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.

In a phase 3, multicenter, double-blind, placebo-controlled trial (know as PSUMMIT I), 615 adults with active PsA who had not previously been treated with TNF inhibitors were randomly assigned to placebo, 45 mg of ustekinumab, or 90 mg of ustekinumab. At week 24, more participants receiving ustekinumab 90 mg achieved 20%, 50%, and 70% improvement in American College of Rheumatology (ACR) criteria (49.5%, 27.9%, and 14.2%, respectively) and PASI 75 (62.4%) versus the placebo group (22.8%, 8.7%, 2.4%, and 11%, respectively).¹⁵ In a phase 3, multicenter, placebo-controlled trial (known as PSUMMIT 2), 312 adult participants with active PsA who had formerly been treated with conventional therapies and/or TNF inhibitors were randomized to receive placebo (at weeks 0, 4, and 16 with crossover to 45 mg of ustekinumab at weeks 24, 28, and 40) or ustekinumab (45 mg or 90 mg at weeks 0, 4, and every 12 weeks).¹⁶For participants with less than 5% improvement, there was an early escape clinical trial design with placebo to 45 mg of ustekinumab, 45 mg of ustekinumab to 90 mg, and 90 mg of ustekinumab maintained at the same dose. The ACR20 was 43.8% for the ustekinumab group versus 20.2% for the placebo group (P<.001).¹⁶

A phase 3, multicenter, randomized, double-blind, placebo-controlled study (known as CADMUS) evaluated the efficacy and safety of ustekinumab in the treatment of adolescents (age range, 12–18 years) with moderate to severe plaque-type psoriasis.¹⁷ The primary outcome of the study was the percentage of participants achieving a physician global assessment (PGA) score of cleared (0) or minimal (1) at week 12. One hundred ten participants started and completed the first period in the study (ie, controlled period [weeks 0–12]) and were randomized into 3 groups: placebo (SC injections at weeks 0 and 4), ustekinumab half-standard dose, and ustekinumab standard dose. At week 12, 101 participants started and completed the second period in the study (weeks 12–60). The placebo group received either ustekinumab half-standard dose or ustekinumab standard dose at weeks 12 and 16, then once every 12 weeks with the last dose at week 40, and the ustekinumab half-standard and standard dose groups received the respective doses every 12 weeks with the last dose at week 40. At week 12, PGA scores of 0 or 1 were reported in 5.4% of the placebo group, 67.6% of the ustekinumab half-standard dose group, and 69.4% of the ustekinumab standard dose group (P<.001), and PASI 75 was achieved in 10.8%, 78.4%, and 80.6%, respectively (P<.001).¹⁷

A phase 4 study (known as TRANSIT) assessed the safety and efficacy of ustekinumab in participants with plaque psoriasis who had a suboptimal response to methotrexate.¹⁸ Participants in the first treatment group received either 45 mg (weight, ≤100 kg) of ustekinumab at weeks 0, 4, and then every 12 weeks until week 40, or 90 mg (weight, >100 kg) in 2 SC injections after immediate discontinuation of methotrexate. The second treatment group followed the same dosing regimen with gradual withdrawal of methotrexate therapy. Adverse events were reported in 61.1% and 64.5% of participants in groups 1 and 2, respectively. In group 1, PASI 75 was observed in 58.1% of participants (95% confi-dence interval [CI], 51.9%-64.3%) at week 12 and 76.3% (95% CI, 70.8%-81.9%) at week 52. In group 2, PASI 75 was observed in 62.2% of participants (95% CI, 56.0%-68.3%) at week 12 and 76.9% (95% CI, 71.4%-82.5%) at week 52.¹⁸

In another study that assessed the efficacy and safety of ustekinumab in 24 participants with moderate to severe palmoplantar psoriasis, 37.5% of participants achieved a palmar/plantar PGA score of 0 or 1 at week 16.¹⁹ A phase 3, multicenter, randomized, double-blind, placebo-controlled study of the safety and effectiveness of ustekinumab in 615 PsA participants showed ACR20 response in 49.5% of the ustekinumab 90-mg group, 42.4% of the ustekinumab 45-mg group, and 22.8% of the placebo group (P<.001).²⁰

A phase 1 study was performed to assess gene expression in the following: (1) IFN-γ modulation in the IL-12 pathway; (2) IL-23 pathway with ustekinumab (45 mg for those weighing <100 kg and 90 mg for ≤100 kg administered SC on day 1 and at weeks 4 and 16); and (3) IL-17 pathway with etanercept (50 mg administered SC twice weekly for 12 weeks, then once weekly for 4 weeks).²¹ The change in gene expression from baseline in the IL-12 pathway with ustekinumab achieved statistical significance by week 1 (P=.016) with increasing levels of gene expression through week 16 (P=.000184). The change in gene expression from baseline in the IL-23 pathway with ustekinumab achieved statistical significance by week 2 (P=.010) with increasing levels of gene expression through week 16 (P=.000215). The results were less powerful for etanercept, with a change in gene expression from baseline in the IL-17 pathway increasing through week 4 (P=.053) and decreasing by week 16 (P=.098).²¹