Biologics: Changing the Treatment Scope for Psoriasis and PsA

This article is also available in the attached pdf version.

biologicsPsoriasis is a common chronic skin disease characterized by cutaneous inflammation and epidermal hyperproliferation. Improvements in psoriasis therapies over the past decade have changed the way dermatologists treat this important disease entity, including increased use of biologic therapies. Biologic agents, which are protein-based drugs made from living cells, have altered the treatment landscape in the management of moderate-to-severe psoriasis and psoriatic arthritis (PsA), leading to improved prognosis, control of symptoms and better quality of life for the millions of individuals affected. Before the first biologic for psoriasis was FDA approved, treatment options consisted of topical agents, phototherapy and conventional systemic agents.

This article discusses the biologics for the treatment of psoriasis and PsA, the efficacy and tolerability of these treatments, cost of therapies, the importance of clinician and patient education and new therapies in the pipeline.

Biologic Agents for Psoriasis
Psoriasis, a disease of T cell dysregulation, is an often debilitating inflammatory condition that significantly impacts a patient’s health-related quality of life, psychological well-being and physical and social aspects of daily living.1,2 A population-based study found that the incidence of psoriasis in the United States is rising, doubling within the past several decades.3,4 Currently, psoriasis affects 1% to 8% of the worldwide population depending on the country.3,5 Psoriasis is associated with PsA, inflammatory bowel disease, cardiovascular disease and depressive illness. The causes of psoriasis are not fully understood, but a number of risk factors are recognized, including family history and environmental risk factors, such as smoking, stress, obesity and alcohol consumption.5,6 PsA is an inflammatory seronegative spondyloarthropathy. The percentage of patients with psoriasis who develop PsA ranges from as low as 6% to as high as 42%. The prevalence of PsA throughout the United States has been estimated between 0.1% to 0.25%.7     

Different from the traditional systemic drugs that impact the entire immune system, biologics target specific parts of the immune system. Biologics used to treat psoriatic diseases block T cell receptors or block proteins in the immune system, such as tumor necrosis factor-alpha (TNF-α) or interleukins (IL) 12 and 23.8

“There are going to be a lot of new drugs. Right now we have 4 approved biologic agents for the treatment of psoriasis, and … in about 5 years that number will at least double, and may be as high as 10 approved biologics and as many as 2 or perhaps 3 new small molecules,” said Bruce E. Strober, MD, PhD, during his presentation on psoriasis at the Winter 2014 American Academy of Dermatology meeting.
Currently, there are 6 FDA-approved biologics for psoriasis and PsA. These therapies belong to 1 of 2 categories: TNF-α inhibitors including adalimumab (Humira, AbbVie Inc), certolizumab pegol (Cimzia, UCB Inc), etanercept (Enbrel, Amgen Inc), golimumab (Simponi, Janssen Biotech Inc) and infliximab (Remicade, Janssen Biotech Inc) or the IL 12/23 monoclonal antibody ustekinumab (Stelara, Janssen Biotech Inc). These biologics are typically effective and well-tolerated in long-term studies.9-15 Each biologic has a unique mechanism of action, dosing schedule and route of administration (Table 1).

“In the past year, more safety data has emerged on biologic therapies and it continues to be encouraging,” said Mark Lebwohl, MD chair of department of dermatology at the Icahn School of Medicine at Mount Sinai, in New York, NY, and chairman emeritus of the National Psoriasis Foundation Medical Board.

Before the emergence of biologics, systemic psoriasis therapies such as methotrexate, cyclosporine, acitretin and mycophenolate mofetil were used when psoriasis was too extensive for topical therapy or refractory to topical therapy and phototherapy. However, these medications suppress the entire immune function, requiring clinicians to do routine laboratory monitoring because of the increased liver and renal toxicity, hematologic conditions (eg, anemia, pancytopenia) and myelosuppresion. Systemic therapies are also contraindicated in various clinical settings, such as pregnancy and nursing mothers and individuals with liver or kidney disease.6,16

Efficacy and Tolerability
Biologics have changed the therapeutic management of psoriasis, providing clinicians with the opportunity to directly target the known key mediators in the pathogenesis of this disease.1 The increasing use of biologic medications may reflect the generally high efficacy rates, relatively good safety profiles and demonstrated improvement in quality of life.17

“We know biologics are effective,” said Steven R. Feldman, MD, PhD, 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. “Every day that goes by, the safety experience grows, giving us greater confidence in the use of biologics.”

Gary Goldenberg, MD, assistant professor of dermatology and pathology in the departments of dermatology and pathology at the Icahn School of Medicine at Mount Sinai in New York, NY, agreed that biologics are efficacious for psoriasis. He also noted that more data on TNFs has shown systemic and cardioprotective benefits. “It’s time to stop looking at psoriasis as just a skin disease. It’s a systemic disease as much as anything else,” he said.

The following review highlights the results from some of the pivotal trials that evaluated the effectiveness of the currently approved biologics for psoriasis and PsA.

REVEAL (The Randomized Controlled Evaluation of Adalimumab Every Other Week in Moderate to Severe Psoriasis Trial), a randomized, double-blind, placebo-controlled, Phase III trial, evaluated the safety and efficacy of adalimumab in 1,212 patients with moderate-to-severe chronic plaque psoriasis over 52 weeks. Patients were randomized to receive adalimumab 40 mg subcutaneously every other week or placebo for 15 weeks. At week 16, 71% of the adalimumab group versus 7% of the placebo group achieved a ≥75 improvement in the Psoriasis Area and Severity Index (PASI) score.1,18 In the recently published open-label extension of the REVEAL trial, patients received adalimumab for 3 years. Patients who initially sustained PASI 75 during REVEAL maintained their improvement after both 100 and 160 weeks of continuous therapy, and a PASI 75 was achieved by 83% and 76% of patients, respectively, with no difference in the safety profile from the original trial.1,19

The efficacy of adalimumab was also shown in the treatment of PsA, according to 2-year data from ADEPT (Adalimumab Effectiveness in Psoriatic Arthritis Trial). Patients with PsA who completed a 24-week, double-blind study of adalimumab versus placebo were eligible to enroll in an open-label extension study and receive adalimumab 40 mg subcutaneously every other week for up to an additional 120 weeks. After 24 weeks of double-blind treatment, the mean change in modified total Sharp Score (mTSS) was −0.2 for the 144 patients in the adalimumab group and 1.0 for the 152 patients in the placebo group. Compared with the 24-week responses, inhibition of radiographic progression and improvements in joint disease were maintained, with >20% of patients achieving the strict criterion of PSAI 100.20

Certolizumab Pegol
Certolizumab pegol is the most recent FDA-approved biologic treatment. Approval for certolizumab pegol for active PsA was based on data from the RAPID-PsA study, an ongoing, Phase III, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of certolizumab pegol in 409 patients with active and progressive adult onset PsA. Patients were randomized 1:1:1 to placebo, or a loading dose of 400 mg certolizumab pegol at weeks 0, 2 and 4 followed by either certolizumab pegol 200 mg every other week or certolizumab pegol 400 mg every 4 weeks. Patients were evaluated for signs and symptoms of PsA using American College of Rheumatology 20% (ACR 20) response at week 12 and for structural damage using mTSS at week 24.21

ACR 20 response at week 12 was significantly greater in patients treated with certolizumab pegol 200 mg every other week and certolizumab pegol 400 mg every 4 weeks than placebo (58.0% and 51.9% vs 24.3%, respectively). Patients treated with certolizumab pegol 200 mg every other week demonstrated greater reduction in radiographic progression compared with placebo-treated patients at week 24, as measured by change from baseline in mTSS. Patients treated with certolizumab pegol 400 mg every 4 weeks did not demonstrate greater inhibition of radiographic progression at week 24 compared with placebo-treated patients.21

The long-term efficacy and safety of etanercept has been evaluated in the treatment of psoriasis and PsA. The CRYSTEL (Clinical Randomized Year-Long Study Assessing the Safety and Efficacy of Etanercept in Psoriasis) study demonstrated that both continuous and intermittent etanercept treatment regimens improved PSAI scores and quality of life. In the 54-week, open-label study of patients with moderate-to-severe plaque psoriasis, the results found both treatment groups had significant improvement in PASI scores from baseline to week 54 (68% and 59%, respectively).1,22-24

Etanercept efficacy in PsA was evaluated in an open-label extension study in which 169 patients continued treatment with etanercept 25 mg twice weekly for up to 48 weeks. The results showed that ACR20, PsA response criteria and PASI 50 were met by 64%, 84% and 62%, respectively, of those patients initially assigned to etanercept at the end of the 48-week open-label period. Patients originally assigned to etanercept maintained an inhibition of radiologic progression for up to 2 years of treatment (mean adjusted change in mTSS of −0.38 from baseline to 2 years).22,25

The 24-week efficacy and safety of golimumab in PsA was assessed in the GO-REVEAL (Golimumab—A Randomized Evaluation of Safety and Efficacy in Subjects with Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody) trial. The Phase III, multicenter, randomized, double-blind, placebo-controlled study randomized patients to receive placebo, golimumab 50 mg or golimumab 100 mg every 4 weeks through week 20. Among the 74% of patients in whom at least 3% of the body surface area was affected by psoriasis at baseline, the results showed that 40% of those in the golimumab 50-mg group and 58% of those in the golimumab 100- mg group had at least 75% improvement in the PASI at week 14 compared with 3% of placebo-treated patients.26

The Phase III EXPRESS (European Infliximab for Psoriasis [Remicade] Efficacy and Safety Study) assessed the efficacy and safety of continuous treatment with infliximab in patients with moderate-to-severe plaque psoriasis. Patients were randomized to receive infusions of either infliximab 5 mg/kg or placebo at weeks 0, 2, and 6, then every 8 weeks to week 46. The results showed that 61% and 45% of infliximab-treated patients achieved PASI 75 and PASI 90, respectively, at 50 weeks.1,27

IMPACT 2 (Induction and Maintenance Psoriatic Arthritis Clinical Trial 2), a randomized, double-blind, placebo-controlled, multicenter, Phase III study, evaluated the efficacy of infliximab in 200 adult patients with active PsA for at least 6 months who had inadequate response to disease-modifying antirheumatic drugs (DMARDs) or nonsteridal   anti-inflammatory drugs (NSAIDs). During the 24-week, double-blind phase, patients received either infliximab 5 mg/kg or placebo at weeks 0, 2, 6, 14 and 22. At week 24, all placebo-treated patients crossed over to infliximab induction. Dosing continued for all patients through week 46. Treatment with infliximab resulted in improvement in signs and symptoms with 58% of infliximab-treated patients achieving ACR 20 at week 14. At 6 months, the ACR 20/50/70 responses were achieved by 54%, 41% and 27%, respectively, of patients receiving infliximab.13

Recently published data from PHOENIX 1 (Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Efficacy and Safety of CNTO 1275 in the Treatment of Subjects with Moderate to Severe Plaque-type Psoriasis) found that through 5 years of continuous treatment ustekinumab demonstrated stable clinical response consistent with previous reports. Patients were randomly assigned to receive ustekinumab 45 mg or 90 mg at weeks 0 and 4, then every 12 weeks or placebo; placebo patients crossed-over to ustekinumab at week 12. Clinical response through week 244 was evaluated using the PASI in the overall population, initial responders and partial responders.28

Initial clinical response were generally maintained through week 244 for patients receiving 45 mg and 90 mg (PASI 75: 63.4% and 72.0%; PASI 90: 39.7% and 49.0%; PASI 100: 21.6% and 26.4%, respectively). Similarly, PASI 75 responses were generally maintained among initial responders receiving 45 mg and 90 mg (79.1% and 80.8%, respectively) and partial responders (57.6% and 55.1%, respectively).28

Ustekinumab was also proven effective in PsA, according to 1-year data from PSUMMIT 1 (Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Ustekinumab, a Fully Human Anti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects with Active Psoriatic Arthritis). The study included 615 adult patients with active PsA for ≥6 months despite treatment with NSAID or DMARD therapy. Patients were randomized 1:1:1 to ustekinumab 45 mg, ustekinumab 90 mg or placebo at week 0, 4 and every 12 weeks thereafter. At week 24, all remaining patients in the placebo group received ustekinumab 45 mg, which they continued at week 28 and then every 12 weeks. The results showed that more patients taking ustekinumab   45 mg and 90 mg achieved ACR20 at week 24 compared with the placebo group (42.4% and 49.5% vs 22.8%, respectively); responses were maintained at week 52.29

Overall, the most commonly reported adverse events (AEs) were mild and did not result in discontinuation of therapy (Table 2).9-14,30 Rare AEs have been reported in the literature and fall into 6 categories: inflammatory skin disease (eg, sarcoidosis), atypical infectious events (eg, herpes zoster), blood disorders (eg, neutropenia), connective tissue disease (eg, lupus), neurologic events (eg, demyelination and axonal polyneuropathy) and cardiac/metabolic abnormalities (eg, worsening of congestive heart failure).31,32

Because there are AEs associated with biologic therapy, clinicians should prescreen patients before initiation and continue monitoring patients during and after treatments. The FDA and Centers for Disease Control and Prevention, in addition to key consensus statements, have outlined recommendations regarding monitoring.1

A potential drawback to biologic therapy is that it has to be given either by injection or intravenous infusion. Infusion can last 2 hours per session (Table 1).

Toll of Biologic Therapy
Another disadvantage of biologics is the cost. The drug costs for treating psoriasis in the United States continues to increase, with a major contribution from biologics. Annual costs of biologics exceed those of other available therapies for psoriasis. The total cost for the first year of treatment ranged from $23,000 to $33,000. The comparison of annual costs for biologics for psoriasis was $26,862 for etanercept, $23,639 for infliximab, $23,538 for adalimumab and $33,576 for ustekinumab.1,33,34

A meta-analysis by Chi et al analyzed the incremental cost-effectiveness ratio (ICER) per patient achieving PASI 75 for etanercept, adalimumab, infliximab and ustekinumab 45 mg and 90 mg. The corresponding 6-month ICER regarding PASI 75 was $32,643, $21,315, $27,782, $25,055 and $46,630, respectively. The researchers concluded that clinicians and policymakers should consider the efficacy and cost-efficacy evidence along with patients’ values and characteristics in deciding how to efficiently allocate resources in treating psoriasis.35

The cost of biologics is also a consideration for patients. One study found that patients with lower income levels had increased cutbacks in personal expenses due to copayments. Further, the mean annual out of pocket expense for current biologics was $557.12 per year, with a range of $0 to $7,000.17

The manufacturers of biologics offer programs to help determine patient eligibility and treatment cost.

Education Is Vital
Education is an important component in biologic therapy for both clinicians and patients. “Patient education is important because patients should be informed and involved in the decision as to what treatment they wish to have,” said Dr. Feldman.

Dr. Goldenberg recommended that physicians continue to be educated on the efficacy and safety of biologic therapy so they in turn can educate patients about the drugs. “Biologics are the gold standard and it’s important for physicians to know how to use all the drugs.”

“When deciding on an appropriate biologic therapy, I think it is helpful to inform patients of the advantages and disadvantages of the reasonable options, then let them choose,” said Dr. Feldman. “If they prefer that the doctor chooses, the efficacy, safety, cost and other practical issues should be considered.” Clinicians also need to factor in “patient comorbidities and determine if biologic therapy will improve or worsen these comorbidities,” added Dr. Lebwohl.

In a Web-based survey that looked at patient satisfaction with current treatment options for psoriasis, patients receiving biologic therapy were significantly most satisfied. Overall, patients rated treatment effectiveness as most important, followed by treatment safety and doctor–patient communication.36 In a separate study, Kamangar et al conducted a survey of 106 psoriasis patients at an academic medical center to discern patient attitudes toward biologics. The survey found that 62.6% of respondents were “very satisfied” with biologics, and 74.5% learned about biologics from their physician. When asked about concern that biologics medications will cause an AE, 57.5% of patients responded, “not worried at all.” The survey also found that compliance rates for biologic therapy was high with 66.6% of respondents reporting “never” or “rarely” missing a dose.17

Biologics in the Pipeline
Many novel and exciting therapies are currently in the pipeline, ranging from developmental stages to clinical trials, that target various cytokines and regulatory molecules involved in the pathogenesis of psoriasis. Several new drugs that specifically target IL-23 such as guselkumab and tildrakizumab are under development.3

One class of drugs getting closer to approval are IL-17 receptor blockers, according to Dr. Strober. “There are 3 [IL-17 inhibitors] that will effectively shutdown psoriasis in the large percentage of patients with moderate-to-severe disease,” he said. These drugs include brodalumab, ixekizumab and secukinumab.

Brodalumab is a human monoclonal antibody targeting the IL-17 receptor that inhibits binding of most of the IL-17 subtypes to the receptor. Phase III data from the AMAGINE-1 study of brodalumab in 661 patients with moderate-to-severe plaque psoriasis is promising. Results showed that 83.3% of patients in the 210-mg group and 60.3% of patients in the 140-mg group achieved PASI 75 responses compared to placebo (2.7%). Findings also showed that 70.3% of patients in the 210-mg group and 42.5% of patients in the 140-mg group achieved PASI 90 responses compared to placebo (0.9%). Further, 41.9% of patients in the 210-mg group and 23.3% of patients in the 140-mg group achieved PASI 100 responses compared to placebo (0.5%).37

Results of a Phase II trial of ixekizumab (n=142), a humanized immunoglobulin (Ig) G4 monoclonal antibody against IL-17A, found that psoriasis area and severity index scores were significantly improved versus placebo.  At 12 weeks in the 150-mg group, patients achieving PSAI 75, 90 and 100 were 82.1% 71.4% and 39.3%, respectively.3,38

A third agent, secukinumab was developed as a human IgG1 monoclonal antibody to IL-17A. Phase II trials including 404 patients showed PASI 75 rates of more than 50% and more than 40% in the early and monthly dosing regimens, respectively, both significantly improved from placebo (P<.001).3

“The more options there are, the better we can take care of our patients,” said Dr. Goldenberg.

The proven efficacy and safety of biologics provides clinicians with more therapeutic options to treat their patients with psoriasis and PsA. As more biologic therapies are FDA approved, the opportunity for improved prognosis and symptom control will benefit patients. Because dermatologists take a frontline role in improving the quality of life for this patient population, it is important they continue to be educated on current and future medications to help them decide what is the best treatment strategy for each patient.

1. Levy LL, Solomon SM, Emer JJ. Biologics in the treatment of psoriasis and emerging new therapies in the pipeline. Psoriasis: Targets and Therapy. 2012;2:29-43.
2. Bhosle MJ, Kulkarni A, Feldman SR, Balkrishnan. Quality of life in patients with psoriasis. Health Qual Life Outcomes. 2006;4:35.
3. Han G. In the pipeline for psoriasis: upcoming psoriasis treatments. Cutis. 2014;93(3):E12-E16.
4. Icen M, Crowson CS, McEvoy MT, Dann FJ, Gabriel SE, Maradit Kremers H. Trends in the incidence of adult-onset psoriasis over three decades: a population-based study. J Am Aacd Dermatol. 2009;60(3):394-401.
5. Parisi R, Symmons DR, Griffiths CE, Ashcroft DM. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133(2):377-385.
6. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58(5):826-850.
7. Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008;58(5):851-864.
8. National Psoriasis Foundation. Moderate to Severe Psoriasis: Biologic Drugs. Accessed June 5, 2014.
9. Humira [prescribing information]. North Chicago, IL: AbbVie Inc; 2013.
10. Cimzia [prescribing information]. Smyrna, GA: UCB Inc; 2013.
11. Enbrel [prescribing information]. Thousand Oaks, CA: Amgen Inc; 2013.
12. Simponi [prescribing information]. Horsham, PA: Janssen Biotech Inc; 2013.
13. Remicade [prescribing information]. Horsham, PA: Janssen Biotech Inc;  2013.
14. Stelara [prescribing information]. Horsham, PA: Janssen Biotech Inc; 2014.
15. Rustin MH. Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data. Br J Dermatol. 2012;167 (suppl 3):3-11.
16. Menter A, Korman NJ, Elmets CA. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61(3):451-485.
17. Kamangar F, Leah I, Bhutani T, et al. How psoriasis patients perceive, obtain, and use biologic agents: Survey from an academic medical center. J Dermatolog Treat. 2013;24(1):13-24.
18. 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.
19. Gordon K, Papp K, Poulin Y, Gu Y, Rozzo S, Sasso EH. Long-term efficacy and safety of adalimumab in patients with moderate to severe psoriasis treated continuously over 3 years: results from an open-label extension study for patients from REVEAL. J Am Acad Dermatol. 2012;66(2):241-251.
20. Mease PJ, Ory P, Sharp JT, et al. Adalimumab for long-term treatment of psoriatic arthritis: 2-year data from Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT). Ann Rheum Dis. 2009;68(5):702-709.
21. Mease PJ, Fleischmann R, Deodhar R, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014;73(1):48-55.
22. Kivelevitch D, Mansouri B, Menter A. Long term efficacy and safety of etanercept in the treatment of psoriasis and psoriatic arthritis. Biologics. 2014;8:169-182.
23. Ortonne JP, Griffiths C, Daudén E, et al. Efficacy and safety of continuous versus paused etanercept treatment in patients with moderate-to-severe psoriasis over 54 weeks: the CRYSTEL study. Exp Rev Dermatol. 2008;3(6):657-665.
24. Daudén E, Griffiths CE, Ortonne JP, et al. Improvements in patient-reported outcomes in moderate-to-severe psoriasis patients receiving continuous or paused etanercept treatment over 54 weeks: the CRYSTEL study. J Eur Acad Dermatol Venereol. 2009;23(12):1374-1382.
25. Mease PJ, Kivitz AJ, Burch FX, et al. Continued inhibition of radiographic progression in patients with psoriatic arthritis following 2 years of treatment with etanercept. J Rheumatol. 2006;33(4):712-721.
26. Kavanaugh A, McInnes I, Mease P, et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum. 2009;60(4):976-986.
27. Reich K, Nestle FO, Papp K, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a Phase III, multicentre, double-blind trial. Lancet. 2005;366(9494):1367-1374.
28. Kimball AB, Papp KA, Wasfi Y, et al. Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years in the PHOENIX 1 study. J Eur Acad Dermatol Venereol. 2013;27(12):1535-1545.
29. McInnes IB, Kavanaugh A, Gottlieb AB, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet. 2013;382(9894):780-789.
30. National Psoriasis Foundations. Biologic Drugs: Fact Sheets.
Accessed June 5, 2014.
31. Townsend M, Stober BE. Rare side effects of biologics: part 1. The Dermatologist. 2013;21(11):28-32.
32. Townsend M, Stober BE. Rare side effects of biologics: part 2. The Dermatologist. 2013;21(12):30-34.
33. Beyer V,  Wolverton SE. Recent trends in systemic psoriasis treatment costs. Arch Dermatol. 2010;146(1):46-54.
34. Schafer JA, Kjesbo NK, Gleason PP. Formulary review of 2 new biologic agents: tocilizumab for rheumatoid arthritis and ustekinumab for plaque psoriasis. J Manag Care Pharm. 2010;16(6):402-416.
35. Chi CC, Wang SH. Efficacy and cost-efficacy of biologic therapies for moderate to severe psoriasis: a meta-analysis and cost-efficacy analysis using the intention-to-treat principle. BioMed Res Int. 2014;2014:862851.
36. van Cranenburgh OD, de Korte J, Sprangers MA, de Rie MA, Smets EM. Satisfaction with treatment among patients with psoriasis: a web-based survey study. Br J Dermatol. 2013;169(2):398-405.
37. Amgen and AstraZeneca announce positive results from phase 3 study of brodalumab (AMG 827) in patients with moderate-to-severe plaque psoriasis [news release]. Thousand Oaks, CA. Amgen Inc; May 9, 2014. Accessed June 7, 2014.
38. Leonardi C, Matheson R, Zachariae C, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366(13):1190-1199.

table 1

table 2