Psoriasis Treatments: Current and Emerging Medications

Approaching our patient


The patient described earlier highlights important clinical points regarding the complex management of psoriasis. First, we must recognize that her obesity, hypertension, dyslipidemia, and non-insulin-dependent diabetes indicate she most likely has metabolic syndrome. Metabolic syndrome and the systemic burden of inflammation caused by her psoriasis increase her risk for infection, cardiovascular disease, and overall mortality. 


Additionally, although she has decreased her daily cigarette smoking, complete cessation of tobacco intake should be advised with the reasoning explained to the patient—that is, that smoking has been shown to exacerbate psoriasis and increase risk of cardiovascular disease and myocardial infarction. The patient should also be encouraged to decrease her daily alcohol intake, as excessive alcohol ingestion is also associated with cardiovascular disease. 


Given these risk factors, many of which are modifiable, patients should see their primary care providers regularly for better control of these comorbidities and to inspire healthy lifestyle changes. 


Although her psoriasis may have been mild in the past, it is now moderate-to-severe given the distress it is causing her and the large percentage of BSA it now covers. She has a history of not adhering to phototherapy treatment regimens and has expressed that it is a burden to come into the clinic weekly for treatment. Furthermore, her recent history of skin cancer is a relative contraindication to phototherapy, which heightens the risk of skin cancer with increased ultraviolet light exposure. She is thus a good candidate for systemic therapies. 

Let us consider the conventional systemic therapies. Although the patient in this vignette is postmenopausal, it is always important to perform urine pregnancy tests and to ascertain the female patient’s potential and desire for pregnancy while medicated. Acitretin, an oral retinoid, has been shown to elevate serum transaminases and triglycerides in a significant number of patients. Furthermore, to be used as a monotherapy, it must be given in high doses that cause many patients significant mucocutaneous xerosis and other side effects. It is not a wise option in a patient who already has several laboratory abnormalities, especially when more effective monotherapies are available. 


Methotrexate and cyclosporine have the lowest monthly costs per number of patients needed to treat to achieve PASI 75, whereas biologic agents such as infliximab and ustekinumab have costs that are more than 10 times greater.³³ As previously stated, cyclosporine has many risk factors that could exacerbate chronic illnesses that our patient already has. That is, renal damage, hypertension, hypertriglyceridemia, electrolyte abnormalities, and increased risk of squamous and basal cell carcinomas. Furthermore, cyclosporine could interfere with her current medications, particularly simvastatin, which is also metabolized through the cytochrome P450 system in the liver. Although none of these are absolute contraindications to the use of cyclosporine, it is, nonetheless, typically reserved as a rescue medication rather than being utilized for long-term maintenance. 


Methotrexate is one of the oldest and most commonly used systemic agents for moderate to severe psoriasis. However, this patient’s obesity indicates she may already have steatohepatitis, which would further increase her risk of liver toxicity from the methotrexate. Furthermore, her moderate alcohol intake and use of simvastatin may have already elevated her liver enzymes, which also increases her risk for liver toxicity from methotrexate and is a relative contraindication. Methotrexate, like cyclosporine and acitretin, is no longer a favorable option.


Biologics are advantageous in patients with significant comorbidities and complex medical histories, because they show no cumulative toxicity or significant interactions with other drugs. For many patients, cost may be the distinguishing factor, and their insurance plans should be taken into account. TNF-α inhibitors are a good choice for this patient, because they will not further exacerbate her existing conditions. Infliximab has weight-based dosing and may be more effective in an obese patient, though etanercept and adalimumab are both options. Should a TNF antagonist not result in adequate disease remission, newer biologic agents remain as options. TNF-α inhibitors increase the risk for infection, so patients should be screened appropriately prior to and during treatment. Apremilast is tempting to use in an obese patient given its potential side effect of weight loss, but it is not as effective in eliminating disease and has a lower PASI 75 than the other biologic agents. Nonetheless, some patients may find its oral form more favorable than an injectable medication, even if it offers partial control. 


As more patients are diagnosed with chronic diseases, it is wise to understand psoriasis in their context and to be able to identify the nuances of treating psoriasis in patients with many comorbid conditions. The list of medications used to treat psoriasis continues to grow, with several other drugs having recently completed phase 3 clinical trials, providing hope and more personalized options for patients with this serious cutaneous disease.

Eman Bahani, BA, is a medical student. Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston.

References


1. Menter MA, Griffiths CE. Psoriasis: the future. Dermatol Clin. 2015;33(1):161-166.

2. Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386(9997):983-994.

3. Ryan C, Kirby B. Psoriasis is a systemic disease with multiple cardiovascular and metabolic comorbidities. Dermatol Clin. 2015;33(1):41-55.

4. Wolff K, Johnson RA, Saavedra AP, eds. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 7th ed. New York, NY: McGraw-Hill Medical; 2013.

5. Christophers E. Psoriasis—epidemiology and clinical spectrum. Clin Exp Dermatol. 2001;26(4):314-320.

6. Nair RP, Stuart PE, Nistor I, et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet. 2006;78:827-851.

7. Capon F, Burden AD, Trembath RC, Barker JN. Psoriasis and other complex trait dermatoses: from loci to functional pathways. J Invest Dermatol. 2012;132(3 Pt 2):915-922.

8. Lowes MA, Kikuchi T, Fuentes-Duculan J, et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol. 2008;128(5):1207-1211.

9. Mason AR, Mason JM, Cork MJ, et al. Topical treatments for chronic plaque psoriasis of the scalp: a systematic review. Br J Dermatol. 2013;169(3):519-527.

10. Hsu S, Papp KA, Lebwohl MG, et al; National Psoriasis Foundation Medical Board. Consensus guidelines for the management of plaque psoriasis. Arch Dermatol. 2012;148(1):95-102.

11. Racz E, Prens EP. Phototherapy and photochemotherapy for psoriasis. Dermatol Clin. 2015;33(1):79-89. 

12. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol. 2010;62(1):114-135.

13. Kelly JB 3rd, Foley P, Strober BE. Current and future oral systemic therapies for psoriasis. Dermatol Clin. 2015;33(1):91-109.

14. Dogra S, Yadav S. Acitretin in psoriasis: an evolving scenario. Int J Dermatol. 2014;53(5):525-538.

15. van Ede AE, Laan RF, Rood MJ, et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2001;44(7):1515-1524.

16. 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(17):1586-1596.

17. Strober BE. Methotrexate-induced liver toxicity: replacing the liver biopsy. JAMA Dermatol. 2014;150(8):862-863. 

18. Heydendael VM, Spuls PI, Opmeer BC, et al. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med. 2003;349(7):658-665.

19. Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate-to-severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol. 2008;58(1):106-115.

20. Saurat JH, Stingl G, Dubertret L, et al; CHAMPION Study Investigators. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs methotrexate vs placebo in patients with psoriasis (CHAMPION). Br J Dermatol. 2008;158(3):558-566.

21. Nast A, Sporbeck B, Rosumeck S, et al. Which antipsoriatic drug has the fastest onset of action? Systematic review on the rapidity of the onset of action. J Invest Dermatol. 2013;133(8):1963-1970.

22. Sugiyama H, McCormick TS, Cooper KD, Korman NJ. Alefacept in the treatment of psoriasis. Clin Dermatol. 2008;26(5):503-508.

23. Lui H, Gulliver W, Tan J, et al. A randomized controlled study of combination therapy with alefacept and narrow band UVB phototherapy (UVB) for moderate to severe psoriasis: efficacy, onset, and duration of response. J Drugs Dermatol. 2012;11(8):929-937.

24. Yiu ZZ, Warren RB. Efficacy and safety of emerging immunotherapies in psoriasis. Immunotherapy. 2015;7(2):119-133.

25. Krueger GG, Langley RG, Leonardi C, et al; CNTO 1275 Psoriasis Study Group. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med. 2007;356(6):580-592.

26. Leonardi CL, Kimball AB, Papp KA, et al; PHOENIX 1 study investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebocontrolled trial (PHOENIX 1). Lancet. 2008;371(9625):1665-1674. 
27. Gooderham M, Posso-De Los Rios CJ, Rubio-Gomez GA, Papp K. Interleukin-17 (IL-17) inhibitors in the treatment of plaque psoriasis: a review. Skin Therapy Lett. 2015;20(1):1-5.

28. Reich K, Griffiths C, Leonardi C, et al. Long-term safety and tolerability of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe psoriasis: results from a phase III, randomized, controlled trial (ESTEEM 1). Poster presented at: 72nd American Academy of Dermatology Annual Meeting; March 21-25, 2014; Denver, CO. Abstract P8296.

29. Otezla [package insert]. Summit, NJ: Celgene Corporation; 2014.

30. Papp KA, Menter A, Strober B, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study. Br J Dermatol. 2012;167(3):668-677. 

31. A phase 3, multi site, randomized, double blind, placebo controlled study of the efficacy and safety comparing CP-690,550 and etanercept in subjects with moderate to severe chronic plaque psoriasis. ClinicalTrials.gov website. Available at clinicaltrials.gov/ct2/show/NCT01241591. Accessed October 1, 2015.
32. Hoffman MB, Farhangian M, Feldman SR. Psoriasis during pregnancy: characteristics and important management recommendations. Expert Rev Clin Immunol. 2015;11(6):709-720.

33. D’Souza LS, Payette MJ. Estimated cost efficacy of systemic treatments that are approved by the US Food and Drug Administration for the treatment of moderate to severe psoriasis. J Am Acad Dermatol. 2015;72(4):589-598.

34. Psoriasis treatments. National Psoriasis Foundation website. Available at psoriasis.org/about-psoriasis/treatments. Accessed November 7, 2017.