Psoriasis and PsA: Beyond Skin and Joint Involvement

Psoriasis is a common, chronic, immune-mediated inflammatory, multisystem skin disease with potential systemic complications. Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints and connective tissue that often affect individuals with psoriasis. Both conditions may require long-term treatment and can impact activities of daily life as well as aspects of quality of life including psychological, social, and occupational elements. Currently, there is no known cure for psoriasis or PsA. However, the development of biologic agents and small molecule inhibitors have changed the treatment paradigm for dermatologists managing patients with these autoimmune diseases.

This article provides an overview of psoriasis and PsA and reviews the efficacy and safety of the newest biologic agent ixekizumab (Taltz) for psoriasis and the oral phosphodiesterase-4 (PDE4) inhibitor apremilast (Otzela) for psoriasis and PsA. The burden of disease including comorbidities, unmet patient needs, and cost is also covered. Additionally, 2 new drugs in development for psoriasis and PsA are reviewed.

Psoriasis and PsA Overview

Psoriasis, an often debilitating condition, is the most prevalent autoimmune disease, affecting 7.5 million people in the United States (approximately 3% of the US population). Of the individuals with psoriasis, 1.5 million US adults have moderate to severe psoriasis. The worldwide prevalence is estimated at 1% to 3%.^1-3 Data from the National Psoriasis Foundation (NPF) estimates that approximately 25% of people with psoriasis have cases that are considered moderate.² Men and women develop psoriasis at equal rates. Onset of psoriasis develops between the ages of 15 and 35, but it can develop at any age.⁴

The causes of psoriasis are not fully understood, but a number of risk factors are recognized, including family history and environmental risk factors. Psoriasis is characterized by scaly, erythematous patches, papules, and plaques that are often painful and pruritic.⁵ Psoriasis can be mild, moderate, or severe, and be classified on the extent of body surface area (BSA) involvement (Figures 1-4). The NPF defines mild psoriasis as affecting <3% of BSA, 3% to 10% of BSA is considered moderate, and >10% of BSA is considered severe. Five types of psoriasis exist and the majority of individuals (80%-90%) have plaque psoriasis (Table 1).⁴

Psoriasis is more than a cosmetic disorder; it has an emotional and physical impact beyond visible plaques as shared by individuals at a recent day-long patient-focused drug development meeting with the FDA in which individuals spoke to officials from the agency about psoriasis and how it impacts their lives. During the meeting, the FDA polled attendees on various aspects of the disease and reported the results in real-time. When asked what are the most bothersome impacts the disease has on daily life, 59% said emotional impacts. Attendees were also asked which benefit would they consider most meaningful when considering a new psoriasis treatment. The majority (64%) said reduced itching and flaking.⁶

Lewis-Beck and colleagues⁷ assessed the relationship between psoriasis self-reported severity of symptoms and health-related quality of life, work productivity, and activity impairment among 199 individuals with moderate to severe psoriasis. Individuals were more likely to miss work with increasing severity of itching (odds ratio [OR], 2.31), pain (OR, 1.78), and scaling (OR, 2.15) symptoms. More severe itching (OR, 1.74), scaling (OR, 1.84), and pain symptoms (OR, 1.53) increased the likelihood that an individual would be less productive at work.

Psoriatic Arthritis

PsA is an inflammatory seronegative spondyloarthropathy associated with psoriasis that can cause pain, swelling and stiffness in around the joints and tendons, nail changes, and overall fatigue. Genes, the immune system, and environmental factors are thought to play a role in the onset of the disease. The prevalence of PsA in the US general population has been estimated between 0.1% to 0.25%; up to 30% of people with psoriasis develop PsA.^8,9 In the majority of cases, joint involvement follows skin involvement, often by 10 years. PsA usually develops between ages 30 and 50, but can develop at any time including childhood; the joint disease affects men and woman equally.^3,8 Table 2 shows manifestations of PsA.

PsA symptoms can range from mild to very severe. The severity of the skin disease and the arthritis usually do not correlate with each other. Nail disease is commonly found in patients with PsA especially those with distal interphalangeal joint involvement. While PsA may start slowly with mild symptoms, the course of PsA is variable and unpredictable ranging from mild and nondestructive to a severe, debilitating, erosive arthropathy. If left untreated, individuals with PsA can have persistent inflammation, progressive joint damage, severe physical limitations, disability, and increased mortality.^8,10

Like psoriasis, PsA can significantly impact quality of life. NPF research revealed that 63% of individuals with PsA are unable to be as active as they once were: 47% reported that the disease impacts their ability to work; and 34% said they have difficulty getting in and out of a car. Furthermore, individuals with PsA are not being diagnosed in a timely manner. Data showed 44% experience symptoms for 1 year or longer before being diagnosed and 30% reported a delay of 2 years or longer to receive diagnosis.¹¹

Comorbidities

Beyond the physical pain and discomfort of psoriasis and PsA, individuals with psoriatic diseases also face higher incidences of comorbidities including cardiovascular disease, diabetes, hypertension, and stroke.¹² Hypertension in particular appears to be a leading comorbidity among patients with PsA. Husted and colleagues¹³ found that hypertension was present in 37% of PsA individuals compared with 20% individuals with only psoriasis. In the same comorbidity study, more individuals with PsA had neurologic conditions, gastrointestinal disorders, and liver disease than individuals with psoriasis alone.

In treating patients with PsA, Philip Mease, MD, clinical professor, University of Washington School of Medicine in Seattle, underscored the importance of looking at comorbidities. “It’s so important to think beyond the joints and skin,” he said during a session at the April Interdisciplinary Autoimmune Summit 2016 that focused on evolving treatment strategies for psoriatic disease. “[We need] to think about some of the associated manifestations including uveitis, inflammatory bowel disease, and comorbidity of cardiovascular disease and metabolic syndrome, fatty liver, depression, suicidal ideation, and fatigue.”

Compared with the general population, individuals with psoriasis have a higher prevalence of atherosclerosis, Crohn disease, cancer, metabolic syndrome, obesity, and liver disease.¹² Psychological comorbidities have also been reported with psoriasis including depression, anxiety, and sleep disturbances affecting quality of life.¹⁴

Economic Burden

Health care expenditures associated with psoriasis and PsA are significant. Brezinski and colleagues¹⁵ conducted a systematic review of 22 studies on the direct, indirect, and comorbidity costs of adult psoriasis in the United States. Individuals with psoriasis incur health care costs that are significantly greater than the general population. Additionally, the economic burden of psoriasis is substantial because this skin disease results in considerable negative physical, psychiatric, and social consequences. Adjusting costs to 2013 US dollars, the annual US cost of psoriasis is approximately $112 billion. The direct costs ranged from $51.7 billion to $63.2 billion, the indirect costs ranged from $23.9 billion to $35.4 billion, and medical comorbidities were estimated to contribute $36.4 billion annually.

Due to the dual skin and joint involvement, Feldman and colleagues¹⁶ found that individuals with moderate to severe psoriasis and comorbid PsA experience higher health care expenditures compared with matched controls free of both conditions. The retrospective study used data from a large US claims database to compare the comorbidities and health care utilization and costs between 1230 matched pairs of individuals with psoriasis and PsA and controls. Individuals with psoriasis and comorbid PsA compared with controls incurred substantially higher annual total health care costs ($27,123 vs $5301, respectively), with a majority of the cost difference driven by pharmacy costs ($18,083 vs $1267, respectively), followed by medical costs ($9040 vs $4035, respectively). Additionally, all medical cost components were higher among the cohort with psoriasis and PsA vs the matched controls, including inpatient services ($2372 vs $1456, respectively), emergency room ($294 vs $137, respectively), outpatient services ($5919 vs $2256, respectively), and other medical costs ($455 vs $185, respectively).

Unmet Patient Needs

The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey aimed to further understand the unmet needs of psoriasis patients. The population-based survey included patients, dermatologists, and rheumatologists. The survey found that both psoriasis and PsA remain undertreated in patients with moderate to severe disease. Unmet needs identified in the management of these conditions included screening, assessment of disease severity, PsA diagnosis, and satisfaction with therapy.¹⁷ Among the patients with psoriasis, 26.9% had been diagnosed with PsA. Of those with psoriasis alone, fewer than 60% had seen a health care provider within 12 months compared with 85.6% of patients with PsA. Joint pain was reported by 51.8% of psoriasis patients without a PsA diagnosis, and 37.6% of dermatologists cited their greatest challenge as being differentiating PsA from other diseases.

Findings from MAPP survey also suggested that patients with psoriasis and dermatologists may assess disease severity differently. Itching was reported by 36.1% of psoriasis patients as the most important factor contributing to disease severity, followed by location and size of lesions (21.8%). In contrast, 76.2% of dermatologists considered the location or size of the skin lesion as the prominent factor contributing to disease severity in their patients, while only 11.9% cited itching. Patients also reported lower rates of current treatment than did dermatologists and rheumatologists. Conventional oral and biologic therapies were used by 24.9% and 17.7% of patients, respectively. Among patients who received injectable biologics, treatment dissatisfaction was related to long-term safety and tolerability, injection-related anxiety and fear, and cost. Overall, 31.3% of patients with psoriasis and 40.7% of patients with PsA reported that their primary goals of therapy, including keeping symptoms at bay, reducing itching, and decreasing flaking, were not met with their current treatment.¹⁷

Evidence has shown that individuals with PsA are often underdiagnosed or misdiagnosed, potentially leading to delays in treatment. Unmet needs and gaps in PsA diagnosis and treatment were identified by the Psoriatic Arthritis Forum.¹⁸ Gaps in awareness and diagnosis include minimal awareness of the PsA among physicians, appropriate screening tools for PsA are lacking, and criteria are unclear regarding rheumatologist referrals and/or treatment. Gaps in treatment included that available treatment algorithms have not been validated, no standard remission criteria, no available validated composite index combining physician- and patient-orientated outcomes, and the need for easy to use treatments with convenient means of administration.

“PsA is a complex heterogeneous disease, no patient is the same,” said Dr Mease, noting that clinicians need to consider the variabilities in the presentation when treating these individuals.

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Treatment

Psoriasis and PsA have been treated successfully for the more than 50 years with oral systemic medicines. The current traditional oral systemic agents for psoriasis (methotrexate, cyclosporine, acitretin, and fumaric acid esters) and PsA (methotrexate, sulfasalazine, and leflunomide) have varying levels of efficacy, and are limited by an array of toxicities. Biological agents targeting tumor necrosis factor-a, IL-12/23, and IL-17 have emerged in the last 10 years for psoriasis and PsA and have added to the armamentarium of treatment options, with greater efficacy and a better overall safety profile than the traditional systemic agents. Novel oral therapies, referred to as small molecule inhibitors, are also emerging for the treatment of psoriatic disease.¹⁹

 “I think one of the most common questions that patients ask when they are put on any medication is ‘When do you think I am going to start seeing a response?’” said Gary Goldenberg, MD, medical director of the Dermatology Faculty Practice in New York City, and assistant clinical professor, dermatology at Icahn School of Medicine at Mount Sinai Hospital in New York, during session on new oral agents for psoriasis at the 2015 American Academy of Dermatology Summer Meeting.²⁰


Currently, ⁸ biologics are FDA-approved for psoriasis, PsA, or both, and one small molecule inhibitor is FDA-approved for psoriasis and PsA—and new therapies remain in the pipeline (Table 3).²¹ Here is a look at data from pivotal trials for the biologic agent ixekizumab for psoriasis and the PDE4 inhibitor apremilast for psoriasis and PsA.

Ixekizumab

Ixekizumab received FDA approval on March 22, 2016, for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. It should not be used patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients. Ixekizumab is designed to specifically target IL-17A, a protein that plays a role in driving underlying inflammation in psoriasis.²²

Ixekizumab’s efficacy and safety was established in 3 multicenter, randomized, double-blind, placebo-controlled, phase 3 trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—of 3866 participants with moderate to severe plaque psoriasis who were candidates for systemic therapy, phototherapy, or both. All participants were aged ≥18 years and had plaque psoriasis with a BSA involvement of ≥10%, a static Physician’s Global Assessment (sPGA) score ≥3, and a Psoriasis Area Severity Index (PASI) score ≥12. The participants in all 3 studies were randomly assigned to subcutaneous placebo, ixekizumab 80 mg (every 2 weeks following a 160-mg starting dose), or ixekizumab 80 mg (every 4 weeks following a 160-mg starting dose). UNCOVER-2 and UNCOVER-3 included an additional comparator arm in which participants received etanercept (Enbrel) 50 mg twice weekly for 12 weeks. At week 12 in the UNCOVER-3 trial, the participants entered a long-term extension period during which they received 80 mg ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the participants who had a response to ixekizumab were randomly reassigned to receive placebo, 80 mg ixekizumab every 4 weeks, or 80 mg ixekizumab every 12 weeks through week 60. The coprimary efficacy endpoints at 12 weeks were the percentage of participants who had sPGA 0 or 1 and PASI 75 or greater reduction from baseline.²³

Gordon and colleagues²³ reported that the majority of participants treated with ixekizumab achieved significant skin clearance (sPGA 0 or 1, PASI 75). At 12 weeks in UNCOVER-1, participants in the 2- and 4-week dosing groups of ixekizumab exhibited better responses compared with placebo. In the 2-week dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-week dosing group, the rates were 76.4% and 82.6%, respectively; and in the placebo groups, the rates were 3.2% and 3.9%, respectively. Among the participants in UNCOVER-1 and UNCOVER-2 who were randomly reassigned at week 12 to receive 80 mg ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0%, respectively. For the participants in UNCOVER-3 who received continuous treatment of ixekizumab from week 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response.

The most common adverse events (AEs) reported with ixekizumab included neutropenia, candida infections, and inflammatory bowel disease. The researchers noted that the benefits of ixekizumab needed to be weighed against the AEs, and the safety profile of longer-term treatment with ixekizumab should be examined.²³

Apremilast

Apremilast was FDA approved in 2014 for the treatment of moderate to severe plaque psoriasis in individuals who are candidates for phototherapy or systemic therapy, and for the treatment of adults with active PsA. It is the only oral PDE4 therapy to receive FDA approval for these 2 autoimmune diseases. Apremilast works by inhibiting intracellular PDE4 resulting in increased levels of cyclic adenosine monophosphate.²⁴

The Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) clinical trial program is evaluating the safety and efficacy of apremilast. ESTEEM comprises 2 similarly designed, multicenter, randomized, double-blind, placebo-controlled, phase 3 trials of apremilast 30 mg twice daily for moderate to severe plaque psoriasis. In a recent ESTEEM 2 study, Paul and colleagues²⁵ evaluated the efficacy and safety of apremilast in 411 individuals with a diagnosis of chronic plaque psoriasis for ≥12 months, PASI score ≥12, BSA involvement ≥10%, sPGA score ≥3, and who were candidates for phototherapy or systemic therapy. The primary endpoint was the proportion of individuals who achieved PASI 75 response at week 16. The major secondary endpoint was the proportion of participants who achieved sPGA response at week 16, defined as an sPGA score of 0 or 1 with ≥2-point reduction from baseline. Participants were randomized 2:1 to apremilast or placebo. At week 16, the placebo cohort switched to apremilast. At week 32, individuals receiving apremilast who achieved a ≥50% reduction in PASI were randomized 1:1 to continue apremilast or receive placebo.

Apremilast significantly reduced the severity of moderate to severe plaque psoriasis over 16 weeks, with responses generally maintained in individuals continuing treatment with the oral therapy for 52 weeks. At week 16, significantly more individuals in the apremilast cohort achieved PASI 75 (28.8%), PASI 50 (55.5%), and sPGA score of 0 or 1 (20.4%) vs placebo (5. 8%, 19.7%, and 4.4%, respectively). The majority of individuals (80%) rerandomized to apremilast at 32 weeks had a PASI 50 response at week 52. Additionally, the researchers found that apremilast demonstrated an acceptable safety profile, and no new significant AEs emerged with continued exposure for up to 52 weeks.²⁵

The effect of apremilast on multiple manifestations of PsA is being assessed in the Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) phase 3 clinical trial program. Edwards and colleagues²⁶ recently reported data the results of the first 52 weeks of PALACE 3 that evaluated apremilast in 505 individuals with active PsA, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents.

Participants were randomized 1:1:1 to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo participants not achieving American College of Rheumatology 20 (ACR20) improvement in swollen and tender joint counts. At week 24, the remaining placebo cohort were then randomized to twice daily 20 mg or 30 mg apremilast. The primary endpoint was the proportion of participants achieving an ACR20 response at week 16. The primary secondary endpoint was the change from baseline in the Health Assessment Questionnaire Index (HAQ-DI) at week 16.

Both apremilast doses demonstrated significant therapeutic effects on disease activity, including improvements in signs and symptoms of PsA as well as psoriasis, and sustained improvements were seen with continued treatment through 52 weeks. At week 16, apremilast demonstrated clinically meaningful improvements in PsA disease severity, marked by significantly greater achievement of ACR20 response in the apremilast 20 mg and 30 mg groups vs placebo (28% and 42%, respectively, vs 18%), and the mean decrease in HAQ-DI score was significantly greater with apremilast 30 mg vs placebo (–0.20 vs –0.07, respectively). Psoriasis severity was also significantly reduced at week 16 among individuals with psoriasis BSA ≥3% at baseline. A greater proportion of individuals receiving apremilast 30 mg achieved PASI 50 vs placebo at week 16 (41% vs 24%, respectively).

The most common adverse reactions associated with apremilast in PsA clinical trials were nausea, diarrhea, headache, upper respiratory tract infection, and vomiting. In the psoriasis clinical trials, diarrhea, nausea, upper respiratory tract infection, tension headache, and headache were the most common adverse reactions.²⁴

Drug Pipeline

Currently, severalpharmacological therapies are under development ranging from developmental stages to clinical trials for psoriasis and PsA. Table 4 shows injectable and oral treatments in phase 3 trials.²⁷

Many novel biologic treatments promise exciting new therapeutic options for psoriasis and PsA that target various cytokines and regulatory molecules involved in the pathogenesis of psoriasis and PsA, including inhibition of IL-23 pathway.²⁸ Tildrakizumab, for example, a humanized IgG1k monoclonal antibody that targets the unique p19 subunit of IL-23 is in phase 3 trials for psoriasis. A randomized, double-blind, phase 2b trial showed that tildrakizumab was effective in treating moderate to severe plaque psoriasis in 355 adults.

Participants were randomized to receive subcutaneous tildrakizumab (5, 25, 100, or 200 mg) or placebo at weeks 0 and 4 and every 12 weeks thereafter until week 52. Tildrakizumab was discontinued at week 52 and participants were followed through week 72. At week 16, the PASI 75 responses was significantly higher at all doses when compared with placebo: 33.3% (5 mg), 64.4% (25 mg), 66.3% (100 mg), and 74.4% (200 mg) compared with 4.4% on placebo. The final drug dose was administered on week 40, and the participants were followed until week 72. Tildrakizumab demonstrated a low relapse rate after cessation of therapy with only 3.6% of participants who achieved PASI 75 at week 52 on any dose of tildrakizumab relapsing before week 72. Phase 3 studies are in progress.²⁹

The investigational drug tofacitinib (Xeljanz) is 1 oral agent in phase 3 trials for psoriasis and PsA. Tofacitinib is a small molecule that targets the Janus kinase pathway, a signaling pathway inside the cells, thought to play a role in chronic inflammatory responses.

Bachelez and colleagues conducted a randomized, multicenter, double-dummy, placebo-controlled, 12-week, noninferiority, phase 3 study comparing 5 mg and 10 mg tofacitinib with high-dose etanercept or placebo in 1101 adults with chronic stable plaque psoriasis who were candidates for systemic therapy or phototherapy. The primary endpoints were the proportion of participants at week 12 with at least a 75% reduction in PASI from baseline and the proportion of participants achieving a PGA score of clear or almost clear.^20,30

Tofacitinib 10 mg twice daily was noninferior to etanercept and was superior to placebo, but tofacitinib 5 mg twice daily did not show noninferiority to etanercept. Of the individuals randomized to tofacitinib 10 mg, 63.6% achieved PASI 75 after 12 weeks of treatment vs 58.8% who were randomized to etanercept.

Additionally, tofacitinib demonstrated superiority to placebo with 5.6% of placebo-treated individuals achieving PASI 75. Among the individuals randomized to tofacitinib 5 mg, 39.5% achieved PASI 75. A PGA response was achieved by 68.2% of individuals taking tofacitinib 10 mg, 66.3% of those on etanercept, 47.1% of those on tofacitinib 5 mg, and 15% taking placebo.^20,30

Conclusion

Psoriasis and PsA can have a profound impact on the quality of life for individuals living with these autoimmune diseases, which require lifelong management and support. While new treatment options have entered the marketplace in the last 10 years and demonstrated proven efficacy and safety in psoriasis and PsA, gaps in diagnosis and treatment still exist.

“Ongoing communication between patients and physicians is needed for better understanding of perception of disease severity, discussion and agreement on treatment options, and establishment of realistic treatment goals. The need for safe, effective, and easy to use therapies for psoriasis and PsA remain,” said Lebwhol and colleagues.¹⁷

Therefore, dermatologists should individualize treatment taking into consideration efficacy, side effects, availability, ease of administration, comorbidities, family history, and coexisting diseases when prescribing treatment. Patient and clinician education is also crucial to optimizing treatment for all categories of disease severity.

References
1. Helmick CG, Lee-Han H, Hirsch SC, Baird TL, Bartlett CL. Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys. Am J Prev. 2014;47(1):37-45.
2. National Psoriasis Foundation. The Psoriasis and Psoriatic Arthritis Pocket Guide: Treatment Options and Patient Management. 3rd ed. Portland, OR; 2009.
3. Van de Kerkhof PC, Reich K, Kavanaugh A, et al. Physician perspectives in the management of psoriasis and psoriatic arthritis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis survey. J Eur Acad Dermatol Venereol. 2015;29(10):2002-2010.
4. About psoriasis. National Psoriasis Foundation website. www.psoriasis.org/about-psoriasis. Accessed June 10, 2016.
5. Menter A, Gottlieb A, Feldman, SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58(5):826-850.
6. Jones K. Patients with psoriasis speak to the FDA. The Dermatologist. 2016;24(6):36-37.
7. Lewis-Beck C, Abouzaid S, Xie L, Baser O, Kim E. Analysis of the relationship between psoriasis symptom severity and quality of life, work productivity, and activity impairment among patients with moderate-to-severe psoriasis using structural equation modeling. Patient Prefer Adherence. 2013;7:199-205.
8. Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008;58(5):851-864.
9. About psoriatic psoriasis. National Psoriasis Foundation website. https://www.psoriasis.org/about-psoriatic-arthritis#types. Accessed June 10, 2016.
10. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol. 2011;65(1):137-174.
11. Facts about psoriatic arthritis. National Psoriasis Foundation website. https://www.psoriasis.org/sites/default/files/for-media/MediaKit.pdf. Accessed June 10, 2016.
12. McCormick Howard L. National Psoriasis Foundation: a patient-centric approach to improve access to psoriatic disease treatment. Am J Manag Care. 2016;22(4 suppl):S104-S107.
13. Husted JA, Thavaneswaran A, Chandran, et al. Cardiovascular and other comorbidities in patients with psoriatic arthritis: a comparison with patients with psoriasis. Arthritis Care Res (Hoboken). 2011;63(12):1729-1735.
14. Prussick L, Jimenez E, Nussbaum D. Psoriasis and psychological comorbidities. J Psoriasis and Psoriatic Arthritis. 2016;1(2):80-85.
15. Brezinski EA, Dhillon JS, Armstrong AW. Economic burden of psoriasis in the United States: A systematic review. JAMA Dermatol. 2015;151(6):651-658.
16. Feldman SR, Zhao Y, Shi L, Tran MH, Lu J. Economic and comorbidity burden among moderate-to-severe psoriasis patients with comorbid psoriatic arthritis. Arthritis Care Res (Hoboken). 2015;67(5):708-717.
17. Lebwohl MG, Kavanaugh A, Armstrong AW, Van Voorhees AS. US perspectives in the management of psoriasis and psoriatic arthritis: patient and physician results from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey. Am J Clin Dermatol. 2016;17(1):87-97.
18. Helliwell P, Coates L, Chandran V, et al. Qualifying unmet needs and improving standards of care in psoriatic arthritis. Arthritis Care Res. 2014;66(12):1759-1766.
19. Yiu ZZ, Warren RB. Novel oral therapies for psoriasis and psoriatic arthritis. Am J Clin Dermatol. 2016;17(3):191-200.
20. Koutnik-Fotopoulos E. New oral therapies to treat psoriasis. The Dermatologist. 2016;24(2):30-34.
21. Psoriasis treatments. National Psoriasis Foundation website. https://www.psoriasis.org/about-psoriasis/treatments. Accessed June 10, 2016.
22. Taltz [prescribing information]. Indianapolis, IN: Eli Lilly and Company; 2016.
23. Gordon KB, Blauvelt KA, Papp RG, et al; UNCOVER-1, UNCOVER-2, and UNCOVER-3 Study Groups. Phase 3 trials of ixekizumab in moderate-to-severe psoriasis [published online June 8, 2016]. N Engl J Med. doi:10.1056/NEJMoa1512711.
24. Otezla [prescribing information]. Summit, NJ: Celegene Corporation; 2015.
25. Paul C, Cather J, Gooderham M, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). Br J Dermatol. 2015;173(6):1387-1399.
26. Edwards CJ, Blanco FJ, Crowley J, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis. 2016;75(6):1065-1073.
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30. Bachelez H, van de Kerkhof PC, Strohoal R, et al; OPT Compare Investigators. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial. Lancet. 2015;386(9993):552-561.

Psoriasis is a common, chronic, immune-mediated inflammatory, multisystem skin disease with potential systemic complications. Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints and connective tissue that often affect individuals with psoriasis. Both conditions may require long-term treatment and can impact activities of daily life as well as aspects of quality of life including psychological, social, and occupational elements. Currently, there is no known cure for psoriasis or PsA. However, the development of biologic agents and small molecule inhibitors have changed the treatment paradigm for dermatologists managing patients with these autoimmune diseases.

This article provides an overview of psoriasis and PsA and reviews the efficacy and safety of the newest biologic agent ixekizumab (Taltz) for psoriasis and the oral phosphodiesterase-4 (PDE4) inhibitor apremilast (Otzela) for psoriasis and PsA. The burden of disease including comorbidities, unmet patient needs, and cost is also covered. Additionally, 2 new drugs in development for psoriasis and PsA are reviewed.

Psoriasis and PsA Overview

Psoriasis, an often debilitating condition, is the most prevalent autoimmune disease, affecting 7.5 million people in the United States (approximately 3% of the US population). Of the individuals with psoriasis, 1.5 million US adults have moderate to severe psoriasis. The worldwide prevalence is estimated at 1% to 3%.^1-3 Data from the National Psoriasis Foundation (NPF) estimates that approximately 25% of people with psoriasis have cases that are considered moderate.² Men and women develop psoriasis at equal rates. Onset of psoriasis develops between the ages of 15 and 35, but it can develop at any age.⁴

The causes of psoriasis are not fully understood, but a number of risk factors are recognized, including family history and environmental risk factors. Psoriasis is characterized by scaly, erythematous patches, papules, and plaques that are often painful and pruritic.⁵ Psoriasis can be mild, moderate, or severe, and be classified on the extent of body surface area (BSA) involvement (Figures 1-4). The NPF defines mild psoriasis as affecting <3% of BSA, 3% to 10% of BSA is considered moderate, and >10% of BSA is considered severe. Five types of psoriasis exist and the majority of individuals (80%-90%) have plaque psoriasis (Table 1).⁴

Psoriasis is more than a cosmetic disorder; it has an emotional and physical impact beyond visible plaques as shared by individuals at a recent day-long patient-focused drug development meeting with the FDA in which individuals spoke to officials from the agency about psoriasis and how it impacts their lives. During the meeting, the FDA polled attendees on various aspects of the disease and reported the results in real-time. When asked what are the most bothersome impacts the disease has on daily life, 59% said emotional impacts. Attendees were also asked which benefit would they consider most meaningful when considering a new psoriasis treatment. The majority (64%) said reduced itching and flaking.⁶

Lewis-Beck and colleagues⁷ assessed the relationship between psoriasis self-reported severity of symptoms and health-related quality of life, work productivity, and activity impairment among 199 individuals with moderate to severe psoriasis. Individuals were more likely to miss work with increasing severity of itching (odds ratio [OR], 2.31), pain (OR, 1.78), and scaling (OR, 2.15) symptoms. More severe itching (OR, 1.74), scaling (OR, 1.84), and pain symptoms (OR, 1.53) increased the likelihood that an individual would be less productive at work.

Psoriatic Arthritis

PsA is an inflammatory seronegative spondyloarthropathy associated with psoriasis that can cause pain, swelling and stiffness in around the joints and tendons, nail changes, and overall fatigue. Genes, the immune system, and environmental factors are thought to play a role in the onset of the disease. The prevalence of PsA in the US general population has been estimated between 0.1% to 0.25%; up to 30% of people with psoriasis develop PsA.^8,9 In the majority of cases, joint involvement follows skin involvement, often by 10 years. PsA usually develops between ages 30 and 50, but can develop at any time including childhood; the joint disease affects men and woman equally.^3,8 Table 2 shows manifestations of PsA.

PsA symptoms can range from mild to very severe. The severity of the skin disease and the arthritis usually do not correlate with each other. Nail disease is commonly found in patients with PsA especially those with distal interphalangeal joint involvement. While PsA may start slowly with mild symptoms, the course of PsA is variable and unpredictable ranging from mild and nondestructive to a severe, debilitating, erosive arthropathy. If left untreated, individuals with PsA can have persistent inflammation, progressive joint damage, severe physical limitations, disability, and increased mortality.^8,10

Like psoriasis, PsA can significantly impact quality of life. NPF research revealed that 63% of individuals with PsA are unable to be as active as they once were: 47% reported that the disease impacts their ability to work; and 34% said they have difficulty getting in and out of a car. Furthermore, individuals with PsA are not being diagnosed in a timely manner. Data showed 44% experience symptoms for 1 year or longer before being diagnosed and 30% reported a delay of 2 years or longer to receive diagnosis.¹¹

Comorbidities

Beyond the physical pain and discomfort of psoriasis and PsA, individuals with psoriatic diseases also face higher incidences of comorbidities including cardiovascular disease, diabetes, hypertension, and stroke.¹² Hypertension in particular appears to be a leading comorbidity among patients with PsA. Husted and colleagues¹³ found that hypertension was present in 37% of PsA individuals compared with 20% individuals with only psoriasis. In the same comorbidity study, more individuals with PsA had neurologic conditions, gastrointestinal disorders, and liver disease than individuals with psoriasis alone.

In treating patients with PsA, Philip Mease, MD, clinical professor, University of Washington School of Medicine in Seattle, underscored the importance of looking at comorbidities. “It’s so important to think beyond the joints and skin,” he said during a session at the April Interdisciplinary Autoimmune Summit 2016 that focused on evolving treatment strategies for psoriatic disease. “[We need] to think about some of the associated manifestations including uveitis, inflammatory bowel disease, and comorbidity of cardiovascular disease and metabolic syndrome, fatty liver, depression, suicidal ideation, and fatigue.”

Compared with the general population, individuals with psoriasis have a higher prevalence of atherosclerosis, Crohn disease, cancer, metabolic syndrome, obesity, and liver disease.¹² Psychological comorbidities have also been reported with psoriasis including depression, anxiety, and sleep disturbances affecting quality of life.¹⁴

Economic Burden

Health care expenditures associated with psoriasis and PsA are significant. Brezinski and colleagues¹⁵ conducted a systematic review of 22 studies on the direct, indirect, and comorbidity costs of adult psoriasis in the United States. Individuals with psoriasis incur health care costs that are significantly greater than the general population. Additionally, the economic burden of psoriasis is substantial because this skin disease results in considerable negative physical, psychiatric, and social consequences. Adjusting costs to 2013 US dollars, the annual US cost of psoriasis is approximately $112 billion. The direct costs ranged from $51.7 billion to $63.2 billion, the indirect costs ranged from $23.9 billion to $35.4 billion, and medical comorbidities were estimated to contribute $36.4 billion annually.

Due to the dual skin and joint involvement, Feldman and colleagues¹⁶ found that individuals with moderate to severe psoriasis and comorbid PsA experience higher health care expenditures compared with matched controls free of both conditions. The retrospective study used data from a large US claims database to compare the comorbidities and health care utilization and costs between 1230 matched pairs of individuals with psoriasis and PsA and controls. Individuals with psoriasis and comorbid PsA compared with controls incurred substantially higher annual total health care costs ($27,123 vs $5301, respectively), with a majority of the cost difference driven by pharmacy costs ($18,083 vs $1267, respectively), followed by medical costs ($9040 vs $4035, respectively). Additionally, all medical cost components were higher among the cohort with psoriasis and PsA vs the matched controls, including inpatient services ($2372 vs $1456, respectively), emergency room ($294 vs $137, respectively), outpatient services ($5919 vs $2256, respectively), and other medical costs ($455 vs $185, respectively).

Unmet Patient Needs

The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey aimed to further understand the unmet needs of psoriasis patients. The population-based survey included patients, dermatologists, and rheumatologists. The survey found that both psoriasis and PsA remain undertreated in patients with moderate to severe disease. Unmet needs identified in the management of these conditions included screening, assessment of disease severity, PsA diagnosis, and satisfaction with therapy.¹⁷ Among the patients with psoriasis, 26.9% had been diagnosed with PsA. Of those with psoriasis alone, fewer than 60% had seen a health care provider within 12 months compared with 85.6% of patients with PsA. Joint pain was reported by 51.8% of psoriasis patients without a PsA diagnosis, and 37.6% of dermatologists cited their greatest challenge as being differentiating PsA from other diseases.

Findings from MAPP survey also suggested that patients with psoriasis and dermatologists may assess disease severity differently. Itching was reported by 36.1% of psoriasis patients as the most important factor contributing to disease severity, followed by location and size of lesions (21.8%). In contrast, 76.2% of dermatologists considered the location or size of the skin lesion as the prominent factor contributing to disease severity in their patients, while only 11.9% cited itching. Patients also reported lower rates of current treatment than did dermatologists and rheumatologists. Conventional oral and biologic therapies were used by 24.9% and 17.7% of patients, respectively. Among patients who received injectable biologics, treatment dissatisfaction was related to long-term safety and tolerability, injection-related anxiety and fear, and cost. Overall, 31.3% of patients with psoriasis and 40.7% of patients with PsA reported that their primary goals of therapy, including keeping symptoms at bay, reducing itching, and decreasing flaking, were not met with their current treatment.¹⁷

Evidence has shown that individuals with PsA are often underdiagnosed or misdiagnosed, potentially leading to delays in treatment. Unmet needs and gaps in PsA diagnosis and treatment were identified by the Psoriatic Arthritis Forum.¹⁸ Gaps in awareness and diagnosis include minimal awareness of the PsA among physicians, appropriate screening tools for PsA are lacking, and criteria are unclear regarding rheumatologist referrals and/or treatment. Gaps in treatment included that available treatment algorithms have not been validated, no standard remission criteria, no available validated composite index combining physician- and patient-orientated outcomes, and the need for easy to use treatments with convenient means of administration.

“PsA is a complex heterogeneous disease, no patient is the same,” said Dr Mease, noting that clinicians need to consider the variabilities in the presentation when treating these individuals.

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Treatment

Psoriasis and PsA have been treated successfully for the more than 50 years with oral systemic medicines. The current traditional oral systemic agents for psoriasis (methotrexate, cyclosporine, acitretin, and fumaric acid esters) and PsA (methotrexate, sulfasalazine, and leflunomide) have varying levels of efficacy, and are limited by an array of toxicities. Biological agents targeting tumor necrosis factor-a, IL-12/23, and IL-17 have emerged in the last 10 years for psoriasis and PsA and have added to the armamentarium of treatment options, with greater efficacy and a better overall safety profile than the traditional systemic agents. Novel oral therapies, referred to as small molecule inhibitors, are also emerging for the treatment of psoriatic disease.¹⁹

 “I think one of the most common questions that patients ask when they are put on any medication is ‘When do you think I am going to start seeing a response?’” said Gary Goldenberg, MD, medical director of the Dermatology Faculty Practice in New York City, and assistant clinical professor, dermatology at Icahn School of Medicine at Mount Sinai Hospital in New York, during session on new oral agents for psoriasis at the 2015 American Academy of Dermatology Summer Meeting.²⁰


Currently, ⁸ biologics are FDA-approved for psoriasis, PsA, or both, and one small molecule inhibitor is FDA-approved for psoriasis and PsA—and new therapies remain in the pipeline (Table 3).²¹ Here is a look at data from pivotal trials for the biologic agent ixekizumab for psoriasis and the PDE4 inhibitor apremilast for psoriasis and PsA.

Ixekizumab

Ixekizumab received FDA approval on March 22, 2016, for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. It should not be used patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients. Ixekizumab is designed to specifically target IL-17A, a protein that plays a role in driving underlying inflammation in psoriasis.²²

Ixekizumab’s efficacy and safety was established in 3 multicenter, randomized, double-blind, placebo-controlled, phase 3 trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—of 3866 participants with moderate to severe plaque psoriasis who were candidates for systemic therapy, phototherapy, or both. All participants were aged ≥18 years and had plaque psoriasis with a BSA involvement of ≥10%, a static Physician’s Global Assessment (sPGA) score ≥3, and a Psoriasis Area Severity Index (PASI) score ≥12. The participants in all 3 studies were randomly assigned to subcutaneous placebo, ixekizumab 80 mg (every 2 weeks following a 160-mg starting dose), or ixekizumab 80 mg (every 4 weeks following a 160-mg starting dose). UNCOVER-2 and UNCOVER-3 included an additional comparator arm in which participants received etanercept (Enbrel) 50 mg twice weekly for 12 weeks. At week 12 in the UNCOVER-3 trial, the participants entered a long-term extension period during which they received 80 mg ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the participants who had a response to ixekizumab were randomly reassigned to receive placebo, 80 mg ixekizumab every 4 weeks, or 80 mg ixekizumab every 12 weeks through week 60. The coprimary efficacy endpoints at 12 weeks were the percentage of participants who had sPGA 0 or 1 and PASI 75 or greater reduction from baseline.²³

Gordon and colleagues²³ reported that the majority of participants treated with ixekizumab achieved significant skin clearance (sPGA 0 or 1, PASI 75). At 12 weeks in UNCOVER-1, participants in the 2- and 4-week dosing groups of ixekizumab exhibited better responses compared with placebo. In the 2-week dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-week dosing group, the rates were 76.4% and 82.6%, respectively; and in the placebo groups, the rates were 3.2% and 3.9%, respectively. Among the participants in UNCOVER-1 and UNCOVER-2 who were randomly reassigned at week 12 to receive 80 mg ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0%, respectively. For the participants in UNCOVER-3 who received continuous treatment of ixekizumab from week 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response.

The most common adverse events (AEs) reported with ixekizumab included neutropenia, candida infections, and inflammatory bowel disease. The researchers noted that the benefits of ixekizumab needed to be weighed against the AEs, and the safety profile of longer-term treatment with ixekizumab should be examined.²³

Apremilast

Apremilast was FDA approved in 2014 for the treatment of moderate to severe plaque psoriasis in individuals who are candidates for phototherapy or systemic therapy, and for the treatment of adults with active PsA. It is the only oral PDE4 therapy to receive FDA approval for these 2 autoimmune diseases. Apremilast works by inhibiting intracellular PDE4 resulting in increased levels of cyclic adenosine monophosphate.²⁴

The Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) clinical trial program is evaluating the safety and efficacy of apremilast. ESTEEM comprises 2 similarly designed, multicenter, randomized, double-blind, placebo-controlled, phase 3 trials of apremilast 30 mg twice daily for moderate to severe plaque psoriasis. In a recent ESTEEM 2 study, Paul and colleagues²⁵ evaluated the efficacy and safety of apremilast in 411 individuals with a diagnosis of chronic plaque psoriasis for ≥12 months, PASI score ≥12, BSA involvement ≥10%, sPGA score ≥3, and who were candidates for phototherapy or systemic therapy. The primary endpoint was the proportion of individuals who achieved PASI 75 response at week 16. The major secondary endpoint was the proportion of participants who achieved sPGA response at week 16, defined as an sPGA score of 0 or 1 with ≥2-point reduction from baseline. Participants were randomized 2:1 to apremilast or placebo. At week 16, the placebo cohort switched to apremilast. At week 32, individuals receiving apremilast who achieved a ≥50% reduction in PASI were randomized 1:1 to continue apremilast or receive placebo.

Apremilast significantly reduced the severity of moderate to severe plaque psoriasis over 16 weeks, with responses generally maintained in individuals continuing treatment with the oral therapy for 52 weeks. At week 16, significantly more individuals in the apremilast cohort achieved PASI 75 (28.8%), PASI 50 (55.5%), and sPGA score of 0 or 1 (20.4%) vs placebo (5. 8%, 19.7%, and 4.4%, respectively). The majority of individuals (80%) rerandomized to apremilast at 32 weeks had a PASI 50 response at week 52. Additionally, the researchers found that apremilast demonstrated an acceptable safety profile, and no new significant AEs emerged with continued exposure for up to 52 weeks.²⁵

The effect of apremilast on multiple manifestations of PsA is being assessed in the Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) phase 3 clinical trial program. Edwards and colleagues²⁶ recently reported data the results of the first 52 weeks of PALACE 3 that evaluated apremilast in 505 individuals with active PsA, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents.

Participants were randomized 1:1:1 to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo participants not achieving American College of Rheumatology 20 (ACR20) improvement in swollen and tender joint counts. At week 24, the remaining placebo cohort were then randomized to twice daily 20 mg or 30 mg apremilast. The primary endpoint was the proportion of participants achieving an ACR20 response at week 16. The primary secondary endpoint was the change from baseline in the Health Assessment Questionnaire Index (HAQ-DI) at week 16.

Both apremilast doses demonstrated significant therapeutic effects on disease activity, including improvements in signs and symptoms of PsA as well as psoriasis, and sustained improvements were seen with continued treatment through 52 weeks. At week 16, apremilast demonstrated clinically meaningful improvements in PsA disease severity, marked by significantly greater achievement of ACR20 response in the apremilast 20 mg and 30 mg groups vs placebo (28% and 42%, respectively, vs 18%), and the mean decrease in HAQ-DI score was significantly greater with apremilast 30 mg vs placebo (–0.20 vs –0.07, respectively). Psoriasis severity was also significantly reduced at week 16 among individuals with psoriasis BSA ≥3% at baseline. A greater proportion of individuals receiving apremilast 30 mg achieved PASI 50 vs placebo at week 16 (41% vs 24%, respectively).

The most common adverse reactions associated with apremilast in PsA clinical trials were nausea, diarrhea, headache, upper respiratory tract infection, and vomiting. In the psoriasis clinical trials, diarrhea, nausea, upper respiratory tract infection, tension headache, and headache were the most common adverse reactions.²⁴

Drug Pipeline

Currently, severalpharmacological therapies are under development ranging from developmental stages to clinical trials for psoriasis and PsA. Table 4 shows injectable and oral treatments in phase 3 trials.²⁷

Many novel biologic treatments promise exciting new therapeutic options for psoriasis and PsA that target various cytokines and regulatory molecules involved in the pathogenesis of psoriasis and PsA, including inhibition of IL-23 pathway.²⁸ Tildrakizumab, for example, a humanized IgG1k monoclonal antibody that targets the unique p19 subunit of IL-23 is in phase 3 trials for psoriasis. A randomized, double-blind, phase 2b trial showed that tildrakizumab was effective in treating moderate to severe plaque psoriasis in 355 adults.

Participants were randomized to receive subcutaneous tildrakizumab (5, 25, 100, or 200 mg) or placebo at weeks 0 and 4 and every 12 weeks thereafter until week 52. Tildrakizumab was discontinued at week 52 and participants were followed through week 72. At week 16, the PASI 75 responses was significantly higher at all doses when compared with placebo: 33.3% (5 mg), 64.4% (25 mg), 66.3% (100 mg), and 74.4% (200 mg) compared with 4.4% on placebo. The final drug dose was administered on week 40, and the participants were followed until week 72. Tildrakizumab demonstrated a low relapse rate after cessation of therapy with only 3.6% of participants who achieved PASI 75 at week 52 on any dose of tildrakizumab relapsing before week 72. Phase 3 studies are in progress.²⁹

The investigational drug tofacitinib (Xeljanz) is 1 oral agent in phase 3 trials for psoriasis and PsA. Tofacitinib is a small molecule that targets the Janus kinase pathway, a signaling pathway inside the cells, thought to play a role in chronic inflammatory responses.

Bachelez and colleagues conducted a randomized, multicenter, double-dummy, placebo-controlled, 12-week, noninferiority, phase 3 study comparing 5 mg and 10 mg tofacitinib with high-dose etanercept or placebo in 1101 adults with chronic stable plaque psoriasis who were candidates for systemic therapy or phototherapy. The primary endpoints were the proportion of participants at week 12 with at least a 75% reduction in PASI from baseline and the proportion of participants achieving a PGA score of clear or almost clear.^20,30

Tofacitinib 10 mg twice daily was noninferior to etanercept and was superior to placebo, but tofacitinib 5 mg twice daily did not show noninferiority to etanercept. Of the individuals randomized to tofacitinib 10 mg, 63.6% achieved PASI 75 after 12 weeks of treatment vs 58.8% who were randomized to etanercept.

Additionally, tofacitinib demonstrated superiority to placebo with 5.6% of placebo-treated individuals achieving PASI 75. Among the individuals randomized to tofacitinib 5 mg, 39.5% achieved PASI 75. A PGA response was achieved by 68.2% of individuals taking tofacitinib 10 mg, 66.3% of those on etanercept, 47.1% of those on tofacitinib 5 mg, and 15% taking placebo.^20,30

Conclusion

Psoriasis and PsA can have a profound impact on the quality of life for individuals living with these autoimmune diseases, which require lifelong management and support. While new treatment options have entered the marketplace in the last 10 years and demonstrated proven efficacy and safety in psoriasis and PsA, gaps in diagnosis and treatment still exist.

“Ongoing communication between patients and physicians is needed for better understanding of perception of disease severity, discussion and agreement on treatment options, and establishment of realistic treatment goals. The need for safe, effective, and easy to use therapies for psoriasis and PsA remain,” said Lebwhol and colleagues.¹⁷

Therefore, dermatologists should individualize treatment taking into consideration efficacy, side effects, availability, ease of administration, comorbidities, family history, and coexisting diseases when prescribing treatment. Patient and clinician education is also crucial to optimizing treatment for all categories of disease severity.

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