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Contemporary Management of Moderate to Severe Plaque Psoriasis
Jashin J. Wu, MD

Contemporary Management of Moderate to Severe Plaque Psoriasis

Jashin J. Wu, MD
Some newer clinical trials have excluded patients with severe depression, any history of depression or suicidal ideation, or other psychiatric disorders, partly because of the aforementioned concerns.86,87 Many trials have used strict exclusion criteria for mental health comorbidities, including studies of adalimumab, apremilast, certolizumab, secukinumab, and ustekinumab.88 Therefore, the studied populations may not be representative of all patients with plaque psoriasis, and may underestimate psychiatric risks associated with the general use of these drugs.

Selective IL-23 Inhibitors

Selective IL-23 inhibitors are an emerging class of biologic agents for the treatment of moderate to severe plaque psoriasis.


Guselkumab was recently approved for the treatment of patients with plaque psoriasis following the results of the phase 3 studies VOYAGE 1 and VOYAGE 2.60 Guselkumab is a monoclonal antibody that blocks the downstream signaling of IL-23. In the VOYAGE 1 and 2 trials,  the proportion of patients who achieved PASI 75 at Week 16 were 86% and 91%; PASI 90 was achieved by 70% and 73%; PASI 100 was achieved by 34% and 37%. In contrast, the respective rates in the active comparator (adalimumab) group at Week 16 were 69% and 73%, 47% and 50%, and 17% and 21%, respectively. VOYAGE 1 reported that at Week 48, the proportion of patients that achieved PASI 75 decreased to 88%, but increased for PASI 90 (76%) and PASI 100 (47%). The rates in the adalimumab group decreased for both PASI 75 (63%) and PASI 90 (48%), but increased for PASI 100 (23%).59,60


Tildrakizumab and risankizumab are monoclonal antibody IL-23 inhibitors currently being evaluated in phase 3 trials for patients with moderate to severe plaque psoriasis. The FDA has accepted the biologics license application for tildrakizumab, which was filed based on results from the phase 3 reSURFACE 1 and reSURFACE 2 trials. Respective PASI 75 responders in the reSURFACE 1 and reSURFACE 2 trials were 62% and 66%, PASI 90 35% and 37%, and PASI 100 12% and 14% at Week 12 in patients receiving tildrakizumab. In comparison, patients receiving active comparator, etanercept, in the reSURFACE 2 trial were 48%, 21%, and 5%. Week 28 results from reSURFACE 1and reSURFACE that the proportion of patients receiving tildrakizumab increased for PASI 75, PASI 90, and PASI 100 to 79% and 73%, 57% in both trials, and 31% and 26%, respectively. Similarly, rates increased for PASI 75, PASI 90, and PASI 100 in the etanercept group with rates of 54%, 29%, and 11%, respectively.56


Risankizumab is another anti–IL-23 monoclonal antibody. Currently, the safety and efficacy results from phase 3 trials, UltIMMa-1 and UltIMMa-2, have not been published to date.89,90 Results of the phase 2 study of risankizumab showed the proportion of patients in the risankizumab high-dose group at Week 12 that achieved PASI 75, PASI 90, and PASI 100 was 88%, 81%, and 48%, compared with 40%, 72%, and 18% response in the ustekinumab group, respectively.61

Nonbiologic Agents

Apremilast is a novel oral, nonbiologic agent that regulates inflammatory mediators through inhibition of phosphodiesterase-4.48 In the phase 3 ESTEEM-1 trial, 33% of patients with chronic plaque psoriasis who received apremilast achieved PASI 75 at Week 16 and 9.8% achieved PASI 90.48 Sixty-one percent of the patients who remained on apremilast through Week 52 achieved PASI 75 response at Week 52.48 Its toxicity profile is milder than traditional oral systemic agents; however, severe diarrhea, nausea, and vomiting can occur in the first few weeks of initiation. Apremilast also has been associated with an increased risk of depression.47 Physicians should carefully evaluate patients for depression prior to starting therapy, and closely monitor for its signs and symptoms while therapy is ongoing.47

Unmet Needs in the Burden of Psychiatric Morbidities

The common psychiatric comorbidities of psoriasis substantially impair QoL. It is important for clinicians to understand the true burden of these psychiatric issues, especially in patients with moderate to severe plaque psoriasis. Patients with psoriasis may perceive their mental and physical burdens to be greater than those of patients with cancer, arthritis, hypertension, heart disease, and diabetes.2 Patients believe that other people do not understand how much the disease negatively affects their lives.24

Although the frequency of psychiatric problems lessens with decreasing clinical symptoms, even patients with mild psoriasis can continue to experience substantial distress.91

Psoriasis profoundly affects QoL, even in patients who do not meet the full criteria for psychiatric illness. In a survey of over 5600 patients with psoriasis and PsA conducted by the NPF, psoriasis negatively affected the well-being of 88% of the population.37  Most patients experienced anger, helpless, embarrassment, and self-consciousness as part of their disorder. 37 Other studies’ results have demonstrated that, regardless of psoriasis severity, nearly 60% of patients believe psoriasis had a major impact on their QoL.92 Patients often report poor self-esteem and body image, as well as feeling of stigma from others.24 Uncontrolled disease impacts patients’ daily activities, work capabilities, social life, and sexual functioning.24

Psoriasis also deserves consideration as a dermatologic psychophysiological disorder. Such disorders are defined by the fact they can fluctuate in severity and may worsen in response to stress, anxiety, or depression.93 Psoriasis may be exacerbated as patients experience anxiety, embarrassment, or sadness about their disease. This promotes a vicious cycle, as emotional distress can worsen the physiological skin symptoms of the disease, further worsening their psychological impact.94

Coordination of Care for Patients With Psoriasis

It is essential that medical providers address the mental health comorbidities of patients with psoriasis. Unfortunately, depression symptoms in patients with psoriasis often go unrecognized or are inadequately treated.95 Comprehensive treatment, including mental health screenings, might lead to cost savings and benefitpatients.77 In general, European clinicians have greater awareness of the mental health burden of patients with psoriasis compared with their American colleagues. Europeans researchers have performed a number of scientific investigations of the topic.19,20,94,96-99

Various European guidelines have also moved to incorporate health-related QoL as part of general clinical assessment.95

Patients with psoriasis may benefit from specialist coordination of care to address their overall mental, emotional, and physical health.91 Patients with comorbid mental health disorders may particularly benefit from such integrated systems of care.99 When integrated multispecialty support is not available, the treating physicians must attempt to care of all aspects of a patient’s QoL.93 Providers must consider the primary symptoms of psoriasis and its potential cardiovascular and mental health comorbidities.

Many patients with psoriasis do not have their CV risk factors adequately assessed or managed. One study reported that approximately 20% of patients with moderate to severe psoriasis had undiagnosed hypertension, diabetes, or hypercholesterolemia. Moreover, 40% to 60% of patients were found not to be optimally managed for these conditions.100 Screening patients with psoriasis for such risk factors helps to identify a high proportion of individuals with potentially modifiable risk factors for CVD.101

Without multispecialty support, dermatologists may feel inadequately trained to address the mental health morbidities of the disease.93 Dermatologists must learn to screen for such problems and refer patients to psychiatrists or other mental health professionals when needed.93 Because of the increased risk of suicide, it is also essential that dermatologists screen for prior history of suicidal thoughts or present suicidality, especially in patients with severe disease.23

Many patients will need input from psychiatrists or psychologists as part of their care. Management of psycho-dermatological conditions, such as psoriasis requires that providers assess the social, familial, and occupational aspects of the condition.36 A variety of techniques are available to practitioners. For example, one study of 40 patients with psoriasis in Italy found that cognitive behavioral therapy combined with biofeedback improved PASI scores, QoL, and reduced the number of minor psychiatric disorders.98 Other prospective randomized trials’ findings have demonstrated that cognitive-behavioral approaches may be able to reduce psoriasis severity.98

Primary health providers can play a key role in care coordination. They may give support for the psychological aspects of psoriasis via referral to patient support groups, stress reduction therapy, psychologist or psychiatrist referral, or administration of psychotropic medications.36 Primary health providers should also be aware of the need for assessing cardiovascular risk factors in these patients.100

Managed health providers are also needed to help ensure that patients get access to the most appropriate treatments for them. Such cost/benefit calculations must consider the varying direct costs of treatment options. However, they must also weigh the costs of AEs, decreased work productivity, and inadequately treated disease and disease morbidities on the overall economic burden.102 At this time, we lack good data on many of these outcomes, and high-quality studies of long-term cost effectiveness are needed to help inform decision making.102


Psoriasis is a source of significant psychological strain and physical discomfort for patients.2 Treatment goals in the management of psoriasis continue to emerge. With the availability of newer and more effective treatments, researchers and clinicians are beginning to use higher standards to assess patient’s therapeutic goals.44 Direct and indirect financial and personal costs of the disease are quite substantial both for individuals and for society as a whole.32 Many of these costs result from the commonly associated disease comorbidities, which include CVD, obesity, PsA, and psychiatric disorders such as depression, which exert considerable personal and financial strain on society.2,32 Yet some practitioners continue to underestimate the severity and prevalence of mental health comorbidities.95 Managed care providers also need to incorporate updated criteria to provide more comprehensive analyses of the full impacts of psoriasis-related costs.31

Over time, we will gain a better understanding of how best to address the needs of patients with psoriasis in terms of their physical, emotional, and mental health.

Author affiliations: Department of Dermatology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA.
Funding source: This publication was sponsored by Ortho Dermatologics.
Author disclosures: Dr Wu reports serving as an investigator for and receiving grants from AbbVie, Inc; Amgen, Inc; Eli Lilly and Company; Janssen Pharmaceutical; Novartis International AG; and Regeneron Pharmaceuticals, Inc.
Authorship information: Concept and design; analysis and interpretation of data; critical revision of the manuscript for important intellectual content; administrative, technical or logistic support; and supervision.
Address correspondence to: E-mail:
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