SOLAPSO

Latin American Clinical Practice Guidelines on the Systemic
Treatment of Psoriasis

SOLAPSO – Sociedad Latinoamericana de Psoriasis
(Latin American Psoriasis Society)

Nora Kogan¹, Nélida Raimondo ², Simon E. Gusis³, Ariel Izcovich⁴, Jorge A. Abarca Duran⁵, Lilia Barahona-Torres⁶, Orestes Blanco⁷, Gerardo B. Quintana⁸, María C.Briones⁹, Carla Castro¹⁰, Evelyn G. Castro Vargas¹¹, Juan Criniti¹², Juan C. Diez de Medina¹³, Manuel Franco¹⁴, Minerva Gómez ¹⁵, Veronica P. Levrero¹⁶, Jaime E. Martínez López¹⁷, and Fernando Valenzuela¹⁸

Methodology

Ariel Izcovich Ariel, Juan Martín Criniti
The CPGs have been prepared following the recommendations of the Methodology Manual for the Development of Clinical Practice Guidelines by the UnderSecretary of Public Health of the Government of Chile, using the GRADE system (Grading of Recommendations Assessment, Development and Evaluation) to assess the quality of the evidence, to produce evidence summaries and translate them into recommendations.

2The GRADE system clearly distinguishes between the quality of the evidence and the strength of the recommendation, and explicitly evaluates the relevance of the outcomes.

Recommendations are produced through a transparent process incorporating patients values and preferences, acceptability, feasibility and resource considerations.3,4 The authors of these CPGs convened by SOLAPSO are experts from several countries in the region and a team of methodologists who searched and organized the evidence.

Questions were collected following the PICO structure to guide the literature search. Two CPGs on psoriasis developed under adequate standards of literature searches were identified and all citations in these CPGs found to be relevant to the purpose of our study were assessed.5,6 A supplementary search of systematic reviews, randomized trials, and observational studies was performed in MEDLINE, Epistemonikos, Cochrane library, LILACS, and Google Scholar with temporal restriction (2012–2015). The search term in all cases was “Psoriasis.”

Relevant information was extracted in ad hoc tables; evidence summaries were prepared for each comparison and each scenario following the GRADE Working Group suggested criteria.7,8 To reach a consensus on each recommendation, the authors considered the balance between benefits and risks, the quality of the evidence, the values and preferences of the patients, as well as costs and other practical issues.

PICO Questions

Questions were selected by consensus of the authors and were based on the questions included in other CPGs on Psoriasis.5All questions were framed using PICO (Population, Intervention, Comparison, Outcome):

Populations

1 Moderate to severe plaque-type psoriasis adult patients.
2 Moderate to severe plaque-type psoriasis pediatric patients.
3 Moderate to severe plaque-type psoriasis adult patients over 65 years old.
4 Moderate to severe plaque-type psoriasis in pregnant or breastfeeding patients.
5 Patients with guttate psoriasis.
6 Patients with erythrodermic psoriasis.

CPG as Tables in the Technical Document (TD) which can be accessed in the online Supplementary Information article.
One table was prepared for each comparison in every clinical scenario. When possible, meta analysis were performed to assess the results of all trials evaluating the same comparison and measuring the same outcome, using Review Manager (RevMan) [Computer program] Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014 Maentel-Haenzel statistical method and random analysis model were used for dichotomous outcomes.
Inverse variance and random analysis model were used for continuous outcomes. Summary of findings (SoF) tables were prepared using the Guideline Development Tool (www. guidelinedevelopment.org). All the SoF tables are presented in the technical document (TD).

Rating the quality of evidence

The quality of the evidence was rated using the GRADE system as summarized in Table 1. For further information on GRADE please refer to http://www.gradeworkinggroup.org/

Assessing resources and costs

Resources and costs were considered informally. No economic evaluations were performed for these CPGs.

Patients values and preferences

In all recommendations, the authors considered the values and preferences of patients for each scenario and comparison based on their clinical experience.
Strong recommendations could only be made in those
scenarios and comparisons where significant variability in the values and preferences of patients was assumed as unlikely.

Producing and formulating recommendations

The panel discussed the SoF tables and analyzed the
information considering other aspects as already mentioned (values and preferences of the patients, costs, resources and implementation issues, among others).
Judgments by the panel regarding each of those aspects were recorded in evidence to decision frameworks as recommended by GRADE.
Each recommendation was reached by consensus of the
authors and written following the GRADE system structure direction (for or against) and strength (strong or weak). The direction and strength of recommendations were expressed as: “The SOLAPSO CPGs Panel recommends …” (strong, for); “… suggests…” (weak, for); “… does not recommend” (strong, against); “… does not suggest” (weak, against) (Table 2). In cases where consensus could not be reached, the direction and strength of the recommendation were decided by voting. For practical reasons, the CPGs have been organized in Chapters, each of which was assigned to one or more authors

 hree studies met the criteria of these CPGs to assess the efficacy and the safety of MTX in the management of adult patients with moderate to severe.^19–21 For the efficacy evaluation, several studies have shown that MTX is probably related to increased probability of reaching PASI 75 and PGA 0–1 (MQE).

In the CHAMPION study,²¹ MTX was compared to placebo in 163 patients, of which 110 received MTX 7.5 mg oral with dose increased as needed and as tolerated to 25 mg weekly for 16 weeks. After 16 weeks, 35.5% of MTX-treated patients achieved PASI 75 vs. 18.9% in the control group.

In one RCT comparing MTX vs. placebo, the mean PASI change from baseline showed an improvement of 73.9% with MTX and 32.0% in the placebo group at month ^6.19No significant AE were identified in the results assessed,²¹ although a meta-analysis of 32 RCT including 13,177 patients²² who received MTX for different rheumatological conditions informed an increase in the risk of hepatic AE (HQE). This
meta-analysis included studies carried out from 1990 to 2014 and was aimed at assessing the relative risk and severity of the hepatic damage in patients treated with MTX. The results of these 32 studies showed that MTX was related to higher total
risk of hepatic AE but not higher risk of hepatic failure, cirrhosis or mortality were found.

Biologics (in alphabetical order)

Adalimumab (TD Table 3.1.2)
ADA is a recombinant human immunoglobulin G1 (IgG1) monoclonal antibody containing only human peptide sequences and used since 2007 in the treatment of psoriasis. It is administered subcutaneously.

Seven RCT comparing ADA vs. placebo met the criteria of these CPGs and were included for efficacy and safety assessment.^{20,21,23–27} Three of these studies – which included about 1,500 patients– informed a significant increase in the probability
of achieving PGA 0, PASI 75, PASI 90, and PASI 100 both at induction and at maintenance (MQE).^21,25,26 In a multicentric, randomized, double-blind, placebo-controlled study, 147 patients received ADA (40 mg every other week or 40 mg/ week) or placebo. At week 12, 53% of patients on ADA every
other week, 80% of patients on ADA weekly, and 4% of the control group achieved PASI 75.²⁶ In another 52-week, multicenter study of 1,212 patients randomized to receive ADA (40 mg) or placebo every other week for the first 15 weeks, 71% of the ADA group of patients reached PASI 75 at week 16, vs. 7% of the placebo-treated patients.²⁵

 In terms of quality of life, a possible clinically relevant  improvement with ADA measured by DLQI was shown (LQE). One RCT assessed the impact of ADA on health-related quality of life in 84 adult patients with moderate to severe psoriasis treated with ADA 80 mg every other week and in 87 patients who received ADA 40 mg, one weekly injection throughout

results at week 24, 54, and 45% PASI 75 in each group of patients, respectively.

Three studies including 1,003 patients evaluated the
effect of ETN on quality of life, showing possible significant improvement. Krueger et al in a multinational, randomized, phase III trial, evaluated 583 patients (193 received placebo, 196 ETN 50 mg per week, and 194 ETN 50 mg twice a week during the initial 12-week, double-blind period. Thereafter, all patients received ETN 50 mg per week). At week 12, in 72–77% of the patients receiving ETN improvement in DLQI was clinically meaningful (≥5-point improvement or 0 score).

Regarding the safety profile of the drug, the results of 28 RCT including 6,174 patients show that ETN is a safe drug. Some studies relate ETN with a probable marginal increase in the risk of AE (MQE) and TB reactivation (HQE).

Infliximab (TD Table 3.1.6)

IFX is a monoclonal antibody that works against TNF-a. It is administered intravenously and has been in use to treat psoriasis since 2005.
Ten RCT were included in the present CPGs in which IFX safety and efficacy was assessed.
The efficacy assessment showed that IFX increases the probability of reaching PASI 75, 90, 100 and improving quality of life both at induction as well as at maintenance therapies (M/HQE).

To show the role of anti-TNFa in the pathogenesis of psoriasis, a double-blind RCT assessed the clinical benefit and safety of IFX against anti-TNFa in 33 patients with moderate to severe plaque psoriasis who were randomly assigned to intravenous placebo, IFX 5 mg/kg, or IFX 10 mg/kg at weeks 0, 2, and 6. Patients were assessed at week 10 for PGA; 3 patients had dropped out; 9/11 (82%) patients in the IFX 5 mg/kg group were responders (good, excellent, or clear rating on PGA), compared with 2/11 (18%) in the placebo group and 10/11 (91%) patients in the IFX 10 mg/kg group.

Gottlieb et al. evaluated 249 patients with severe plaque psoriasis in a multicenter, double-blind, placebo-controlled trial, randomly assigned to receive IFX 3 or 5 mg/kg intravenous infusions or placebo given at weeks 0, 2, and 6. At week 10,72% of patients treated with IFX 3 mg/kg and 88% of patients treated with IFX 5 mg/kg achieved PASI 75 compared with 6% of patients treated with placebo. PASI 90 was observed in 58% of the patients in the IFX 5 mg/kg group, 46% in those receiving 3 mg/kg and 2% for placebo. To assess the duration of the response, patients were followed up for 20 weeks after the last induction infusion; at week 20, 33% of the patients receiving IFX 5 mg/kg were still at PASI 75.

In the EXPRESS phase III, multicenter, double-blind trial, 301/378 patients with moderate to severe plaque psoriasis received IFX 5 mg/kg infusions or placebo at weeks 0, 2, and 6, then every 8 weeks to week 46. At week 10, the proportion of

4.9% with placebo. Similar results in PASI 75 at 12 weeks have been reported by other authors.

The assessment of response over time in the ERASURE study showed that 80.5% of the patients in the SEC 300 mg treatment group maintained PASI 75 at week 52 and 72.4% of those in SEC 150 mg. In the FIXTURE study, these rates were 84.3 and 82.2%, respectively.

The quality of life results assessment showed higher probability of significant improvement with SEC (HQE). The proportion of patients with a DLQI score of 0 or 1, indicating no impairment of health-related quality of life, was significantly higher at week 12 in each SEC-dose group than in the placebo group and showed similar absolute improvement variations in both groups (10.1 with SEC 150 mg and 11.4 with SEC 300).

The safety results of 5 RCT with 1,716 patients showed a probable marginal increase of severe AE and possible no higher risk of major cardiovascular events with SEC (M/LQE). Nasopharyngitis, headache, upper respiratory tract infection, and diarrhea were among the most frequent AE. The incidence of reactions at the injection site was low. Some infections, particularly Candida sp. were observed at the induction treatment period. Grade 3 neutropenia occurred in 9 patients receiving SEC (1.0%) and one patient receiving ETN (0.3%) developed grade 4 neutropenia.

Ustekinumab (TD Table 3.1.9)

UST is a human monoclonal antibody directed against IL-12 and IL-23, and has been used for the treatment of psoriasis since 2008.

The results of 5 RCT with 2,596 patients were considered for the efficacy assessment and showed a higher probability of achieving PASI 75, 90, and 100 with UST both at induction and at maintenance, and that the drug is also probably related to a significant increase in the quality of life of these patients (HQE).

Two long-term phase III, double-blind, placebo-controlled studies: PHOENIX 1 (Leonardi et al., 766 patients, 76 weeks) and PHOENIX 2 (Papp et al., 1,230 patients, 52 weeks) evaluated UST in two dose regimens: 45 mg and 90 mg at weeks 0 and 4 and then every 12 weeks. The primary endpoint was the
proportion of patients achieving PASI 75 at week 12: 67.1– 66.7% with UST 45 mg in PHOENIX 1 and 2, respectively, and 66.4–77.5% with UST 90 mg in PHOENIX 2. In PHOENIX 1, at week 40, patients were randomly assigned to maintenance UST or withdrawal. PASI 75 response was better maintained to at least 1 year in those receiving maintenance UST than in those withdrawn from treatment.

For the quality of life assessment, the results of 5 RCT with 1,836 patients were considered. All of these studies measured DLQI at induction and showed a probable improvement in quality of life; absolute score decrease in treated patients was 8.24 points higher (7.24–9.24) than in the control groups
(MQE).

ACT vs. ETN (TD Table 3.1.11)

The results of two RCT including 102 patients were assessed to compare the efficacy and safety of ACT vs. ETN suggesting that ETN could be superior than ACT in achieving PASI 75 at induction (LQE). There is uncertainty about the possibility of differences in the long term between both drugs (VLQE). No AE
were reported in these studies.

ADA vs. MTX (TD Table 3.1.14)

One RCT with 218 patients showed better results with ADA in 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-treated patients (7.3%) achieved complete clearance of disease. MTX might be related to an increased risk of severe AE leading to study discontinuation (LQE).

IFX vs. MTX (TD Table 3.1.17)

The results of one RCT including 868 MTX-na€ıve patients (RESTORE 1) 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 (LQE).

Patients were randomized 3:1 to receive IFX 5 mg/kg at weeks 0, 2, 6, 14, and 22 or MTX 15 mg weekly with a dose increase to 20 mg weekly at week 6 for patients with PASI < 25 or switch at week 16 for patients with PASI < 50. The efficacy endpoints were PASI 75 and PGA 0–1 at weeks 16 and 26. PASI 75 was achieved by a significantly greater proportion of IFX-treated patients (78%) than MTX-treated patients (42%). Key secondary endpoints also were achieved by a greater proportion of IFX-treated patients. Similar responses were observed at week 26 in patients who switched from MTX to IFX at week 16. The safety assessment showed that IFX could be associated with a higher risk of severe AE leading to treatment discontinuation (LQE). The overall incidence of AE was comparable among the groups, with a mild increase of serious and severe AE in IFX-treated patients.

ETN vs. SEC (TD Table 3.1.18)

In the FIXTURE Study, with 973 patients, SEC showed better results than ETN in PASI 75, 90, 100 outcomes and in the evaluation of quality of life both at induction and maintenance (M/HQE). 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 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, 27.2% with ETN. In the evaluation of the response over time, the rates according to PASI 75, PASI 90, PASI 100, and PGA 0–1 were higher with SEC than with ETN through week 52: 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).

ETN vs. UST (TD Tables 3.1.20.1 y 3.1.20.2)

The results of one RCT with 903 patients showed that UST is probably superior to achieve PASI 75, 90, 100 at the induction phase (MQE).

In this study, Griffiths et al. compared UST and ETN randomly assigning patients to one of three treatment groups; UST at a dose of 45 or 90 mg at weeks 0 and 4 or ETN at a dose of 50 mg twice weekly for 12 weeks. At week 12, a total of 67.5% of patients who received 45 mg of UST and 73.8% of patients who received 90 mg of UST had at least 75% improvement in the PASI score, as compared with 56.8% of those who received ETN. The proportion of patients who reached PGA 0–1 at week 12 was also significantly higher in each UST group: 65.1% with UST 45 mg, 70.6% in UST 90 mg vs. 49.0% of patients who received high-dose ETN. 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 discontinuation (MQE).

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 responses. Better results were also obtained with SEC at induction in the health-related quality of life evaluations (HQE). In this 52-week, double-blind study 676 subjects were randomized to receive SEC 300 mg subcutaneous injection or UST per label. Primary end point PASI 90 was achieved in 79.0% of patients treated with SEC in comparison with 57.6% of those receiving UST. The 100% improvement from baseline PASI score at week 16 was also significantly greater with SEC (44.3%) than UST (28.4%). Percentage of subjects with the DQLI score 0/1 at week 16 was significantly higher with SEC (71.9%) than UST (57.4%). The safety profiles of both drugs were comparable, there

Comments:
The panel valued the evidence on the efficacy of biologics as second line treatment in patients previously exposed to these agents, and considered that there is insufficient data to decide which biological agent should be indicated in the event of a prior failure.

(TD Tables 3.3.1–3.3.3)

Seven studies met the criteria of these CPGs to evaluate the efficacy and safety of the interventions in treating adult patients over 65 years of age with moderate to severe plaque-type psoriasis and to compare differences in treatment results between adult patients younger or older than 65 years of age. The results assessed, including three observational studies with ADA and one RCT 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 related with a higher risk of AE in older adults (LQE).

Comments:

In the light of the limited evidence available for this group of patients, the panel considered that the treatment options assessed are probably similarly effective in adult patients younger or older than 65 years of age, although a marginal increase of AE could occur among the latter. Special attention should be given by the treating physician to comorbidities in patients older than 65 years of age, particularly those counter-indicating some drugs as CsA in nephrosclerosis (see 13.2).

Two placebo-controlled RCT, one with ETN (211 patients), another with UST (110 patients) and two observational studies evaluating MTX in children. Both drugs are probably comparable to achieve the outcomes PASI 75, 90, and 100 and also to improve health related quality of life at induction (MQE).

The trial assessing long-term efficacy of this drug in children with moderate to severe plaque-psoriasis aged 4–17 related ETN to a probable significantly higher probability of reaching PASI 75, 90 and PGA 0–1 at 12 weeks, and also probably higher probability of improved health related quality of life, as measured by DLQI scale (MQE). In a 48-week double-blind trial by Paller et al., 211 children with psoriasis aged 4–17 were initially randomly assigned to ETN
0.8 mg/kg/day (maximum dose 50 mg) or placebo 1 daily subcutaneous 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 proportion of the patients in the ETN group had PASI 50 (75% vs. 23%), PASI 90 (27% vs. 7%), and PGA 0–1 was 53% vs. 13%.

In the long-term follow-up study responses at week 96 were similar to those observed in the double-blind trial: PASI 50, 89%; PASI 75, 61%; PASI 90, 30% nd PGA 0–1 in 47% of patients. AE were reported in 80.1% of cases: upper tract respiratory infections 24.9%, nasopharyngitis 17.1%, streptococcal pharyngitis 12.7%, acne 11.6%, sinusitis 10.5%; there were two withdrawals related to AE.
The two OS assessing MTX vs. placebo in 37 patients found good treatment response at induction and maintenance phases and reported AE: increased transaminases 24%; gastrointestinal symptoms 40%, oral ulcers 3%, night cough and leg pain 3% (VLQE).

In the phase III CADMUS study, Landells et al. evaluated UST in 110 patients aged 12–17 years who had moderate to severe plaque-type psoriasis. High-quality evidence showed increased probability of achieving all the percent improvement end-points assessed.

Patients were randomly assigned to UST standard dosing or 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 branch with UST. At week 12, 67.6 and 69.4% of patients receiving UST (standard of half-standard, respectively) achieved PGA 0–1 vs. 5.4% for placebo. Significantly greater proportions receiving UST achieved PASI 75 (78.4, 80.6, 10.8%) or PASI 90 (54.1, 61.1, 5.4%) (UST standard dosing, half-standard dosing or placebo, respectively).

Comments:

In the absence of evidence supporting that the efficacy and safety of the available therapeutic alternatives might be different in children and adults, the panel agreed to make the same recommendations (see 1.1).

No studies comparing biological agents in children were identified. In the absence of specific evidence to answer this question, the panel decided to refer to the evidence assessed for the same question in adult patients.

Comments:

The panel acknowledges that age (besides history and comorbidities) is a relevant factor at the time of indicating a biological agent The panel emphasizes that special consideration should be given to reduce the burden of the treatment in children whenever possible.
In patients who strongly value short term effectiveness or treatment burden (less number of injections) it might be preferable to start therapy with Anti IL 12-23 or Anti IL 17.

Trials comparing different biological agents in the treatment of children with psoriasis were not identified. In the absence of specific evidence to answer this question, the panel decided to use indirect information from the same scenario in adult patients.

the panel decided to consider all the drugs that showed beneficial effects in published studies in which patients with erythrodermic psoriasis were treated.

No studies comparing the different therapeutic alternatives for the management of patients with erythrodermic psoriasis were found.

Comments:

In the absence of comparative studies the panel weighed the pharmacodynamic properties of CsA and IFX which appear as first choice therapy, based on their rapid action which is essential for these patients.

Patients with guttate psoriasis

(TD Tables 3.5.1–3.5.3)
The results of one RCT comparing penicillin or erythromycin for 14 days with a placebo or rifampin added during the last 5 days of treatment show no apparent benefit for the patients in improving their psoriasis (VLQE). In assessing the effect of tonsillectomy in these patients, the authors reported total remission results in 9/10 patients and no AE (VLQE).

Comments:

The panel considered the results of small studies evaluating antibiotics and tonsillectomy plus other pathophysiologic grounds.
The NBUVB suggestion as first line option, as well as MTX or RE, were based on the clinical experience of the panel members, since evidence in this particular scenario is scarce.

Exploring alternative differential diagnosis is recommended, to discard other auto inflammatory pustular diseases (DITRA) generally treated with anti-IL-1 drugs.
In adult patients showing patterns of generalized pustular psoriasis of subacute presentation ACT may be considered an alternative to the agents suggested.

Patients with palmoplantar pustular psoriasis

(TD Tables 3.8.1–3.8.5)
We assessed the results of a systematic review of RCTs including patients with chronic palmoplantar pustular psoriasis randomized to receive one or more interventions.
The review included 23 trials and 724 people. The studies comparing CsA and UST vs. placebo, PUVA and retinoids, alone or in combination found a possible significant improvement with CsA persisting after 12 months in one RCT with 58 subjects (LQE). The use of systemic retinoids and PUVA appears as a valid alternative; however, a combination of both was better than the individual 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).
Considering that phototherapy is one of the most frequent interventions for this localization, the results of studies evaluating NBUVB vs. PUVA were also assessed. 3 One RCT with 50 patients 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).
One patient at this study had a phototoxic reaction with PUVA; palmar hyperpigmentation was found in 52% of the patients. No serious AE were reported in all the other assessed studies.
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 response rates with IFX and lack of response with CsA (VLQE).

Comments:

In the absence of evidence on the efficacy of biologics in the management of patients with palmoplantar pustular psoriasis, except for the results of one report with UST in adult patients, considering that phototherapy is usually indicated to treat these patients and also considering the efficacy, administration and less AE observed in clinical practice with PUVA, the panel decided to suggest this intervention as first-choice, followed by

In one OS with 11 patients, 36% reached PGA 0–1 and 72% showed improvement in the health related quality of life measurements (VLQE). A RCT comparing IFX vs. placebo included 24 patients; although the PASI 75 end- oint at week 14 was not achieved, at that point PPASI 75 and PPPASI 50 were achieved in 33.3 and 66.7% of patients, respectively, as well as a 50.3% reduction in the affected area in palms and soles, compared to a 14.9% increase in the control group; and uncertainty about the long-term impact on PPPASI 100 (VLQE).
A review of 44 OS comparing MTX vs. placebo showed that 75% of the patients receiving MTX reached PGA 0–1 (VLQE). ACT.

The results from four RCT with 127 patients in all, evaluating SEC vs. placebo in patients with palmoplantar psoriasis show a significant increase in the probability of reaching PASI 75, PASI 90, and PASI 100 with this biologic (HQE).
The efficacy of UST was assessed through the results of an OS with 20 patients: 35% reached PGA 0–1 in palms and soles and 60% achieved over 50% PGA improvement at week 16 (LQE).
One RCT compared MTX vs. ACT in 111 patients with palmoplantar psoriasis, randomized to receive MTX 0.4 mg/kg weekly or ACT 0.5 mg/kg daily. Patients were evaluated by modified PPPASI (m-PPPASI) score for palm and sole involvement at baseline and subsequent intervals for 12 weeks.
Marked improvement (m-PPPASI 75) was achieved in 12 (24- %) 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).
The safety assessment showed data comparable to the observations for each drug in different localizations.

Comments:

In the absence of reliable evidence, the panel based their suggestions on the clinical experience with the use of these drugs. The comparison of MTX and ACT did not provide enough information to prioritize one over the other.
No data was found on the use of CsA for this localization. Treatment with biologics should be considered after prior treatment failures, following the suggestions in the management of patients with plaque-type psoriasis.

Comments:

In the absence of high quality evidence on efficacy and long term studies, the panel based their recommendation on clinical experience with MTX.

Patients with inverse psoriasis

(TD Table 3.13)
To assess if there are specific considerations that might lead to different therapeutic approaches of inverse psoriasis with respect to palmoplantar psoriasis, only one case report was identified, providing VLQE to support any intervention.
Studies comparing different therapeutic choices in the treatment of inverse psoriasis could not be identified.

Comments:

Based on the limited available evidence, the panel considered that the therapeutic approach of palmoplantar psoriasis and nail psoriasis should be similar. CsA and phototherapy were not considered in this scenario.

Chapter 5: Arthritis

Simon Gusis, Nora Kogan

Patients with plaque-type psoriasis and predominant joint involvement
(TD Tables 3.12.1–3.12.9)

To define which interventions should be considered for this scenario, the CPG assessed the results of the studies meeting the inclusion criteria which compared each intervention vs. placebo and measured the outcomes previously defined: ACR20, 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)
Two RCT with 413 patients in all showed a possible increase in ACR20, 50 and 70 with ADA at induction (MQE). These results persisted up to week 24 in one of these studies, with 313 patients. An OS with 298 patients showed sustained efficacy levels at 2 years follow-up, with 58.7% ACR 20, 42.7% ACR 50, and 29.8% ACR 70 (LQE).

Comments:

In the absence of high quality evidence on efficacy and long term studies, the panel based their recommendation on clinical experience with MTX.

Patients with inverse psoriasis

(TD Table 3.13)
To assess if there are specific considerations that might lead to different therapeutic approaches of inverse psoriasis with respect to palmoplantar psoriasis, only one case report was identified, providing VLQE to support any intervention.
Studies comparing different therapeutic choices in the treatment of inverse psoriasis could not be identified.

Comments:

Based on the limited available evidence, the panel considered that the therapeutic approach of palmoplantar psoriasis and nail psoriasis should be similar. CsA and phototherapy were not considered in this scenario.

Chapter 5: Arthritis

Simon Gusis, Nora Kogan

Patients with plaque-type psoriasis and predominant joint involvement
(TD Tables 3.12.1–3.12.9)

To define which interventions should be considered for this scenario, the CPG assessed the results of the studies meeting the inclusion criteria which compared each intervention vs. placebo and measured the outcomes previously defined: ACR20, 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)
Two RCT with 413 patients in all showed a possible increase in ACR20, 50 and 70 with ADA at induction (MQE). These results persisted up to week 24 in one of these studies, with 313 patients. An OS with 298 patients showed sustained efficacy levels at 2 years follow-up, with 58.7% ACR 20, 42.7% ACR 50, and 29.8% ACR 70 (LQE).

Ustekinumab (TD Table 3.12.7)

Three RCT evaluating UST vs. placebo in patients with PsA, with over 1,000 patients controlled for 12 and 24 weeks, showed a probable improvement in ACR 20, 50, and 70 with UST (MQE) and improvements in PsA signs/symptoms in a diverse population of patients (HQE).

Golimumab (TD Table 3.12.8)

GOL is a human anti-TNF monoclonal antibody, which has shown benefits in the management of patients with rheumatoid arthritis. Continued clinical efficacy and safety through 1 and 5 years was found for GOL in the RCT assessed comparing GOL 150 and 300 mg vs. placebo in 405 patients with PsA
(146 patients at each branch receiving GOL and 113 patients in the control group) (LQE).

Apremilast (TD Table 3.12.9)

APM is an oral phosphodiesterase 4 inhibitor (PDE4). The results of 5 RCT evaluating APM vs. placebo in over 1,400 patients showed improvement in ARC 20 at 16 and 24 weeks, as well as the probability of sustained clinical efficacy through 1 year of treatment (M/HQE). Improvement in quality of life as measured by HAQ-DI was also reported, although the clinical significance of these results is uncertain (HQE).

Comments:

Although APM is not available in Latin America, the panel considered the value of the results assessed and the experience with the use of this drug.

The panel notes that CER and GOL have not been approved for the treatment of skin psoriasis.

To answer this question, the results of trials meeting the inclusion criteria of these CPGs comparing ETN vs. ADA, ETN vs. IFX, and MTX vs. CsA were considered. The evaluation was completed with the results of each intervention compared
with placebo.

To answer this question, the results of a study comparing ETN vs. ADA vs. IFX were considered and the assessment was completed by also considering the results of the studies evaluating each agent vs. placebo.

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 heterogeneous.
All agents may be used in patients without skin involvement; CER and GOL should only be considered in patients with minor skin involvement.

The information of cohorts of patients who interrupted their treatments and the response rates after restart was considered as first end-point to assess this decision. All studies identified provided HQE for re-treatment with each intervention.

The results found by Gottlieb et al. in two OS with 123 patients showed that 67% of patients reached PASI 75 at week 26 with IFX 10 mg/kg and 87.9% at week 10 with IFX 5 mg/ kg. One study using ADA reported effectiveness (76% of patients reaching PGA 0–1), similarly to one using UST (85.6% reaching PASI 75).

treatment. Griffiths et al. found 90% response (PGA < 2) after treatment with ETN.

About the use of these CPGs

These CPGs summarize the judgment of the group of experts convened by SOLAPSO and includes recommendations which have been agreed after a careful assessment of the evidence, in the expectation that they may become a useful reference standard in clinical practice.
Under no circumstances should these recommendations replace the criteria of the treating physician about a therapeutic decision based on each patient and circumstance, as well as on the values, the preferences and the opinions of the patient or caregivers.

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Supporting Information

Additional Supporting Information may be found in the online version of this

article:

Appendix S1. SOLAPSO Clinical Practice Guidelines – Technical Document.