For part 1, click here.
The rapid changes in the treatment of psoriasis have provided many new options for the approximately 7.5 million Americans who live with psoriasis, of whom 30% may also develop psoriatic arthritis (PsA).1 The tremendous variation in psoriasis—with common, guttate, inverse, pustular, and erythrodermic variants as well as variation in the parts of the body affected by the disease—complicates the treatment decision. Psoriasis not only has a large direct effect on patients’ quality of life; psoriasis is associated with many comorbidities such as obesity, cardiovascular disease, diabetes, and depression.
The development of new targets for psoriasis treatments have paralleled our growing understanding of immunological pathways involved in the pathogenesis of psoriasis. Our improved understanding of the human factors that contribute to how well people use their medications has also led to major improvements in our ability to control the disease. With new evolving information, both topical and systemic medications, have been developed to selectively take advantage of these developments.2
Small Molecule Systemic Treatments
Small molecule drugs for psoriasis target a broad range of mediators in the pathogenesis of psoriasis. Aside from apremilast, these drugs have been used for many years in the treatment of psoriasis (Table 3), but the studies on which they were based have not used the same outcome measures as has become standard in psoriasis treatment.
Methotrexate has been prescribed since the 1970s for psoriasis and is still considered a first-line systemic treatment. Although newer medications are more effective and have fewer side effects, insurance companies may not cover newer therapies unless methotrexate is contraindicated or until it has been tried and failed. Methotrexate is a dihydrofolic acid reductase antagonist and has a greater affinity for the enzyme than does folic acid. Inhibition of folate production decreases T-cell proliferation and causes T-cell apoptosis. Methotrexate also suppresses joint inflammation for patients affected by PsA. Most patients take methotrexate orally at a dose of 7.5 to 25 mg weekly (either as a single dose or as 3 doses taken at 12-hour intervals); methotrexate can also be taken by intramuscular or subcutaneous injection. The majority of patients see improvement in their psoriasis after starting methotrexate at 3 to 6 weeks, with maximal improvement occurring at 6 months. In a study published in 2017, the effectiveness of subcutaneous methotrexate was tested in 120 patients with moderate to severe psoriasis in a randomized, placebo-controlled trial. After 16 weeks of treatment, 41% of patients in the treatment group experienced a 75% improvement in their Psoriasis Area Severity Index (PASI 75) score compared with 10% achieving this level of improvement in the placebo group.1,3,4,6
Side effects commonly observed are nausea, vomiting, fatigue, stomatitis, diarrhea, dizziness, fever, and alopecia. Taking 1 mg of folic acid daily may help to protect against some of these side effects. Methotrexate is cleared renally; therefore, patients with kidney disease are prescribed a lower dose or the drug is avoided altogether. One potential serious adverse effect is hepatotoxicity, and patients with a history of liver disease, hyperlipidemia, and obesity are at an increased risk. Liver biopsies are occasionally performed for patients on long-term methotrexate therapy, but current recommendations regarding the frequency of the procedure are controversial as the risk of the procedure may exceed the benefit. In addition, pulmonary fibrosis is a rare side effect but should be considered in any patient taking methotrexate who develops new onset respiratory symptoms. Methotrexate toxicity can also cause serious myelosuppression, and patients should be monitored with complete blood counts (CBCs) regularly. Folinic acid (Leucovorin) given at 20 mg is the reversal agent for acute toxicity and may need to be given at multiple doses every 6 hours until the methotrexate is cleared. Lastly, methotrexate is teratogenic and an abortifacient medication; it is contraindicated during pregnancy and in women who are trying to become pregnant.1,3,4
Cyclosporine is an immunosuppressive oral medication that was initially used to prevent rejection in organ transplant patients. Since 1997, it has been prescribed for psoriasis. Cyclosporine decreases IL-2 production and other T-lymphocyte-produced cytokines. Cyclosporine is dosed at 2 to 5 mg/kg per day and causes rapid clearance of psoriasis. While effective and valuable for short-term use, cyclosporine is infrequently prescribed because recurrence is rapid upon discontinuation and because it can cause long-term renal complications. Cyclosporine is generally reserved for acute, short-term treatment to achieve improvement while transitioning to another systemic medication or phototherapy that is safer for long-term disease management.1,3,4
Acitretin is a second generation oral systemic retinoid medication that normalizes keratinization. It reduces hyperproliferation and the scale produced in psoriasis and thins psoriatic plaques making topical medications and phototherapy more effective. Although a systemic medication, it is not a treatment for PsA. Acitretin is generally prescribed at 25 to 50 mg either daily or every other day. It is considered first-line therapy for pustular and erythrodermic psoriasis and is also effective in treating plaque psoriasis particularly in combination with phototherapy. In 2 previous studies testing the efficacy of acitretin, 66% and 85% of patients achieved PASI 50, and 34% and 52% achieved PASI 75 after 12 weeks of treatment.11
Common side effects observed are similar to those seen when oral isotretinoin therapy is used for acne and include chelitis, xerosis, headache, joint pain, and alopecia. Other adverse events are elevations in liver enzymes, cholesterol, and triglycerides, so these levels should be routinely monitored. Severe depression can also occur with oral retinoid treatment. Side effects are usually reversible when the medication is stopped. Acitretin is also a teratogen; therefore, it is contraindicated in women who are pregnant, nursing, and in women of childbearing potential. Note: Because of the long half-life of acitretin, it should rarely if ever be used by a woman who might someday become pregnant.1,3,4
Apremilast decreases inflammatory cytokines by inhibiting phosphodiesterase-4. This prevents the conversion of cyclic adenosine monophosphate (cAMP) to AMP; the resulting higher levels of cAMP decrease production of inflammatory cytokines such as TNF-α and IL-23. Apremilast was approved by the FDA in 2014 for the treatment of moderate to severe plaque psoriasis and PsA. It is typically dosed at 30 mg twice a day. In previous clinical trials, 31% of patients taking apremilast achieved PASI 75 after 16 weeks, and about 38% experienced a 20% improvement in their arthritis severity score. Compared with biologics, such as adalimumab (Humira), etanercept (Enbrel), and ustekinumab (Stelara), apremilast is less effective at treating psoriasis; however, apremilast is a reasonable option for patients who do not wish to start an injectable medication.
The most common side effect is diarrhea; nausea, vomiting, headache, and upper respiratory tract infection are also common. With continued treatment, especially after the first 2 weeks, these adverse effects tend to resolve so patients should be encouraged to continue taking the medication. Although apremilast decreases inflammatory cytokines, an increased risk of opportunistic infection has not been found in clinical trials, and there is no requirement in the label for laboratory monitoring.12 For unknown reasons, 10% to 12% of patients taking apremilast experienced a weight loss of 5% to 10%. In addition, gastroesophageal reflux disease, hypersensitivity, migraine, and suicidal ideation have been observed. This medication has not been studied in pregnancy and is considered pregnancy category C.1-3,6
Janus kinases (JAK)—such as JAK1, JAK2, JAK3, and tyrosine kinase 2—are a group of tyrosine kinases found in hematopoietic cells that are responsible for signaling that mediate the signal when cytokines bind to their receptors. By targeting JAKs and interrupting the signaling process, the immune system is modulated and inflammation can be reduced. Tofacitinib (Xeljanz) is a small molecule that has been FDA approved as an oral medication for the treatment of rheumatoid arthritis. It primarily targets JAK3 and has been investigated for its role in the treatment of psoriasis. So far, tofacitnib has been well tolerated and shown rapid results in patients with psoriasis, but there is concern for an increased risk of infection. Another oral medication, baricitinib is an inhibitor of JAK1 and JAK2 and is being studied for its role in the treatment of psoriasis. Side effects associated with these medications are increased risk of infection, elevations in cholesterol and creatinine phosphokinase levels, anemia, neutropenia, and lymphopenia.6,13
Systemic Treatments: Biologics
The introduction of biologic treatments has revolutionized the treatment of patients with moderate to severe psoriasis. As standards for how much improvement can be achieved and how little side effects should be tolerated have become much more stringent, disease clearing has become a realistic expectation for many patients (Table 4).
Story continues on page 2
TNF-α is an inflammatory cytokine that plays a large role in psoriasis. TNF-α causes inflammation as well as hyperproliferation of the epidermis and high levels are present in the skin and joints of patients with psoriasis. By blocking this cytokine, TNF-α inhibitors decrease inflammation and improve clinical symptoms. Their development had a colossal impact on the approach to treating psoriasis. Currently, there are 5 TNF-α inhibitor medications used to treat psoriasis. Three medications—infliximab (Remicade), adalimumab, and etanercept—are indicated for moderate to severe plaque psoriasis and PsA, and the other 2 medications, golimumab (Simponi) and certolizumab pegol (Cimzia), are indicated for PsA.
Although all the TNF-α inhibitors are effective for psoriasis, they differ in some characteristics. Infliximab is a chimeric (human and murine) monoclonal antibody to TNF-α and is given by intravenous infusion. Infliximab is typically dosed at 5 mg/kg once every 8 weeks after being initially given at baseline, week 2, and week 6. In clinical trials, 80% of patients on infliximab achieved PASI 75 at 10 weeks, making it the most effective TNF-α inhibitor, at least in the short term. Adalimumab is a subcutaneous injectable human IgG1 monoclonal antibody to TNF-α. It is dosed at 80 mg at baseline and at 40 mg 1 week later and every 2 weeks thereafter. Adalimumab closely follows infliximab in terms of effectiveness with 70% of patients achieving PASI 75 after 12 weeks. Etanercept is a fusion protein of human TNF type II receptor and the Fc region of IgG1 and acts as a receptor decoy through competitive inhibition. It is also given via subcutaneous injection and is dosed 50 mg once per week after being initially given at 50 mg twice per week for the first 12 weeks. In clinical trials, etanercept is the least effective TNF-α inhibitor used for psoriasis with about 49% of patents achieving PASI 75 after 12 weeks of therapy (and with some loss of activity often occurring when the dose is reduced at week 12). For PsA, there seems to be less difference among these TNF-α inhibitors. Certolizumab pegol and golimumab are both human monoclonal antibodies of TNF-α delivered via subcutaneous injection. In clinical trials, about 64% of patients taking certolizumab pegol and 50% of patients taking golimumab experienced a 20% improvement in their arthritis severity score after one 24-week and 14-week course, respectively.
Common side effects to all TNF-α inhibitors are increased risk of infections, injection site reactions (especially with etanercept), exacerbation of congestive heart failure, and drug interactions. Rare side effects are the development or reactivation of tuberculosis, hepatitis B, and a demyelinating disorder, in addition to hematologic diseases, drug-induced lupus, liver injury, and increased risk of cancer (especially lymphoma). Routine labs—including tuberculosis and hepatitis B screening, a CBC, and a complete metabolic panel, including liver function tests—have been recommended, though only tuberculosis testing and hepatitis B screening (triple serology with hepatitis B surface antigen, surface antibody, and core antibody) have strong evidence supporting routine use.14-17 TNF-α inhibitors are contraindicated for individuals at risk for infection, malignancy, those with a demyelinating disorder, active or latent tuberculosis, and congestive heart failure. They are pregnancy category B so should be used with caution in women who are pregnant, planning to become pregnant, or nursing.1-4,18
The first IL inhibitor approved for psoriasis, ustekinumab, was approved by the FDA in 2009 for the treatment of moderate to severe psoriasis. It was later approved in 2013 for the treatment of PsA. Ustekinumab is a human monoclonal antibody that binds the p40 subunit common to IL-12 and IL-23. By preventing these ILs from binding to their receptor, Th17 and Th1 signaling pathways are inhibited. The Th17 pathway plays an integral role in the pathogenesis of psoriasis. Several genes linked to psoriasis are IL-23 genes.
Ustekinumab is administered by subcutaneous injection, and dosing is weight based. Standard dosing is 45 mg given at baseline, week 4, and then every 12 weeks for patients weighing less than 220 lb. The dose is 90 mg if the patient weighs more than 220 lb. Ustekinumab is very efficacious and is about as effective as adalimumab in clinical trials. About 67% of patients taking ustekinmab achieved a PASI 75 after 12 weeks of treatment. Patients on ustekinumab tend to have better drug survival (they stay on drug longer without drug failure) than patients treated with TNF inhibitors.19,20 Common side effects—upper respiratory tract infection, nasopharyngitis, headache, fatigue, diarrhea, back pain, and dizziness—may not be drug related. Rare side effects seen are injection site reactions and hypersensitivity reactions. Also, patients taking ustekinumab may have, in theory, an increased risk of malignancy and infections since ustekinumab affects the immune system, yet so far the available data show no evidence of infections or malignancy.21 There were no reported cases in clinical trials in which patients taking the medication were at an increased risk compared with placebo, and a large registry found fewer malignancies in ustekinumab-treated patients than in patients who were not treated with any systemic medication.22 Usetekinumab is pregnancy category B so caution is advised when prescribing to women who are pregnant, nursing, or of childbearing potential. Like the TNF-α inhibitors, routine lab tests have been recommended and the product label recommends baseline tuberculosis testing, but there is no strong evidence to support a need for any laboratory monitoring.1,3,4,6
Specific IL-23 inhibitors are being developed for psoriasis. Guselkumab (Tremfya), tildrakizumab, and rizankizumab target the p19 subunit of IL-23. They show great promise and may soon become available.6,23
A family of IL-17 inhibitors has recently expanded, and they are at the forefront of psoriasis treatment. These medications are human monoclonal antibodies that act against IL-17A, a proinflammatory cytokine involved in psoriasis. By neutralizing this cytokine, hyperkeratosis and inflammation are prevented. The first IL-17A inhibitor, secukinumab (Cosentyx), was approved by the FDA in January 2015 for moderate to severe plaque psoriasis and in 2016 for PsA. It is dosed at 300 mg subcutaneously (2 subcutaneous injections of 150 mg each) to be given at baseline, week 1, week 2, week 3, week 4, and then every 4 weeks. When only treating PsA, 150 mg is recommended at the same dosing frequency. In clinical trials, secukinumab was highly effective, more than other self-administered biologic medications, with PASI 75 being achieved by 82% of patients. Even the 150-mg dose is a highly effective treatment with about 70% of patients achieving PASI 75 at week 12.1-3,6
In March 2016, ixekizumab (Taltz) was the second IL-17A inhibitor approved by the FDA for moderate to severe plaque psoriasis. It is administered via subcutaneous injection starting at 160 mg, then 80 mg every 2 weeks for 3 months, then monthly for maintenance. Compared with secukinumab, ixekizumab had even higher rates of improvement in clinical trials with nearly 90% of patients achieving PASI 75, and about 40% having 100% improvement/complete clearing.1,2,6
Brodalumab (Siliq) is the newest IL-17A inhibitor approved by the FDA. It works slightly different than the other IL-17 inhibitors; instead of targeting the IL-17A cytokine itself, brodalumab targets the IL-17A receptor and inhibits the binding of IL-17A and IL-17F. In February 2017, it was FDA approved for individuals with moderate to severe plaque psoriasis who have not improved using other therapies. In phase 2 clinical trials, 82% of patients taking brodalumab achieved PASI 75 after 12 weeks of therapy. In clinical trials, 2 patients enrolled who were taking the medication committed suicide; any relation to the drug seems dubious. Brodalumab is approved for use with a Risk Evaluation and Mitigation Strategy program.2,6,23,24
Side effects that can occur with all IL-17 inhibitors are increased risk of mild infections (such as nasopharyngitis and candidiasis), headache, pruritus, and diarrhea. An increased risk of superficial candidal infections is consistent with IL-17A’s role in immunity against mucocutaneous fungi (congenital deficiencies in the IL-17 pathway are associated with chronic mucocutaneous candidiasis). Although there is a 4-fold increased risk of superficial yeast infection, this increase amounts to only a 1.2% rate (0.3% in the placebo group) and can be managed with antifungal treatment without stopping the IL-17 inhibitor. A rare side effect is exacerbation of inflammatory bowel disease. The association of IL-17 inhibition and inflammatory bowel disease was confirmed in phase 2 studies of IL-17 inhibitors as treatments for Crohn disease; patients treated with the IL-17 antagonists did worse than patients treated with placebo. Mild neutropenia may occur but is not clinically significant; no monitoring is recommended beyond tuberculosis screening (and there is not strong evidence that even tuberculosis screening is required). These medications should be used with caution in women who are pregnant; however, no adverse events have been reported.1,6
As biologics lose their patent protection, biosimilars will become available. Biosimilars are medications similar to current biologic medications in terms of efficacy and safety profile, but are not created identically. Biologics are such large, complicated proteins that they cannot be perfectly duplicated. Not even the innovator companies can duplicate the products, and each batch consists of a mixture of variants that varies from batch-to-batch. Biosimilars can be thought of as being like a new batch of the innovator product, although biosimilars undergo far more testing than different batches of an innovator product do to demonstrate that the biosimilars will function in the same manner as the innovator does.
In November of 2016, 3 biosimilars were FDA approved for the treatment of psoriasis and PsA. These 3 medications, adalimumab-atto (Amjevita), etanercept-szzs (Erelzi), and infliximab-dyyb (Inflectra), are modeled after an already FDA-approved biologic medication (the “reference product”) for psoriasis, such as adalimumab, etanercept, and infliximab, respectively. These medications are delivered the same as their reference product. While it is anticipated that biosimilars will reduce the cost of biologics somewhat, it seems unlikely that the reduction would be so large as to change patients’ access to these life-altering medications.1
Numerous topical and systemic therapies are available to provide patients who have plaque psoriasis and PsA with treatment options. New medications are being developed with greater efficacy and less side effects to improve the patient outcome. Regardless of the treatment regimen chosen, it will not be effective if the patient does not comply. Treating psoriasis can be a tedious, lifelong commitment for the patient. Although there is not one ideal solution for all, the available options can be tailored to each patient’s individual situation and preferences. Making sure that the patient is held accountable, creating a trusting and supportive relationship, and helping patients find ways to build a habit can improve adherence and help patients to see optimal outcomes.25 Depending on the extent of disease, the patient’s wishes, previous therapies, and insurance coverage, providers can work with patients to find the best treatment that fits their needs.
Dr Glass is with the Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC. She received her medical degree at the Edward Via College of Osteopathic Medicine in Blacksburg, VA. She completed a traditional rotating internship at Sampson Regional Medical Center and is currently a resident in dermatology at North Fulton Hospital in Roswell, GA.
Dr Feldman is with the Center for Dermatology Research and the Departments of Dermatology, Pathology, and Public Health Sciences at Wake Forest University School of Medicine in Winston-Salem, NC.
Disclosure: Dr Glass reports no relevant financial relationships. The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P.
Dr Feldman is a consultant and/or speaker for Amgen, Abbvie, Abbott Labs, Advanced Medical, BiogenIdec, Bristol-Myers Squibb, Caremark, Galderma, Genentech, Janssen, Pfizer Inc, Photomedex, Regeneron, Sanofi, Stiefel/GlaxoSmithKline, Taro,and Warner Chilcott. Dr Feldman has received grants from Abbott Labs, Abbvie, Amgen, Anacor, Astellas, Aventis Pharmaceuticals, Basilea, BiogenIdec, Bristol-Myers Squibb, Celgene, Eli Lilly, Galderma, Genentech, Gerson Lehrman Group, Guidepoint Global, HanAll Pharmaceuticals, Janssen, Kikaku, Leo Pharma Inc, Medicis, Merck & Co., Inc, Mylan, Novartis, Ortho Pharmaceuticals, Photomedex, Pharmaderm, Pfizer Inc, Regeneron, Roche Dermatology, 3M, Sanofi, Sienna, Stiefel/GlaxoSmithKline, Sun Pharma, Suncare Research, Taro, Valeant, Warner Chilcott, and Xenoport, and he has received stock options from Photomedex. He receives royalties from Informa, UptoDate, and Xlibis. He is owner of www.DrScore.com and a founder of Causa Research.
1. Fact sheet library. National Psoriasis Foundation website. https://www.psoriasis.org/publications/patient-education/fact-sheets. Accessed June 15, 2017.
2. Mahil SK, Capon F, Barker JN. Update on psoriasis immunopathogenesis and targeted immunotherapy. Sem Immunopathol. 2016;38(1):11-27.
3. Farhangian ME, Anderson KL, Feldman SR. Practical Psoriasis Management. Winston-Salem, NC: Steven R. Feldman; 2015.
4. James WD, Berger TG, Elston DM. Seborrheic dermatitis, psoriasis, recalcitrant palmoplantar eruptions, pustular dermatitis, and erythroderma. In: James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin. 12th ed. Philadelphia, PA: Elsevier. 2016:85-198.
5. Trémezaygues L, Reichrath J. Vitamin D analogs in the treatment of psoriasis: Where we are standing and where we will be going? Dermatoendocrinol. 2011;3(3):180-186.
6. Feldman SR. Treatment of psoriasis. UpToDate. http://www.uptodate.com/contents/treatment-of-psoriasis. Updated May 25, 2017. Accessed June 15, 2017.
7. Margolis DJ, Abuabara K, Hoffstad OJ, Wan J, Raimondo D, Bilker WB. Association between malignancy and topical use of pimecrolimus. JAMA Dermatol. 2015;151(6):594-599.
8. Margolis DJ, Hoffstad O, Bilker W. Lack of association between exposure to topical calcineurin inhibitors and skin cancer in adults. Dermatology. 2007;214(4):289-295.
9. Callen J, Chamlin S, Eichenfield LF, et al. A systematic review of the safety of topical therapies for atopic dermatitis. Br J Dermatol. 2007;156(2):203-221.
10. Nakamura M, Farahnik B., Bhutani T. Recent advances in phototherapy for psoriasis. F1000Res. 2016;5(F1000 Faculty Rev):1684. doi: 10.12688/f1000research.8846.1
11. Geiger JM. Efficacy of acitretin in severe psoriasis. Skin Therapy Lett. 2003;8(4):1-3,7.
12. Mease PJ, Kavanaugh A, Gladman D, et al. SAT0408 long-term safety and tolerability of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis: pooled safety analysis of three phase 3, randomized, controlled trials. Ann Rheum Dis. 2014;73(suppl 2):742-743.
13. Gooderham M. Small molecules: an overview of emerging therapeutic options in the treatment of psoriasis. Skin Therapy Lett. 2013;18(7):1-4.
14. Ahn CS, Dothard EH, Garner ML, Feldman SR, Huang WW. To test or not to test? An updated evidence-based assessment of the value of screening and monitoring tests when using systemic biologic agents to treat psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2015;73(3):420-428.e1.
15. Huang W, Cordoro KM, Taylor SL, Feldman SR. To test or not to test? An evidence-based assessment of the value of screening and monitoring tests when using systemic biologic agents to treat psoriasis. J Am Acad Dermatol. 2008;58(6):970-977.
16. Chan M, Huang Y, Wen Y, et al. Compliance with risk management plan recommendations on laboratory monitoring of antitumor necrosis factor-α therapy in clinical practice. J Formos Med Assoc. 2016;115(2):83-93.
17. Motaparthi K, Stanisic V, Van Voorhees AS, Lebwohl MG, Hsu S; Medical Board of the National Psoriasis Foundation. From the Medical Board of the National Psoriasis Foundation: Recommendations for screening for hepatitis B infection prior to initiating anti-tumor necrosis factor-alfa inhibitors or other immunosuppressive agents in patients with psoriasis. J Am Acad Dermatol. 2014;70(1):178-186.
18. Meglio PD, Villanova F, Nestle FO. Psoriasis. Cold Spring Harb Perspect Med. 2014;4(8):1-30.
19. Arnold T, Schaarschmidt ML, Herr R, Fischer JE, Goerdt S, Peitsch WK. Drug survival rates and reasons for drug discontinuation in psoriasis. J Dtsch Dermatol Ges. 2016;14(11):1089-1099.
20. Menter A, Papp KA, Gooderham M, et al. Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Eur Acad Dermatol Venereol. 2016;30(7):1148-1158.
21. Kalb RE, Fiorentino DF, Lebwohl MG, et al. Risk of serious infection with biologic and systemic treatment of psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatology. 2015;151(9):961-969.
22. Papp K, Gottlieb AB, Naldi L. Safety surveillance for ustekinumab and other psoriasis treatments from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Drugs Dermatol. 2015;14(7):706-714.
23. Campa M, Mansouri B, Warren R, Menter A. A Review of biologic therapies targeting IL-23 and IL-17 for use in moderate-to-severe plaque psoriasis. Dermatol Ther Heidelb. 2016;(6):1-12.
24. FDA approves new psoriasis drug [news release]. Silver Spring, MD: Food and Drug Administration; February 15, 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm541981.htm. Accessed June 15, 2017.
25. Feldman SR, Vrijens B, Gieler U, Piaserico S, Puig L, van de Kerkhof P. Treatment adherence intervention studies in dermatology and guidance on how to support adherence. Am J Clin Dermatol. 2017;18(2):253-271.