Psoriasis: A Year-in-Review

Research and Clinical Studies
Each year comes with new advances in treatment options, and 2019 was no exception. Research further characterized methods of action and considerations for biologics, such as the effects of biologics on plaque in coronary arteries and the IL-17 inhibitor impact on inflammatory bowel disease. In psoriasis, biologics affect T-cell activity by acting on proteins, including tumor necrosis factor (TNF) alpha, IL-12, IL-23, and IL-17. Some biologics may even help treat comorbidities in patients with psoriasis; this is new knowledge due to recently published research surrounding biologics slowing or preventing the
progression of comorbidities.

According to the findings of a recent study,¹ biologic therapies may reduce coronary plaques in patients with psoriasis. “Psoriasis severity is related to the burden of coronary disease–our findings suggest treating the psoriasis may potentially benefit coronary heart disease,” said corresponding author Nehal Mehta, MD, MSCE, FAHA, chief of inflammation and cardiometabolic diseases at the National Heart, Lung, and Blood Institute with the National Institutes of Health in Bethesda, MD, in a press release.²

In the prospective observational study, 121 participants with psoriasis who had not been treated with biologics at baseline were recruited. Mean participant age was 50.2 years, more than half of the participants were male (n=70) with low cardiovascular risk based on the Framingham risk score, and participants had moderate to severe skin disease at baseline. Total coronary plaque burden and plaque subcomponents (calcified and noncalcified) in the three main coronary vessels were assessed by a reviewer blinded to the treatment group.

Elnabawi et al¹ found treatment with a biologic was associated with a 6% reduction in noncalcified plaque burden and reduction in necrotic core, with no effect on fibrous burden. In comparisons between plaque characteristic changes over 1 year, they observed that decreases in noncalcified plaque burden associated with biologic treatment were significant compared with slow plaque progression among those not treated with biologics and were associated with biologic therapy after adjusting for traditional cardiovascular risk factors.

In addition to cardiovascular benefits, researchers found that patients with psoriasis and concurrent malignancy may be safely treated with biologic therapies and apremilast (Otezla) without the risk of recurrence or progression of cancer.³

Although many studies have assessed the risk of developing malignancy during treatment, few have assessed the use of biologic therapy among patients with a history of established malignancy, the researchers said. They conducted a retrospective chart review of 690 patients with psoriasis who attended their clinic between January 1, 2012, and May 31, 2018. Sixteen patients with a history of malignancy, excluding nonmelanoma skin cancer, who were treated with biologics or apremilast were identified.

The researchers found that the average time from cancer diagnosis to initiation of biologics or apremilast was 4.7 years, with nine patients (56%) initiating treatment within 5 years. Three patients (19%) received concurrent cancer therapy during biologic treatment, the researchers observed.

Out of 16 patients, none experienced clinical or radiographic recurrence or progression of their cancer during biologic treatment, and most patients experienced improvements in their psoriasis.³

In an abstract presented at the annual meeting of the American College of Rheumatology and Association of Rheumatology Professionals, a research group from New York University School of Medicine found a larger percentage of patients with psoriatic arthritis (PsA) and depression received treatment with biologics than their nondepressed counterparts, but the patient outcomes varied between the two groups.⁴

Haberman et al⁴ prospectively recruited 436 patients (54% men, mean age 47 years, 74.1% Caucasian) who met Classification Criteria for Psoriatic Arthritis criteria. Of these patients, 19.5% had depression and 15.6% had anxiety. They found that patients with PsA and depression were more likely to receive treatment for PsA (80% vs 65%; P=.01) and had a higher percentage of biologic use (47.5% vs 40.4%; P=.126) than those without depression.

The authors compared disease severity between the two groups. Patients with PsA and depression had a statistically significant lower mean of psoriatic activity as measured by body surface area (BSA) than the nondepressed cohort (1.4% vs 3.03%; P=.001). The group with depression also had a statistically significant higher mean RAPID3 score than the nondepressed group (12.7 vs 10.4;  P=.035); the authors hypothesized that the contrast between patient-reported outcomes (RAPID3) and the BSA of psoriatic activity could be a “manifestation of how depression could affect the way patients experience their PsA despite apparent improvement in skin and joint symptoms.”⁴

Furthermore, their study concluded that depression should be considered a “critical comorbidity” of PsA.⁴ This is similar to another 2019 study⁵ that examined psychopathological and sexual consequences related to psoriasis. In a comparative study between 220 patients with psoriasis (110 men, 110 women) and 220 age- and sex-matched healthy controls, researchers found significantly higher rates of depression, anxiety, and low self-esteem in patients with psoriasis. The researchers⁵ noted that women had a significantly higher frequency of self-reported sexual dysfunction than men and that this dysfunction was commonly affected by depression, presentation of psoriasis on genital areas, and increased disease severity.

“Assessment of psychopathological and sexual comorbidities in psoriasis patients and [their] partners should be an integral part of the management plan,” concluded the authors.⁵

New Therapies Available
The number of treatment options available for patients increased in 2019 with the addition of several new therapeutics approved by the FDA. 

The FDA approved Skyrizi (risankizumab-rzaa), an IL-23 inhibitor, for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.⁶ This treatment is administered as two 150-mg subcutaneous injections every 12 weeks following two initiation doses at week 0 and 4. Patients can administer the injections themselves after training or can elect to have the therapy administered in an office setting.⁷

In two clinical trials, UltIMMa-1 and UltIMMa-2, 82% and 81% of participants achieved 90% skin clearance after 1 year of treatment, and 56% and 60% achieved 100% skin clearance, respectively (P<.001).⁸ In an integrated analysis of the two clinical studies, 88% of patients who achieved 90% skin clearance and 80% of those who achieved 100% skin clearance at week 16 maintained this response after 1 year. 

The etanercept (Enbrel) biosimilar Eticovo was granted FDA approval as well. With approval across all eligible indications, including psoriasis and PsA, the TNF inhibitor is now approved for marketing in 38 countries.⁹ 

In addition, halobetasol propionate tazarotene 0.01%/0.045% lotion (Duobrii), a topical treatment for plaque psoriasis, received FDA approval in April 2019.¹⁰ The product was officially launched in the United States in June 2019.¹¹

In clinical trials, the topical was consistently more effective than vehicle for treating psoriasis. Phase 3 trials showed that 36% and 45% of participants achieved clear or almost clear skin after 8 weeks compared with 7% and 13% of those treated with vehicle, respectively.¹² An additional phase 3, open-label study also demonstrated the long-term safety of the topical treatment over a year.¹³

Of note, the FDA approved SORILUX (calcipotriene) foam, 0.005%, in adolescents.¹⁴ While available since 2010 for adult patients, calcipotriene foam is now indicated to treat plaque psoriasis of the scalp and body of patients aged 12 years and older. The foam product was initially approved following positive patient outcomes in two 8-week, placebo-controlled clinical trials in patients with mild to moderate psoriasis of the body and one 8-week, placebo-controlled clinical trial in patients with moderate psoriasis of the scalp.¹⁴ Adolescent approval came after a follow-on, open-label study of patients aged 12 to 17 years.¹⁴

Recommendations and Guidelines
In an effort to inform patient care with evidence-based practice, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) have released several joint guidelines for the management and treatment of psoriasis.^15-19

The first set of guidelines¹⁵ discussed the treatment of psoriasis using biologics, including:

• TNF-α inhibitors, such as etanercept, infliximab (Remicade), adalimumab (Humira), and certolizumab (Cimza);
• IL-12/IL-23 inhibitors, such as ustekinumab (Stelara);
• IL-17 inhibitors, such as secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq); and
• IL-23 inhibitors, such as guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab.

The second set of guidelines¹⁶ published addressed common extracutaneous manifestations associated with psoriasis, including PsA, cardiovascular disease, metabolic syndrome, mental health conditions, and inflammatory bowel disease. This guideline detailed the importance of knowing that these conditions can present as comorbidities, how their presence can affect patient care and the management of psoriasis, and the importance of screening for these diseases in patients with psoriasis.

The third set of guidelines were on the use of phototherapy for the management and treatment of psoriasis.¹⁷ This set detailed the use of UV light therapies, including narrowband and broadband UV-B, UV-A as an adjunct to photosensitizing agents, targeted UV-B treatments, pulsed dye lasers, intense pulse light, and light-emitting electrodes.

Most recently, the AAD-NPF released guidelines of care for the management and treatment of psoriasis in pediatric patients.¹⁸ This guideline highlights this special patient group, discussing the unique physiology, pharmacokinetics, and patient-parent-provider interactions. 

Development of guidelines for nonbiologic systemic therapy and topical therapy are underway and will be available in the first quarter and second quarter of 2020, respectively.¹⁹

References
1. Elnabawi YA, Dey AK, Goyal A, et al. Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study [published online February 5, 2019]. Cardiovasc Res. doi:10.1093/cvr/cvz009

2. Psoriasis medication may improve heart disease in patients with the skin condition [press release]. Sophia Antipolis, France: European Society of Cardiology; February 5, 2019. https://www.escardio.org/The-ESC/Press-Office/Press-releases/Psoriasis-medication-may-improve-heart-disease-in-patients-with-the-skin-condition. Accessed December 2, 2019.

3. Kahn JS, Casseres RG, Her MJ, Dumont N, Gottlieb AB, Rosmarin D. Treatment of psoriasis with biologics and apremilast in patients with a history of malignancy: a retrospective chart review. J Drugs Dermatol. 2019;18(4):387-390.

4. Haberman R, Adhikari S, Ramirez D, et al. The paradoxical effect of depression on psoriatic arthritis outcomes in a combined psoriasis-psoriatic arthritis center. Presented at: American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting; November 9-13, 2019: Atlanta, GA.

5. Alariny AF, Farid CI, Elweshahi HM, Abbood SS. Psychological and sexual consequences of psoriasis vulgaris on patients and their partners. J Sex Med. 2019;16(12):1900-1911. doi:10.1016/j.jsxm.2019.08.017

6. AbbVie expands immunology portfolio in the U.S. with FDA approval of SKYRIZI™ (risankizumab-rzaa) for moderate to severe plaque psoriasis [press release]. North Chicago, IL: AbbVie; April 23, 2019. https://www.prnewswire.com/news-releases/abbvie-expands-immunology-portfolio-in-the-us-with-fda-approval-of-skyrizi-risankizumab-rzaa-for-moderate-to-severe-plaque-psoriasis-300836934.html. Accessed December 2, 2019.

7. SKYRIZI (risankizumab) [package insert]. North Chicago, IL: AbbVie Inc. April 2019.

8. Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650-661. doi:10.1016/S0140-6736(18)31713-6

9. FDA approves ETICOVO™ (etanercept-ykro), Samsung Bioepis’ second anti-TNF medicine in the United States [press release]. Incheon, Korea: Samsung Bioepis Co, Ltd; April 29, 2019. https://www.businesswire.com/news/home/20190429005252/en/FDA-Approves-ETICOVO%E2%84%A2-etanercept-ykro-Samsung-Bioepis-Anti-TNF. Accessed December 2, 2019.

10. FDA approves Bausch Health’s DUOBRII™ (halobetasol propionate and tazarotene) lotion 0.01%/0.045% for plaque psoriasis in adults [press release]. Raleigh, NC: Ortho Dermatologics; April 25, 2019. https://ortho-dermatologics.com/wp-content/uploads/20190425-Trade-Release-FDA-approves-DUOBRII-Lotion.pdf. Accessed December 2, 2019.

11. Ortho Dermatologics announces U.S. launch of Duobriitm (halobetasol

propionate and tazarotene) lotion 0.01%/0.045% for plaque psoriasis in adults [press release]. Raleigh, NC: Ortho Dermatologics; June 25, 2019. https://ortho-dermatologics.com/wp-content/uploads/20190425-Trade-Release-FDA-approves-DUOBRII-Lotion.pdf. Accessed December 10, 2019.

12. DUOBRII^TM [package insert]. Bridgewater, NJ: Bausch Health US, LLC. April 2019.

13. Lebwohl MG, Sugarman JL, Gold LS. Long-term safety results from a phase 3 open-label study of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% lotion in moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2019;80(1):382-385. doi:10.1016/j.jaad.2019.09.002

14. FDA approves SORILUX(R) for adolescent plaque psoriasis [press release]. Adelaide, Australia: Mayne Pharma Group Ltd; May 22, 2019. https://www.prnewswire.com/news-releases/fda-approves-soriluxr-for-adolescent-plaque-psoriasis-300854930.html. Accessed December 2, 2019.

15. Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80(4):1029-1072. doi:10.1016/j.jaad.2018.11.057

16. Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80(4):1073-1113. doi:10.1016/j.jaad.2018.11.058

17. Elmets CA, Lim HW, Stoff B, et al. Joint American Academy of Dermatology–National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy. J Am Acad Dermatol. 2019;81(3):775-804. doi:10.1016/j.jaad.2019.04.042

18. Menter A, Cordoro KM, Davis DMR, et al. Joint American Academy of Dermatology–National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients [published online November 5, 2019].
J Am Acad Dermatol. doi:10.1016/j.jaad.2019.08.049

19. Psoriasis Clinical Guideline. American Academy of Dermatology. https://www.aad.org/member/clinical-quality/guidelines/psoriasis. Accessed December 2, 2019.