimumab for both end points).¹⁷

At week 16, serious AEs were reported in 3.0% of patients on risankizumab and 3.0% of patients on adalimumab. One patient receiving risankizumab died of an acute MI during the treatment phase.¹⁷

TNF Inhibitor

Certolizumab Pegol
Certolizumab pegol is a human PEGylated anti-TNF agent. In vitro studies have shown that certolizumab binds to soluble and membrane-bound TNF.¹⁹ Unlike other TNF inhibitors, certolizumab pegol is a Fab‘ portion of anti-TNF conjugated to a molecule of polyethylene glycol.¹⁹ The drug is approved in the United States for treating psoriatic arthritis, Crohn disease, and rheumatoid arthritis; its potential for treating psoriasis has been confirmed. Results of 1 phase 2 trial have been published¹⁹; data from 3 phase 3 trials are forthcoming.

This randomized, placebo-controlled, double-blind phase 2 study comprised 176 patients who received certolizumab 200 mg, certolizumab 400 mg, or placebo. The dosing schedule was 400 mg at week 0, followed by either 200 or 400 mg every other week until week 10. Co-primary end points were PASI 75 and a PGA score of 0 or 1 at week 12.¹⁹

Certolizumab was significantly more effective than placebo at week 12: 74.6% of the 200-mg group and 82.8% of the 400-mg group achieved PASI 75 compared to 6.8% of the placebo group (P<.001). Certolizumab also performed better for the PGA score: 52.5% and 72.4% of patients attained a score of 0 or 1 in the 200-mg and 400-mg groups compared to 1.7% in the placebo group.¹⁹

Adverse events were reported equally across all groups: 72% of patients in the 200-mg group, 70% in the 400-mg group, and 71% in the placebo group reported at least 1 AE, most commonly nasopharyngitis, headache, and pruritis.¹⁹

COMMENT

With the development of new insights into the pathogenesis of psoriasis, therapies that are targeted toward key cytokines may contribute to improved management of the disease. The results of these clinical trials demonstrate numerous promising options for psoriatic patients.

IL-17 Inhibitors Ixekizumab and Brodalumab

When comparing these 2 biologics, it is important to consider that these studies were not performed head to head, thereby inhibiting direct comparisons. Moreover, dosage ranges of the investigative drugs were not identical, which also makes comparisons challenging. However, when looking at the highest dosages of ixekizumab and brodalumab, results indicate that ixekizumab may be slightly more effective than brodalumab based on the percentage of patients who achieved a PASI 75 and a static PGA score of 0 or 1 (eTable 1).

Phase 3 trials have shown ixekizumab to maintain efficacy over 60 weeks of treatment.⁶ Ixekizumab also has been shown to alleviate other symptoms of psoriasis, such as itching, pain, and nail involvement.^20,21 Furthermore, ixekizumab appears to be equally effective in patients with or without prior exposure to biologics²²; therefore, ixekizumab may benefit patients who have not experienced success with other biologics.

Across the UNCOVER trials, 11 cases of inflammatory bowel disease were reported in patients receiving ixekizumab (ulcerative colitis in 7; Crohn disease in 4)⁶; it appears that at least 3 of these cases were new diagnoses. In light of a study suggesting that IL-17A might have a protective function in the intestine,²³ these findings may have important clinical implications and require follow-up studies.

Brodalumab also has been shown to maintain efficacy and acceptable safety for as long as 120 weeks.²⁴ In the extension period of the AMAGINE-1 trial, patients who experienced a return of disease during a withdrawal period recaptured static PGA success with re-treatment for 12 weeks (re-treatment was successful in 97% of those given a dosage of 210 mg and in 84% of those given 140 mg).⁸

Furthermore, phase 2 trials also have shown that brodalumab is effective in patients with a history of biologic use.²⁵ Across all AMAGINE trials, only 1 case of Crohn disease was reported in a patient taking brodalumab.⁹ There are concerns about depression, despite data from AMAGINE-1 stating patients on brodalumab actually had greater improvements in Hospital Anxiety and Depression Scale scores after 12 weeks of treatment (P<.001) for both brodalumab 140 mg and 210 mg compared to placebo.⁸ Regardless, brodalumab has a black-box warning for suicidal ideation and behavior, and availability is restricted through a Risk Evaluation and Mitigation Strategy (REMS) program.²⁶

Bimekizumab

Although no phase 2 or phase 3 clinical trial data have been published for bimekizumab (phase 2 trials are underway), it has been shown in a phase 1 trial to be effective for psoriasis. Bimekizumab also is unique; it is the first dual inhibitor of IL-17A and IL-17F.¹⁸

IL-23 Inhibitors Guselkumab, Tildrakizumab, and Risankizumab

Making comparisons among the IL-23 inhibitors also is difficult; studies were not head-to-head comparison trials, and the VOYAGE and reSURFACE studies used different time points for primary end points. Furthermore, only phase 2 trial data are available for risankizumab. Despite these limitations, results of these trials suggest that guselkumab and risankizumab may be slightly more efficacious than tildrakizumab. However, future studies, including head-to-head studies, would ultimately provide further information on how these agents compare.

Guselkumab was shown to remain efficacious at 48 weeks, though patients on maintenance dosing had better results than those who were re-treated.¹² Moreover, guselkumab was found to be effective in hard-to-treat areas, such as the scalp,¹¹ and in patients who did not respond to adalimumab. Guselkumab may therefore benefit patients who have experienced limited clinical improvement on other biologics.¹²

Tildrakizumab was shown to improve PASI 75 and PGA scores through week 28 of treatment. Moreover, a higher percentage of patients taking tildrakizumab scored 0 or 1 on the dermatology life quality index, suggesting that the drug improves quality of life.¹⁴ No specific safety concerns arose in either reSURFACE trial; however, long-term studies are needed for further evaluation.

Risankizumab appears to be a promising new therapy based on phase 2 trial results. Improvements also were seen in dermatology life quality index scores, scalp and fingernail symptoms, and palmoplantar psoriasis.¹⁵ Of note, neutralizing antidrug antibodies were found in 3 patients during this study,¹⁵ which may present potential problems for long-term efficacy. However, preliminary data from 3 phase 3 trials—ultIMMa-1, ultIMMa-2, and IMMvent—are promising.¹⁷

CONCLUSION

Advances in the understanding of psoriasis have led to new targeted therapies. Ongoing clinical trials have shown encouraging results for treating physical and psychological symptoms of psoriasis. The findings of these trials support the idea that therapies targeting IL-23, specifically its p19 subunit, are effective against psoriasis while sparing IL-12. Long-term data from open-label extension studies would help guide clinical recommendations regarding the safety profiles of these agents and determine their long-term utility.

References

Langley RG, Krueger GG, Griffiths CE. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis. 2005;64(suppl 2):ii18-ii23; discussion, ii24, ii25.
Lynde CW, Poulin Y, Vender R, et al. Interleukin 17A: toward a new understanding of psoriasis pathogenesis. J Am Acad Dermatol. 2014;71:141-150.
Amin M, Darji K, No DJ, et al. Review of phase III trial data on IL-23 inhibitors tildrakizumab and guselkumab for psoriasis. J Eur Acad Dermatol Venereol. 2017;31:1627-1632.
Arican O, Aral M, Sasmaz S, et al. Levels of TNF-alpha, IFN-gamma, IL6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm. 2005:273-279.
Griffiths CE, Reich K, Lebwohl M, et al; UNCOVER-2 and UNCOVER-3 investigators. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386:541-551.
Gordon KB, Blauvelt A, Papp KA, et al; UNCOVER-1 study group, UNCOVER-2 study group, UNCOVER-3 study group. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:345-356.
FDA approves new psoriasis drug Taltz [news release]. Silver Spring, MD: US Food and Drug Administration; March 22, 2016. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm491872.htm. Accessed January 29, 2018.
Papp KA, Reich K, Paul C, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2016;175:273-286.
Lebwohl M, Strober B, Mentor A, et al. Phase 3 studies comparing brodalumab with ustekinumab for psoriasis. N Engl J Med. 2015;373:1318-1328.
FDA approves new psoriasis drug [news release]. Silver Spring, MD: US Food and Drug Administration; February 15, 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm541981.htm. Accessed January 29, 2018.
Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate-to-severe plaque psoriasis: results from the phase III, double-blinded placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76:405-417.
Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76:418-431.
Janssen announces U.S. FDA approval of Tremfya™ (guselkumab) for the treatment of moderate to severe plaque psoriasis [news release]. Horsham, PA: Johnson & Johnson; July 13, 2017. https://www.jnj.com/media-center/press-releases/janssen-announces-us-fda-approval-of-tremfya-guselkumab-for-the-treatment-of-moderate-to-severe-plaque-psoriasis. Accessed January 29, 2018.
Reich K, Papp KA, Blauvelt A, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE1 and reSURFACE 2): results from two randomized controlled, phase 3 trials. Lancet. 2017;390:276-288.
Papp KA, Blauvelt A, Bukhalo M, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017;376:1551-1560.
Risankizumab. AbbVie Inc website. https://www.abbvie.com/our-science/pipeline/risankizumab.html. Accessed January 29, 2018.
Risankizumab meets all co-primary and ranked secondary endpoints, achieving significantly greater efficacy versus standard biologic therapies in three pivotal phase 3 psoriasis studies [news release]. North Chicago, IL: AbbVie Inc; October 26, 2017. https://news.abbvie.com/news/risankizumab-meets-all-co-primary-and-ranked-secondary-endpoints-achieving-significantly-greater-efficacy-versus-standard-biologic-therapies-in-three-pivotal-phase-3-psoriasis-studies.htm. Accessed January 29, 2018.
Glatt S, Helmer E, Haier B, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017;83:991-1001.
Reich K, Ortonne JP, Gottlieb AB, et al. Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab‘ certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension. Br J Dermatol. 2012;167:180-190.
Kimball AB, Luger T, Gottlieb A, et al. Impact of ixekizumab on psoriasis itch severity and other psoriasis symptoms: results from 3 phase III psoriasis clinical trials. J Am Acad Dermatol. 2016;75:1156-1161.
Dennehy EB, Zhang L, Amato D, et al. Ixekizumab is effective in subjects with moderate to severe plaque psoriasis with significant nail involvement: results from UNCOVER 3. J Drugs Dermatol. 2016;15:958-961.
Gottlieb AB, Lacour JP, Korman N, et al. Treatment outcomes with ixekizumab in patients with moderate-to-severe psoriasis who have not received prior biological therapies: an integrated analysis of two phase III randomized studies. J Eur Acad Dermatol Venereol. 2017;31:679-685.
Hueber W, Sands BE, Lewitsky S, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61:1693-1700.
Papp K, Leonardi C, Menter A, et al. Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment. J Am Acad Dermatol. 2014;71:1183-1190.
Papp K, Menter A, Strober B, et al. Efficacy and safety of brodalumab in subpopulations of patients with difficult-to-treat moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2015;72:436-439.
SILIQ [package insert]. Thousand Oaks, CA: Amgen, Inc; 2017.

Article PDF

The eTables are available in the PDF.

Author and Disclosure Information

Ms. Lee is from the John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu. Ms. Amin is from the School of Medicine, University of California, Riverside. Dr. Bhutani is from the Department of Dermatology, University of California, San Francisco. Dr. Wu is from the Department of Dermatology, Kaiser Permanente Los Angeles Medical Center, California.

Ms. Lee and Ms. Amin report no conflict of interest. Dr. Bhutani is an investigator for Eli Lilly and Company; Janssen Biotech, Inc; Merck & Co; and STRATA Skin Sciences. Dr. Wu is an investigator for AbbVie Inc; Amgen Inc; Eli Lilly and Company; Janssen Biotech, Inc; Novartis; and Regeneron Pharmaceuticals, Inc.

Correspondence: Jashin J. Wu, MD, Kaiser Permanente Los Angeles Medical Center, Department of Dermatology, 1515 N Vermont Ave, 5th Floor, Los Angeles, CA 90027 (jashinwu@gmail.com).

Issue

Cutis - 101(3S)

Publications

Topics

Page Number

5-9

Read more about Emerging Therapies In Psoriasis: A Systematic Review

Sections

The eTables are available in the PDF.

Author(s)

Author(s)

Author and Disclosure Information

Correspondence: Jashin J. Wu, MD, Kaiser Permanente Los Angeles Medical Center, Department of Dermatology, 1515 N Vermont Ave, 5th Floor, Los Angeles, CA 90027 (jashinwu@gmail.com).

Author and Disclosure Information

The eTables are available in the PDF.

Correspondence: Jashin J. Wu, MD, Kaiser Permanente Los Angeles Medical Center, Department of Dermatology, 1515 N Vermont Ave, 5th Floor, Los Angeles, CA 90027 (jashinwu@gmail.com).

Article PDF

Article PDF

METHODS

RESULTS

IL-17 Inhibitors

IL-23 Inhibitors

At week 16, serious AEs were reported in 3.0% of patients on risankizumab and 3.0% of patients on adalimumab. One patient receiving risankizumab died of an acute MI during the treatment phase.¹⁷

TNF Inhibitor

COMMENT

IL-17 Inhibitors Ixekizumab and Brodalumab

Bimekizumab

IL-23 Inhibitors Guselkumab, Tildrakizumab, and Risankizumab

CONCLUSION

METHODS

RESULTS

IL-17 Inhibitors

IL-23 Inhibitors

At week 16, serious AEs were reported in 3.0% of patients on risankizumab and 3.0% of patients on adalimumab. One patient receiving risankizumab died of an acute MI during the treatment phase.¹⁷

TNF Inhibitor

COMMENT

IL-17 Inhibitors Ixekizumab and Brodalumab

Bimekizumab

IL-23 Inhibitors Guselkumab, Tildrakizumab, and Risankizumab

CONCLUSION

References

Langley RG, Krueger GG, Griffiths CE. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis. 2005;64(suppl 2):ii18-ii23; discussion, ii24, ii25.
Lynde CW, Poulin Y, Vender R, et al. Interleukin 17A: toward a new understanding of psoriasis pathogenesis. J Am Acad Dermatol. 2014;71:141-150.
Amin M, Darji K, No DJ, et al. Review of phase III trial data on IL-23 inhibitors tildrakizumab and guselkumab for psoriasis. J Eur Acad Dermatol Venereol. 2017;31:1627-1632.
Arican O, Aral M, Sasmaz S, et al. Levels of TNF-alpha, IFN-gamma, IL6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm. 2005:273-279.
Griffiths CE, Reich K, Lebwohl M, et al; UNCOVER-2 and UNCOVER-3 investigators. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386:541-551.
Gordon KB, Blauvelt A, Papp KA, et al; UNCOVER-1 study group, UNCOVER-2 study group, UNCOVER-3 study group. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:345-356.
FDA approves new psoriasis drug Taltz [news release]. Silver Spring, MD: US Food and Drug Administration; March 22, 2016. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm491872.htm. Accessed January 29, 2018.
Papp KA, Reich K, Paul C, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2016;175:273-286.
Lebwohl M, Strober B, Mentor A, et al. Phase 3 studies comparing brodalumab with ustekinumab for psoriasis. N Engl J Med. 2015;373:1318-1328.
FDA approves new psoriasis drug [news release]. Silver Spring, MD: US Food and Drug Administration; February 15, 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm541981.htm. Accessed January 29, 2018.
Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate-to-severe plaque psoriasis: results from the phase III, double-blinded placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76:405-417.
Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76:418-431.
Janssen announces U.S. FDA approval of Tremfya™ (guselkumab) for the treatment of moderate to severe plaque psoriasis [news release]. Horsham, PA: Johnson & Johnson; July 13, 2017. https://www.jnj.com/media-center/press-releases/janssen-announces-us-fda-approval-of-tremfya-guselkumab-for-the-treatment-of-moderate-to-severe-plaque-psoriasis. Accessed January 29, 2018.
Reich K, Papp KA, Blauvelt A, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE1 and reSURFACE 2): results from two randomized controlled, phase 3 trials. Lancet. 2017;390:276-288.
Papp KA, Blauvelt A, Bukhalo M, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017;376:1551-1560.
Risankizumab. AbbVie Inc website. https://www.abbvie.com/our-science/pipeline/risankizumab.html. Accessed January 29, 2018.
Risankizumab meets all co-primary and ranked secondary endpoints, achieving significantly greater efficacy versus standard biologic therapies in three pivotal phase 3 psoriasis studies [news release]. North Chicago, IL: AbbVie Inc; October 26, 2017. https://news.abbvie.com/news/risankizumab-meets-all-co-primary-and-ranked-secondary-endpoints-achieving-significantly-greater-efficacy-versus-standard-biologic-therapies-in-three-pivotal-phase-3-psoriasis-studies.htm. Accessed January 29, 2018.
Glatt S, Helmer E, Haier B, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017;83:991-1001.
Reich K, Ortonne JP, Gottlieb AB, et al. Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab‘ certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension. Br J Dermatol. 2012;167:180-190.
Kimball AB, Luger T, Gottlieb A, et al. Impact of ixekizumab on psoriasis itch severity and other psoriasis symptoms: results from 3 phase III psoriasis clinical trials. J Am Acad Dermatol. 2016;75:1156-1161.
Dennehy EB, Zhang L, Amato D, et al. Ixekizumab is effective in subjects with moderate to severe plaque psoriasis with significant nail involvement: results from UNCOVER 3. J Drugs Dermatol. 2016;15:958-961.
Gottlieb AB, Lacour JP, Korman N, et al. Treatment outcomes with ixekizumab in patients with moderate-to-severe psoriasis who have not received prior biological therapies: an integrated analysis of two phase III randomized studies. J Eur Acad Dermatol Venereol. 2017;31:679-685.
Hueber W, Sands BE, Lewitsky S, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61:1693-1700.
Papp K, Leonardi C, Menter A, et al. Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment. J Am Acad Dermatol. 2014;71:1183-1190.
Papp K, Menter A, Strober B, et al. Efficacy and safety of brodalumab in subpopulations of patients with difficult-to-treat moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2015;72:436-439.
SILIQ [package insert]. Thousand Oaks, CA: Amgen, Inc; 2017.

References

Langley RG, Krueger GG, Griffiths CE. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis. 2005;64(suppl 2):ii18-ii23; discussion, ii24, ii25.
Lynde CW, Poulin Y, Vender R, et al. Interleukin 17A: toward a new understanding of psoriasis pathogenesis. J Am Acad Dermatol. 2014;71:141-150.
Amin M, Darji K, No DJ, et al. Review of phase III trial data on IL-23 inhibitors tildrakizumab and guselkumab for psoriasis. J Eur Acad Dermatol Venereol. 2017;31:1627-1632.
Arican O, Aral M, Sasmaz S, et al. Levels of TNF-alpha, IFN-gamma, IL6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm. 2005:273-279.
Griffiths CE, Reich K, Lebwohl M, et al; UNCOVER-2 and UNCOVER-3 investigators. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386:541-551.
Gordon KB, Blauvelt A, Papp KA, et al; UNCOVER-1 study group, UNCOVER-2 study group, UNCOVER-3 study group. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:345-356.
FDA approves new psoriasis drug Taltz [news release]. Silver Spring, MD: US Food and Drug Administration; March 22, 2016. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm491872.htm. Accessed January 29, 2018.
Papp KA, Reich K, Paul C, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2016;175:273-286.
Lebwohl M, Strober B, Mentor A, et al. Phase 3 studies comparing brodalumab with ustekinumab for psoriasis. N Engl J Med. 2015;373:1318-1328.
FDA approves new psoriasis drug [news release]. Silver Spring, MD: US Food and Drug Administration; February 15, 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm541981.htm. Accessed January 29, 2018.
Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate-to-severe plaque psoriasis: results from the phase III, double-blinded placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76:405-417.
Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76:418-431.
Janssen announces U.S. FDA approval of Tremfya™ (guselkumab) for the treatment of moderate to severe plaque psoriasis [news release]. Horsham, PA: Johnson & Johnson; July 13, 2017. https://www.jnj.com/media-center/press-releases/janssen-announces-us-fda-approval-of-tremfya-guselkumab-for-the-treatment-of-moderate-to-severe-plaque-psoriasis. Accessed January 29, 2018.
Reich K, Papp KA, Blauvelt A, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE1 and reSURFACE 2): results from two randomized controlled, phase 3 trials. Lancet. 2017;390:276-288.
Papp KA, Blauvelt A, Bukhalo M, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017;376:1551-1560.
Risankizumab. AbbVie Inc website. https://www.abbvie.com/our-science/pipeline/risankizumab.html. Accessed January 29, 2018.
Risankizumab meets all co-primary and ranked secondary endpoints, achieving significantly greater efficacy versus standard biologic therapies in three pivotal phase 3 psoriasis studies [news release]. North Chicago, IL: AbbVie Inc; October 26, 2017. https://news.abbvie.com/news/risankizumab-meets-all-co-primary-and-ranked-secondary-endpoints-achieving-significantly-greater-efficacy-versus-standard-biologic-therapies-in-three-pivotal-phase-3-psoriasis-studies.htm. Accessed January 29, 2018.
Glatt S, Helmer E, Haier B, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017;83:991-1001.
Reich K, Ortonne JP, Gottlieb AB, et al. Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab‘ certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension. Br J Dermatol. 2012;167:180-190.
Kimball AB, Luger T, Gottlieb A, et al. Impact of ixekizumab on psoriasis itch severity and other psoriasis symptoms: results from 3 phase III psoriasis clinical trials. J Am Acad Dermatol. 2016;75:1156-1161.
Dennehy EB, Zhang L, Amato D, et al. Ixekizumab is effective in subjects with moderate to severe plaque psoriasis with significant nail involvement: results from UNCOVER 3. J Drugs Dermatol. 2016;15:958-961.
Gottlieb AB, Lacour JP, Korman N, et al. Treatment outcomes with ixekizumab in patients with moderate-to-severe psoriasis who have not received prior biological therapies: an integrated analysis of two phase III randomized studies. J Eur Acad Dermatol Venereol. 2017;31:679-685.
Hueber W, Sands BE, Lewitsky S, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61:1693-1700.
Papp K, Leonardi C, Menter A, et al. Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment. J Am Acad Dermatol. 2014;71:1183-1190.
Papp K, Menter A, Strober B, et al. Efficacy and safety of brodalumab in subpopulations of patients with difficult-to-treat moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2015;72:436-439.
SILIQ [package insert]. Thousand Oaks, CA: Amgen, Inc; 2017.

Issue

Cutis - 101(3S)

Issue

Cutis - 101(3S)

Page Number

5-9

Page Number

5-9

Publications

Publications

Topics

Article Type

Display Headline

Emerging Therapies In Psoriasis: A Systematic Review

Display Headline

Emerging Therapies In Psoriasis: A Systematic Review

Sections

Citation Override

Cutis. 2018 March;101(3S):5-9

Inside the Article

Practice Points

Tumor necrosis factor α, IL-23, and IL-17A are key targets for psoriasis therapy based on an understanding of the key role that these cytokines play in the pathophysiology of disease.
The biologic agents secukinumab and ixekizumab are approved for use in the management of psoriasis. Other biologics—brodalumab, bimekizumab, guselkumab, tildrakizumab, risankizumab, and certolizumab pegol—have been (and some continue to be) the focus of phase 2 and phase 3 clinical trials.
Findings of several of those trials support the idea that therapies targeting IL-23, specifically its p19 subunit, but that spare IL-12 are effective against psoriasis.
Longer-term studies are needed to determine whether the agents reviewed here, including those approved for clinical use, are suitable for prolonged administration.

Disallow All Ads

Content Gating

No Gating (article Unlocked/Free)

Alternative CME

Disqus Comments

Default

Article PDF Media

Teambase ID

18000E02.SIG

Pushing the Limits: Developing a New Standard of Care for Psoriasis

Article Type

Changed

Thu, 12/15/2022 - 14:52

Display Headline

Pushing the Limits: Developing a New Standard of Care for Psoriasis

Author(s)

Jeffrey M. Weinberg, MD

We are now in the midst of a second revolution in the care of patients with psoriasis. Since biologic therapies for psoriasis were first introduced in 2003 with the approval of alefacept, the psoriasis treatment paradigm has shifted and continues to evolve. Interestingly, the first 2 biologic agents approved for psoriasis, alefacept and efalizumab, are no longer on the market in the United States.

We certainly have made progress since the early days of psoriasis treatment. Over the years, we have come to understand the nature of psoriasis as a systemic inflammatory condition rather than as simply a skin disease. With this knowledge, we have continued to identify systemic comorbidities associated with psoriasis, including cardiovascular risk, diabetes, and metabolic syndrome. It is therefore the role of the dermatologist to serve as the gatekeeper for these individuals and help to screen for comorbidities of psoriasis, as well as provide appropriate counseling and referral.

Additionally, psoriasis therapies have been approved for new segments of the population. In 2016, the US Food and Drug Administration approved a supplemental biologics license application for use of etanercept in children aged 4 years and older with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Last year, the US Food and Drug Administration also approved an expanded indication for ustekinumab for the treatment of adolescents (aged 12 years and older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

Another treatment development included the approval of apremilast as a new oral therapeutic option for psoriasis patients. This agent, which is approved for both psoriasis and psoriatic arthritis, has become an attractive therapy for many patients who are new to systemic treatment. Many patients prefer an oral medication and like the fact that no routine laboratory monitoring is required. Often patients leave their dermatologist’s office with 2- to 4-weeks’ worth of samples and can begin their course immediately.

A treat-to-target approach also has been established for psoriasis. In 2016, the Medical Board of the National Psoriasis Foundation¹ created specific treatment goals in order to make achieving clear or almost clear skin the new standard of care. A consensus-building study conducted among 25 psoriasis experts revealed that the most preferred instrument for evaluating disease severity was body surface area (BSA). The time at which most participants preferred to evaluate patient response after starting a new psoriasis therapy was 3 months, and an acceptable response at this timepoint was considered to be either BSA involvement of 3% or less or improvement in BSA involvement of 75% or more compared to baseline. The target response at 3 months after starting treatment was BSA involvement of 1% or less. During the maintenance period, evaluation every 6 months was most preferred, and the target response at every 6-month follow-up evaluation was BSA involvement of 1% or less.¹ These standards enable and encourage both clinicians and patients to maximize their treatment success.

Over the past several years, a variety of new biologic agents also have come to the market, including 3 IL-17 inhibitors (ixekizumab, brodalumab, and secukinumab) and one IL-23 inhibitor (guselkumab). All of these agents have added new options to the armamentarium for psoriasis treatment and are highly effective. Overall, the clinical improvement and safety profiles for these agents are promising, and these new drugs may be equal to or more efficacious than the currently available therapeutic options for psoriasis treatment; however, long-term studies are still needed to further establish the safety and efficacy profiles for these biologic agents. Even more novel therapies are in development, as will be discussed by Lee et al² in this issue.

It is the purpose of this special issue to review new standards of care for psoriasis in 2018. We hope that you find this issue enjoyable and informative.

References

Armstrong AW, Siegel MP, Bagel J, et al. From the Medical Board of the National Psoriasis Foundation: treatment targets for plaque psoriasis [published online November 28, 2016]. J Am Acad Dermatol. 2017;76:290-298.
Lee EB, Amin M, Bhutani T, et al. Emerging therapies in psoriasis: a systematic review. Cutis. 2018;101(suppl 3):5-9.

Article PDF

Author and Disclosure Information

From the Icahn School of Medicine at Mount Sinai, New York, New York.

Dr. Weinberg is a speaker for and has received research grants from AbbVie Inc, Amgen Inc, Celgene Corporation, and Novartis. He also is a speaker for Eli Lilly and Company.

Correspondence: Jeffrey M. Weinberg, MD, 10 Union Square E, Ste 3C, New York, NY 10003 (jmw27@columbia.edu).

Issue

Cutis - 101(3S)

Publications

Topics

Page Number

Read more about Pushing the Limits: Developing a New Standard of Care for Psoriasis

Sections

Commentary

Author(s)

Jeffrey M. Weinberg, MD

Author(s)

Jeffrey M. Weinberg, MD

Author and Disclosure Information

From the Icahn School of Medicine at Mount Sinai, New York, New York.

Dr. Weinberg is a speaker for and has received research grants from AbbVie Inc, Amgen Inc, Celgene Corporation, and Novartis. He also is a speaker for Eli Lilly and Company.

Correspondence: Jeffrey M. Weinberg, MD, 10 Union Square E, Ste 3C, New York, NY 10003 (jmw27@columbia.edu).

Author and Disclosure Information

From the Icahn School of Medicine at Mount Sinai, New York, New York.

Dr. Weinberg is a speaker for and has received research grants from AbbVie Inc, Amgen Inc, Celgene Corporation, and Novartis. He also is a speaker for Eli Lilly and Company.

Correspondence: Jeffrey M. Weinberg, MD, 10 Union Square E, Ste 3C, New York, NY 10003 (jmw27@columbia.edu).

Article PDF

Article PDF

It is the purpose of this special issue to review new standards of care for psoriasis in 2018. We hope that you find this issue enjoyable and informative.

References

Armstrong AW, Siegel MP, Bagel J, et al. From the Medical Board of the National Psoriasis Foundation: treatment targets for plaque psoriasis [published online November 28, 2016]. J Am Acad Dermatol. 2017;76:290-298.
Lee EB, Amin M, Bhutani T, et al. Emerging therapies in psoriasis: a systematic review. Cutis. 2018;101(suppl 3):5-9.

References

Armstrong AW, Siegel MP, Bagel J, et al. From the Medical Board of the National Psoriasis Foundation: treatment targets for plaque psoriasis [published online November 28, 2016]. J Am Acad Dermatol. 2017;76:290-298.
Lee EB, Amin M, Bhutani T, et al. Emerging therapies in psoriasis: a systematic review. Cutis. 2018;101(suppl 3):5-9.

Issue

Cutis - 101(3S)

Issue

Cutis - 101(3S)

Page Number

Publications

Publications

Topics

Article Type

Display Headline

Pushing the Limits: Developing a New Standard of Care for Psoriasis

Display Headline

Pushing the Limits: Developing a New Standard of Care for Psoriasis

Sections

Commentary

Citation Override

Cutis. 2018 March;101(3S):4

Disallow All Ads

Content Gating

No Gating (article Unlocked/Free)

Alternative CME

Disqus Comments

Default

Article PDF Media

Teambase ID

18000DFF.SIG

Asymptomatic Subcutaneous Nodule on the Cheek

Article Type

Changed

Thu, 01/10/2019 - 13:49

Display Headline

Asymptomatic Subcutaneous Nodule on the Cheek

Author(s)

Daria Marley Kemp, MD

Ben J. Friedman, MD

Joshua Trufant, MD

Jason B. Lee, MD

The Diagnosis: Lymphoepitheliomalike Carcinoma of the Skin

The term lymphoepitheliomalike carcinoma of the skin (LELCS) initially was proposed by Swanson et al¹ in 1988 when they described 5 patients with cutaneous neoplasms histologically resembling nasopharyngeal carcinoma, also known as lymphoepithelioma. A PubMed search of articles indexed for MEDLINE using the term lymphoepitheliomalike carcinoma of the skin revealed over 60 cases of LELCS since 1988. However, unlike nasopharyngeal carcinoma, LELCS has not been associated with Epstein-Barr virus, with the exception of 1 known reported case.² The clinical appearance of LELCS is nonspecific but usually presents as a flesh-colored to erythematous nodule, as was seen in the current case. Lesions commonly are found on the head and neck in middle-aged to elderly patients with a slight male predominance.²

On histology, LELCS is characterized by aggregations of large, atypical epithelioid cells surrounded by a dense lymphoplasmocytic infiltrate (right quiz image). The neoplasm tends to reside within the deep dermis and/or subcutis¹ without appreciable epidermal involvement (left quiz image). The atypical epithelioid cells demonstrate positive immunoreactivity for cytokeratins (right quiz image inset), p40/p63, and epithelial membrane antigen,³ and the surrounding lymphocytic infiltrate stains positively for leukocyte common antigen. The tumor histogenesis still is unknown, although an epidermal origin has been suggested given its staining pattern.² Other investigators have postulated on an adnexal origin, citing the tumor's dermal location along with case reports describing possible glandular, sebaceous, or follicular differentiation.^2,4

Treatment for LELCS can include either standard surgical excision or Mohs micrographic surgery, with radiation reserved for lymph node involvement, tumor recurrence, or poor surgical candidates.^2,3,5 With appropriate therapy, prognosis may be considered favorable. Data from 49 LELCS patients presenting from 1988 and 2008 showed that 36 (73.5%) had no evidence of recurrence after treatment with standard surgical excision, 4 (8.2%) had local recurrence, and 6 (12.2%) developed lymph node metastasis, which led to death in 1 (2.0%) patient.²

Given the histologic similarity of LELCS to nasopharyngeal carcinoma, it is important to rule out the possibility of cutaneous metastasis, which can be done by testing for Epstein-Barr virus and performing either computed tomography imaging or comprehensive laryngoscopic examination of the head and neck region. In the current case, the patient was referred for laryngoscopy, at which time no suspicious lesions were identified. He subsequently underwent treatment with Mohs micrographic surgery, and the tumor was cleared after 2 surgical stages. At 5-month follow-up, the patient continued to do well with no signs of clinical recurrence.

Cutaneous lymphadenoma may be included in the differential diagnosis for LELCS on histopathology. This neoplasm is characterized by a well-circumscribed dermal proliferation of basaloid tumor islands within a fibrotic stroma (Figure 1). The basaloid cells may display peripheral palisading, and lymphocytes often are seen infiltrating the tumor lobules and the surrounding stroma (Figure 1 inset). Clinically, cutaneous lymphadenomas are slowly growing nodules that typically occur in young to middle-aged patients,^4,6 unlike LELCS, which is more commonly observed in middle-aged to elderly patients.²

Figure 1. Lymphadenoma consisting of a well-circumscribed dermal proliferation of basaloid tumor islands within a fibrotic stroma and dense lymphocytic infiltrate (H&E, original magnification ×50 [inset, original magnification ×400]).

The dense lymphocytic infiltrate seen in LELCS may obscure the neoplastic epithelioid cells and in doing so may mimic a lymphoproliferative disorder, such as lymphomatoid papulosis (LyP). Lymphomatoid papulosis is a chronic CD30⁺ lymphoproliferative disorder consisting of recurrent crops of self-resolving papulonodules occurring on the trunk, arms, and legs. The average age of onset is in the third to fourth decades of life. Histology is dependent on the subtype; type A, the most common subtype, displays a wedge-shaped dermal infiltrate consisting of small lymphocytes (Figure 2) admixed with larger CD30⁺ atypical lymphocytes with prominent nucleoli (Figure 2 inset).⁷ Bizarre, binucleated forms resembling Reed-Sternberg cells also may be observed along with hallmark cells, which contain a horseshoe-shaped nucleus. The presence of admixed neutrophils and eosinophils also are common in type A LyP, a feature that is not characteristic of LELCS. Moreover, the atypical cells in LyP would not stain positively for epithelial markers as they would in LELCS.

Figure 2. Type A lymphomatoid papulosis showing enlarged, pleomorphic lymphocytes with prominent nucleoli admixed with small lymphocytes (H&E, original magnification ×200). CD30 staining highlights large atypical lymphocytes (inset, original magnification ×200).

Rosai-Dorfman disease is a rare condition that usually presents with painless cervical lymphadenopathy, typically in the first and second decades of life. Skin involvement can be seen in a small subset of extranodal cases, but cutaneous involvement alone is uncommon. On histopathology, cutaneous lesions are characterized by a dense dermal infiltrate of atypical histiocytes with vesicular nuclei and pale cytoplasm admixed with inflammatory cells, including lymphocytes, neutrophils, and plasma cells (Figure 3). Intracytoplasmic inflammatory cells or emperipolesis often is appreciated (Figure 3 inset).^8,9 The atypical histiocytes stain positively for S100 and negatively for CD1a.

Figure 3. Rosai-Dorfman disease displaying atypical, pale-staining histiocytes admixed with a dense dermal infiltrate of inflammatory cells (H&E, original magnification ×200) and emperipolesis (arrow)(inset [H&E, original magnification ×400]).

Lymphoepitheliomalike carcinoma of the skin sometimes is considered to be a poorly differentiated, inflamed variant of squamous cell carcinoma (SCC).¹⁰ A number of features may allow distinction of a primary cutaneous SCC from LELCS; for instance, SCC is more likely to have an epidermal connection and at least focal signs of squamous differentiation,11 which can include the presence of poorly differentiated epithelial cells with mitoses (Figure 4), keratin pearls, dyskeratotic cells, or intercellular bridges.¹² Moreover, SCCs have a more variable surrounding inflammatory infiltrate compared to LELCS.

Figure 4. Squamous cell carcinoma with poorly differentiated, mitotically-active eosinophilic cells with surrounding suppurative inflammatory infiltrate (H&E, original magnification ×200).

References

Swanson SA, Cooper PH, Mills SE, et al. Lymphoepithelioma-like carcinoma of the skin. Mod Pathol. 1988;1:359-365.
Aoki R, Mitsui H, Harada K, et al. A case of lymphoepithelioma-like carcinoma of the skin associated with Epstein-Barr virus infection. J Am Acad Dermatol. 2010;62:681-684.
Morteza Abedi S, Salama S, Alowami S. Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical pathology sign out. Rare Tumors. 2013;5:E47.
Requena L, Sánchez Yus E, Jiménez E, et al. Lymphoepithelioma-like carcinoma of the skin: a light-microscopic and immunohistochemical study. J Cutan Pathol. 1994;21:541-548.
Welch PQ, Williams SB, Foss RD, et al. Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:78-86.
Santa Cruz DJ, Barr RJ, Headington JT. Cutaneous lymphadenoma. Am J Surg Pathol. 1991;15:101-110.
Patterson JW. Cutaneous infiltrates--lymphomatous and leukemic. In: Patterson JW, Hosler GA, eds. Weedon's Skin Pathology. 4th ed. London, United Kingdom: Churchill Livingstone; 2016:1186-1189.
Patterson JW. Cutaneous infiltrates--nonlymphoid. In: Patterson JW, Hosler GA, eds. Weedon's Skin Pathology. 4th ed. London, United Kingdom: Churchill Livingstone; 2016:1158.
Skiljo M, Garcia-Lora E, Tercedor J, et al. Purely cutaneous Rosai-Dorfman disease. Dermatology. 1995;191:49-51.
Wang G, Bordeaux JS, Rowe DJ, et al. Lymphoepithelioma-like carcinoma vs inflamed squamous cell carcinoma of the skin. JAMA Dermatol. 2014;150:1367-1368.
Hall G, Duncan A, Azurdia R, et al. Lymphoepithelioma-like carcinoma of the skin: a case with lymph node metastases at presentation. Am J Dermatopathol. 2006;28:211-215.
Lind AC, Breer WA, Wick MR. Lymphoepithelioma-like carcinoma of the skin with apparent origin in the epidermis--a pattern or an entity? a case report. Cancer. 1999;85:884-890.

Article PDF

Author and Disclosure Information

From the Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.

The authors report no conflict of interest.

Correspondence: Daria Marley Kemp, MD, Department of Dermatology and Cutaneous Biology, Thomas Jefferson Hospital, 833 Chestnut St, Ste 740, Philadelphia, PA 19107 (daria.kemp@jefferson.edu).

Issue

Cutis - 101(3)

Publications

Topics

Dermatopathology

Page Number

170, 183-184

Read more about Asymptomatic Subcutaneous Nodule on the Cheek

Sections

Dermpath Diagnosis

Author(s)

Daria Marley Kemp, MD

Ben J. Friedman, MD

Joshua Trufant, MD

Jason B. Lee, MD

Author(s)

Daria Marley Kemp, MD

Ben J. Friedman, MD

Joshua Trufant, MD

Jason B. Lee, MD

Author and Disclosure Information

From the Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.

The authors report no conflict of interest.

Correspondence: Daria Marley Kemp, MD, Department of Dermatology and Cutaneous Biology, Thomas Jefferson Hospital, 833 Chestnut St, Ste 740, Philadelphia, PA 19107 (daria.kemp@jefferson.edu).

Author and Disclosure Information

From the Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.

The authors report no conflict of interest.

Correspondence: Daria Marley Kemp, MD, Department of Dermatology and Cutaneous Biology, Thomas Jefferson Hospital, 833 Chestnut St, Ste 740, Philadelphia, PA 19107 (daria.kemp@jefferson.edu).

Article PDF

Article PDF

The Diagnosis: Lymphoepitheliomalike Carcinoma of the Skin

References

Swanson SA, Cooper PH, Mills SE, et al. Lymphoepithelioma-like carcinoma of the skin. Mod Pathol. 1988;1:359-365.
Aoki R, Mitsui H, Harada K, et al. A case of lymphoepithelioma-like carcinoma of the skin associated with Epstein-Barr virus infection. J Am Acad Dermatol. 2010;62:681-684.
Morteza Abedi S, Salama S, Alowami S. Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical pathology sign out. Rare Tumors. 2013;5:E47.
Requena L, Sánchez Yus E, Jiménez E, et al. Lymphoepithelioma-like carcinoma of the skin: a light-microscopic and immunohistochemical study. J Cutan Pathol. 1994;21:541-548.
Welch PQ, Williams SB, Foss RD, et al. Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:78-86.
Santa Cruz DJ, Barr RJ, Headington JT. Cutaneous lymphadenoma. Am J Surg Pathol. 1991;15:101-110.
Patterson JW. Cutaneous infiltrates--lymphomatous and leukemic. In: Patterson JW, Hosler GA, eds. Weedon's Skin Pathology. 4th ed. London, United Kingdom: Churchill Livingstone; 2016:1186-1189.
Patterson JW. Cutaneous infiltrates--nonlymphoid. In: Patterson JW, Hosler GA, eds. Weedon's Skin Pathology. 4th ed. London, United Kingdom: Churchill Livingstone; 2016:1158.
Skiljo M, Garcia-Lora E, Tercedor J, et al. Purely cutaneous Rosai-Dorfman disease. Dermatology. 1995;191:49-51.
Wang G, Bordeaux JS, Rowe DJ, et al. Lymphoepithelioma-like carcinoma vs inflamed squamous cell carcinoma of the skin. JAMA Dermatol. 2014;150:1367-1368.
Hall G, Duncan A, Azurdia R, et al. Lymphoepithelioma-like carcinoma of the skin: a case with lymph node metastases at presentation. Am J Dermatopathol. 2006;28:211-215.
Lind AC, Breer WA, Wick MR. Lymphoepithelioma-like carcinoma of the skin with apparent origin in the epidermis--a pattern or an entity? a case report. Cancer. 1999;85:884-890.

References

Swanson SA, Cooper PH, Mills SE, et al. Lymphoepithelioma-like carcinoma of the skin. Mod Pathol. 1988;1:359-365.
Aoki R, Mitsui H, Harada K, et al. A case of lymphoepithelioma-like carcinoma of the skin associated with Epstein-Barr virus infection. J Am Acad Dermatol. 2010;62:681-684.
Morteza Abedi S, Salama S, Alowami S. Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical pathology sign out. Rare Tumors. 2013;5:E47.
Requena L, Sánchez Yus E, Jiménez E, et al. Lymphoepithelioma-like carcinoma of the skin: a light-microscopic and immunohistochemical study. J Cutan Pathol. 1994;21:541-548.
Welch PQ, Williams SB, Foss RD, et al. Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:78-86.
Santa Cruz DJ, Barr RJ, Headington JT. Cutaneous lymphadenoma. Am J Surg Pathol. 1991;15:101-110.
Patterson JW. Cutaneous infiltrates--lymphomatous and leukemic. In: Patterson JW, Hosler GA, eds. Weedon's Skin Pathology. 4th ed. London, United Kingdom: Churchill Livingstone; 2016:1186-1189.
Patterson JW. Cutaneous infiltrates--nonlymphoid. In: Patterson JW, Hosler GA, eds. Weedon's Skin Pathology. 4th ed. London, United Kingdom: Churchill Livingstone; 2016:1158.
Skiljo M, Garcia-Lora E, Tercedor J, et al. Purely cutaneous Rosai-Dorfman disease. Dermatology. 1995;191:49-51.
Wang G, Bordeaux JS, Rowe DJ, et al. Lymphoepithelioma-like carcinoma vs inflamed squamous cell carcinoma of the skin. JAMA Dermatol. 2014;150:1367-1368.
Hall G, Duncan A, Azurdia R, et al. Lymphoepithelioma-like carcinoma of the skin: a case with lymph node metastases at presentation. Am J Dermatopathol. 2006;28:211-215.
Lind AC, Breer WA, Wick MR. Lymphoepithelioma-like carcinoma of the skin with apparent origin in the epidermis--a pattern or an entity? a case report. Cancer. 1999;85:884-890.

Issue

Cutis - 101(3)

Issue

Cutis - 101(3)

Page Number

170, 183-184

Page Number

170, 183-184

Publications

Publications

Topics

Article Type

Display Headline

Asymptomatic Subcutaneous Nodule on the Cheek

Display Headline

Asymptomatic Subcutaneous Nodule on the Cheek

Sections

Dermpath Diagnosis

Questionnaire Body

H&E, original magnification ×20 (left); H&E, original magnification ×200 (inset, cytokeratin, original magnification ×100)(right).

An 81-year-old man with history of melanoma and nonmelanoma skin cancer presented with a subcutaneous nodule on the left cheek of 3 months' duration. The lesion was reportedly asymptomatic and measured 2.6×2.9 cm. A punch biopsy of the lesion was obtained for histopathologic evaluation.

Disallow All Ads

Content Gating

No Gating (article Unlocked/Free)

Alternative CME

Disqus Comments

Default

Gate On Date

Tue, 03/06/2018 - 10:45

Un-Gate On Date

Tue, 03/06/2018 - 10:45

Teaser Media

Article PDF Media

Teambase ID

18000DF6.SIG

Bullous Eruption in 2 Brothers

Article Type

Yevgeniya B. Rainwater, MD

Changed

Thu, 01/10/2019 - 13:49

Display Headline

Bullous Eruption in 2 Brothers

Author(s)

Allison L. Wang, MD

Melissa M. Mauskar, MD

The Diagnosis: Bullous Scabies

Scabies infection is caused by the mite Sarcoptes scabiei var hominis. It is commonly transmitted via direct skin-to-skin contact.¹ Classic manifestations include pruritus that worsens at night. It commonly presents with burrows and papules in the interdigital web spaces, as well as flexor surfaces of the wrists, elbows, axillae, buttocks, and genitalia. Pruritus occurs from infestation and delayed hypersensitivity reaction to mites. The recommended treatment of classic scabies is permethrin cream 5% for all occupants of the household and a repeat application for just the patients in 1 week. Posttreatment pruritus can last up to 3 weeks.² At-risk populations include school-aged children and patients in long-term care facilities.

In our case, bullous lesions in a classic distribution with potassium hydroxide preparation of a scabietic mite (Figure) confirmed the diagnosis of bullous scabies. Treatment of bullous scabies is the same as classic scabies. Both patients were treated with 1 application of permethrin cream 5% before we evaluated them. We instructed to repeat application in 7 days for both boys and all family members.

Potassium hydroxide preparation showing a female scabies mite.

Bullae may be secondary to hypersensitivity response³ or superinfection with Staphylococcus aureus causing bullous impetigo.⁴ Bullous scabies may present a diagnostic challenge and requires a high index of suspicion. Although childhood bullous pemphigoid can involve the palms and soles, patients usually present in infancy. Diagnoses such as dyshidrotic eczema and bullous tinea can present with pustules on the hands and feet; however, involvement of the genitalia would be uncommon.

References

Chosidow O. Clinical practices. scabies. N Engl J Med. 2006;354:1718-1727.
Currie BJ, McCarthy JS. Permethrin and ivermectin for scabies. N Engl J Med. 2010;362:717-725.
Ansarin H, Jalali MH, Mazloomi S, et al. Scabies presenting with bullous pemphigoid-like lesions. Dermatol Online J. 2006;12:19.
Herman PS. Letter: scabies and bullae. JAMA. 1975;231:1134.

Article PDF

Yevgeniya B. Rainwater, MD

Author and Disclosure Information

From the Department of Dermatology, UT Southwestern Medical Center, Dallas, Texas.

The authors report no conflict of interest.

Correspondence: Allison L. Wang, MD, UT Southwestern Medical Center, 5939 Harry Hines Blvd, 4th Floor, Ste 100, Dallas, TX 75390 (Allison.Wang@utsouthwestern.edu).

Issue

Cutis - 101(3)

Publications

Topics

Page Number

169, 178

Read more about Bullous Eruption in 2 Brothers

Sections

Photo Challenge

Author(s)

Allison L. Wang, MD

Melissa M. Mauskar, MD

Author(s)

Allison L. Wang, MD

Yevgeniya B. Rainwater, MD

Melissa M. Mauskar, MD

Author and Disclosure Information

From the Department of Dermatology, UT Southwestern Medical Center, Dallas, Texas.

The authors report no conflict of interest.

Correspondence: Allison L. Wang, MD, UT Southwestern Medical Center, 5939 Harry Hines Blvd, 4th Floor, Ste 100, Dallas, TX 75390 (Allison.Wang@utsouthwestern.edu).

Author and Disclosure Information

From the Department of Dermatology, UT Southwestern Medical Center, Dallas, Texas.

The authors report no conflict of interest.

Correspondence: Allison L. Wang, MD, UT Southwestern Medical Center, 5939 Harry Hines Blvd, 4th Floor, Ste 100, Dallas, TX 75390 (Allison.Wang@utsouthwestern.edu).

Article PDF

Article PDF

The Diagnosis: Bullous Scabies

References

Chosidow O. Clinical practices. scabies. N Engl J Med. 2006;354:1718-1727.
Currie BJ, McCarthy JS. Permethrin and ivermectin for scabies. N Engl J Med. 2010;362:717-725.
Ansarin H, Jalali MH, Mazloomi S, et al. Scabies presenting with bullous pemphigoid-like lesions. Dermatol Online J. 2006;12:19.
Herman PS. Letter: scabies and bullae. JAMA. 1975;231:1134.

References

Chosidow O. Clinical practices. scabies. N Engl J Med. 2006;354:1718-1727.
Currie BJ, McCarthy JS. Permethrin and ivermectin for scabies. N Engl J Med. 2010;362:717-725.
Ansarin H, Jalali MH, Mazloomi S, et al. Scabies presenting with bullous pemphigoid-like lesions. Dermatol Online J. 2006;12:19.
Herman PS. Letter: scabies and bullae. JAMA. 1975;231:1134.

Issue

Cutis - 101(3)

Issue

Cutis - 101(3)

Page Number

169, 178

Page Number

169, 178

Publications

Publications

Topics

Article Type

Display Headline

Bullous Eruption in 2 Brothers

Display Headline

Bullous Eruption in 2 Brothers

Sections

Photo Challenge

Questionnaire Body

Brothers aged 7 and 8 years with a history of atopic dermatitis presented to the emergency department with similar diffuse pruritic eruptions of 1 week's duration. They previously were treated with permethrin cream 5% without improvement. Two days prior to presentation they developed painful pustules on the hands and feet. No other family members were affected. Physical examination revealed numerous yellow pustules and vesicles in the interdigital web spaces, elbows, and knees. Notably, the penis and scrotum also were involved in both brothers. A potassium hydroxide preparation of small pustules was obtained.

Disallow All Ads

Content Gating

No Gating (article Unlocked/Free)

Alternative CME

PubMed ID

29718021

Disqus Comments

Default

Gate On Date

Tue, 03/06/2018 - 10:30

Un-Gate On Date

Tue, 03/06/2018 - 10:30

Consolidated Pubs: Do Not Show Source Publication Logo

Use ProPublica

Teaser Media

Article PDF Media