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Am J Clin Dermatol (2014) 15:165180

DOI 10.1007/s40257-014-0064-x

EVIDENCE-BASED REVIEW

Systemic Therapies for Psoriasis: An Evidence-Based Update


Laura F. Sandoval Allison Pierce

Steven R. Feldman

Published online: 5 February 2014


Springer International Publishing Switzerland 2014

Abstract effective as the biologic agents, they may be an option as


Background The treatment of psoriasis has evolved over an alternative to traditional oral agents, with more favor-
the years, with the focus now largely on the use of biologic able safety profiles. Several systematic reviews focused on
agents. With treatment options expanding, evidence-based efficacy among the biologics, with infliximab consistently
studies to guide physicians treatment decisions become superior to the others, and etanercept the least effective of
increasingly important. the tumor necrosis factor-alpha inhibitors. Longer-term
Objective Our objective was to review current literature safety data on biologics is now available and encouraging.
to provide an evidence-based update on systemic therapies Limitations Current studies of traditional oral therapies
for psoriasis. are lacking.
Methods A systematic review of the literature was con- Conclusions Current studies continue to support the use
ducted from 1 January 2012 through 1 July 2013 to identify of biologic agents in the treatment of moderate to severe
all randomized clinical trials and systematic reviews of psoriasis, with better efficacy and safety profiles than tra-
systemic psoriasis treatments. ditional systemic agents. Newer anti-IL-17 agents and
Results A total of 46 publications were identified and several new oral agents are in development and have
reviewed. Randomized clinical trials for the treatment of shown promise in clinical trials.
psoriasis focused heavily on biologic agents, both currently
approved agents and anti-interleukin (IL)-17 agents in
development. The anti-IL-17 agents appear effective 1 Introduction
according to phase II clinical trials. Several new oral agents
are being studied, and, although they do not appear as Psoriasis is a chronic inflammatory skin disease that
requires long-term treatment. Systemic treatments,
including oral and biologic agents and phototherapy, are
used to treat moderate to severe disease. According to
L. F. Sandoval  A. Pierce  S. R. Feldman (&)
Department of Dermatology, Center for Dermatology Research, current guidelines on the management of psoriasis, these
Wake Forest School of Medicine, Medical Center Boulevard, therapies should be considered in patients when adequate
Winston-Salem, NC 27157-1071, USA control of the disease cannot be accomplished with topical
e-mail: sfeldman@wakehealth.edu agents. Guidelines state that the definition of adequate
L. F. Sandoval control should be determined according to the patients
e-mail: lsandova@wakehealth.edu own perception of disease burden and not by severity of
S. R. Feldman disease based on measures that are often used to define
Department of Pathology, Wake Forest School of Medicine, moderate to severe disease (i.e. the use of body surface area
Winston-Salem, NC, USA affected) [1]. Individualized treatment based on needs of
the patient is emphasized; to accomplish this, physicians
S. R. Feldman
Department of Public Health Sciences, Wake Forest School of must have up-to-date knowledge of treatment options in
Medicine, Winston-Salem, NC, USA order to make appropriate recommendations.
166 L. F. Sandoval et al.

Systemic treatment of psoriasis has evolved over the Psoriasis Area and Severity Index (PASI) score (PASI-75)
years, and the focus is now largely on biologic agents. compared with placebo (2 %) at week 12 [2]. Other effi-
Traditional oral therapy, primarily methotrexate, cyclo- cacy and health-related quality of life (HRQoL) measures,
sporine, and acitretin, has remained relatively unchanged including PASI-50, PASI-90, Physicians Global Assess-
for many years, and the use of these drugs continues to be ment (PGA) response rates, and change in Dermatology
limited due to their end-organ toxicity and/or teratogenicity Life Quality Index (DLQI) score were also higher in all
[1]. However, while research continues to focus heavily on treatment groups compared with placebo [2, 3]. The inci-
biologics, with newer agents targeting interleukin (IL)-17, dence of adverse effects was comparable across all groups,
there are also several oral agents currently in development. with five serious adverse events reported. The 15-mg group
As the treatment options for psoriasis expand, with new was more likely to have a decline in hemoglobin and
oral and biologic agents in development, and with long- absolute neutrophil count. There was also a dose-dependent
term efficacy and safety data on existing approved thera- increase in total cholesterol, high-density lipoprotein cho-
pies now available, evidence-based studies to guide phy- lesterol, and low-density lipoprotein cholesterol, which
sicians treatment decisions become increasingly returned to baseline after treatment.
important. The objective of this study was to review cur- Apremilast is an oral phosphodiesterase inhibitor cur-
rent literature to provide an evidence-based update on rently in phase III clinical trials for the treatment of pso-
systemic therapies for psoriasis. riasis. At week 16 of a phase II trial, in patients treated with
apremilast 10 mg, 20 mg, 30 mg, or placebo twice daily,
significantly more patients in the 20- (29 %) and 30-mg
2 Methods (41 %) groups achieved a PASI-75 compared with placebo
(6 %) [4]. There were also significantly more patients
We conducted a systematic review of the literature from 1 reaching a PGA of clear/minimal and a greater reduction
January 2012 through 1 July 2013 to identify all random- in DLQI in the 20- and 30-mg groups compared with
ized clinical trials (RCTs) and systematic reviews of sys- placebo [4, 5]. Most adverse effects were mild or moderate
temic psoriasis treatments. We searched PubMed for the and included headache, nausea, diarrhea, and vomiting,
term psoriasis treatment, limiting the results to RCTs and with half occurring in the first 2 weeks and resolving in 1
systematic reviews. The publications were reviewed for week; headache and diarrhea were more common in the
content, and duplicates and publications in languages other 30-mg group. There were no significant laboratory abnor-
than English were excluded (Fig. 1). malities. In a separate phase II trial, 20 mg twice daily was
The RCTs were grouped by oral therapy and biologic significantly more effective (24 % achieving PASI-75) than
therapy. Biologic agents were further sub-grouped either 20 mg daily or placebo (10 % achieving PASI-75)
according to mechanisms of action: anti-IL-12/23, tumor [6]. Common adverse effects were again headache, diar-
necrosis factor (TNF)-alpha inhibitors, and anti-IL-17. rhea, and nausea.
The third new oral drug currently being studied for the
treatment of psoriasis is CF101, an anti-inflammatory agent
3 Results that binds and inhibits A3 adenosine receptors. Psoriasis
patients in a phase II trial were treated with 1 mg, 2 mg,
A total of 46 relevant publications met inclusion criteria, 4 mg, or placebo twice daily for 12 weeks, with a signifi-
with 28 RCTs (21 on biologic therapy and seven con- cant change in PASI in patients in the 2-mg group com-
cerning oral therapy) and 18 systematic reviews (Fig. 1). pared with placebo [7]. The 4-mg dose was less effective
than the 2-mg dose, and the 1-mg dose was not therapeutic.
3.1 Oral Therapies Of patients in the 2-mg group, 35 % reached a PASI-50 and
24 % reached a PGA score of 0 or 1. Incidences of adverse
Four studies (six publications) reported on three new oral affects were comparable between all groups, with one
drugs currently in clinical trials: tofacitinib, apremilast, and serious adverse event reported in the placebo group.
CF101 (Table 1). One additional study assessed the efficacy of low-dose
A new therapy targeting Janus kinase has been studied cyclosporine (2.5 mg/kg/day) in combination with live
in psoriasis, showing promising results. Tofacitinib is an attenuated varicella vaccine or placebo [8]. Significantly
oral Janus kinase inhibitor approved for the treatment of more patients receiving cyclosporine in addition to four
rheumatoid arthritis and is currently in phase III trials for doses of varicella vaccine every 3 weeks achieved PASI-50
the treatment of psoriasis. In a phase II trial, significantly at 12 weeks (83 and 47 %, respectively). The combination
more patients treated with 2 mg (25 %), 5 mg (41 %), or group was also more likely to reach a PGA of clear or
15 mg (67 %) twice daily reached a 75 % reduction in almost clear.
Psoriasis Systemic Therapies: Evidence-Based Update 167

Fig. 1 Flowchart of literature


search. RCT randomized
clinical trial

3.2 Biologic Agents response comparable to that of the treatment group at week
28. Using the same study design in Korean and Taiwanese
A total of 21 of the identified RCTs studied a biologic patients, a significant improvement in HRQoL was
agent (six studies of anti-IL-12/23 agents, nine studies of achieved in the treatment group compared with placebo,
TNF-alpha inhibitors, five studies of anti-IL-17 agents, and with a decrease in DLQI of 11.2 points versus 0.5,
one study of an anti-T-cell agent) (Table 2). respectively [12]. The placebo crossover group achieved
similar improvement at week 28. Improvement in DLQI
3.2.1 Anti-Interleukin (IL)-12/23 was significantly correlated with improvement in PASI and
PGA.
Six publications reported on anti-IL-12/23 agents, four Briakinumab, an anti-IL-12/23, was studied in psoriasis
evaluating ustekinumab in Asian populations and two patients but has since been withdrawn from further devel-
efficacy studies covering briakinumab. In Japanese opment [13, 14]. In a 52-week study that included an
patients, ustekinumab 45 mg and 90 mg significantly induction phase and a maintenance phase, at the end of
improved HRQoL at week 12 compared with placebo, and 12 weeks (induction), 76 % of briakinumab-treated
was maintained through week 64 [9]. In this same popu- patients reached a PGA of clear/minimal and 81 %
lation, 59 % of patients treated with ustekinumab 45 mg achieved PASI-75 compared with 4 and 5 %, respectively,
and 68 % treated with 90 mg achieved a PASI-75, com- in the placebo group [13]. At 52 weeks, more patients
pared with 7 % of the placebo group, with responses receiving briakinumab every 4 weeks reached a PGA of
maintained through week 64 in 65 and 79 % of treated clear/minimal (79 %) than those receiving the drug every
patients, respectively [10]. Patients also showed improve- 12 weeks (42 %) or placebo (6 %). There were more
ment in Nail Psoriasis Severity Index (NAPSI) scores and adverse events, including serious infections, non-mela-
joint pain at week 64. Results in terms of efficacy and noma skin cancers (NMSCs), and major cardiovascular
safety in this population were consistent with the findings events in treated patients compared with placebo. Bria-
of the larger PHOENIX 1 and 2 trials, in which the kinumab also had an effect on HRQoL, work productivity,
majority of patients were White. In Chinese patients, us- and activity impairment, with 76 % of treated patients
tekinumab 45 mg was significantly more effective than reaching minimum clinically important difference (MCID)
placebo, with 83 versus 11 % reaching PASI-75 at week 12 for DLQI, 65 % for psoriasis-related pain scores and 54 %
[11]. Placebo patients crossed-over at week 12 and had a for psoriatic arthritis-related pain scores at week 12 [14].
Table 1 Randomized clinical trials of oral therapies for the treatment of psoriasis
168

Oral therapy (total no. No. Ave % Dose Duration BL % achieving Change in Other outcomes AEs
pts) pts age males (wks) PASI PASI-75 DLQI

Tofacitinib [2, 3] 49 46 59 2 mg bid 12 22 25 -7.7 Most frequently reported AEs:


(n = 197) 49 44 59 5 mg bid 21 41 -7.3 infections and infestations
(2 mg = 22 %, 5 mg = 20 %,
49 44 63 15 mg bid 23 67 -9.4
15 mg = 37 %, PL = 6 %).
50 44 72 PL 22 2 -2 Five SAEs: angina pectoris,
pyelonephritis, urosepsis, and
AF in 2 mg; and angina
pectoris in 5 mg. 15-mg more
likely to have decrease in
hemoglobin and absolute
neutrophil count. Dose-
dependent increase in lipids
Apremilast [4, 5] 89 44 71 10 mg bid 16, pc 18 11 at wk 16; -3.2 wk 16; 10 % PGA of 0 or 1 Most AEs were mild/moderate
(n = 352) 18 at wk -3.4 wk at wk 16/13 % wk and included nausea, upper
24 24 24; pruritus VAS respiratory infection,
-10.2 diarrhea, nasopharyngitis,
87 45 63 20 mg bid 19 29 at wk 16; -5.9 wk 16; 24 % PGA of 0 or 1 headache, arthralgia (PL),
26 at wk -6.2 wk at wk 16/24 % wk gastroenteritis, dyspepsia. 8
24 24 24; pruritus VAS SAEs: 3 in PL, 3 in 20 mg, 2
-35.5 in 30 mg
88 44 57 30 mg bid 19 41 at wk 16; -4.4 wk 16; 33 % PGA of 0 or 1
40 at wk -4.9 wk at wk 16/34 % wk
24 24 24; pruritus VAS
-43.7
88 44 60 PL 18 6 at wk 16 -1.9 wk 16 13 % PGA of 0 or 1;
pruritus VAS -6.1
34 PL, then 20 mg bid 8, active 24 at wk 24 -4 wk 24 41 % PGA of 0 or 1
36 PL, then 30 mg bid tx 33 at wk 24 -3.5 wk 24 50 % PGA of 0 or 1
Apremilast [6] 87 46 70 20 mg daily 12 19 24 -0.8 change in Most common AEs headache,
(n = 259) sPGA nasopharyngitis, diarrhea,
85 48 58 20 mg bid 21 10 -1.3 change in and nausea. 2 pts with SAEs,
sPGA neither thought to be related
to drug
87 44 61 PL 19 10 -0.7 change in
sPGA
CF101 [7] (n = 75) 24 52 79 1 mg bid 12 17 AEs were 58 % in 1 mg, 18 %
17 48 88 2 mg bid 23 35 (PASI-50) 24 % PGA of 0 or 1 in 2 mg, 13 % in 4 mg. Two
SAEs in 1 mg: pruritus and
15 45 67 4 mg bid 22
skin rash/psoriasis
19 51 74 PL 17 0 PGA of 0 or 1 exacerbation
L. F. Sandoval et al.
Table 1 continued
Oral therapy (total no. No. Ave % Dose Duration BL % achieving Change in Other outcomes AEs
pts) pts age males (wks) PASI PASI-75 DLQI

Cyclosporine plus 18 Cyclosporine 2.5 mg/kg/d plus 12 34 83 (PASI-50) 33 % PGA of 0 or 1 Minimal AEs with no
varicella vaccine [8] 4 doses of Varilrix once q3w discontinuation
(n = 35) 17 Cyclosporine 2.5 mg/kg/day 31 47 (PASI-50) 18 % PGA of 0 or 1
plus PL
AE adverse event, AF atrial fibrillation, bid twice daily, BL baseline, DLQI Dermatology Life Quality Index, PASI Psoriasis Area and Severity Index, pc placebo controlled, PGA Physicians
Global Assessment, PL placebo, pt(s) patient(s), q3w every 3 wks, SAE serious adverse events, sPGA Static Physicians Global Assessment, tx treatment, VAS visual analog scale, wk(s) week(s)
Psoriasis Systemic Therapies: Evidence-Based Update

Table 2 Randomized clinical trials of biologic therapy for the treatment of psoriasis
Biologic therapy No. Ave % Dose Duration BL PASI % achieving Change in DLQI Other outcomes AEs
(total no. pts) pts age males PASI-75

Anti IL-12/23
Approved drugs
Ustekinumab [9, 64 45 83 45 mg SC at wks 0, 64 wks 30 59 at wk 12; -8 at wk 12; 7.5 change in SF-36 PCS; Most common reported AE was exacerbation of psoriasis.
10] (n = 158) 4, then q12w 65 at wk -7.4 at wk 64 8.6 change in PDI; Low proportion of SAEs through wk 12. Pneumonia in PL,
64 eosinophilia, one case of prostate cancer. No CV deaths.
58 % PGA 0 or 1 at wk 12 AEs comparable in 45 mg and 90 mg through wk 72.
62 44 76 90 mg SC at wks 0, 29 68 at wk 12; -7.4 at wk 12; 5.1 change in SF-36 PCS; SAEs 7.6 % in 45 mg and 9.3 % in 90 mg. No cases of
4, then q12w 79 at wk -7.9 at wk 64 12 change in PDI; TB. One cerebral hemorrhage. No CV events/deaths
64
69 % PGA 0 or 1 at wk 12
32 32 84 PL 9 12 wks, then 30 7 at wk 12 -0.3 at wk 12 -1 change in SF-36 PCS;
ustekinumab -0.1 change in PDI;
45 mg at wk 12,
16, and then 10 % PGA 0 or 1 at wk 12
q12w
PL 9 12 wks, then
ustekinumab
90 mg at wk 12,
16, and then
q12w
169
Table 2 continued
170

Biologic therapy No. Ave % Dose Duration BL PASI % achieving Change in DLQI Other outcomes AEs
(total no. pts) pts age males PASI-75

Ustekinumab [11] 160 40 78 45 mg SC wk 0, 4, 16 16 wks 23 83 at wk 12; -9.3 at wk 12; 79 % PGA 0 or 1 at Proportion of pts with AEs
(n = 322) 92 at wk 28 -10.7 at wk 28 wk 12; 86 % at wk 28 and SAEs were
comparable between the
162 39 76 PL, then ustekinumab 23 11 at wk 12; -1.9 at wk 12; 15 % PGA 0 or 1 at wk 12; groups, with most
45 mg SC wk 12, 16 92 at wk 28 -9.9 at wk 28 86 % at wk 28 common AEs
nasopharyngitis and upper
respiratory infections. 5
pts with markedly
abnormal ALT (3 PL, 3 tx
group), all with
concomitant isoniazid
Ustekinumab [12] 61 41 82 45 mg SC wk 0, 4, 16 16 wks 25 -11.2 at wk 12; Not reported
(n = 121) -10.8 at wk 28;
-12.3 for pts with a
PASI-75 at wk 12
60 40 88 PL, then ustekinumab 23 -0.5 at wk 12;
45 mg SC wk 12, 16 -10 at wk 28
In development
Briakinumab [13, 981 46 68 200 mg SC wks 0 and 4, 12 wks, induction 19 81 -10.1; 76 % 72 % PGA 0 or 1 Overall, 3 % of
14] (n = 1465) then 100 mg wk 8 phase achieved MCID briakinumab pts had
DLQI SAEs: 5 MACE in tx
484 45 71 PL 19 5 -0.52; 19 % MCID 4 % PGA 0 or 1 group vs. 0 in control; 4
SCC of the skin in tx
298 45 70 100 mg SC q4w Wks 1352, 18 -11.3 from BL; 79 % PGA 0 or 1 group vs. 0 in control; 5
maintenance 72 % MCID serious infections in tx
298 46 67 100 mg SC q12w phase 18 -8.8 from BL; 42 % PGA 0 or 1 group vs. 1 control
43 % MCID
149 45 67 PL 19 -5.9 from BL; 6 % PGA 0 or 1
12 % MCID
Anti TNF-alpha
Approved drugs
Etanercept [15, 62 39 53 50 mg SC twice wkly 9 24 wks 16 (BL 59 at wk 12; 71 % improvement 87 % PSSI improvement, 86 % Similar rates of AEs in both
16] (n = 124) 12 wks, then 50 mg SC PSSI = 35) 69 at wk 24 DLQI at wk 12 achieving PSSI-75 at wk 12; groups at wk 12 and 24.
once wkly 9 12 wks scalp pruritus score 1 and At wk 24, 3 pts (3 %)
pain score 0.7 at wk 12 reported 5 SAEs:
91 % PSSI improvement, 86 % cholecystitis/
achieving PSSI-75 at wk 24 cholelithiasis, fall/rib
fracture, metastatic
62 42 58 SC PL twice wkly 9 15 (BL 5 at wk 12; 20 % improvement 20 % PSSI improvement, 11 % malignant melanoma
12 wks, then etanercept PSSI = 30) 59 at wk 24 DLQI at wk 12; reaching PSSI-75 at wk 12;
50 mg SC twice wkly 9 67 % at wk 24 scalp pruritus score 2.9 and
12 wks pain score 3.4 at wk 12
79 % PSSI improvement, 72 %
achieving PSSI-75 at 24 wks
L. F. Sandoval et al.
Table 2 continued
Biologic therapy No. Ave % Dose Duration BL PASI % achieving Change in DLQI Other outcomes AEs
(total no. pts) pts age males PASI-75

Etanercept plus 239 43 64 50 mg SC twice wkly 9 24 wks 18 70 at wk 12; 66 % PGA of 0 or 1 at wk 12; AEs in 75 % combination
MTX [17] 12 wks, then once wkly 9 77 at wk 24 72 % at wk 24 and 60 % monotherapy
(n = 478) 12 wks, plus MTX 9 with 3 SAEs in each arm
24 wks
239 45 70 50 mg SC twice wkly 9 18 54 at wk 12; 47 % PGA of 0 or 1 at wk 12;
12 wks, then once wkly 9 60 at wk 24 54 % at wk 24
12 wks, plus PL
Infliximab [18] 84 39 71 5 mg/kg IV wks 0, 2, and 6, 10 wks induction 24 81 at wk 10; -8 at wk 10; 88 % PGA of 0 or 1 at wk 10; 3 cases of TB in infliximab
(n = 129) 14, 22 phase/12 wks 93 at wk 26 -10.1 at wk 26 87 % at wk 26 groups through 26 wks.
maintenance One case of drug-induced
45 40 78 PL, then infliximab wks 10, 25 2 at wk 10; -1.5 at wk 10; 7 % PGA of 0 or 1; 71 % at wk hepatitis and pancreatic
12, 16 80 at wk 26 -7.6 at wk 26 26 cancer with liver and
spleen metastasis
resulting in death. Ten
subjects with newly
developed ANA and 4
Psoriasis Systemic Therapies: Evidence-Based Update

with new dsDNA


antibodies, vs 3 and 1 in
PL respectively. 12 %
infusion reactions
Adalimumab [19] 557 42 70 40 mg SC eow 16 wks 19 -13.4 change in TWPI; -18.8 Not reported
(n = 827) change in TAI; -12.9 change
in work impairment when
present
270 44 73 PL 19 -2.3 change in TWPI; -3.3
change in TAI; -1.5 change
in work impairment when
present
Adalimumab [20] 49 49 43 80 mg SC wk 0, then 40 mg 16 wks 9 31 % hfPGA clear or almost Not reported
(n = 72) eow clear; 57 % NAPSI-50
23 55 35 PL 6 4 % hfPGA clear or almost
clear; 12.5 % NAPSI
In development
Certolizumab 59 43 75 400 mg SC at wk 0, then 12 wks 21 75 -8.3 53 % PGA 0 or 1 6 pts with SAEs, all in first
pegol [21] 200 mg eow 9 10 wks tx phase. One
(n = 176) 58 44 72 400 mg SC eow 9 10 wks 22 83 -9.9 72 % PGA 0 or 1 disseminated TB in
400-mg group
59 43 63 PL 23 7 -0.8 2 % PGA 0 or 1
Positive antibodies in 5 % after
34 400 mg SC at wk 0, then 12 wks re-tx phase 68 -8.3 from BL 53 % PGA 0 or 1 first tx and 18 % after re-tx
200 mg eow 9 10 wks (-3.5 from re-tx with 200 mg and 4 and
BL) 25 %, respectively, with
37 400 mg SC eow 9 10 wks 87 -7.9 from BL 57 % PGA 0 or 1 400 mg. The majority
(-7.9 from re-tx showed no changes from BL
BL) for ANA, dsDNA,
anticardiolipin IgG and IgM
171
Table 2 continued
172

Biologic therapy No. Ave % Dose Duration BL PASI % achieving Change in DLQI Other outcomes AEs
(total no. pts) pts age males PASI-75

Anti T-cell
Approved- no longer available
Alefacept plus 49 47 65 15 mg IM every wk plus 12 wks 18 45 at wk 16 -5.3 at wk 16 43 % PGA of 0 or 1 at wk 16 Combination group had
nbUVB [44] nbUVB 9 12 wks more AEs vs.
(n = 98) 49 48 76 15 mg IM every wk 9 18 22 at wk 16 -4 at wk 16 23 % PGA of 0 or 1 at wk 16 monotherapy, with
12 wks erythema and pruritus
most common. 3 SAEs in
combination group with 1
(leg edema) possibly tx
related
Anti IL-17
In development
Secukinumab [22] 66 43 80 150 mg SC once, wk 0 12 wks induction 20 11 No ISRs. No
(n = 404) 133 45 79 150 mg SC wks 0,1,2,4 phase 20 55 immunogenicity.
Infections in 35 % of pts
138 44 75 150 mg SC wks 0, 4, 8 21 42 in induction phase, with
67 44 66 PL 21 2 all active groups similar
65 150 mg SC wks 12, 24 20 wks 85 to or lower than PL.
maintenance Infections in 32 % of pts
67 PL, then 150 mg SC wks 67 in maintenance phase,
12, 24 at start of relapse phase
with slightly higher rate
in fixed interval and open-
label groups vs. start of
relapse group. Grade 1 or
2 neutropenia in 4.7 %
active induction phase tx
vs. 0.2 % PL and 7.9 %
active maintenance.
Serious AEs in 3.2 % of
pts in induction and 4.7 %
in maintenance periods
Secukinumab [24] 25 46 69 25 mg SC once, wk 0 12 wks tx 22 Higher incidence of AEs in
(n = 125) 26 46 85 25 mg SC wks 0, 4, 8 21 150 mg group compared
to other dose regimens,
21 46 67 75 mg SC wks 0, 4, 8 20 57 at wk 12; 33 % IGA 0 or 1 at wk 12 which were comparable to
19 at wk 36 PL. 4 % SAEs (2 in PL, 2
27 45 78 150 mg SC wks 0, 4, 8 21 82 at wk 12; 48 % IGA 0 or 1 at wk 12 in 25 mg 9 3 doses
group, 1 in 75 mg group)
26 at wk 36 none of which were
22 46 64 PL 22 9 at wk 12; 9 % IGA 0 or 1 at wk 12 thought to be related to
4 at wk 36 drug. 2 cases of
neutropenia in the 150 mg
group
L. F. Sandoval et al.
Table 2 continued
Biologic therapy No. Ave % Dose Duration BL PASI % achieving Change in DLQI Other outcomes AEs
(total no. pts) pts age males PASI-75

Ixekizumab [25] 28 48 57 10 mg SC wks 0, 2, 4, 8, 12, 16 wks 19 29 at wk 12 -43 % PSSI change; 25 % No serious AEs in any
(n = 142) 16 PGA 0 or 1 at wk 12 group; frequency of AEs
30 46 60 25 mg SC wks 0, 2, 4, 8, 12, 19 77 at wk 12 -7.1 at wk 12 -87 % PSSI change; 70 % similar across all groups.
16 PGA 0 or 1 at wk 12 Four pts discontinued
study due to AEs: 1 pt
29 46 66 75 mg SC wks 0, 2, 4, 8, 12, 17 83 at wk 12 -8.5 at wk 12 -95 % PSSI change; 72 % each for
16 PGA 0 or 1 at wk 12 hypertriglyceridemia
28 46 50 150 mg SC wks 0, 2, 4, 8, 18 82 at wk 12 -7.8 at wk 12 -85 % PSSI change; 71 % (PL), peripheral edema
12, 16 PGA 0 or 1 at wk 12 (10 mg), hypersensitivity
27 45 52 PL 17 8 at wk 12 -2.4 at wk 12 -31 % PSSI change; 8 % PGA (10 mg), and urticaria
0 or 1 at wk 12 (25 mg). 6 pts with ISRs.
2 pts with grade 2
neutropenia (75- and
150-mg groups)
Brodalumab [27] 39 42 56 70 mg SC at day 1 and wks 12 wks 18 33 DLQI score 6.5 26 % PGA 0 or 1 AEs: 70 mg = 68 %, 140
(n = 198) 1, 2, 4, 6, 8, 10 mg = 69 %, 210 mg =
Psoriasis Systemic Therapies: Evidence-Based Update

39 44 72 140 mg SC at day 1 and wks 19 77 DLQI score 2 85 % PGA 0 or 1 82 %, 280 mg = 73 %,


1, 2, 4, 6, 8, 10 PL = 62 %. One
discontinuation in 280 mg
40 42 62 210 mg SC at day 1 and wks 21 82 DLQI score 2 80 % PGA 0 or 1 for urticaria. 3 serious
1, 2, 4, 6, 8, 10 AEs: renal colic in 70-mg
42 42 71 280 mg SC at day 1 and wk 18 67 DLQI score 3.9 69% PGA 0 or 1 pt (resolved with no
4, 8 change in drug), ectopic
38 42 58 PL 19 0 DLQI score 10.3 3 % PGA 0 or 1 pregnancy in PL, 2 pts
with asymptomatic grade
3 neutropenia in 210 mg.
Incidence of brodalumab
binding antibodies was
similar across all tx
groups. No neutralizing
antibodies on bioassay
Brodalumab 4 43 76 140 mg SC 85 days 14 0 No SAEs. AEs were mild to
(AMG 827) [28] 8 350 mg SC 38 at day 43 moderate, and similar
(n = 25) between active tx and PL
8 700 mg IV 88 at day 43 groups. 2 pts (one each
5 PL 0 from 350 mg and
700 mg) developed anti-
AMG 827 antibodies at
day 85

AE adverse events, ALT alanine aminotransferase, ANA antinuclear antibodies, BL baseline, CV cardiovascular, DLQI Dermatology Life Quality Index, dsDNA double-stranded DNA, eow every other week, hfPGA
Physicians Global Assessment of hands and/or feet, IGA Investigators Global Assessment, IgG/M immunoglobulin G/M, IL interleukin, IM intramuscular, ISR injection site reaction, IV intravenous, MACE major
adverse cardiovascular event, MCID minimal clinically important difference, MTX methotrexate, NAPSI Nail Psoriasis Severity Index, nbUVB narrowband ultraviolet B, PASI Psoriasis Area and Severity Index, PCS
Physical Component Scale, PDI Psoriasis Disability Index, PGA Physicians Global Assessment, PL placebo, PSSI Psoriasis Scalp Severity Index, pt(s) patient(s), qxw every x weeks, SAE serious adverse events, SC
subcutaneous, SCC squamous cell carcinoma, TAI total activity impairment, TB tuberculosis, TNF tumor necrosis factor, TWPI total work productivity impairment, tx treatment, wk(s) week(s)
173
174 L. F. Sandoval et al.

At 52 weeks, these measures were better in patients (57 and 4 %, respectively), and those patients who
receiving the drug every 4 weeks than in those receiving achieved a NAPSI-50 were more likely to reach hfPGA of
the drug every 12 weeks. clear or almost clear compared with non-responders.
Certizumab pegol (CZP), a PEGylated Fab monoclonal
3.2.2 Tumor Necrosis Factor (TNF)-Alpha Inhibitors antibody against TNF-alpha that is currently US FDA
approved for the treatment of Crohns disease and rheu-
Bagel et al. [15] reported that etanercept was effective in matoid arthritis, was studied in psoriasis [21]. Of patients
treating both overall psoriasis and scalp psoriasis. At week treated with 400 mg subcutaneous CZP followed by
12, 86 % of patients receiving etanercept 50 mg subcuta- 200 mg every 2 weeks for 10 weeks, 75 % reached a
neously twice weekly achieved a Psoriasis Scalp Severity PASI-75 at week 12, compared with 83 % of patients who
Index (PSSI)-75 and 59 % a PASI-75 versus 11 and 5 %, received 400 mg every other week, and 7 % of the placebo
respectively, of patients receiving placebo. Patients also group. Patients in treatment groups also had significant
had significantly less scalp pruritus and pain and an improvements in DLQI and in PGA scores compared with
improvement in DLQI compared with placebo at week 12 placebo. In patients who at least achieved a PASI-75 who
[16]. Rates of side effects were similar between both subsequently relapsed and were retreated with their same
groups. In patients treated with a combination of etanercept initial treatment, 68 % in the 200-mg group and 87 % in
and methotrexate for 24 weeks, significantly more patients the 400-mg group reached PASI-75 at week 12. Efficacy of
reached a PASI-75 in the combination group compared first treatment and retreatment in both groups was similar.
with etanercept monotherapy (77 vs. 60 %, respectively) There were no significant differences between patients
[17]. More adverse effects were reported in the combina- previously treated with TNF-alpha inhibitors and nave
tion group; however, most were mild to moderate. patients in terms of PASI-75 and PGA 0 or 1.
The efficacy and safety of infliximab was studied in
Chinese patients with moderate to severe psoriasis [18]; 3.2.3 Anti-IL-17
81 % of treated patients achieved a PASI-75 at week 10
compared with 2 % in the placebo group during the Several anti-IL-17 biologic agents are currently in devel-
induction phase and 88 % of treated patients reached a opment. Secukinumab, a fully human immunoglobulin G
PGA of clear or minimal (0 or 1) compared with 7 % of (IgG)-1j monoclonal anti-IL-17A antibody, is currently in
placebo patients. The treatment group also achieved a phase III clinical trials. In phase II clinical trials, signifi-
significant reduction in the DLQI score (-8), while the cantly more patients who received early or monthly
placebo groups remained almost unchanged (-1.5). The induction regimens reached PASI-75 compared with pla-
improvements in PASI, PGA, and DLQI scores were cebo (55, 42, and 2 %, respectively) [22]. During the
maintained through the maintenance phase to the end of the maintenance phase, 85 % of patients in the fixed-interval
study (week 26). More adverse effects were reported in the regimen reached PASI-75 compared with the group of
infliximab group than in the placebo group, though this was patients who restarted treatment at relapse (67 %). No
not significant. Most adverse effects were mild to moder- injection site reactions or development of antibodies
ate; however, three patients receiving active treatment against the drug occurred. Neutropenia, a concern with the
developed tuberculosis over the study period, highlighting IL-17 inhibitors since IL-17 plays a role in neutrophil
the need to screen for this disease. recruitment, was reported in 5 % of patients during the
Kimball et al. [19] reported on improvement in self- induction phase and 8 % during the maintenance phase
reported work productivity in psoriasis patients treated [23]. In a separate study, significantly more patients
with adalimumab, with these patients achieving greater receiving either 75 or 150 mg secukinumab at weeks 0, 4,
improvement in total work productivity impairment and 8 reached PASI-75 at week 12 compared with placebo
(TWPI) and total activity impairment (TAI) scores than (57 and 82 vs. 9 %, respectively) [24]. Two patients
those receiving placebo (16 and 11 % greater, respec- developed transient neutropenia in the higher dose (150-
tively). Patients who achieved a PASI-75 had significantly mg) group.
greater improvements in work productivity and activity Ixekizumab, a humanized IgG4 monoclonal anti-IL-
impairment (WPAI) outcomes, except employment rate, at 17A, was effective in phase II trials at treating psoriasis at
16 weeks. Adalimumab was also studied in patients with three doses (25, 75, 150 mg) compared with placebo at
moderate to severe psoriasis of the hands and feet [20]. 16 weeks of treatment, with 77, 83, and 82 % of patients,
Significantly more patients treated with adalimumab respectively, reaching PASI-75 compared with 8 % of
(57 %) achieved a PGA of hands and/or feet (hfPGA) of placebo patients [25]. A total 39 % of the 150-mg group and
clear or almost clear compared with placebo. More 38 % of the 75-mg group reached PASI-100 compared with
patients also reached a NAPSI-50 compared with placebo none in the placebo group. Adverse effects were similar
Psoriasis Systemic Therapies: Evidence-Based Update 175

between treatment groups and placebo, and no serious studied the effects of adalimumab in vascular inflammation
adverse reactions were reported. Two patients (150-mg and through positron emission tomography (PET) in psoriasis
75-mg groups) developed asymptomatic grade 2 neutrope- patients with risk factors or history of coronary athero-
nia. The phase I and II trials of ixekizumab show promise, sclerosis. At 15 weeks, there was a significant change in
with efficacy comparable to that of currently approved bi- inflammation in the vessel with the greatest baseline target
ologics; however, these clinical studies have been small and : background ratio in the adalimumab group (-0.23) but
have not assessed treatment past 16 weeks [26]. not in the control group (-0.1), though the difference
Brodalumab, an anti-IL-17-receptor monoclonal anti- between the groups was not significant. There was a sig-
body, is another biologic currently in development for the nificant improvement in the target : background ratio in
treatment of psoriasis. In a phase II trial, four doses (70 mg, both the ascending aorta and carotid artery for the treat-
140 mg, 210 mg subcutaneously at day 1, week 1, 2, 4, 6, 8, ment group compared with the control group. Adalimumab
10; or 280 mg subcutaneously at day 1, week 4 and 8) were patients also had a 51 % reduction in C-reactive protein
significantly more effective at achieving a PASI-75 com- compared with 5 % in the control group. In patients with
pared with placebo (33, 77, 82, and 67 % of patients, both psoriasis and sleep apnea, treatment with adalimumab
respectively, compared with 0 % for placebo) [27]. DLQI did not result in a significant improvement in apnea/
scores were also significantly lower in all treatment groups hypopnea index (AHI) compared with placebo group as
compared with placebo. Two cases of asymptomatic grade assessed by polysomnography [30].
3 neutropenia occurred in the 210-mg group. In the earlier
phase I trial, patients were treated with a single dose of
either 140 mg subcutaneously, 350 mg subcutaneously, or 4 Discussion
700 mg intravenously, with 38 and 88 % of patients in the
350- and 700-mg groups reaching PASI-75 by day 43 With numerous systemic agents now available for the
compared with no patients in the 140-mg and placebo treatment of moderate to severe psoriasis, practitioners
groups [28]. The 350-mg and 700-mg doses also led to often rely on treatment guidelines to direct their therapeutic
significant reductions in epidermal thickness on skin biopsy recommendations. Current consensus guidelines for the
and rapid improvement in several skin biomarkers. There management of psoriasis do not provide a specific treat-
were no serious adverse effects. Two patients (350-mg and ment algorithm, but instead provide options for first-line
700-mg groups) developed drug antibodies. therapies. In terms of oral therapies, methotrexate is con-
sidered a first-line therapy for moderate to severe psoriasis,
3.2.4 Non-Psoriasis Outcomes and acitretin is a first-line systemic treatment for chronic
palmoplantar or pustular psoriasis. Several biologic agents
In addition to the studies of biologic agents that focused on also may be used as first-line therapy, including ada-
psoriasis outcomes, two studies of adalimumab reported on limumab, etanercept, and ustekinumab. Infliximab is rec-
non-psoriasis outcomes (Table 3). Bissonnette et al. [29] ommended as a second- or third-line biologic agent [1].

Table 3 Adalimumab non-psoriasis outcomes


Biologic No. Ave % Dose Duration BL % Other outcomes AEs
therapy (total pts age males PASI achieving
no. pts) PASI-75

Adalimumab 20 56 85 80 mg SC wk 0, 4 months 12 Change in target:background Not reported


[29] then ratio of adalimumab vs.
(n = 30) 40 mg wk 1 control ascending aorta
and eow -0.23/carotid artery -0.26;
10 57 60 Topicals, 13 51 % decrease in CRP with
phototherapy, adalimumab vs. 5 % in
or no tx control
Adalimumab 10 56 90 80 mg SC wk 0, 56 days 12 30 9.6 change in AHI Proportion of pts
[30] then 40 mg with AEs was
(n = 20) eow similar between
10 49 90 PL 10 10 -1.23 change in AHI groups, with no
SAEs and no
discontinuations
AE adverse events, AHI Apnea/Hypopnea Index, BL baseline, CRP C-reaction protein, eow every other wk, PASI Psoriasis Area and Severity
Index, PL placebo, pt(s) patient(s), SAE serious adverse events, SC subcutaneous, tx treatment
176 L. F. Sandoval et al.

Table 4 Systematic reviews of systemic treatment for psoriasis


Systematic review Drugs reviewed No. of publications Results
reviewed

Efficacy
Lucka et al. [31] Ustekinumab, adalimumab, 33 (27 trials) Infliximab and ustekinumab (90 mg every 12 wks) were the
infliximab, etanercept, most efficacious tx in regards to proportion of pts achieving
cyclosporine, methotrexate, PASI-75 and reduction in DLQI at 24 wks. A decrease
fumaric acid in efficacy for infliximab, adalimumab and etanercept was
observed after 24 wks. Insufficient and unreliable data on
long-term efficacy of non-biologic agents
Galvan-Banqueri Ustekinumab, adalimumab, 14 Indirect comparison showed ustekinumab, adalimumab, and
et al. [32] infliximab, etanercept infliximab were significantly superior to etanercept with an
absolute risk difference for PASI-75 of 12, 11, and 24 %,
respectively, although the 95 % CI does not achieve clinical
relevance. These biologics can be considered clinically
equivalent
Brezinski and Etanercept, adalimumab, 23 Off-label dose escalation in non-responders generally resulted
Armstrong [36] infliximab, ustekinumab, in increased efficacy. Continuous tx with anti-TNF agents
alefacept and anti-IL-12/23 agent results in better efficacy than
interrupted therapy
Nast et al. [45] Adalimumab, alefacept, 49 Time to onset of action (time for 25 % of pts to reach a PASI-
etanercept, infliximab, 75) of the biologics: infliximab has shortest (3.5 wks),
ustekinumab, cyclosporine, followed by ustekinumab (4.6 wks for 90 mg; 5.1 wks for
fumaric acid, methotrexate, 45 mg) and adalimumab (4.6 wks), then etanercept (6.6 wks
retinoids for 50 mg twice wkly; 9.5 wks for 50 mg wkly). For orals,
cyclosporine is the fastest (6 wks), and methotrexate 3.2 wks
if pts are started on 7.5 mg then increased the next wk to
15 mg and 9.9 wks for a slower taper
Kim et al. [33] Adalimumab, infliximab, Adalimumab, infliximab, ustekinumab, and alefacept were
ustekinumab, alefacept effective in treating moderate-to-severe psoriasis. Weighted
average PASI-75 scores for infliximab, ustekinumab,
adalimumab, etanercept, and alefacept were 78.6, 72.1, 70.5,
48.1, and 21 %, respectively over 12 wks
Reich et al. [34] Adalimumab, efalizumab, 20 Meta-analysis showed infliximab was most effective at
infliximab, ustekinumab, reaching PASI-50, 75, and 90, followed by ustekinumab
etanercept (90 mg, then 45 mg), adalimumab, etanercept, and then
finally efalizumab from indirect comparison in short-term
studies (1030 wks)
Lin et al. [35] Ustekinumab, adalimumab, 17 Bayesian network meta-analysis showed ustekinumab has
alefacept, etanercept, significantly higher odds of achieving PASI-75 vs.
infliximab adalimumab, alefacept, and etanercept, but not infliximab
Mattei et al. [38] Adalimumab, efalizumab, 23 The correlation coefficient for mean percent reduction in PASI
infliximab, ustekinumab, vs. mean reduction DLQI was 0.898 in psoriasis pts treated
etanercept, alefacept with biologics. Pts reaching a PASI-75 had a significant
reduction in DLQI vs. pts reaching a PASI 50-75 or \50
Baker et al. [46] Alefacept, efalizumab, 38 Using Bayesian MTC, all biologics had significant
infliximab, etanercept, improvement in PGA vs. PL, with anti-ILs showing greater
adalimumab, ustekinumab, response vs. anti-T-cells. Anti-TNFs and anti-ILs showed
briakinumab significant improvement in DLQI vs. PL. Anti-TNFs, but not
anti-T cells showed significant improvement in SF-36 and
physical component scores
Strohal et al. [37] Etanercept 12 Short term, more than half of pts reach a PASI-75. Etanercept
50 mg twice wkly more effective at wk 24 than lower doses.
After 24 wk, etanercept is effective as continuous or
intermittent therapy, although continuous is better. Approved
and effective in children as young as 6 years. Most common
AEs were cutaneous skin reactions. Less risk of serious
infections and malignancies such as skin cancer and
lymphoma than adalimumab and infliximab. No additional
safety risk with long-term vs. short-term use
Psoriasis Systemic Therapies: Evidence-Based Update 177

Table 4 continued
Systematic review Drugs reviewed No. of publications Results
reviewed

Wu et al. [47] Ustekinumab 7 Most relative risk showed significant differences for both high
(90 mg) and low dose (45 mg) in terms of efficacy vs. PL.
Studies comparing high vs. low dose show both are effective,
with only one study in four showing high dose to be
significantly more effective. Types, severity, and frequency
of AEs were similar between tx and PL groups
Kwatra et al. [48] Tasocitinib and ruxolitinib 3 JAK inhibitors, oral tasocitinib, and topical ruxolitinib were
effective in psoriasis clinical trials. Tasocitinib 2, 5, and
15 mg bid resulted in a PASI-75 in 25, 40.8, and 66.7 % of
pts, respectively, for moderate to severe psoriasis
Ren and Dao [26] Ixekizumab 39 (2 trials) Phase I and II trials of ixekizumab show promise, with efficacy
in terms of reduction in PASI comparable to currently
approved biologics; however, these clinical studies have been
small and have not assessed tx past 16 wks. Evidence of
histopathologic improvement of psoriasis
Malhotra et al. [49] Thiazolidinediones 4 Pioglitazone alone or with concomitant acetretin use had
greater reduction in PASI scores vs. control groups in two
studies. No significant improvement in PASI was reached
with rosiglitazone tx in 3 studies
Safety
Rustin [39] Etanercept, infliximab, Long-term ([1 year) safety data on biologics. Except for
adalimumab, efalizumab, efalizumab which is no longer available due to risk for
alefacept, ustekinumab progressive multifocal leukoencephalopathy, the biologics
are well tolerated in long-term studies. 4-year data for
etanercept in psoriasis show few serious infections,
malignancies, or CV events. Well tolerated in children.
Infliximab studied up to 78 wks showed hepatotoxicity with
elevated ALT and AST, and increased infection, as well as
infusion reactions. AEs stable for adalimumab over 3 years,
with no association to serious infections. May be increased
risk for NMSC, but no lymphomas reported. 4-year safety
data on ustekinumab, with overall infections and malignancy
comparable between all groups and did not increase over
time. No increase in MACE vs. general population
Tzellos et al. [41] Ustekinumab, briakinumab 9 A possible higher risk of MACEs in pts treated with anti-IL-12/
23 vs. PL from studies of 20 wks or less
Armstrong et al. [42] Methotrexate, cyclosporine, 20 Methotrexates cardioprotective effects in psoriasis are
TNF-alpha inhibitors, inconclusive. Long-term use of cyclosporine associated with
ustekinumab hypertension and discontinuation of drug. TNF-alpha
inhibitors may reduce risk for cardiovascular events but
larger RCTs are needed. IL-12/23 inhibitors are not
associated with increased CV events vs. general population
from short-term studies
Kamangar et al. [40] Etanercept, infliximab, 9 8 trials showed increased risk of NMSC while on tx. Data
adalimumab, efalizumab, suggest a possible increased risk in pts with history of prior tx
alefacept, ustekinumab with drugs known to increase risk of skin cancer
AE adverse events, ALT alanine aminotransferase, AST aspartate aminotransferase, bid twice daily, CI confidence interval, CV cardiovascular,
DLQI Dermatology Life Quality Index, IL interleukin, JAK Janus kinase, MACE major adverse CV event, MTC mixed treatment comparison,
NMSC non-melanoma skin cancer, PASI Psoriasis Area and Severity Index, PGA Physicians Global Assessment, PL placebo, pt(s) patient(s),
RCT randomized clinical trial, TNF tumor necrosis factor, tx treatment, wk(s) week(s)

Systematic reviews and meta-analyses on efficacy, reviewed 33 publications (27 trials) of both oral and bio-
safety, and cost can also provide some guidance on treat- logic agents, and through meta-analysis concluded that
ment options. Our review of the literature resulted in 14 infliximab and ustekinumab (90 mg every 12 weeks) were
systematic reviews reporting on the efficacy of systemic the most efficacious treatments in regards to the proportion
treatments for psoriasis (Table 4). Lucka et al. [31] of patients achieving PASI-75 and reduction in DLQI at
178 L. F. Sandoval et al.

Table 5 Approved systemic therapies for psoriasis and grade of recommendations based on published clinical trials from 1 January 2012
through 1 July 2013
Approved systemic agents recommended Grade of recommendation Comments
for tx of moderate to severe psoriasis

Etanercept Strong recommendation; high-quality evidence May also be considered first-line


[16, 17, 32, 37, 39, 46] therapy for children [37]
Adalimumab Strong recommendation; high-quality evidence
[3234, 39, 46]
Infliximab Strong recommendation; high-quality evidence
[18, 31, 32, 34, 35, 39, 46]
Ustekinumab Strong recommendation; high-quality evidence
[911, 3135, 39, 46, 47]
There were no published clinical trials reporting on methotrexate, cyclosporine, or acitretin during the review period available to provide
evidence for a level of recommendation for the therapies

24 weeks. A review using an indirect comparison of biol- Cost is an important factor in treatment decisions. Our
ogics alone had similar findings, with infliximab and us- review of the literature did not identify any articles com-
tekinumab, as well as adalimumab, superior to etanercept paring the cost of the current systemic psoriasis therapies.
in terms of absolute risk difference for PASI-75 [32]. Three In a previous study, the annual cost of methotrexate was
additional reviews provided further support for these three the lowest and it was the most cost effective in terms of
agents, with infliximab most effective in terms of patients cost per person to achieve a PASI-75 [43]. Phototherapy
achieving PASI-75, followed by ustekinumab, then ada- was the most cost effective in terms of cost per person to
limumab [3335]. For patients who are non-responders to a achieve a DLQI MID. Alefacept was the least cost effec-
biologic agent, off-label dose escalation generally leads to tive for both. Data on long-term psoriasis treatment are
improvement in efficacy [36]. This review also concluded lacking from the current literature and may provide better
that continuous treatment with biologics is more effective insight into the cost of treatment. Potential long-term
than interrupted therapy. However, a review of etanercept sequelae, including organ toxicity from some of the oral
found that, after 24 weeks, it was effective as continuous or drugs like methotrexate and cyclosporine, may make what
interrupted treatment [37]. Mean improvement in PASI seems like a less costly treatment more expensive in the
correlated with DLQI changes (correlation coefficient long term.
0.898) in patients treated with biologics, and patients who
reached a PASI-75 had a significant reduction in DLQI
compared with patients reaching a PASI 5075 or PASI 5 Conclusion
\50 [38].
With longer-term safety data now available for the TNF- The appropriate treatment regime should be individualized
alpha inhibitors (which have long been studied in rheu- to meet the needs of each patient, taking into consideration
matologic diseases), and 5-year safety data now available efficacy, safety, and cost, and patients personal prefer-
for ustekinumab, support for their use as first-line therapy ences. Several first-line systemic treatment options can be
is strengthened. In a review of long-term safety data in considered. Current literature focuses heavily on biologic
psoriasis, all biologics were well tolerated (except ef- agents, providing more support for their use first-line over
alizumab, which has been removed from the market) [39]. oral therapy in terms of efficacy and safety (Table 5).
In general, the rate of infections is comparable between Studies of the newer anti-IL-17 agents support their effi-
treatment groups and placebo. The risk for serious infec- cacy and they have the potential to become a valuable
tions is a concern for biologics; however, data show that option in the treatment of psoriasis. New oral agents,
they are not common. There does appear to be an increased though their efficacy does not appear to match that of the
risk of NMSC while receiving biologic therapy [40]. Data biologic agents (head-to-head trials are lacking), may also
suggest a possible increase risk in patients who have had play a role in the treatment of psoriasis, providing an
prior treatment with drugs known to increase the risk of alternative to current oral therapies with more favorable
skin cancer. Data are conflicting as to whether or not us- safety profiles.
tekinumab is associated with greater risk of major acute
cardiovascular events; any uncertainty suggests that if there Acknowledgments The Center for Dermatology Research is sup-
ported by an unrestricted educational grant from Galderma Labora-
is an association, it is not of large magnitude [39, 41, 42] tories, L.P. Dr. Feldman is a consultant and speaker for Galderma,
(Table 4).
Psoriasis Systemic Therapies: Evidence-Based Update 179

Stiefel/GlaxoSmithKline, Abbott Labs, Warner Chilcott, Janssen, moderate to severe plaque-type psoriasis: results from a phase 3
Amgen, Photomedex, Genentech, BiogenIdec, and Bristol Myers clinical trial (LOTUS). J Drugs Dermatol. 2013;12(2):16674.
Squibb. Dr. Feldman has received grants from Galderma, Astellas, 12. Tsai TF, Song M, Shen YK, Schenkel B, Choe YB, Kim NI, et al.
Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Ustekinumab improves health-related quality of life in Korean
Genentech, BiogenIdec, Coria/Valeant, Pharmaderm, Ortho Pharma- and Taiwanese patients with moderate to severe psoriasis: results
ceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3 M, Bristol from the PEARL trial. J Drugs Dermatol. 2012;11(8):9439.
Myers Squibb, Stiefel/GlaxoSmithKline, Novartis, Medicis, Leo, 13. Gordon KB, Langley RG, Gottlieb AB, Papp KA, Krueger GG,
HanAll Pharmaceuticals, Celgene, Basilea, and Anacor and has Strober BE, et al. A phase III, randomized, controlled trial of the
received stock options from Photomedex. Dr. Feldman is the founder fully human IL-12/23 mAb briakinumab in moderate-to-severe
and holds stock in Causa Research. Dr. Sandoval and Ms. Pierce have psoriasis. J Invest Dermatol. 2012;132(2):30414.
no conflicts to disclose. 14. Papp KA, Sundaram M, Bao Y, Williams DA, Gu Y, Signorov-
itch JE, et al. Effects of briakinumab treatment for moderate to
severe psoriasis on health-related quality of life and work pro-
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