Clinical Review

Emerging Therapies In Psoriasis: A Systematic Review

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

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.
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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.
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SILIQ [package insert]. Thousand Oaks, CA: Amgen, Inc; 2017.

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