Clinical Review

Novel Psoriasis Therapies and Patient Outcomes, Part 2: Biologic Treatments

Cutis. 2015 May;95(5):282-290

References

1. Lee S, Coleman CI, Limone B, et al. Biologic and nonbiologic systemic agents and phototherapy for treatment of chronic plaque psoriasis. Rockville, MD: Agency for Healthcare Research and Quality; 2012.

2. Nagler AR, Weinberg JM. Research pipeline III: biologic therapies. In: Weinberg JM, Lebwohl M, eds. Advances in Psoriasis. New York, NY: Springer; 2014:243-251.

3. 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.

4. Gladman D, Fleischmann R, Coteur G, et al. Effect of certolizumab pegol on multiple facets of psoriatic arthritis as reported by patients: 24-week patient-reported outcome results of a phase III, multicenter study. Arthritis Care Res (Hoboken). 2014;66:1085-1092.

5. Coherus announces initiation of Phase 3 trial of CHS-0214 (investigational etanercept biosimilar) in chronic plaque psoriasis (RaPsOdy) [press release]. Redwood City, CA: Coherus BioSciences, Inc; July 16, 2014.

6. Coherus announces CHS-0214 (proposed etanercept biosimilar) meets primary endpoint in pivotal pharmacokinetic clinical study [press release]. Redwood City, CA: Coherus BioSciences, Inc; October 28, 2013.

7. Tang C, Chen S, Qian H, et al. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology. 2012;135:112-124.

8. Strober BE, Crowley JJ, Yamauchi PS, et al. Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol. 2011;165:661-668.

9. Reich K, Langley RG, Papp KA, et al. A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis. N Engl J Med. 2011;365:1586-1596.

10. Papp KA, Sundaram M, Bao Y, et al. Effects of briakinumab treatment for moderate to severe psoriasis on health-related quality of life and work productivity and activity impairment: results from a randomized phase III study. J Eur Acad Dermatol Venereol. 2014;28:790-798.

11. Stelara (ustekinumab) receives FDA approval to treat active psoriatic arthritis. first and only anti-IL-12/23 treatment approved for adult patients living with psoriatic arthritis [press release]. Horsham, PA: Johnson & Johnson; September 23, 2013.

12. FDA approves new drug to treat psoriasis [press release]. Silver Spring, MD: US Food and Drug Administration; April 17, 2013.

13. Griffiths CE, Strober BE, van de Kerkhof P, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med.  2010;362:118-128.

14. Papp KA, Griffiths CE, Gordon K, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol. 2013;168:844-854.

15. McInnes IB, Kavanaugh A, Gottlieb AB, et al. Ustekinumab in patients with active psoriatic arthritis: results of the phase 3, multicenter, double-blind, placebo-controlled PSUMMIT I study. Ann Rheum Dis. 2012;71(suppl):S107-S148.

16. Ritchlin C, Rahman P, Kavanaugh A, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial [published online ahead of print Jan 30, 2014]. Ann Rheum Dis. 2014;73:990-999.

17. A study of the safety and efficacy of ustekinumab in adolescent patients with psoriasis (CADMUS)(NCT01090427). https://clinicaltrials.gov/ct2/show/NCT01090427?term=NCT01090427&rank=1. Updated January 16, 2015. Accessed April 16, 2015.

18. A safety and efficacy study of ustekinumab in patients with plaque psoriasis who have had an inadequate response to methotrexate (NCT01059773). https://clinicaltrials.gov/ct2/show/NCT01059773?term=NCT01059773&rank=1. Updated November 13, 2014. Accessed April 16, 2015.

19. Efficacy and safety of ustekinumab in patients with moderate to severe palmar plantar psoriasis (PPP)(NCT01090063). https://clinicaltrials.gov/ct2/show/NCT01090063?term=NCT01090063&rank=1. Updated January 31, 2013. Accessed April 16, 2015.

20. A study of the safety and effectiveness of ustekinumab in patients with psoriatic arthritis (NCT01009086). https://clinicaltrials.gov/ct2/show/NCT01009086?term=NCT01009086&rank=1. Updated February 11, 2015. Accessed April 16, 2015.

21. A study to assess the effect of ustekinumab (Stelara) and etanercept (Enbrel) in participants with moderate to severe psoriasis (MK-0000-206)(NCT01276847). https://clinicaltrials.gov/ct2/show/NCT01276847?term=NCT01276847&rank=1. Updated January 13, 2015. Accessed April 16, 2015.

22. Sofen H, Smith S, Matheson RT, et al. Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis. J Allergy Clin Immunol. 2014;133:1032-1040.

23. Callis Duffin K, Wasfi Y, Shen YK, et al. A phase 2, multicenter, randomized, placebo- and active-comparator-controlled, dose-ranging trial to evaluate Guselkumab for the treatment of patients with moderate-to-severe plaque-type psoriasis (X-PLORE). Poster presented at: 72nd Annual Meeting of the American Academy of Dermatology; March 21-25, 2014; Denver, CO.

24. Papp K. Monoclonal antibody MK-3222 and chronic plaque psoriasis: phase 2b. Paper presented at: 71st Annual Meeting of the American Academy of Dermatology; March 1-5, 2013; Miami, FL.

25. Huynh D, Kavanaugh A. Psoriatic arthritis: current therapy and future approaches. Rheumatology (Oxford). 2015;54:20-28.

26. FDA approves new psoriasis drug Cosentyx [press release]. Silver Spring, MD: US Food and Drug Administration; January 21, 2015.

27. Multiple-loading dose regimen study in patients with chronic plaque-type psoriasis (NCT00805480). https://clinicaltrials.gov/ct2/show/NCT00805480?term
=NCT00805480&rank=1. Updated January 28, 2015. Accessed April 16, 2015.

28. AIN457 regimen finding study in patients with moderate to severe psoriasis (NCT00941031). https://clinicaltrials.gov/ct2/show/NCT00941031?term=NCT00941031&rank=1. Updated March 23, 2015. Accessed April 16, 2015.

29. Efficacy and safety of intravenous and subcutaneous secukinumab in moderate to severe chronic plaque-type psoriasis (STATURE)(NCT014712944). https://clinical trials.gov/ct2/show/NCT01412944?term=efficacy+and+safety+of+intravenous+and+subcutaneoussecukinumab&rank=1. Updated March 17, 2015. Accessed April 16, 2015.

30. Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis–results of two phase 3 trials. N Engl J Med. 2014;371:326-338.

31. Coimbra S, Figueiredo A, Santos-Silva A. Brodalumab: an evidence-based review of its potential in the treatment of moderate-to-severe psoriasis. Core Evid. 2014;9:89-97.

32. Leavitt M. New biologic clears psoriasis in 42 percent of patients. National Psoriasis Foundation Web site. https://www.psoriasis.org/advance/new-biologic-clears-psoriasis-in-42-percent-of-patients. Accessed April 10, 2015.

33. Leonardi C, Matheson R, Zachariae C, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366:1190-1199.

34. Herrero-Beaumont G, Martínez Calatrava MJ, Castañeda S. Abatacept mechanism of action: concordance with its clinical profile. Rheumatol Clin. 2012;8:78-83.

35. Abrams JR, Lebwohl MG, Guzzo CA, et al. CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest. 1999;103:1243-1252.

36. Mease P, Genovese MC, Gladstein G, et al. Abatacept in the treatment of patients with psoriatic arthritis: results of a six-month, multicenter, randomized, double-blind, placebo-controlled, phase II trial. Arthritis Rheum. 2011;63:939-948.

37. Suárez-Fariñas M, Arbeit R, Jiang W, et al. Suppression of molecular inflammatory pathways by Toll-like receptor 7, 8, and 9 antagonists in a model of IL-23-induced skin inflammation. PLoS One. 2013;8:e84634.

38. A 12-week dose-ranging trial in patients with moderate to severe plaque psoriasis (8400-201)(NCT01899729). https://clinicaltrials.gov/ct2/show/NCT01899729. Updated October 16, 2014. Accessed April 27, 2015.

The phase 3 STATURE trial assessed the safety and effectiveness of SC and IV AIN457 in moderate to severe psoriasis in partial AIN457 nonresponders.²⁹ Nonresponders were participants who demonstrated a PASI score of 50% or more but less than 75%. Participants in this study design who received SC AIN457 demonstrated a PASI 75 of 66.7%, with a 2011 investigator global assessment score of 0 (clear) or 1 (almost clear) in 66.7%. In those receiving IV AIN457, the PASI 75 was 90.5%, with a 2011 investigator global assessment score of 0 or 1 in 33.3%.²⁹

In a 52-week phase 3 efficacy trial (known as FIXTURE), 1306 participants received 1 dose of AIN457 300 mg or 150 mg weekly for 5 weeks, then every 4 weeks; 12 weeks of etanercept 50 mg twice weekly, then once weekly; or placebo. The PASI 75 was 77.1% for AIN457 300 mg, 67.0% for AIN457 150 mg, 44.0% for etanercept, and 4.9% for placebo (P<.001).³⁰ In a 52-week efficacy and safety trial (known as ERASURE), 738 participants received 1 dose of AIN457 300 mg or 150 mg weekly for 5 weeks, then every 4 weeks, versus placebo. The PASI 75 was 65.3% for AIN457 300 mg, 51.2% for AIN457 150 mg, and 2.4% for placebo (P<.001). There was a comparable incidence of infection among participants with AIN457 and etanercept, which was greater than placebo.³⁰

Brodalumab (AMG 827)

Brodalumab (formerly known as AMG 827)(Amgen Inc) is a human monoclonal antibody that targets the IL-17A receptor. In a phase 1 randomized trial, 25 participants received either IV brodalumab 700 mg, SC brodalumab 350 mg or 140 mg, or placebo.³¹ Results demonstrated improvement in PASI score that correlated with increased dosage of brodalumab as well as decreased psoriasis gene expression and decreased thickness of the epidermis in participants receiving the 700-mg IV or 350-mg SC doses. In a phase 2 trial, 198 participants received either brodalumab 280 mg at week 0, then every 4 weeks for 8 weeks, or brodalumab 210 mg, 140 mg, 70 mg, or placebo at week 0, then every 2 weeks for 10 weeks. At week 12, PASI 75 was observed in 82% and 77% of the 210-mg and 140-mg groups, respectively, with no benefit noted in the placebo group (P<.001).³¹ In a phase 3 trial, 661 participants received brodalumab 210 mg or 140 mg or placebo. At week 12, PASI 75 was observed in 83% of the 210-mg group versus 60% of the 140-mg group; PASI 100 was observed in 42% of the 210-mg group versus 23% of the 140-mg group.³²

Ixekizumab (LY2439821)

Ixekizumab (formerly known as LY2439821)(Eli Lilly and Company) is a human monoclonal antibody that targets IL-17A. In a phase 2 double-blind, placebo-controlled trial, 142 participants with chronic moderate to severe plaque psoriasis were randomized to receive 10-mg, 25-mg, 75-mg, or 150-mg SC injections of ixekizumab or placebo at 0, 2, 4, 8, 12, and 16 weeks. At week 12, the percentage of participants with a 75% reduction in PASI score was significantly greater with ixekizumab (150 mg [82.1%], 75 mg [82.8%], and 25 mg [76.7%]), except the 10-mg group, than with placebo (7.7%)(P<.001 for each comparison).³³

Inhibition of T-Cell Activation in Antigen-Presenting Cells

Abatacept

Abatacept (Bristol-Myers Squibb) is a fusion protein designed to inhibit T-cell activation by binding receptors for CD80 and CD86 in antigen-presenting cells.³⁴ A phase 1 study of 43 participants demonstrated improved PGA scores of 50% in 46% of psoriasis participants who were treated with abatacept, indicating a dose-responsive association with abatacept in psoriasis patients refractory to other therapies.³⁵ In a 6-month, phase 2, multicenter, randomized, double-blind, placebo-controlled trial, 170 participants with PsA were randomized to receive placebo or abatacept at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg (2 initial doses of 30 mg/kg followed by 10 mg/kg).³⁶ At day 169, ACR20 was observed in 19%, 33%, 48%, and 42% of the placebo and abatacept 3 mg/kg, 10 mg/kg, and 30/10 mg/kg groups, respectively. Compared with placebo, improvements were significantly higher for the abatacept 10-mg/kg (P=.006) and 30/10-mg/kg (P=.022) groups but not for the 3-mg/kg group (P=.121). The authors concluded that abatacept 10 mg/kg could be an appropriate dosing regimen for PsA, as is presently used in the FDA-approved management of rheumatoid arthritis.³⁶ At the time of publication, a phase 3 trial evaluating the efficacy and safety of abatacept SC injection in adults with active PsA was ongoing but was not actively recruiting participants (NCT01860976).

Activation of Regulatory T Cells

Tregalizumab (BT061)

Tregalizumab (formerly known as BT061)(Biotest) is a human monoclonal antibody that activates regulatory T cells. A phase 2, randomized, placebo-controlled, double-blind, multicenter, multiple-dose, cohort study with escalating doses evaluating the safety and efficacy of BT061 in patients with moderate to severe chronic plaque psoriasis was completed, but the results were not available at the time of publication (NCT01072383).