Solapso

Review
Latin American Clinical Practice Guidelines on the Systemic

Treatment of Psoriasis
SOLAPSO – Sociedad Latinoamericana de Psoriasis
(Latin American Psoriasis Society)
Nora Kogan1, Ne lida Raimondo2, Simon E. Gusis3, Ariel Izcovich4, Jorge A. Abarca
Duran , Lilia Barahona-Torres6, Orestes Blanco7, Gerardo B. Quintana8, Marıa C.
5
Briones9, Carla Castro10, Evelyn G. Castro Vargas11, Juan Criniti12, Juan C. Diez de
Medina13, Manuel Franco14, Minerva Go mez15, Vero
nica P. Levrero16, Jaime E.
pez17, and Fernando Valenzuela18
Martınez Lo
1
Dermatology, Hospital Ramos Mejıa, Abstract
Buenos Aires, Argentina, 2Hospital This Clinical Practice Guideline on the systemic treatment of Psoriasis includes the
Aerona utico Central, Buenos Aires,
recommendations elaborated by a panel of experts from the Latin American Psoriasis
Argentina, 3Rheumatology, Hospital Ramos
Mejıa, Buenos Aires, Argentina, 4Program
Society SOLAPSO, who assessed the quality of the available evidence using the GRADE
on Evidence Based Medicine, Hospital system and the PICO process to guide the literature search. To answer each question, the
Aleman, Buenos Aires, Argentina, experts discussed the results of randomized controlled trials, observational studies and
5
Dermatology, Hospital CIMA San Jose , metanalysis evaluating the interventions identified (non-biologics, biologics and
Costa Rica, 6Dermatology, Instituto
phototherapy) in different populations of patients with moderate to severe plaque-psoriasis,
Honduren ~o de Seguridad Social,
Tegucigalpa, Honduras, 7Parasitology,
which was summarized in Tables ad-hoc. The main end-points considered to assess
Institute of Tropical Medicine Pedro Kouri, efficacy were PASI 50, 75, 90 and 100, PGA 0-1 and significant improvement of health-
La Habana, Cuba, 8Centro Clınico Cuta neo, related quality of life. Specific adverse events, either severe or leading to treatment
Guatemala,Guatemala, 9Centro Privado de interruption, were also evaluated. The 31 recommendations included in this CPG follow the
Piel “Dr. Enrique Uraga”, Guayaquil,
structure proposed by GRADE: direction (for or against) and strength (strong or weak). The
Ecuador, 10Pediatric Dermatology, Hospital
goal of this CPG is to improve the management of patients with psoriasis by
Universitario Austral, Pilar, Argentina,
11
Clınica San Felipe, Lima, Lima, Peru , recommending interventions of proved benefit and providing a reference standard for the
12
Program on Evidence Based Medicine, treating physician. Adhering to the contents of this CPG does not guarantee therapeutic
Hospital Aleman, Buenos Aires, Argentina, success. The final decision on the specific treatment is the responsibility of the physician
13
Medical Education and Research,
based on the individual circumstances and considering the values, the preferences and the
Fundación Piel Bolivia, La Paz, Bolivia,
14
Universidad del Bosque, Bogotá,
opinions of the patient or caregivers.
Colombia, 15Dermatology, University
Hospital, Monterrey, Nueva León, Mexico,
16
Centro Dermatológico, Montevideo,
Uruguay, 17Dermatology, Medicentro La
Esperanza, San Salvador, El Salvador, and
18
Dermatology, Hospital Clinico Universidad
de Chile, Santiago, Chile
Correspondence
Nora Kogan, MD
Dermatology
Hospital Ramos Mejıa
Gral. Urquiza 609
C1221ADC Buenos Aires
Argentina
E-mail: [email protected]
doi: 10.1111/ijd.14471
4
International Journal of Dermatology 2019, 58 (Suppl. 1), 4–28 ª 2019 The International Society of Dermatology
Kogan et al. SOLAPSO Clinical Practice Guidelines 2017 Review 5
Introduction
Methodology
Nora Kogan
Ariel Izcovich Ariel, Juan Martın Criniti
The CPGs have been prepared following the
Background
recommendations of the Methodology Manual for the
In 2009, SOLAPSO published the updated edition of their Treat-
Development of Clinical Practice Guidelines by the Under-
ment Guidelines on Psoriasis with a view to improving the
Secretary of Public Health of the Government of Chile, using
knowledge on the disease and fostering its multi-disciplinary
the GRADE system (Grading of Recommendations
approach.1 In 2015, SOLAPSO announced a new Clinical Prac-
Assessment, Development and Evaluation) to assess the
tice Guidelines (CPG) to offer evidence-based recommenda-
quality of the evidence, to produce evidence summaries and
tions for the management of psoriatic patients who would
translate them into recommendations.2
benefit from systemic treatment and convened a multi-disciplin-
The GRADE system clearly distinguishes between the quality
ary group of experts; the present Latin American Clinical Prac-
of the evidence and the strength of the recommendation, and
tice Guidelines on the Systemic Treatment of Psoriasis is the
explicitly evaluates the relevance of the outcomes.
result of their work.
Recommendations are produced through a transparent process
It is relevant to distinguish between CPGs and consensus
incorporating patients values and preferences, acceptability,
guidelines. CPGs are based on a systematic, comprehensive,
feasibility and resource considerations.3,4
transparent and objective search and assessment of the avail-
The authors of these CPGs convened by SOLAPSO are
able evidence, whereas consensus guidelines summarize the
experts from several countries in the region and a team of
agreements reached by a group of experts which may not
methodologists who searched and organized the evidence.
strictly be based on clinical evidence. The systematic classifica-
Questions were collected following the PICO structure to guide
tion of the evidence reduces biases and facilitates the interpre-
the literature search. Two CPGs on psoriasis developed under
tation of medical guidelines. CPGs have the potential of
adequate standards of literature searches were identified and all
improving patient management by promoting clinically proved
citations in these CPGs found to be relevant to the purpose of our
interventions, disregarding the noneffective. To achieve this
study were assessed.5,6 A supplementary search of systematic
goal, CPGs need to be referenced by physicians in their clinical
reviews, randomized trials, and observational studies was
practice, replacing subjective criteria and experience by objec-
performed in MEDLINE, Epistemonikos, Cochrane library, LILACS,
tive data. This process of change is sometimes complex and for
and Google Scholar with temporal restriction (2012–2015). The
several reasons it is relatively frequent that doctors keep on
search term in all cases was “Psoriasis.”
their usual practices even despite they are not evidence-based.2
Relevant information was extracted in ad hoc tables;
The CPGs provides the treating physician with reference stan-
evidence summaries were prepared for each comparison and
dards on practical aspects relevant for drug selection and
each scenario following the GRADE Working Group suggested
patients monitoring.
criteria.7,8 To reach a consensus on each recommendation, the
Adhering to the guidelines does not guarantee treatment suc-
authors considered the balance between benefits and risks, the
cess. The final decision on the specific therapies must be taken
quality of the evidence, the values and preferences of the
by physicians and their patients, considering all circumstances
patients, as well as costs and other practical issues.
of each case in particular.
SOLAPSO is proud to present the Latin American CPGs on
PICO Questions
the systemic treatment of psoriasis and hopes it will reach all
Questions were selected by consensus of the authors and were
health care professionals involved in the management of psoria-
based on the questions included in other CPGs on Psoriasis.5
sis and that it may contribute to increase the efficacy in control-
All questions were framed using PICO (Population, Intervention,
ling this disease, which still poses significant impairment in the
Comparison, Outcome):
patients’ quality of life.
Populations
Goals
The CPG on the systemic treatment of Psoriasis aims at offer- 1 Moderate to severe plaque-type psoriasis adult patients
ing updated therapeutic information and become a reference 2 Moderate to severe plaque-type psoriasis pediatric patients
frame to Latin American physicians, for their therapeutic deci- 3 Moderate to severe plaque-type psoriasis adult patients over
sions, with the main goal of improving patient care. 65 years old
Treatment being the core of the CPGs, the authors have 4 Moderate to severe plaque-type psoriasis in pregnant or
deliberatively excluded definitions, classifications, epidemiology, breastfeeding patients
presentation and diagnosis of the disease, which can be found 5 Patients with guttate psoriasis
in the 2009 Guidelines.1 6 Patients with erythrodermic psoriasis
ª 2019 The International Society of Dermatology International Journal of Dermatology 2019, 58 (Suppl. 1), 4–28
6 Review SOLAPSO Clinical Practice Guidelines 2017 Kogan et al.
7 Patients with generalized pustular psoriasis CPG as Tables in the Technical Document (TD) which can be
8 Patients with palmoplantar pustular psoriasis accessed in the online Supplementary Information article.
9 Patients with psoriasis of specific locations One table was prepared for each comparison in every clinical
10 Psoriasis (any type) and psoriatic arthritis patients scenario. When possible, metanalysis were performed to
11 Psoriatic patients (any type) with specific comorbidities assess the results of all trials evaluating the same comparison
12 Relapsing psoriatic patients (50% decrease from basal PASI) and measuring the same outcome, using Review Manager
13 Rebounding psoriatic patients (125–150% increase from (RevMan) [Computer program] Version 5.3. Copenhagen: The
basal PASI) Nordic Cochrane Centre, The Cochrane Collaboration, 2014
Maentel-Haenzel statistical method and random analysis model
Interventions were used for dichotomic outcomes.
1 Nonbiologics (listed alphabetically): Acitretin (ACT) – Inverse variance and random analysis model were used for
Cyclosporine (CsA) – Methotrexate (MTX) continuous outcomes. Summary of findings (SoF) tables were
2 Biologics (listed alphabetically): Adalimumab (ADA) – prepared using the Guideline Development Tool (www.
Etanercept (ETN) – Infliximab (IFX) – Secukinumab (SEC) – guidelinedevelopment.org). All the SoF tables are presented in
Ustekinumab (UST) the technical document (TD).
3 Phototherapies:
a Narrow band ultraviolet B phototherapy (NBUVB) Rating the quality of evidence
b Broad band ultraviolet B phototherapy (BBUVB) The quality of the evidence was rated using the GRADE system
c Psoralen and ultraviolet A phototherapy (PUVA) as summarized in Table 1. For further information on GRADE
4 The following interventions were also included for psoriatic please refer to http://www.gradeworkinggroup.org/
arthritis patients: Certolizumab (CER) – Golimumab (GOL) –
Apremilast (APM) Assessing resources and costs
Resources and costs were considered informally. No economic
Outcomes evaluations were performed for these CPGs.
PASI 50: Proportion of patients with 50% or above reduction in
Patients values and preferences
the PASI index
In all recommendations, the authors considered the values and
preferences of patients for each scenario and comparison
the PASI index
based on their clinical experience.
Strong recommendations could only be made in those
the PASI index
scenarios and comparisons where significant variability in the
PASI 100: Proportion of patients with 100% reduction in the
values and preferences of patients was assumed as unlikely.
PASI index
PGA 0–1: Proportion of patients reaching 0–1 in PGA score
Significant improvement in quality of life: Proportion of Producing and formulating recommendations
patients with a significant improvement in quality of life reported The panel discussed the SoF tables and analyzed the
directly or measured by the Dermatology Life Quality Index information considering other aspects as already mentioned
(DLQI) (4–5 points improvement) (values and preferences of the patients, costs, resources and
Severe adverse events (AE): Percentage of patients with implementation issues, among others).
severe AE Judgments by the panel regarding each of those aspects
AE leading to treatment discontinuation: Proportion of were recorded in evidence to decision frameworks as
patients with AE that lead to treatment discontinuation recommended by GRADE.
Specific AE: Proportion of patients with specific AE Each recommendation was reached by consensus of the
considered relevant authors and written following the GRADE system structure
Specific outcomes were considered for different patient direction (for or against) and strength (strong or weak). The
subpopulations (e.g. NAPSI for ungueal involvement or ACR direction and strength of recommendations were expressed as:
50, 70, and 90 for psoriatic arthritis patients). “The SOLAPSO CPGs Panel recommends . . .” (strong, for); “. . .
suggests. . .” (weak, for); “. . . does not recommend” (strong,
Summarizing the evidence against); “. . . does not suggest” (weak, against) (Table 2). In
Based on the questions and comparisons identified, ad hoc cases where consensus could not be reached, the direction and
tables were prepared summarizing the data from studies in the strength of the recommendation were decided by voting.
two reference CPGs and those studies found in the systematic For practical reasons, the CPGs have been organized in
reviews. These tables have been referenced throughout the Chapters, each of which was assigned to one or more authors
Table 1 GRADE’s approach to rating quality of evidence
1. 2. 3.
Establish initial level of confidence Consider lowering or raising level of Final level of confidence
confidence rating
Reasons for considering lowering or
Initial
raising confidence Confidence in an
confidence in
Study design estimate effect across
an estimate of
Lower if Higher if * those considerations
effect
Risk of Bias Large effect
Randomized High High
trials confidence Inconsistency Dose response ⊕⊕⊕⊕
Indirectness All plausible

Moderate
confounding &
Imprecision bias ⊕⊕⊕
* would reduce a
demonstrated effect Low
Observational Low Publication or
trials confidence * would suggest a ⊕⊕
bias spurious effect if no
effect was observed Very low
⊕
Table 2 GRADE System: direction and strength of recommendations
Strong recommendation Weak recommendation
For patients Most individuals in this situation would want the recommended The majority of individuals in this situation would want the
course of action and only a small proportion would not. suggested course of action, but many would not.
For clinicians Most individuals should receive the recommended course of Recognize that different choices will be appropriate for
action. Adherence to this recommendation according to the different patients, and that each patient should be aided so as
guidelines could be used as a criterion or performance to arrive at a management decision consistent with her or his
indicator. Formal decision aids are not likely to be needed to values and preferences. Decision aids may be useful in
help individuals make decisions consistent with their values helping individuals to make decisions consistent with their
and preferences. values and preferences. Clinicians should expect to spend
more time with patients when working towards a decision.
For policy makers The recommendation can be adapted as policy in most Policy making will require substantial debates and involvement
situations including the use as performance indicators. of many stakeholders. Policies are also more likely to vary
between regions. Performance indicators would have to focus
on the fact that adequate deliberation about the management
options has taken place.
who summarized the evidence and provided additional

To define which interventions should be considered, we
comments to the recommendations.
assessed the results of the studies meeting the inclusion crite-
ria: each intervention should be compared to placebo and mea-
Declaration of interests
sure the outcomes previously defined: PASI 50, PASI 75, PASI
All authors filled in the declaration of interests form of WHO.
90, PASI 100, PGA 0–1, QoL and AE. Following is a summary
of the results assessed for each drug.
Chapter 1. Plaque-Type Psoriasis

Nora Kogan, Nelida
Raimondo, Minerva Gomez Flores, Fer- Nonbiologics (in alphabetical order)
nando Valenzuela Acitretin (TD Table 3.1.1)
ACT is a retinoid introduced in 1094 and widely used in the
treatment of psoriasis, although it is not available in some Latin
In adult patients with moderate to severe plaque-
American countries.
type psoriasis, which interventions should be con-
Two RCT including 194 patients9,10 informed that ACT would
sidered?
probably significantly improve the possibility of achieving PASI 75
(moderate quality evidence, MQE). In one of these trials, 47–69% Three studies met the criteria of these CPGs to assess the
of the patients reached PASI 75 at week 12, with better results efficacy and the safety of MTX in the management of adult
with 35 mg/kg/day doses9 Two trials11,12 reported high probability patients with moderate to severe psoriasis.19–21
of minor AE such as peeling, pruritus, alopecia, rhinitis, spasms, For the efficacy evaluation, several studies have shown that
and erythema which significantly increased at higher doses (50 MTX is probably related to increased probability of reaching
vs. 25 mg/kg/day) (high quality evidence, HQE). Other AE PASI 75 and PGA 0–1 (MQE).
remained at similar levels with both doses (cheilitis, dry mouth, In the CHAMPION study,21 MTX was compared to placebo in
xerophthalmia). 163 patients, of which 110 received MTX 7.5 mg oral with dose
increased as needed and as tolerated to 25 mg weekly for
Cyclosporine (TD Tables 3.1.3.1–3.1.3.2) 16 weeks. After 16 weeks, 35.5% of MTX-treated patients
CsA is an immunosuppressive drug widely used in the treat- achieved PASI 75 vs. 18.9% in the control group.
ment of psoriasis since the 1990s, currently presented in cap- In one RCT comparing MTX vs. placebo, the mean PASI
sules. Nine randomized controlled trials (RCT) were found to change from baseline showed an improvement of 73.9% with
meet the criteria of these CPGs to assess the efficacy and MTX and 32.0% in the placebo group at month 6.19
13–17
safety of CsA vs. placebo. The results showed that CsA No significant AE were identified in the results assessed,21
may be associated with a higher probability to reach PGA or although a meta-analysis of 32 RCT including 13,177 patients22
PASI 75 and increased risk of AE (low quality evidence, LQE). who received MTX for different rheumatological conditions
In most of these trials a relevant clinical response was seen informed an increase in the risk of hepatic AE (HQE). This
after 4–8 weeks of treatment. Ellis et al.13 evaluated CsA 3, 5 meta-analysis included studies carried out from 1990 to 2014
and 7.5 mg/kg/day vs. placebo in 85 patients controlled for and was aimed at assessing the relative risk and severity of the
16 weeks and observed PGA 0–1 at week 8 in 65% of the hepatic damage in patients treated with MTX. The results of
patients in the CsA 5 mg/kg/day group and 36% in the patients these 32 studies showed that MTX was related to higher total
receiving 3 mg/kg/day, with a statistically significant superiority risk of hepatic AE but not higher risk of hepatic failure, cirrhosis
of treatment vs. placebo. or mortality were found.
The relapse rate in 189 patients previously treated with CsA
was reported in the PREVENT study.18 Biologics (in alphabetical order)
CsA was discontinued for 8 days previous to the patients being Adalimumab (TD Table 3.1.2)
randomized to oral CsA 5 mg/kg/day or placebo for two consecu- ADA is a recombinant human immunoglobulin G1 (IgG1) mono-
tive days/week, for a total period of 24 weeks. A total of 162 clonal antibody containing only human peptide sequences and
patients were randomized to CsA and 81 to placebo. At 24 weeks, used since 2007 in the treatment of psoriasis. It is administered
66.9% of the CsA-treated patients with moderate-severe psoriasis subcutaneously.
showed clinical success rates as defined for this study (no relapse Seven RCT comparing ADA vs. placebo met the criteria of
or PASI 75) and 46.3% with placebo. This trial had a high with- these CPGs and were included for efficacy and safety assess-
drawal rate (22.2% of randomized patients), which was not related ment.20,21,23–27 Three of these studies – which included about
to side effects and may have led to an overestimation of efficacy. 1,500 patients– informed a significant increase in the probability
Another RCT and an observational study (OS) also showed high of achieving PGA 0, PASI 75, PASI 90, and PASI 100 both at
withdrawal rates which might be related to AE (13.9–17%).15,16 induction and at maintenance (MQE).21,25,26 In a multicentric,
The results of a prospective long-term cohort OS which investi- randomized, double-blind, placebo-controlled study, 147
gated the incidence of malignancies in 1,252 severe psoriasis patients received ADA (40 mg every other week or 40 mg/
patients treated with CsA and followed up for 5 years show a pos- week) or placebo. At week 12, 53% of patients on ADA every
sible increase in the incidence of malignancies in the long term other week, 80% of patients on ADA weekly, and 4% of the
(compared to the general population, the standardized incidence control group achieved PASI 75.26
rate was 1.8) (LQE).16 Furthermore, the results of 16 RCT (HQE) In another 52-week, multicenter study of 1,212 patients ran-
show a relation between renal impairment and CsA. Over 50% of domized to receive ADA (40 mg) or placebo every other week
the patients treated for ≥2 years might have ≥30% impairment in for the first 15 weeks, 71% of the ADA group of patients
the creatinine value, 12.5% incidence of glomerulosclerosis at reached PASI 75 at week 16, vs. 7% of the placebo-treated
3 years and 26% at 10 years.17 CsA is probably related to higher patients.25
13,17
risk of renal impairment when used for long periods. In terms of quality of life, a possible clinically relevant
improvement with ADA measured by DLQI was shown (LQE).
Methotrexate (TD Tables 3.1.7.1–3.1.7.2) One RCT assessed the impact of ADA on health-related quality
MTX was discovered by mid of the 20th century and has been of life in 84 adult patients with moderate to severe psoriasis
widely used for the treatment of psoriasis since FDA approval in treated with ADA 80 mg every other week and in 87 patients
1971. who received ADA 40 mg, one weekly injection throughout
16 weeks. The absolute reduction in the DLQI score in the results at week 24, 54, and 45% PASI 75 in each group of
ADA-treated patients was 3.3 and 5.7 points higher than the patients, respectively.
score of the placebo group, for both treatment groups, respec- Three studies including 1,003 patients30,31,33 evaluated the
tively.20 effect of ETN on quality of life, showing possible significant
Nineteen RCT including a total of 6,672 patients informed a improvement. Krueger et al30 in a multinational, randomized,
marginal increase in the risk of severe AE (MQE). The local phase III trial, evaluated 583 patients (193 received placebo,
reactions at the injection site (erythema, itching, pain, swelling, 196 ETN 50 mg per week, and 194 ETN 50 mg twice a
and bleeding) were the most frequent AE and they were week during the initial 12-week, double-blind period. There-
observed in 20% of the ADA-treated patients vs. 14% of the after, all patients received ETN 50 mg per week). At week
untreated groups.27 ADA was related with a possible increase 12, in 72–77% of the patients receiving ETN improvement in
in the risk of AE that lead to discontinue treatment, in the DLQI was clinically meaningful (≥5-point improvement or 0
assessment of results of 22 RCT with 7,622 patients (LQE). score).
The main infections reported in these studies among patients Regarding the safety profile of the drug, the results of 28
treated with ADA were upper respiratory infections, bronchitis, RCT including 6,174 patients show that ETN is a safe drug.
urinary tract infections, and some more severe such as pneu- Some studies relate ETN with a probable marginal increase in
monia, septic arthritis, prosthetic or postsurgical infections, ery- the risk of AE (MQE) and TB reactivation (HQE).
sipelas, cellulitis, diverticulitis, and pyelonephritis.5 The results
of the PSOLAR registry,28 evaluating the risk of severe infec- Infliximab (TD Table 3.1.6)
tions in 12,095 psoriasis patients treated with biologicals or sys- IFX is a monoclonal antibody that works against TNF-a. It is
temic drugs informed a possible significant increased risk in administered intravenously and has been in use to treat psoria-
patients treated with ADA, although the global incidence (1.45 sis since 2005.
each 100 patients per year) might be related to the fact that Ten RCT were included in the present CPGs in which IFX
ADA is more frequently used compared with other alternatives safety and efficacy was assessed.40–49
(LQE) (see 13.1). The efficacy assessment showed that IFX increases the
probability of reaching PASI 75, 90, 100 and improving quality
Etanercept (TD Table 3.1.4) of life both at induction as well as at maintenance therapies
ETN is a soluble TNF inhibitor, administered subcutaneously, (M/HQE).
used for the treatment of patients with moderate to severe pso- To show the role of anti-TNFa in the pathogenesis of psoria-
riasis since 2004 and which plays an important role in the man- sis, a double-blind RCT assessed the clinical benefit and safety
agement of other inflammatory diseases such as rheumatoid of IFX against anti-TNFa in 33 patients with moderate to severe
arthritis. plaque psoriasis who were randomly assigned to intravenous
The results of the 10 studies assessed29–39 and showed the placebo, IFX 5 mg/kg, or IFX 10 mg/kg at weeks 0, 2, and 6.
efficacy of ETN in the probability of achieving PASI 50, 75, 90, Patients were assessed at week 10 for PGA; 3 patients had
100 and improving quality of life (HQE). dropped out; 9/11 (82%) patients in the IFX 5 mg/kg group were
In a study with adult patients with plaque psoriasis, 112 responders (good, excellent, or clear rating on PGA), compared
patients were randomly assigned to treatment groups and with 2/11 (18%) in the placebo group and 10/11 (91%) patients
received placebo or ETN 25 mg, subcutaneously twice a week in the IFX 10 mg/kg group.42
for 24 weeks. After 12 weeks of treatment, 17 (30%) of the 57 Gottlieb et al. evaluated 249 patients with severe plaque pso-
ETN-treated patients and 1 (2%) of the 55 in the placebo group riasis in a multicenter, double-blind, placebo-controlled trial, ran-
had achieved PASI 75, and after 24 weeks this score was domly assigned to receive IFX 3 or 5 mg/kg intravenous
found in 32 (56%) and 3 (5%), respectively.29 infusions or placebo given at weeks 0, 2, and 6. At week 10,
A 24-week, double-blind study compared ETN at a low dose 72% of patients treated with IFX 3 mg/kg and 88% of patients
(25 mg once weekly), a medium dose (25 mg twice weekly), or treated with IFX 5 mg/kg achieved PASI 75 compared with 6%
a high dose (50 mg twice weekly), vs. placebo. At week 12, of patients treated with placebo. PASI 90 was observed in 58%
PASI 75 was achieved in 4% of the patients in the placebo of the patients in the IFX 5 mg/kg group, 46% in those receiving
group, as compared with 14% of those in the low-dose ETN 3 mg/kg and 2% for placebo. To assess the duration of the
group, 34% percent in the medium-dose–ETN group, and 49 response, patients were followed up for 20 weeks after the last
percent in the high-dose–ETN group. At week 24, the scores induction infusion; at week 20, 33% of the patients receiving
with ETN were 25, 44, and 59%, respectively.35 Similar results IFX 5 mg/kg were still at PASI 75.45
were found by Papp et al.,32 in a multicenter 24-week study in In the EXPRESS phase III, multicenter, double-blind trial,
the U.S.A., Canada, and Western Europe, reporting 49 and 301/378 patients with moderate to severe plaque psoriasis re-
34% of patients reaching PASI 75 at week 12 in the ETN ceived IFX 5 mg/kg infusions or placebo at weeks 0, 2, and 6,
50 mg and 25 mg twice weekly treatment groups, with better then every 8 weeks to week 46. At week 10, the proportion of
patients achieving PASI 75 from baseline was 80% in the treat- 4.9% with placebo. Similar results in PASI 75 at 12 weeks have
ment group, while 57% achieved PASI 90 vs. 3% and 1% for been reported by other authors.51,53
placebo, respectively. At week 50, 170/281 (61%) evaluable The assessment of response over time in the ERASURE
patients achieved PASI 75. Based on a predefined analysis on study showed that 80.5% of the patients in the SEC 300 mg
PASI 75 responders at week 10, the response to IFX was sus- treatment group maintained PASI 75 at week 52 and 72.4% of
tained, with most PASI 75 responders at week 10 maintaining those in SEC 150 mg. In the FIXTURE study, these rates were
this response through week 24 (203/229 patients; 89%) and 84.3 and 82.2%, respectively.
week 50 (153/225; 68%).41 As part of the EXPRESS study, The quality of life results assessment showed higher proba-
Reich et al.47 used DLQI and other self-evaluation parameters bility of significant improvement with SEC (HQE).55,56 The pro-
to assess the impact of long-term IFX maintenance therapy on portion of patients with a DLQI score of 0 or 1, indicating no
health-related quality of life in patients with psoriasis. At week impairment of health-related quality of life, was significantly
10, IFX-treated patients had significantly greater improve- higher at week 12 in each SEC-dose group than in the placebo
ment in DLQI scores than placebo-treated patients, persisting group and showed similar absolute improvement variations in
at week 24 with patients achieving PASI 100 reporting the both groups (10.1 with SEC 150 mg and 11.4 with SEC 300).
greatest benefit (HQE). The safety results of 5 RCT with 1,716 patients showed a
The safety profile of IFX in psoriasis appears to be similar to probable marginal increase of severe AE and possible no higher
what has been observed with this drug in other indications. The risk of major cardiovascular events with SEC (M/LQE).
most frequent AE are injection site reactions, infections and TB Nasopharyngitis, headache, upper respiratory tract infection,
reactivation.5 In the studies considered in these CPGs to and diarrhea were among the most frequent AE. The incidence
assess AE IFX was related with a probable increase of severe of reactions at the injection site was low. Some infections, par-
AE (MQE). In the EXPRESS study, three cases (1%) of non- ticularly Candida sp. were observed at the induction treatment
melanoma skin tumors were reported in the IFX treatment period.51–53,55 Grade 3 neutropenia occurred in 9 patients
group and the drug was also related to probable treatment inter- receiving SEC (1.0%) and one patient receiving ETN (0.3%)
ruption due to AE (MQE).41 developed grade 4 neutropenia.55
Secukinumab (TD Table 3.1.8) Ustekinumab (TD Table 3.1.9)

SEC is a recombinant, high-affinity, fully human immunoglobulin UST is a human monoclonal antibody directed against IL-12
G1j monoclonal antibody that selectively binds and neutralizes and IL-23, and has been used for the treatment of psoriasis
interleukin-17A. The drug was approved by the FDA in 2015 for since 2008.
the treatment of patients with moderate to severe psoriasis; it is The results of 5 RCT with 2,596 patients were considered for
administered subcutaneously with pre-filled syringes or self- the efficacy assessment and showed a higher probability of
injection devices (SensoreadyTM pen). achieving PASI 75, 90, and 100 with UST both at induction and
Six RCT met the criteria to be included in these CPGs to at maintenance, and that the drug is also probably related to a
assess the efficacy and safety of SEC.50–55 In terms of efficacy, significant increase in the quality of life of these patients
all outcomes assessed showed a significant increase in the (HQE).57–61
probability of achieving PASI 50, 75, 90, 100 and improving Two long-term phase III, double-blind, placebo-controlled
quality of life with SEC (M/HQE). Langley et al.55 combined the studies: PHOENIX 1 (Leonardi et al., 766 patients, 76 weeks)58
results of two phase 3, double-blind, 52-week RCT, ERASURE and PHOENIX 2 (Papp et al., 1,230 patients, 52 weeks)59 eval-
(Efficacy of Response and Safety of Two Fixed Secukinumab uated UST in two dose regimens: 45 mg and 90 mg at weeks 0
Regimens in Psoriasis, 738 patients) and FIXTURE (Full Year and 4 and then every 12 weeks. The primary endpoint was the
Investigative Examination of Secukinumab vs. Etanercept Using proportion of patients achieving PASI 75 at week 12: 67.1–
Two Dosing Regimens to Determine Efficacy in Psoriasis, 1,306 66.7% with UST 45 mg in PHOENIX 1 and 2, respectively, and
patients). Patients were randomly assigned to subcutaneous SEC 66.4–77.5% with UST 90 mg in PHOENIX 2. In PHOENIX 1, at
at a dose of 300 mg or 150 mg (administered once weekly for week 40, patients were randomly assigned to maintenance UST
5 weeks, then every 4 weeks), or to placebo. The FIXTURE study or withdrawal. PASI 75 response was better maintained to at
also included one group treated with ETN at a dose of 50 mg least 1 year in those receiving maintenance UST than in those
administered twice weekly for 12 weeks, then once weekly. withdrawn from treatment.
At week 12, the proportion of patients who met the criterion For the quality of life assessment, the results of 5 RCT with
for PASI 75 was higher with each SEC dose than with placebo 1,836 patients were considered. All of these studies measured
or ETN: in the ERASURE study, the rates were 81.6% with DLQI at induction and showed a probable improvement in
300 mg of SEC, 71.6% with 150 mg of SEC, and 4.5% with pla- quality of life; absolute score decrease in treated patients was
cebo; in the FIXTURE study, the rates were 77.1% with 300 mg 8.24 points higher (7.24–9.24) than in the control groups
of SEC, 67.0% with 150 mg of SEC, 44.0% with ETN, and (MQE).57–61
Regarding safety, 5 RCT with 2,595 patients57–61 showed ACT vs. ETN (TD Table 3.1.11)
probable absence of increased risk of severe AE and AE that lead The results of two RCT including 102 patients were assessed to
to treatment discontinuation (MQE), and marginal increase in the compare the efficacy and safety of ACT vs. ETN12,63 suggesting
risk of severe AE in the long term (LQE). Papp et al.62 evaluated that ETN could be superior than ACT in achieving PASI 75 at
the safety of UST with data pooled from four studies induction (LQE). There is uncertainty about the possibility of dif-
of UST for psoriasis. Analyses included 3,117 patients who ferences in the long term between both drugs (VLQE). No AE
received one or more doses of UST (45, 90 mg), of which were reported in these studies.
1,482 were treated ≥4 years (838 patients ≥5 years). At year 5,
event rates for overall AE were comparable between the two dose ADA vs. MTX (TD Table 3.1.14)
groups, and no dose-related or cumulative toxicity was observed One RCT21 with 218 patients showed better results with ADA in
with increasing duration of UST exposure for up to 5 years. the outcomes PASI 75, 90, and PGA 0–1 (HQE).
In this study, after 16 weeks, 79.6% of ADA-treated patients
achieved PASI 75, compared with 35.5% for MTX. Statistically
significantly more ADA-treated patients (16.7%) than MTX-trea-
Recommendation # 1 ted patients (7.3%) achieved complete clearance of disease.
MTX might be related to an increased risk of severe AE leading
In adult patients with moderate to severe plaque-type
to study discontinuation (LQE).
psoriasis, the SOLAPSO CPGs panel recommends the
following therapeutic interventions as valid alternatives:
IFX vs. MTX (TD Table 3.1.17)
ACT, ADA, CsA, ETN, IFX, MTX, PUVA, SEC, UST,
The results of one RCT including 868 MTX-na€ıve patients
NBUVB (interventions are listed alphabetically).
(RESTORE 1)40 showed that IFX is probably superior to
achieve PASI 50, 75, 90 both at induction and at
maintenance, and is also superior to improve quality of life
Comments:
(LQE).
Although ACT is not available in all Latin American countries,
9–12 Patients were randomized 3:1 to receive IFX 5 mg/kg at
the panel valued the information assessed, the cost and the
weeks 0, 2, 6, 14, and 22 or MTX 15 mg weekly with a dose
experience with the use of this drug.
increase to 20 mg weekly at week 6 for patients with PASI < 25
The experts agreed to include CsA as an alternative despite the
6 or switch at week 16 for patients with PASI < 50. The efficacy
quality of evidence about efficacy was low, based on their per-
endpoints were PASI 75 and PGA 0–1 at weeks 16 and 26.
sonal experience with this drug, regarded as a possible choice
PASI 75 was achieved by a significantly greater proportion of
at 3 or 5 mg/kg per day doses.
IFX-treated patients (78%) than MTX-treated patients (42%).
About phototherapy, the panel decided to exclude BBUVB from
Key secondary endpoints also were achieved by a greater pro-
this scenario, based on the fact that the intervention is not indi-
portion of IFX-treated patients. Similar responses were
cated for psoriasis and since no qualifying evidence was found
observed at week 26 in patients who switched from MTX to IFX
compared to placebo. The same criteria were used with excimer
at week 16.
laser, although the panel acknowledged the use of the latter to
The safety assessment showed that IFX could be associated
treat local lesions.
with a higher risk of severe AE leading to treatment discontinua-
tion (LQE). The overall incidence of AE was comparable among
the groups, with a mild increase of serious and severe AE in
IFX-treated patients.
type psoriasis, which should be the first-choice
treatment?
To assess whether biological vs. nonbiological drugs should Recommendation # 2

be indicated in adult patients with moderate to severe plaque-
In adult patients with moderate to severe plaque-type
type psoriasis, the results of comparative studies among drugs
psoriasis, the SOLAPSO CPGs panel suggests to start
of both categories were analyzed, also taking into account the
therapy with a nonbiological drug rather than with a bio-
results of each intervention vs. placebo. Several studies met
logical drug.
the criteria of these CPGs and compared ETN vs. ACT, ADA
vs. MTX, and IFX vs. MTX.
comparisons meta-analysis, where no significant differences

were found in the risk of severe AE for both drugs (LQE).27
Recommendation # 3
In adult patients with moderate to severe plaque-type ETN vs. SEC (TD Table 3.1.18)
psoriasis who will start therapy with a nonbiological In the FIXTURE Study, with 973 patients, SEC showed better
drug, the SOLAPSO CPGs panel suggests MTX above results than ETN in PASI 75, 90, 100 outcomes and in the evalua-
all other available choices. tion of quality of life both at induction and maintenance (M/HQE).55
The proportion of patients who achieved PASI 75 at week 12
was higher with each SEC dose (150/300 mg) than with ETN,
the rates were 77.1% with 300 mg of SEC, 67.0% with 150 mg
of SEC, and 44.0% with ETN. The proportion of patients with
Recommendation # 4 PGA 0–1 at week 12 was higher with each SEC dose than with
ETN: 62.5% with 300 mg of SEC, 51.1% with 150 mg of SEC,
In adult patients with moderate to severe plaque-type 27.2% with ETN. In the evaluation of the response over time,
psoriasis who value short-term effectiveness, the the rates according to PASI 75, PASI 90, PASI 100, and PGA
SOLAPSO CPGs panel suggests biological drugs as 0–1 were higher with SEC than with ETN through week 52:
first-choice therapy. 72.5% ETN, 82.2% SEC 150 mg, and 84.3% SEC 300 mg.
Possibly no significant differences in the risk of severe AE or
MACE were found between these two interventions (LQE).54,55
Comments:
The panel acknowledged that biological drugs could be more ETN vs. UST (TD Tables 3.1.20.1 y 3.1.20.2)
effective than nonbiologicals for the treatment of patients with The results of one RCT with 903 patients showed that UST is
moderate to severe plaque-type psoriasis, but they weighed the probably superior to achieve PASI 75, 90, 100 at the induction
availability of long term safety information, the costs and the phase (MQE).65
accessibility of nonbiologicals. In this study, Griffiths et al. compared UST and ETN randomly
Since no difference was found in risk-benefit, the panel weighed assigning patients to one of three treatment groups; UST at a dose
experience, cost and availability to recommend MTX. of 45 or 90 mg at weeks 0 and 4 or ETN at a dose of 50 mg twice
In patients with prior failure, adverse events or absolute con- weekly for 12 weeks. At week 12, a total of 67.5% of patients who
traindication of MTX, all other available therapeutic options received 45 mg of UST and 73.8% of patients who received
should be considered. The panel decided not to formulate a 90 mg of UST had at least 75% improvement in the PASI score,
statement recommendation for this scenario. as compared with 56.8% of those who received ETN. The propor-
The panel agreed that specialists should be in charge of pre- tion of patients who reached PGA 0–1 at week 12 was also signifi-
scribing and using biologics, considering that the use of these cantly higher in each UST group: 65.1% with UST 45 mg, 70.6% in
drugs demand an adequate patient selection and follow-up, due UST 90 mg vs. 49.0% of patients who received high-dose ETN.
to the potential adverse events and costs. The safety of UST and ETN appeared to be generally similar,
with probably no significant differences between both drugs
regarding severe AE and those leading to treatment discontinu-
ation (MQE).
type psoriasis who are started on biologics (either
as first or second line therapy), which should be
the first-choice treatment?
SEC vs. UST (TD Table 3.1.19)
The results of one RCT with 676 patients showed that SEC
was superior to UST as assessed by the PASI 75, 90, and 100
The results of studies comparing biologics were assessed responses. Better results were also obtained with SEC at induc-
and completed considering also the results of each drug vs. pla- tion in the health-related quality of life evaluations (HQE).66
cebo. Studies comparing ETN vs. IFX, ETN vs. SEC, ETN vs. In this 52-week, double-blind study 676 subjects were random-
UST, and SEC vs. UST were included. ized to receive SEC 300 mg subcutaneous injection or UST per
label. Primary end point PASI 90 was achieved in 79.0% of
ETN vs. IFX (TD Table 3.1.12) patients treated with SEC in comparison with 57.6% of those
The results of one RCT with 48 patients were assessed64 sug- receiving UST. The 100% improvement from baseline PASI score
gest that IFX could be superior in achieving PASI 75, both at at week 16 was also significantly greater with SEC (44.3%) than
induction and as maintenance (LQE). UST (28.4%). Percentage of subjects with the DQLI score 0/1 at
Due to the lack of direct comparative studies assessing the week 16 was significantly higher with SEC (71.9%) than UST
risk of AE, these CPGs considered the information of a multiple (57.4%). The safety profiles of both drugs were comparable, there
are probably no differences between them in the risk of severe AE biological agent might reach PASI 75 if shifted to IFX and PASI
and those leading to treatment discontinuation (MQE). 50, 75 and 100 if shifted to UST (HQE).
Recommendation # 5 Recommendation # 7
In patients with moderate to severe plaque-type psoria- In adult patients with moderate to severe plaque-type
sis who are started on biologics, the SOLAPSO CPGs psoriasis with prior exposure and failure of a biological
panel suggests anti TNF (ADA, ETN, INF) or anti-IL-12/ therapy, the SOLAPSO CPGs panel suggests that a dif-
23 (UST) as first-choice treatment. ferent biological agent should be indicated other than
shifting to a nonbiological drug or indicating a new
course of therapy with the previously failing drug.
Recommendation # 6 Comments:
The panel valued the evidence on the efficacy of biologics as sec-
In patients with moderate to severe plaque-type psoria-
ond line treatment in patients previously exposed to these agents,
sis who are started on biologics and show preference
and considered that there is insufficient data to decide which bio-
for short-term efficacy, the SOLAPSO CPGs panel sug-
logical agent should be indicated in the event of a prior failure.
gests SEC as first-choice treatment.
Which is the best treatment scheme for adult

Comments:
patients with moderate to severe plaque-type psori-
In the efficacy assessment, the panel considered SEC to be
asis over 65 years of age?
superior than all other biologics. However, in their recommenda-
tions the panel prioritized the safety profile assessment weigh-
ing the long-term data available for all biologics, excepting SEC.
They also agreed that further comparative studies are neces- (TD Tables 3.3.1–3.3.3)
sary to choose UST before anti-TNF (e.g. UST vs. ADA). Seven studies met the criteria of these CPGs to evaluate the
On assessing the comparative studies available, the panel efficacy and safety of the interventions in treating adult patients
acknowledged that some aspects -such as ETN safety shown in over 65 years of age with moderate to severe plaque-type pso-
long-term studies or the intravenous administration of IFX- have riasis68–74 and to compare differences in treatment results
as much weigh as superior efficacy, as found for SEC and UST. between adult patients younger or older than 65 years of age.
Due to the particular profile of each biologic, regardless of effi- The results assessed, including three observational studies
cacy, initial treatment with anti-TNF might be necessary. with ADA69,70,73 and one RCT72 showed possibly no differences
in efficacy for ETN and ADA in adult patients younger or older
than 65 years of age, and that ETN, ADA, and IFX could be
In adult patients with moderate to severe plaque- related with a higher risk of AE in older adults (LQE).
type psoriasis with prior exposure and failure of
biological therapies: which should be the treatment
of choice?
Recommendation # 8
In adult patients older than 65 years of age with moder-

(TD Tables 3.15.1 y 3.15.2) ate to severe plaque-type psoriasis, the SOLAPSO
The CPGs assessed the results of a study designed to evaluate CPGs panel suggests the same therapeutic options
the potential cost effectiveness of sequential biologic therapies used for younger adults.
in patients with psoriasis who have been exposed to previous
biologic therapy.67
The PASI response rates from subgroup analyses of three Comments:
randomized placebo-controlled trials evaluating IFX (121 In the light of the limited evidence available for this group of
patients) and UST (2 studies, 691 patients) showed a consider- patients, the panel considered that the treatment options assessed
ably higher probability that patients previously treated with a are probably similarly effective in adult patients younger or older
than 65 years of age, although a marginal increase of AE could presents moderate to severe disease and require systemic
occur among the latter. Special attention should be given by the treatment.
treating physician to comorbidities in patients older than 65 years All interventions were considered, with a view to assessing any
of age, particularly those counter-indicating some drugs as CsA in special case that might imply that a different therapeutic approach
nephrosclerosis (see 13.2). should be indicated in children with moderate to severe psoriasis,
as compared to treating adult patients. The trials identified which
met the criteria for this CPGs compared ETN vs. placebo, MTX vs.
Which is the best treatment scheme in pregnant or placebo and UST vs. placebo81–85: Two placebo-controlled RCT,
breast-feeding women with moderate to severe pla- one with ETN (211 patients),81 another with UST (110 patients)85
que-type psoriasis ? and two observational studies evaluating MTX in children.83,84
Both drugs are probably comparable to achieve the outcomes
PASI 75, 90, and 100 and also to improve health related quality
(TD Tables 3.4.1. y 3.4.2) of life at induction (MQE).
Treatment of pregnant or breast-feeding women with moderate The trial assessing long-term efficacy of this drug in children
to severe plaque-type psoriasis will probably demand special with moderate to severe plaque-psoriasis aged 4–1781 related
considerations, particularly regarding treatment safety for both ETN to a probable significantly higher probability of reaching
the patient and the fetus or the newborn. PASI 75, 90 and PGA 0–1 at 12 weeks, and also probably
No trials were identified to provide specific information to higher probability of improved health related quality of life, as
answer this question. Three cohort trials were therefore identified measured by DLQI scale (MQE).
to assess the incidence of AE in pregnant women 75–77
and case In a 48-week double-blind trial by Paller et al.,82 211 children
reports were analyzed to determine drug levels in the babies of with psoriasis aged 4–17 were initially randomly assigned to ETN
breast-feeding women with psoriasis under therapy. 78–80 0.8 mg/kg/day (maximum dose 50 mg) or placebo 1 daily subcu-
taneous injection, followed by ETN for 24 weeks. At week 12,
57% of patients receiving ETN achieved PASI 75, as compared
with 11% of those receiving placebo; a significantly higher propor-
Recommendation # 9 tion of the patients in the ETN group had PASI 50 (75% vs. 23%),
In pregnant or breast-feeding women with moderate to PASI 90 (27% vs. 7%), and PGA 0–1 was 53% vs. 13%.
severe plaque-type psoriasis, the SOLAPSO CPGs panel In the long-term follow-up study81 responses at week 96
suggests phototherapy or CsA as treatments of choice. were similar to those observed in the double-blind trial: PASI
50, 89%; PASI 75, 61%; PASI 90, 30% and PGA 0–1 in 47% of
patients. AE were reported in 80.1% of cases: upper tract respi-
Comments: ratory infections 24.9%, nasopharyngitis 17.1%, streptococcal
The panel strongly weighed the uncertainty regarding safety of pharyngitis 12.7%, acne 11.6%, sinusitis 10.5%; there were two
biologics in pregnant or breast-feeding women and their fetus or withdrawals related to AE.
newborns. The two OS assessing MTX vs. placebo83,84 in 37 patients
Treating pregnant or breast-feeding patients with these drugs found good treatment response at induction and maintenance
might be considered when short term effectiveness is a priority phases and reported AE: increased transaminases 24%; gas-
(e.g. severe disease and patients who do not respond to CsA). trointestinal symptoms 40%, oral ulcers 3%, night cough and
In addition, the panel emphasized the counter-indication of BCG leg pain 3% (VLQE).
immunization in newborns of women who have been treated In the phase III CADMUS study, Landells et al.85 evaluated
with anti-TNF, particularly IFX, and the counter-indication of UST in 110 patients aged 12–17 years who had moderate to
CsA, MTX, and ACT in breast-feeding women. severe plaque-type psoriasis. High-quality evidence showed
increased probability of achieving all the percent improvement
end-points assessed.
Chapter 2: Children Patients were randomly assigned to UST standard dosing or
Carla Castro half-standard dosing at weeks 0 and 4 and every 12 weeks or
placebo at weeks 0 and 4 and at week 12 were shifted to either
Treatment of children with moderate to severe plaque- branch with UST. At week 12, 67.6 and 69.4% of patients re-
psoriasis ceiving UST (standard of half-standard, respectively) achieved
PGA 0–1 vs. 5.4% for placebo. Significantly greater proportions
(TD Tables 3.2.1, 3.2.2 y 3.2.3) receiving UST achieved PASI 75 (78.4, 80.6, 10.8%) or PASI
Although most cases of psoriasis in children are mild and 90 (54.1, 61.1, 5.4%) (UST standard dosing, half-standard dos-
may be managed with topical treatment, a small percentage ing or placebo, respectively).
AE with ETN, MTX, and ADA in children may be comparable

to the findings in adult patients (L/MQE), with probably more AE
at medium term (5.5% AE and 3.6% AE leading to treatment Recommendation # 11
discontinuation). The most frequently reported AE were infec- In children with moderate to severe plaque-type psoriasis
tions: nasopharyngitis (34.5%), upper respiratory tract infections the SOLAPSO CPGs panel suggests treatment with a non-
(12.7%), and pharyngitis (8.2%) (MQE). biological agent, considering MTX as first treatment choice.
Recommendation # 10 Comments:
In the absence of evidence supporting that the efficacy and
In children with moderate to severe plaque-type psoria- safety of the available therapeutic alternatives might be different
sis the SOLAPSO CPGs panel recommends the follow- in children and adults, the panel agreed to make the same rec-
ing therapeutic alternatives: ACT, ADA (patients ommendations (see 1.1).
≥4 years old), CsA, ETN (patients ≥8 years old), MTX
and UST (patients ≥12 years old) and phototherapy
(drugs listed alphabetically) When biologicals are indicated in children with
moderate to severe plaque-type psoriasis (either as
first line or after a prior failure), which should be
Comments: the first-choice?
The panel weighed the safety profile showed by ACT, MTX,
and phototherapy in clinical experience.
No studies comparing biological agents in children were iden-
Some case reports and small case series showed that ACT
tified. In the absence of specific evidence to answer this ques-
may be moderately effective in children with moderate to sev-
tion, the panel decided to refer to the evidence assessed for the
ere plaque psoriasis and that, overall, the use of acitretin
same question in adult patients.
was well tolerated, with minimal adverse effects (Di Lernia,
Napolitano).86,87 ADA was approved by the European Com-
mission in April 2015 for the treatment of children with severe
plaque psoriasis. The results of two trials evaluating ADA vs. Recommendation # 12
MTX were also considered.88,89 Based on these results and
In children with moderate to severe plaque-type psoria-
their personal experience, the panel agreed to recommend
sis who are started on biologicals either as first-line
ADA in children with moderate to severe plaque-type psoria-
treatment or after a prior therapeutic failure, the
sis.
SOLAPSO CPGs panel suggests any of the agents
The panel acknowledged that age (besides history and comor-
approved for use in pediatric patients (ADA, ETN).
bidities) is a relevant factor at the time of indicating a biological
agent, and emphasized that special consideration should be
given to reduce the burden of the treatment in children when-
Comments:
ever possible.
The panel acknowledges that age (besides history and comor-
bidities) is a relevant factor at the time of indicating a biological
In children with moderate to severe plaque-psoria- agent.
sis, which should be the first-choice treatment? The panel emphasizes that special consideration should be
given to reduce the burden of the treatment in children when-
ever possible.
In patients who strongly value short term effectiveness or treat-
(TD Tables 3.2.1-3.2.3; 3.1.1-3.1.9) ment burden (less number of injections) it might be preferable
To assess which of the recommended drugs should be indi- to start therapy with Anti IL 12-23 or Anti IL 17.
cated as first choice in pediatric patients with moderate to sev-
ere plaque-type psoriasis these CPGs included the results of
two trials comparing drugs of each category and the analysis In children with moderate to severe plaque-psoria-
was completed considering also the results of each agent vs. sis with prior exposure and failure of biological
placebo. No specific comparative studies were found for this therapies: which should be the treatment of
subgroup to enlarge the assessment. choice?
Trials comparing different biological agents in the treatment of could be identified. Therefore, the panel decided to consider all the
children with psoriasis were not identified. In the absence of drugs that showed beneficial effects in published studies in which
specific evidence to answer this question, the panel decided to patients with erythrodermic psoriasis were treated.
use indirect information from the same scenario in adult patients.
In patients with erythrodermic psoriasis, which

should be the first-choice treatment?
Recommendation # 13
In children with moderate to severe plaque-type psoria-

sis with prior exposure and failure of a biological ther- No studies comparing the different therapeutic alternatives for
apy, the SOLAPSO CPGs panel suggests a different the management of patients with erythrodermic psoriasis were
biological agent other than either shifting to a nonbiolog- found.
ical or indicating a new course of therapy with the previ-
ously failing drug.
Recommendation # 15
Chapter 3: Clinical Presentations In adult patients with erythrodermic psoriasis the

Juan Carlos Diez de Medina, Manuel Franco, Jorge Alex SOLAPSO CPGs panel suggests treatment with CsA or
Abarca Duran, Marıa Cecilia Brions IFX above all other alternatives. In children, CsA or
ACT is suggested as first-choice therapy.
Patients with erythrodermic psoriasis
(TD Tables 3.6.1–3.6.8)
The results of meta-analysis evaluating the efficacy of biologics Comments:
in psoriasis subtypes showed that these drugs appear to be In the absence of comparative studies the panel weighed the
effective in treating erythrodermic psoriasis (VLQE).90 pharmacodynamic properties of CsA and IFX which appear as
Data from a meta-analysis by Sighn et al.27 showed probably first choice therapy, based on their rapid action which is essen-
no differences among IFX, ADA, and ETN in the risk of serious tial for these patients.
AE or those leading to treatment discontinuation. The long-term
Patients with guttate psoriasis
safety results from Papp et al.62 were also considered to
assess UST safety profile for this localization (MQE).
(TD Tables 3.5.1–3.5.3)
The results of one RCT comparing penicillin or erythromycin for
To assess the efficacy of interventions to treat erythrodermic psori-
91 14 days with a placebo or rifampin added during the last 5 days
asis in children, the results of a systematic review by Van Geel et al.
of treatment show no apparent benefit for the patients in
were considered. The studies evaluating the efficacy of ACT, CsA,
improving their psoriasis (VLQE).92 In assessing the effect of
ETN, and MTX reported complete remission with ACT, one failure
tonsillectomy in these patients, the authors reported total remis-
with CsA, three patients reaching PASI 75 with ETN 0.8 mg/kg per
sion results in 9/10 patients and no AE (VLQE).93,94
week vs. no improvement with inferior doses; and 6/6 patients treated
with MTX reaching PASI 75 at induction. No AE were reported in
these series (VLQE). For the safety assessment the CPG considered
the results of studies with adult patients for each intervention.
Recommendation # 16
In patients with guttate psoriasis the SOLAPSO CPGs

panel suggests treatment with NBUVB phototherapy as
Recommendation # 14
first choice, followed by MTX or RE. Searching and even-
In patients with erythrodermic psoriasis the SOLAPSO tually treating the focus of infection is also suggested.
CPGs panel recommends the following therapeutic
alternatives: ACT, ADA, CsA, ETN, IFX, and UST
(drugs listed alphabetically). Comments:
The panel considered the results of small studies evaluating antibi-
otics and tonsillectomy plus other pathophysiologic grounds.
Comments: The NBUVB suggestion as first line option, as well as MTX or
Erythrodermic psoriasis is infrequent, there are few studies on this pre- RE, were based on the clinical experience of the panel mem-
sentation. No comparative studies between drugs or any other RCT bers, since evidence in this particular scenario is scarce.
Patients with generalized pustular psoriasis Exploring alternative differential diagnosis is recommended, to
(TD Tables 3.7.1–3.7.6 and .7.7–3.7.10) discard other auto inflammatory pustular diseases (DITRA) gen-
The results of a meta-analysis evaluating biologic therapy in erythro- erally treated with anti-IL-1 drugs.
dermic and pustular psoriasis were included to assess ADA, ETN, In adult patients showing patterns of generalized pustular psori-
90
IFX, and UST as well as the results of a 52-week OS evaluating the asis of subacute presentation ACT may be considered an alter-
95
efficacy and safety of SEC in generalized pustular psoriasis. native to the agents suggested.
High rates of response were reported with ADA 6/6 (100%),
ETN 9/10 (90%), IFX 28/30 (96%), and UST 7/7 (100%).90 In the Patients with palmoplantar pustular psoriasis
study by Imafu et al95 at week 12, PASI 75 was reached in 83.3% (TD Tables 3.8.1–3.8.5)
of the patients; PASI 90 in 58.3% and PASI 100 in 16.6% (VLQE). We assessed the results of a systematic review of RCTs includ-
The AE assessment found serious AE reported in 10–12% of ing patients with chronic palmoplantar pustular psoriasis ran-
the patients in the meta-analysis comparing ADA, ETN, IFX and domized to receive one or more interventions.97
UST90; over the 52-week treatment period, SEC was well toler- The review included 23 trials and 724 people. The studies com-
ated: nasopharyngitis, urticaria, diabetes mellitus, and arthralgia paring CsA and UST vs. placebo, PUVA and retinoids, alone or in
were the most frequently reported AE (VLQE).95 combination found a possible significant improvement with CsA
To assess the management of generalized pustular psoriasis persisting after 12 months in one RCT with 58 subjects (LQE). The
in children, the results of 8 OS with ACT, CsA, IFX, and MTX use of systemic retinoids and PUVA appears as a valid alternative;
vs. placebo were considered. Good treatment response was however, a combination of both was better than the individual
found for all interventions (VLQE).96 treatments, with a probable significant higher clearance (MQE).
The results of 5 OS with a total of 33 participants showed
variable response rates with UST: some studies reported 100%
and others 50% (LQE).98–103
Recommendation # 17 Considering that phototherapy is one of the most frequent inter-
In patients with generalized pustular psoriasis, the ventions for this localization, the results of studies evaluating
SOLAPSO CPGs panel suggests all the therapeutic alter- NBUVB vs. PUVA were also assessed.103 One RCT with 50 patients
natives indicated for erythrodermic psoriasis, plus SEC. followed-up for 9 weeks suggests that PUVA may be more effective
than UBV-BE, with percentages of improvement of 85.4% for PUVA
and 61% for UBV-BE measured by severity index scores (LQE).
Comments: One patient at this study had a phototoxic reaction with PUVA;
The panel considered that there is no evidence to support that palmar hyperpigmentation was found in 52% of the patients. No
pustular psoriasis should be treated as a different entity com- serious AE were reported in all the other assessed studies.
pared to other presentations. Studies comparing CsA, ETN, and IFX vs. placebo in children
with palmoplantar pustular psoriasis in the systematic review by
Van Geel et al.95 reported excellent response rates with ETN, good
In patients with generalized pustular psoriasis, response rates with IFX and lack of response with CsA (VLQE).
which should be the first-choice treatment?
Recommendation # 19
Recommendation # 18 In patients with palmoplantar pustular psoriasis pho-

totherapy, the SOLAPSO CPGs panel recommends
In adult patients with generalized pustular psoriasis, the PUVA, RE-PUVA, and NBUVB and suggests RE-PUVA
SOLAPSO CPGs panel suggests treatment with CsA or as first-choice.
IFX above all other alternatives and suggests CsA and
ACT as first-choice in children.
Comments:
In the absence of evidence on the efficacy of biologics in the man-
Comments:
agement of patients with palmoplantar pustular psoriasis, except
In the absence of reliable evidence, the panel weighed the
for the results of one report with UST in adult patients, considering
pharmacodynamic properties of CsA and IFX which appear as
that phototherapy is usually indicated to treat these patients and
first-choice drugs based on their rapid action. ACT should be
also considering the efficacy, administration and less AE observed
considered, despite its delayed onset of action. SEC is also
in clinical practice with PUVA, the panel decided to suggest this
considered a therapeutic option in this scenario.
intervention as first-choice, followed by UVA or UVB, based on the management of patients with palmoplantar psoriasis, as well
their clinical experience and availability. as one comparative study of MTX vs. ACT.
In one OS with 11 patients, 36% reached PGA 0–1 and
72% showed improvement in the health related quality of life
Chapter 4: Special Localizations
measurements (VLQE).110 A RCT comparing IFX vs. placebo
Jaime Martınez, Gerardo Bran Quintana, Lilia Barahona, Evelyn included 24 patients; although the PASI 75 end-point at week
Castro Vargas 14 was not achieved, at that point PPASI 75 and PPPASI 50
were achieved in 33.3 and 66.7% of patients, respectively, as
Patients with scalp psoriasis well as a 50.3% reduction in the affected area in palms and
(TD Tables 3.9.1–3.9.5) soles, compared to a 14.9% increase in the control group; and
Studies comparing ADA, ETN and UST vs. placebo and one uncertainty about the long-term impact on PPPASI 100
comparative study of ADA vs. IFX met the criteria of these (VLQE).111
CPGs to assess the efficacy of these drugs in the management A review of 44 OS comparing MTX vs. placebo showed that
of adult patients with scalp psoriasis. 75% of the patients receiving MTX reached PGA 0–1
An observational study with 663 patients showed that 68.2% (VLQE).112
of the patients treated with ADA reached PASI 75 at week 16, The results from four RCT with 127 patients in all, evaluating
and there were also large improvements in their scalp symp- SEC vs. placebo in patients with palmoplantar psoriasis show a
toms as shown by a median decrease from baseline significant increase in the probability of reaching PASI 75, PASI
PSSI of 100% (77.2 96.9%) (LQE).104 90, and PASI 100 with this biologic (HQE).51,53,113,114
The results for ETN showed a possible higher probability of The efficacy of UST was assessed through the results of an
reaching PASI 50, 75, and 90 at induction (MQE).105 OS with 20 patients: 35% reached PGA 0–1 in palms and soles
Two OS found a very rapid treatment response with UST, 4/4 and 60% achieved over 50% PGA improvement at week 16
patients showed complete remission at week 16 (VLQE).106,107 (LQE).98
The results of a RCT comparing ADA vs. IFX in patients with One RCT compared MTX vs. ACT in 111 patients with pal-
scalp psoriasis were not conclusive uncertain to support better moplantar psoriasis, randomized to receive MTX 0.4 mg/kg
results with either intervention (VLQE).108 weekly or ACT 0.5 mg/kg daily. Patients were evaluated by
modified PPPASI (m-PPPASI) score for palm and sole involve-
ment at baseline and subsequent intervals for 12 weeks.
In patients with scalp psoriasis, which should be Marked improvement (m-PPPASI 75) was achieved in 12 (24-
the first-choice treatment? %) patients treated with MTX compared with 4 (8%) in the ACT
group. There are possible no differences in the possibility of
reaching PPPASI 50 (LQE).115
The safety assessment showed data comparable to the
observations for each drug in different localizations.
Recommendation # 20
In patients with severe scalp psoriasis, the SOLAPSO

CPGs panel suggests treatment with phototherapy,
Recommendation # 21
MTX or ACT above all other alternatives.
In patients with palmoplantar psoriasis, the SOLAPSO
CPGs panel suggests to start treatment with ACT or
Comments: MTX above all other alternatives.
Scalp psoriasis is the most frequent presentation of the disease.
Only severe forms require systemic treatment.
Although evidence is limited, the panel agreed to privilege topi- Comments:
cal therapy and indicate MTX or ACT when needed.109 In the absence of reliable evidence, the panel based their sug-
The panel acknowledged that despite the available gestions on the clinical experience with the use of these drugs.
evidence, the use of biologics in this presentation is still infrequent. The comparison of MTX and ACT did not provide enough infor-
mation to prioritize one over the other.
Patients with palmoplantar psoriasis No data was found on the use of CsA for this localization.
(TD Tables 3.10.1–3.10.7) Treatment with biologics should be considered after prior treat-
Comparative studies of ADA, IFX, MTX, SEC, and UST vs. pla- ment failures, following the suggestions in the management of
cebo were found to assess the results of these interventions in patients with plaque-type psoriasis.
Patients with nail psoriasis

(TD Tables 3.11.1–3.11.5)
Comments:
To assess the efficacy of ADA, one RCT was considered com-
In the absence of high quality evidence on efficacy and long-
paring ADA vs. placebo to treat moderate to severe chronic pla-
term studies, the panel based their recommendation on clinical
que psoriasis involving the hands and/or feet.116 The trial
experience with MTX.
included 36 patients and the authors concluded that ADA is
effective in these localizations, with efficacy largely maintained
Patients with inverse psoriasis
to 28 weeks (VLQE).
(TD Table 3.13)
The efficacy of IFIX for the treatment of nail psoriasis was
To assess if there are specific considerations that might lead to
assessed through the results of a long-term phase III RCT
different therapeutic approaches of inverse psoriasis with
(50 weeks) involving 305 patients randomized 4:1 to IFX (5 mg/
respect to palmoplantar psoriasis, only one case report was
kg) or placebo at weeks 0, 2, 6, and every 8 weeks through week
identified, providing VLQE to support any intervention.119
46, with placebo crossover to IFX at week 24.117 Of the patients
Studies comparing different therapeutic choices in the treat-
receiving IFX 6.9, 26.2, and 44.7% had nail disease clearance at
ment of inverse psoriasis could not be identified.
weeks 10, 24, and 50, respectively, vs. 5.1% in the placebo group
at week 24. IFX might increase the probability of reaching total
improvement at induction (MQE) and maintenance (LQE).
To assess SEC in this localization, a phase 2 placebo-con- Recommendation # 24
trolled regimen-finding study was considered. Subjects treated
received any of 3 SEC 150-mg induction regimens either 1, 3, In patients with inverse psoriasis, the SOLAPSO CPGs
or 4 injections at different intervals. SEC showed a beneficial Panel recommends the systemic treatment alternatives
effect on psoriasis of the nails, as assessed by the composite indicated for adult patients with moderate to severe pla-
fingernail score which improved with the 3 and 4 injections que-type psoriasis (Recommendation # 1) but does not
induction regimens and worsened with placebo (LQE).113 recommend CsA and phototherapy.
One RCT designed to evaluate and compare the effi-
cacy and safety of MTX and CsA in psoriatic nail118 with
NAPSI as primary outcome included 34 patients controlled for
3 months. The mean percentages of reduction of the NAPSI
score with MTX and CsA were 43.3 and 37.2%, respectively, Recommendation # 25
showing moderate effectiveness on psoriatic nail and no sig-
In patients with inverse psoriasis, the SOLAPSO CPGs
nificant differences between both agents (LQE).
panel suggests MTX or ACT as first line interventions
Studies comparing different therapeutic choices in the treat-
above all other alternatives.
ment of nail psoriasis could not be identified.
Regarding safety, all the studies assessed were comparable
with the findings for all other localizations.
Comments:
Based on the limited available evidence, the panel considered
that the therapeutic approach of palmoplantar psoriasis and nail
Recommendation # 22 psoriasis should be similar. CsA and phototherapy were not
considered in this scenario.
In patients with nail psoriasis, the SOLAPSO CPGs
panel recommends the same systemic treatment alter-
natives indicated for adult patients with moderate to Chapter 5: Arthritis
severe plaque-type psoriasis (Recommendation # 1) Gusis, Nora Kogan
Simon
Patients with plaque-type psoriasis and predominant

joint involvement
(TD Tables 3.12.1–3.12.9)
Recommendation # 23 To define which interventions should be considered for this sce-
nario, the CPG assessed the results of the studies meeting the
In patients with nail psoriasis, the SOLAPSO CPGs inclusion criteria which compared each intervention vs. placebo
panel suggests MTX as first line therapy above all other and measured the outcomes previously defined: ACR20,
alternatives. ACR50, ACR70, PsARC, HAQ-DI, DAS28, and AE. Following is
a summary of the results assessed for each drug.
Adalimumab (TD Table 3.12.1) Ustekinumab (TD Table 3.12.7)

Two RCT with 413 patients in all120,121 showed a possible Three RCT evaluating UST vs. placebo in patients with PsA,
increase in ACR20, 50 and 70 with ADA at induction (MQE). with over 1,000 patients controlled for 12 and 24 weeks,
These results persisted up to week 24 in one of these studies, showed a probable improvement in ACR 20, 50, and 70 with
with 313 patients.121 An OS with 298 patients showed sustained UST (MQE) and improvements in PsA signs/symptoms in a
efficacy levels at 2 years follow-up, with 58.7% ACR 20, 42.7% diverse population of patients (HQE).132–134
122
ACR 50, and 29.8% ACR 70 (LQE). Severe AE were also
reported in this study with ADA (18.1%) as well as AE which Golimumab (TD Table 3.12.8)
lead to treatment discontinuation (6.7%). GOL is a human anti-TNF monoclonal antibody, which has
shown benefits in the management of patients with rheumatoid
Certolizumab (TD Table 3.12.2) arthritis. Continued clinical efficacy and safety through 1 and
CER is an anti-TNF monoclonal antibody which has shown to be 5 years was found for GOL in the RCT assessed comparing
clinically effective for the treatment of rheumatoid arthritis and is GOL 150 and 300 mg vs. placebo in 405 patients with PsA
also considered for psoriasis. One phase 3 trial in patients with (146 patients at each branch receiving GOL and 113 patients in
psoriatic arthritis showed that CER could be effective to reach the control group) (LQE).135,136
123
ACR 20, 50, and 70 (M/HQE). The authors reported that
ACR20 response at week 12 was significantly higher in the Apremilast (TD Table 3.12.9)
group of patients receiving CER 200 mg every 2 weeks and APM is an oral phosphodiesterase 4 inhibitor (PDE4). The results of 5
400 mg every 4 weeks (58.0 and 51.9%, respectively vs. 24.3% RCT evaluating APM vs. placebo in over 1,400 patients showed
in the control group). The study also showed a probable higher improvement in ARC 20 at 16 and 24 weeks, as well as the probability
probability of improved quality of life as measured by HAQ-DI of sustained clinical efficacy through 1 year of treatment (M/HQE).
( 0.50 CER vs. 0.19 placebo) and PsARC at week 24 (MQE). Improvement in quality of life as measured by HAQ-DI was also
reported, although the clinical significance of these results is uncertain
Etanercept (TD Table 3.12.3) (HQE).137–143
The results of the RCT assessed showed probable improve-
ment with ETN at 12 and 24 weeks follow-up (MQE) and proba-
ble improvement in quality of life (LQE).124–126
Recommendation # 26
Infliximab (TD Table 3.12.4)
In patients with plaque-type psoriasis and predominant
The results of two RCT with 304 patients showed a possible
joint involvement, the SOLAPSO CPGs panel recom-
increase in ACR 20, 50, and 70 at induction (LQE) and a
mends the following agents as therapeutic alternatives:
probable improvement in quality of life (clinically meaningful
ADA, APM, CER, ETN, GOL, IFX, MTX, SEC, and UST
improvement in HAQ; ~0.3 unit decrease) at week 14
(drugs listed alphabetically).
(MQE).127,128
Methotrexate (TD Table 3.12.5)

Comments
The results of one RCT were assessed to evaluate MTX vs.
Although APM is not available in Latin America, the panel con-
placebo in PsA. This was a 6-month double-blind RCT compar-
sidered the value of the results assessed and the experience
ing MTX (15 mg/week) with placebo in 221 patients with active
with the use of this drug.
PsA; the primary outcome was PsARC. The study provided
129 The panel notes that CER and GOL have not been approved
LQE to support MTX as a disease-modifying drug in PsA.
for the treatment of skin psoriasis.
Secukinumab (TD Tables 3.12.6.1–3.12.6.3)

Two RCT evaluating the efficacy of SEC 75, 150, and 300 mg
vs. placebo were included to assess the effectiveness of this In patients with plaque-type psoriasis and predomi-
biologicin the treatment of PsA. With a total of 1,000 patients nant joint involvement, which should be the first-
and 24 weeks follow-up, the results of these studies showed choice treatment?
the probable efficacy of SEC in improving ACR 20, 50, and 70
(M/HQE). Higher doses schemes showed even better results. In
To answer this question, the results of trials meeting the
the safety profile assessment, a probable increase in AE was
inclusion criteria of these CPGs comparing ETN vs. ADA, ETN
found for SEC after 52 weeks follow-up in PsA patients
vs. IFX, and MTX vs. CsA were considered. The evaluation
(LQE).130,131
was completed with the results of each intervention compared patients who have specific counter-indication for treatment with
with placebo. nonbiologics.
ETN vs. ADA vs. IFX (TD Tables 3.12.10 y 3.12.11)

One RCT compared the efficacy and safety of ETN vs. ADA vs. In patients with plaque-type psoriasis and predomi-
IFX in patients with PsA with inadequate response to a previous nant joint involvement who are started on biologics
DMARD (INF 5 mg/Kg every 6–8 weeks, ETN 50 mg weekly, or (either as first or second line therapy), which
ADA 40 mg every other week, or placebo). Efficacy was defined should be the first-choice treatment? (TD Tables
as the percentage of ACR20 responders and as clinical remis- 3.12.10, 3.12.11)
sion and/or minimal disease activity at 12 months treatment.
Possible no relevant differences in ACR 20 were found among
all the interventions evaluated. No differences were observed in To answer this question, the results of a study comparing
HAQ and there is uncertainty about the impact of all three ETN vs. ADA vs. IFX were considered144 and the assessment
agents on this efficacy parameter (LQE).144 was completed by also considering the results of the studies
evaluating each agent vs. placebo.
MTX vs. CsA (TD Table 3.12.12)
Two RCT comparing MTX vs. CsA in PsA found similar efficacy
of both agents to improve PsA signs/symptoms as measured by
DAS 28 (LQE).145,146 Recommendation # 29
In patients with moderate to severe plaque-type psoria-

sis and joint involvement who are started on therapy
with a biological agent, the SOLAPSO CPGs panel sug-
Recommendation # 27
gests anti–TNF (ADA, ETN, INF), CER, GOL or anti-IL-
In patients with plaque-type psoriasis and predomi- 12/23 above SEC or APM.
nant joint involvement, the SOLAPSO CPGs panel
suggests treatment with nonbiological drugs as
first-choice. Comments:
The recommendation of one biologic over the others is based on
the currently available information about long-term efficacy and
safety.
Which biological to choose should be decided considering the
cutaneous involvement, assuming that the effect on the skin is
Recommendation # 28 heterogeneous.
All agents may be used in patients without skin involvement;
In patients with plaque-type psoriasis and predominant
CER and GOL should only be considered in patients with minor
joint involvement who are started with a nonbiological,
skin involvement.
the SOLAPSO CPGs panel suggests MTX above all
other alternatives.
Chapter 6: Considerations about Routes of
Administration, Co-morbidities, and Adverse
Comments: Effects of Biologicals
In the absence of comparative studies between biological and
Patricia Levrero, Orestes Blanco Gonzalez
nonbiological agents, the panel weighed the experience with the
use of nonbiologics, their wide availability, the information on
In patients with plaque-type psoriasis who discontinue
long-term safety and their low cost. Suggesting MTX as first-
an effective treatment, which should be the next
choice is based on the experience with this drug compared with
choice? (TD Table 3.14.1)
other nonbiologics (DMARDS), considering that the evidence
currently available does not show the superiority of any agent.
In treatment failures, all other alternatives should be consid-
The information of cohorts of patients who interrupted their
ered.
treatments and the response rates after restart was considered
Treatment with biological drugs as first-choice is suggested for
as first end-point to assess this decision. All studies identified
those patients who prioritize short-term effectiveness and
provided HQE for re-treatment with each intervention.
The results found by Gottlieb et al.147 in two OS with 123 treatment.150 Griffiths et al.151 found 90% response (PGA < 2)
patients showed that 67% of patients reached PASI 75 at week after treatment with ETN.
26 with IFX 10 mg/kg and 87.9% at week 10 with IFX 5 mg/
kg.45 One study using ADA reported effectiveness (76% of
patients reaching PGA 0–1), similarly to one using UST (85.6%
Recommendation # 30
reaching PASI 75).58,148
Three OS were found to assess ETN in this scenario, their In patients with moderate to severe plaque-type psoria-
results are consistent to suggest that ETN is effective in re- sis who interrupt an effective therapy, the SOLAPSO
treatment. Gordon et al. did not find differences in PASI with CPGs panel recommends to resume the scheme,
ETN as initial therapy or as re-treatment.149 Moore et al., except in the case of patients who discontinue therapy
reported PGA < 2 in 72% of responders at week 12 and 59% at with IFX, who should be shifted to a different drug.
week 24, and significantly better results at week 24 in continued
Table 3 Risk factors for complications in the treatment of psoriasis
Interpretation Quality Source
Psoriatic Psoriatic arthritis could increase the risk of infections LQEa Prospective cohort studies (PSOLAR registry) and
arthritis retrospective.28,153–155
Metabolic No studies could be identified – –
syndrome
Diabetes Diabetic patients could be at a higher risk of infections LQEa Prospective cohort studies (PSOLAR registry).153
Previous severe The risk of severe infection could be higher in patients with a LQEa Prospective cohort studies (PSOLAR registry).153
infections history of previous severe infections.
Tuberculosis The risk of TB reactivation could probably be higher in patients LQEb Randomized studies and prospective cohorts suggest
with a history of TB that treatment with biologics increases the risk of
reactivation.27,151,156
Cardiovascular Patients with a history of cardiovascular disease are LQEa Prospective cohort studies (PSOLAR registry).153
disease significantly at a higher risk of cardiovascular events
Liver disease The risk of hepatic fibrosis is higher in patients with a history of VLQEa,c Prospective cohort studies.153,157
liver disease when treated with MTX.
Possible higher risk of severe adverse effects in patients treated
for their psoriasis with or without biologics
Hepatitis B or C Previous hepatitis B could lead to psoriasis reactivation with VLQEa,c,d Series of cases, prospective cohort studies.154,157,158
treatment. Hepatitis B or C could be associated with an
increased risk of severe adverse effects
Mental No studies were identified – –
disorders or
diseases
Neurologic No studies were identified – –
disease
Chronic renal The risk of severe adverse effects could be higher in patients VLQEa,c Prospective cohort studies.159,160
disease with chronic renal disease
Respiratory No studies were identified – –
disease
Gastrointestinal No studies were identified – –
diseases
History of The risk of malignancy is significantly higher in patients with LQEa Prospective cohort studies (PSOLAR
neoplasias neoplasia registry).28,153,160
HIV HIV infection would not increase the risk of severe adverse VLQEa,c Prospective cohort studies.155
effects
a
Correlation identified in observational studies.
b
Despite the relation between latent TB and reactivation has been well shown, the increased risk with biologic treatment is uncertain (LQE)
due to the limited number of events.
c
The limited number of events results in wide CI which include the possibility of absence of harms.
d
Inconsistency in the results.
Comments: registry28,153 with 12,095 participants, which suggest a possible

The panel considered that patients who discontinue an effec- increase in the risk of infections with IFX and ADA and a possi-
tive treatment course should restart therapy with the same ble absence of increased risk of cancer or cardiac events. ADA
drug, which has already proved to be effective and safe for and IFX could increase the incidence of severe infections as
the patient; this decision should also be regarded as a means compared to the other therapeutic alternatives, with an inci-
for not to disregard valid therapeutic alternatives. dence of 1.45 each 100 patients per year (LQE).
The recommendation about avoiding re-treatment with IFX This finding is somehow inferior in the PsoBest Registry161
was based on the probability of severe reactions to infusion. with 2,699 patients at 1 year: 0.56 severe infections each 100
patients per year and no differences as compared with nonbio-
logicals (LQE).
Which is the best administration scheme for biolog-
ics in patients with moderate to severe plaque-type
About the use of these CPGs
psoriasis? (TD Table 3.18.1)
These CPGs summarize the judgment of the group of experts
convened by SOLAPSO and includes recommendations which
Two RCT were considered, evaluating the efficacy and safety have been agreed after a careful assessment of the evidence,
of continued vs. intermittent administration of IFX in over 500 in the expectation that they may become a useful reference
patients with moderate to severe plaque-type psoriasis who standard in clinical practice.
were followed up through 52 weeks. The results show that there Under no circumstances should these recommendations
is a higher probability of reaching PASI 75, PASI 90, PGA 1–2 replace the criteria of the treating physician about a therapeutic
and improving quality of life with continuous treatment decision based on each patient and circumstance, as well as on
(MQE). 46,152 the values, the preferences and the opinions of the patient or
caregivers.
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Recommendation # 31
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Review

Latin American Clinical Practice Guidelines on the Systemic

Table 1 GRADE’s approach to rating quality of evidence

Indirectness All plausible

Table 2 GRADE System: direction and strength of recommendations

Strong recommendation Weak recommendation

who summarized the evidence and provided additional

Secukinumab (TD Table 3.1.8) Ustekinumab (TD Table 3.1.9)

To assess whether biological vs. nonbiological drugs should Recommendation # 2

comparisons meta-analysis, where no significant differences

Which is the best treatment scheme for adult

In adult patients older than 65 years of age with moder-

AE with ETN, MTX, and ADA in children may be comparable

In patients with erythrodermic psoriasis, which

In children with moderate to severe plaque-type psoria-

Chapter 3: Clinical Presentations In adult patients with erythrodermic psoriasis the

In patients with guttate psoriasis the SOLAPSO CPGs

Recommendation # 18 In patients with palmoplantar pustular psoriasis pho-

In patients with severe scalp psoriasis, the SOLAPSO

Patients with nail psoriasis

Patients with plaque-type psoriasis and predominant

Adalimumab (TD Table 3.12.1) Ustekinumab (TD Table 3.12.7)

Methotrexate (TD Table 3.12.5)

Secukinumab (TD Tables 3.12.6.1–3.12.6.3)

ETN vs. ADA vs. IFX (TD Tables 3.12.10 y 3.12.11)

In patients with moderate to severe plaque-type psoria-

Table 3 Risk factors for complications in the treatment of psoriasis

Interpretation Quality Source

Comments: registry28,153 with 12,095 participants, which suggest a possible

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