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.

Several clinical trials are underway and are currently recruiting participants (Table 2).

Guselkumab (CNTO 1959)

Guselkumab (formerly known as CNTO 1959)(Janssen Research & Development, LLC) is a human monoclonal antibody targeting the p19 subunit of IL-23. In a double-blind, randomized study of 24 participants receiving 1 dose of CNTO 1959 at 10 mg, 30 mg, 100 mg, or 300 mg versus placebo, a PASI 75 of 50% for the 10-mg subset, 60% for the 30- and 100-mg group, and 100% for the 300-mg group was achieved as opposed to 0% in the placebo group at 12 weeks.²² The rate of AEs was 65% in the CNTO 1959 treatment arm versus 50% in the placebo group at 24 weeks. Furthermore, decreased serum IL-17A titers and gene expression for psoriasis was demonstrated as well as decreased thickness of the epidermis and less dendritic and T-cell expression for the CNTO 1959 study population histologically.²² Results of a phase 2 trial in 293 participants who received CNTO 1959, adalimumab, or placebo indicated PASI 75 at 16 weeks for 81% of the CNTO 1959 50-mg group versus 71% of the adalimumab group, with serious AEs in 3% of participants treated with CNTO 1959 versus 5% treated with adalimumab.²³

Tildrakizumab (MK-3222/SCH 900222)

Tildrakizumab (formerly known as MK-3222/SCH 900222)(Merck & Co Inc) is a monoclonal antibody that also targets the p19 subunit of IL-23. Results of a phase 2b trial were promising. This study reported on 355 participants who received placebo versus MK-3222 5 mg, 25 mg, 100 mg, or 200 mg, with PASI 75 scores of 4.4%, 33%, 64%, 66%, and 74%, respectively, noted at 16 weeks.²⁴ A 64-week phase 3 study currently is underway to assess the long-term benefit and safety of MK-3222, but it is not recruiting participants (NCT01722331).

Inhibition of the IL-17 Pathway

The T helper 17 cells (T_H17) produce IL-17, a cytokine mediating inflammation that is implicated in psoriasis. Two products target IL-17A, while another targets the IL-17 receptor.²⁵

Secukinumab (AIN457)

Secukinumab (formerly known as AIN457)(Novartis Pharmaceutical Corporation) was FDA approved for treatment of moderate to severe psoriasis in adult patients who are candidates for systemic therapy or phototherapy in January 2015.²⁶ Secukinumab is a human monoclonal antibody that inhibits IL-17A. There are many clinical trials underway including a phase 2 extension study (NCT01132612). Many phase 3 studies also are underway evaluating the effectiveness and safety of AIN457 in patients with psoriasis resistant to TNF inhibitors (NCT01961609); its usability and tolerability (NCT01555125), including 2-year extension studies (NCT01640951; NCT01544595); its effectiveness as opposed to ustekinumab (NCT02074982); effectiveness using an autoinjector (NCT01636687); and the PASI 90 in HLA-Cw6–positive and HLA-Cw6–negative patients with moderate to severe psoriasis (known as SUPREME)(NCT02394561).

Other phase 3 trials are being undertaken in patients with moderate to severe palmoplantar psoriasis (NCT01806597; NCT02008890); moderate to severe nail psoriasis (known as TRANSFIGURE)(NCT01807520); moderate to severe scalp psoriasis (NCT02267135); and PsA (NCT01989468; NCT02294227; NCT01892436), including a 5-year study for PsA (known as FUTURE 2)(NCT01752634).

Other studies that are completed with pending results include a phase 1 trial to evaluate its mechanism of action in vivo by studying the spread of AIN457 in tissue as assessed by open flow microperfusion (NCT01539213), a phase 2 trial of the clinical effectiveness of AIN457 at 12 months and biomarker changes (NCT01537432), as well as phase 3 trials of the clinical efficacy of various dosing regimens (known as SCULPTURE)(NCT01406938); safety and effectiveness at 1 year (known as ERASURE)(NCT01365455); and the effectiveness, tolerability, and safety of AIN457 over 2 years in PsA (known as FUTURE 1)(NCT01392326).

In a 56-week phase 2 clinical trial of 100 participants, the PASI scores at 12 weeks and percentage of participants without relapse up to 56 weeks were evaluated.²⁷ There were 4 arms in the study: (1) AIN457 3 mg/kg (day 1) then placebo (days 15 and 29); (2) AIN457 10 mg/kg (day 1) then placebo (days 15 and 29); (3) AIN457 10 mg/kg (days 1, 15, and 29); and (4) placebo (days 1, 15, and 29), with AIN457 and the placebo administered IV. The mean (standard deviation) change from baseline for PASI scores for these respective groups was -12.46 (7.668), -13.35 (6.195), -18.02 (6.792), and -4.18 (4.698), respectively. At week 56, the percentage of participants without a relapse at any point during the study was 12.5%, 22.2%, and 27.8%, respectively.²⁷

In a phase 2 study of 404 participants, PASI 75 scores were assessed at 12 weeks with the SC administration of AIN457 in participants with moderate to severe psoriasis at 3 dosing regimens: (1) a single dose of 150 mg (week 1), (2) monthly doses of 150 mg (weeks 1, 5, and 9), (3) early loading doses of 150 mg (weeks 1, 2, 3, 5, and 9), as compared to placebo. At 12 weeks, PASI 75 scores were 7%, 58%, 72%, and 1%, respectively.²⁸