ANNALS OF MEDICINE 2021, VOL. 53, NO. 1, 1727–1736 https://doi.org/10.1080/07853890.2021.1986637 ORIGINAL ARTICLE Therapeutic goals and treatment response evaluation in moderate to severe psoriasis: an experts opinion document Isabel Belincho  n Romeroa, Esteban Daudenb, Carlos Ferrandiz Forasterc, Alvaro Gonzalez-Canterod and c Jose Manuel Carrascosa Carrillo ; on behalf of The Psoriasis Group of the Spanish Academy of Dermatology and Venereology a Department of Dermatology, Hospital General Universitario de Alicante-ISABIAL-UMH, Alicante, Spain; bDepartment of Dermatology, Hospital Universitario de La Princesa, Instituto de Investigacion Sanitaria La Princesa (IIS-IP), Madrid, Spain; cDepartment of Dermatology, Hospital Universitari Germans Trias i Pujol, Badalona, e IGTP, Universitat Autonoma de Barcelona, Barcelona, Spain; d Department of Dermatology, Hospital Universitario Ramon y Cajal, Madrid, Spain ABSTRACT ARTICLE HISTORY Objective: To critically analyse and define therapeutic objectives, response to treatment evalu- Received 17 February 2021 ation and related decisions in psoriasis. Revised 11 August 2021 Methods: Expert consensus meetings, a systematic and narrative reviews and a collaborative Accepted 22 September 2021 Delphi procedure were carried out. A steering committee from the Spanish Group of Psoriasis KEYWORDS was established who based on the reviews generated a set of related statements. Subsequently, Psoriasis; therapeutic a group of 40 experts tested their agreement with the statements, through 3 Delphi rounds. objective; treatment Results: We found a great variability in clinical guidelines regarding to the definition of treat- response; systematic ment goal and the response. In general, treatment failure was considered if a PASI50 is not literature review; Delphi achieved. The panel of experts agreed on (1) clearly differentiate between ideal and a realistic goals when establishing the therapeutic goal in moderate to severe psoriasis; (2) treatment goals should be in general established regardless of the type of drug for psoriasis; (3) treatment failure if PASI75 response is not reached; (4) an absolute PASI is in general preferred to the rate of PASI improvement from baseline; (5) disease characteristics, patients and physicians opinions/ needs and treatment adherence influence treatment goals. Conclusions: A clear treatment decision making framework is vital to improve management of psoriasis. KEY MESSAGES  Psoriasis characteristics, patients and physicians opinions/needs and treatment adherence influence treatment goals.  Different disease indexes could be used to assess treatment response but absolute PASI is preferred  In general psoriasis treatment failure should be considered if PASI75 response is not reached Introduction provide targeted inhibition of immune-mediated path- ways involving specific cytokines, such as tumour Psoriasis is a chronic, immune-mediated inflammatory necrosis factor (TNF), interleukin (IL)-17, or IL-23. Their skin disease affecting 2–3% of the Caucasian population clinical efficacy have been extensively demonstrated in in western countries [1,2]. It is associated with increased randomised clinical trials (RCTs) and observational incidence and prevalence of certain comorbidities and studies that have also depicted superiority compared significant impact on patients’ quality of life [3]. to traditional systemic drugs like methotrexate [5]. In recent years, new treatments and treatment On the other hand, the role of patients in the man- strategies have emerged and changed the paradigm agement of the psoriasis have also changed. of psoriasis, especially for patients with moderate to Nowadays, patients are more active in the manage- severe disease [4]. Among new treatments, biologics ment of the disease, and their opinion is taking into CONTACT Isabel Belinch on Romero belinchon_isa@gva.es Department of Dermatology, Hospital General Universitario de Alicante, Pintor Baeza 11, Alicante 03010, Spain Supplemental data for this article can be accessed here. ß 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1728 I. BELINCHÓN ROMERO ET AL. account in the decision making [6]. Besides, currently, Steering committee establishment many studies include not only objective variables to A group of 5 experts in psoriasis was established. The assess efficacy like the Psoriasis Area and Severity criteria for the selection were the following ones: (1) Index (PASI), the Psoriasis Global Assessment (PGA) or Dermatologist; (2) Specialised in psoriasis with demon- the Body Surface Area (BSA) [7], but also patient- strated clinical experience; (3) Clinical experience reported outcomes (PROs) including quality of life 8 years and/or 5 publications; (4) Participation in clin- because objective assessment of the disease does not ical trials or other observational projects in psoriasis; (5) always strictly correspond to the patient’s subjective Members of the psoriasis working group of the Spanish perception [8–10]. Academy of Dermatology and Venereology (AEDV). However, it has been shown that psoriasis is often They were responsible of: (1) The selection and invi- less than optimally treated, especially in patients with tation of the expert panel; (2) Protocol of the system- moderate to severe psoriasis. According to different atic literature review (SLR) and the identification of the studies, overall, patient satisfaction with existing thera- main psoriasis clinical guidelines; (3) Generation of pies remains modest [11], and many of them present clinical statements and modifications after each Delphi high disease burden despite treatments [12]. Different round; (4) Definition of the consensus levels and factors might explain this results [13,14]. One of them agreement on methodology; (5) Interpretation of the is the lack of a generally accepted consensus defin- results from the Delphi rounds; (6) final edition of the ition of either treatment goals or treatment success/ publication. failure (and subsequent treatment modifications) [15]. As highly effective new treatments and treatment SLR and narrative review of clinical guidelines/ strategies are available and patient’s involvement is consensus documents increasing, this turns out vital. Taking into account all of the exposed above, we The aim of the SLR was to assess PASI 100 response proposed this project to explore current definitions of of topic and systemic therapies in psoriasis (will be therapeutic objectives, response to treatment and published in a separate article). Along with the SLR, a related clinical decisions in moderate to severe psoria- narrative literature review was conducted in which sis, in order to propose an appropriate (and agreed) several national and international clinical guidelines/ treatment decision making framework. For this pur- consensus documents were analysed in order to col- pose, we developed a systematic literature review lect their definitions of treatment goal and treatment (SLR), analysed main clinical guidelines/consensus success/failure, objective measures and treatment documents and tested different statements through a decisions/modifications [16–25]. Delphi procedure. Nominal group meeting The steering committee analysed and discussed the results of the SLR and of the national and inter- Methods national clinical guidelines/consensus documents. This study was conducted in accordance with Good Based on them and their experience, they generated Clinical Practice guidelines and the current version of several clinical statements that were organised in 2 the revised World Medical Association’s Declaration of main topics. The first one related to therapeutic goal, Helsinki. This study did not require formal ethical and the second one on treatment response evaluation approval because this was not a study involving and related clinical decisions (see supplementary humans. This was a qualitative study based on expert material). In both cases, different definitions, limits, opinion. See Figure 1. objective measures and associated factors were Figure 1. Project methodology flowchart. Abbreviation. SLR: systematic literature review. ANNALS OF MEDICINE 1729 examined and tested in order to be accurate with the Therapeutic goal agreements (see supplementary material). The steering The definition and approach of moderate to severe committee also defined the Delphi methodology and psoriasis treatment goal varies depending on the clin- consensus levels. ical guideline/consensus document (Table 1). In sum- mary, these initiatives formulate (1) a set of overarching principles (a final therapeutic goal/s and Delphi process their characteristics); (2) a context (different factors that influence and modulate the therapeutic goal/s) The clinical statements were subsequently submitted and measures to objectively describe/analyse the to a Delphi process. For this purpose, apart from the treatment goals. steering committee, 35 more expert dermatologists Some of clinical guideline/consensus documents members of the psoriasis working group of the AEDV define the overarching principles regarding to treat- that were invited to participate in an on-line 3 Delphi ment goal as an ideal clinical situation in which psor- rounds. In order to ensure appropriate methodological iasis disease is not present, for example, “The ultimate rigour, consistent agreement and consistent disagree- goal of any psoriasis treatment is to achieve complete ment (consensus) required fulfilment of  2 of the fol- clearance of skin symptoms” [15,18]. A Spanish consen- lowing 3 criteria. Criterion 1: Mean is 8 or 9, or 1 or 2 sus also comprises a time frame and the possibility of and standard deviation (SD) <2. Criterion 2: The an additional and less strict therapeutic goal in these median is 8 or 9, Q3 > 7, and Interquartile range (IQR) overarching principles as follows “ … to maintain in the <2, or the median is 1 or 2, Q3 < 3, and IQR <2. long term complete or almost complete clearing or, fail- Criterion 3: If 70% of experts vote 8 or 9 (consistent ing that, a minimal and localized affected area … ” agreement), or if 70% vote 1 or 2 (consistent dis- [18,25]. These documents also propose measures (and agreement). After each round, a facilitator provided an different cut-offs) like PASI 75 [24], PASI 90 [24,25], anonymous summary of the experts’ forecasts from absolute PASI score <5 [18], BSA [18], PGA ¼ 0 the previous round. The results of the first and second [20,21], PGA  1 [18,24,25], PGA  2 [18,24] or DLQI Delphi rounds were analysed by the steering group. < 5 [24], to objectively define treatment goals. Clinical statements that achieved consensus were not Besides, most of these clinical guideline/consensus voted on a subsequent round. Those that did not, documents estate that treatment goal should be were reassessed by the steering committee and, if established taking into account different disease, appropriate, re-edited and voted on in a second patients, treatments and other local factors (the con- round. After the first second round, the inclusion of text), like disease severity, patients preferences, no new clinical statements was allowed. worsening of comorbidities or the risk–benefit ratio of continuous systemic treatment [15,23,25,27]. On the other hand, connected to the evaluation of the treatment response, the European consensus of Results psoriasis treatment goal [15] depicts that it needs a Delphi process minimal degree of improvement (principle of the low- est hurdle) and drug-specific evaluation time points A total of 30 statements were voted in the first Delhi [15]. The same way, the Spanish consensus generated round of which 9 achieved consensus (agreement) a set of criteria for an appropriate response at the and were not included in the next round. Six were start of treatment and in the long term (see Table modified, and 37 new statements were also incorpo- 1) [25]. rated into the second Delphi round. After this round, All of these questions were tested in the Delphi 18 statements reached consensus (all but 1 on the process (Table 2 and supplementary material). The agreement). The remaining statements went to the panel of experts agreed on clearly differentiate third Delhi round in which 9 more achieved consensus between ideal and a realistic goals when establishing (all but 2 on the agreement). See supplementary the therapeutic goal in moderate to severe psoriasis. material for more details. And, based on this, several criteria to define them Here, we present the main results of the Delphi were also agreed. For ideal goals, 2 types of criteria process along with those from the reviewed clinical were accepted. Those reflecting a complete resolution guidelines/consensus documents in the management of the disease like the absence of psoriasis-related of moderate to severe psoriasis patients. symptoms, impact and in terms of measures a PASI 1730 I. BELINCHÓN ROMERO ET AL. Table 1. Treatment goals definitions for patients with moderate to severe psoriasis according to clinical guidelines/consen- sus documents. # Document Definition 1 French guideline of systemic -Several factors should be taken into account when establishing treatment goals for therapy [23] systemic therapy:  Disease severity (measured as either an absolute value or by comparison with baseline values)  Presence of PsA or any other comorbidities  Disease impact on the physical, psychological and social well-being of the patient  The risk–benefit ratio of continuous systemic treatment  Patient’s point of view and level of satisfaction 2 Australian consensus of -Not clearly stated treatment goal [26] -Based on treatment response and failure 3 European consensus of -The ultimate goal of any psoriasis treatment is to achieve complete clearance of skin treatment goal [15] symptoms -It has to be based upon the results achievable with available treatments as indicated by the results of RCTs and the outcomes observed in clinical practice -It needs a minimal degree of improvement (principle of the lowest hurdle) and the drug- specific evaluation time points 4 Spanish consensus of systemic -The ideal outcome is to achieve: PASI 90, PGA  1, or alternatively a minimal and therapy [18,25] controllable localised involvement with topical treatments (PGA  2 and PASI < 5), DLQI  1, prolonged remissions without loss of efficacy, no worsening of comorbidities -Criteria for an appropriate response initially and in the long term (more than 6 months), 1 of: PASI 75, PASI < 5, PGA  1, DLQI < 5 -Criteria for the minimum efficacy required: PASI 50, PASI <50 if the patient is satisfied with the result, DLQI < 5 5 European guideline of systemic -Not specifically stated therapy [20,21] -PGA 0/1 (i.e. “clear”/“almost clear”) in the induction and in long-term is considered as critical 6 European consensus of -It uses the same criteria of the European consensus of systemic therapy [20,21] apremilast / secukinumab [22] 7 Italian guideline of systemic -Treatment goals should be agreed with the patient based on therapy [24] informed discussion  PASI 75  PASI 90  There is a need to define the minimum absolute PASI (i.e. <1 or 2)  DLQI < 5 8 British guideline of systemic -Tailor the choice of agent to the needs of the person and take into account the therapy [27] following factors  Psoriasis factors:  Goal of therapy (e.g. PGA of clear or nearly clear)  Disease phenotype and pattern of activity  Disease severity and impact  The presence of psoriatic arthritis (in consultation with an adult or paediatric rheumatologist)  Other factors:  Person’s age  Past or current comorbid conditions (e.g. inflammatory bowel disease, cardiovascular disease)  Conception plans  Body weight  Person’s views and any stated preference on administration route or frequency  Adherence 9 American consensus of -Not specifically stated fototherapy and systemic therapy [16,17] Abbreviations. PsA: psoriatic arthritis; PASI: Psoriasis Area and Severity Index; BSA: Body Surface Area; DLQI: dermatology life quality index; RCT: rando- mised controlled trial; PGA: Physician’s Global Assessment. 100 response, absolute PASI score 0 or skin clearance, goals, and just for some patients, a PASI 75 or PASI but also those that might reflect “an almost reso- score 5 could be considered a realistic goal. lution” of the disease like PASI 90 and PASI score 1 We would like to point out that regarding to the or 2 were considered. Interestingly, PASI 90 and PASI context, similar factors as those shown in clinical score 2 were included in the realistic goals as well guidelines/consensus documents were agreed, but the along with a PASI score 3. Besides, in this group of experts specifically added that in general, treatment ANNALS OF MEDICINE 1731 Table 2. Main messages from the statements that achieved consensus in the Delphi process regarding to therapeutic goals in moderate to severe psoriasis. # Consensus (on the agreement) 1 The therapeutic goal should be: 1.1  Individualized 1.2  Adapted to the characteristics of the disease 1.3  Adapted to the characteristics of the patient 1.4  Established in general regardless of the type of drug for psoriasis 2 When establishing the therapeutic goal in moderate to severe psoriasis, it is advisable to differentiate between an ideal goal and a realistic goal 3 Ideal goals should include: 3.1  PASI 100 response, absolute PASI score 0 or skin clearance 3.2  Absence of psoriasis-related symptoms 3.3  Absence of impact of psoriasis on patient’s psychological, emotional, social and occupational domains 3.4  Achieving PASI 90 response 3.5  Achieving an absolute PASI score 1 3.6  Achieving an absolute PASI score 2 4 Realistic goals should include: 4.1  Achieving PASI 90 response 4.2  In general, realistic goals should include achieving PASI 90 response, but sometimes, achieving PASI 75 response may also be realistic 4.3  Achieving an absolute PASI score 2 4.4  Achieving an absolute PASI score 3 4.5  In general, realistic goals should include achieving an absolute PASI score 3, but sometimes, achieving an absolute PASI score 5 might also be a realistic goal 4.6  In general, realistic goals should include achieving an absolute PASI score 3, but, with some drugs for psoriasis, achieving a PASI score 1 might also be possible Abbreviation. PASI: Psoriasis Area and Severity Index. goals should be established regardless of the type of have been met (see Table 3). All of the clinical guide- drug for psoriasis. lines/consensus documents agree on modifications of However, the experts did not differentiate treat- treatment when the response rate is not reached. The ment goals depending on the treatment time point. modifications include different strategies/actions like Treatment goals are the same along the time. dose increase, combinations or biologic switch. The main results of the Delphi regarding to this section are shown in Table 4 (more details are Response to treatment and related exposed in the supplementary material). In this case, a clinical decisions part of the discussions and statements were related to We next analyse response to treatment definitions the assessment of response to treatment with the across the clinical guidelines/consensus documents. absolute PASI score or the PASI response (change Many of them stablish criteria/definitions for 2 (consid- from the initiation of the treatment). Based on the ered) different phases, the induction and the mainten- Delphi results, in general, in daily practice, the abso- ance phases [18,20,21,25,26], see Table 3. In general, lute PASI score was preferred to the rate of PASI treatment failure is defined when an improvement of improvement. However, the experts also consider that PASI of 50% is not achieved. The same way, if an the last one sometimes can provide additional infor- improvement of PASI of  50% but <75% is achieved mation to the absolute PASI score. The same way, but a DLQI < 5 not, then this situation is also consid- when complete clear skin is assessed, it was agreed ered as treatment failure. that either the PASI 100 response or the PASI absolute More specifically the Spanish consensus of systemic score 0 can be used, but the absolute score was con- therapy [18,25] states that definitions for treatment sidered more appropriated. failure can be established based on an absolute PASI Following, when evaluating treatment response, score or response, PGA, and a quality-of-life score, according to this project experts, treatment failure in either individually or in combination. Lack of response daily practice was if PASI 75 response, or an absolute or primary failure occurs when there is no adequate PASI score 3 or 5 were not achieved with a treat- response by the end of the induction phase, according ment following recommended doses (Table 4). The to both the physician and the patient. Similarly, the attitude in case of treatment failure (type of treatment British guideline of systemic therapy [27], depicts a list modification) varied depending on the outcome. More of factors (related to patients, disease and treatment) specifically, if PASI 75 response is not reached with a that should be analyse when reviewing the response treatment, the experts agreed that a treatment change to biologic therapy. They also recommend to assess would be justified even if it implies a cost increase. whether the pre-defined minimal response criteria There was a trend towards to consider as well 1732 I. BELINCHÓN ROMERO ET AL. Table 3. Definitions of treatment response and/or failure and treatment modifications for patients with moderate to severe psor- iasis according to clinical guidelines/consensus documents. # Document Definition 1 French guideline of -Treatment response is considered as adequate if PASI 75 from baseline, or PASI 50 and a DLQI systemic therapy [23] score 5 -Primary treatment failure as not achieving a PASI 50 response 2 Australian consensus -Treatment failure after induction phase: of treatment goal [26]  If at the end an improvement of PASI of 50% as compared to disease severity at the time of treatment initiation has not been achieved  If at the end an improvement of PASI of 50% but <75% as compared to disease severity at the time of treatment initiation has been achieved (intermediate response), but DLQI  5 has not been achieved -Treatment success during maintenance phase:  If an improvement of PASI of 75% as compared to disease severity at the time of treatment initiation has been achieved -Treatment failure during maintenance treatment:  If an improvement of PASI of 50% as compared to disease severity at the time of treatment initiation has not been achieved  If an improvement of PASI of 50% but <75% as compared to disease severity at the time of treatment initiation can be maintained, but DLQI <5 has not been achieved -When treatment failure modification of the treatment regimen is recommended 3 European guideline of -During induction and maintenance phase: systemic therapy [20,21]  Treatment can be continued if PASI 75 is achieved  Treatment regimen should be modified if improvement of PASI 50 is not achieved  If PASI response is between 50 and75%, therapy should be modified if the DLQI is >5 but can be continued if the DLQI is 5 4 Spanish consensus of -Primary therapeutic failure: systemic therapy [18,25]  Lack of response or primary failure occurs when at the end of the induction phase a score is equal to or greater than those constituting the criteria for moderate-to-severe psoriasis  Lack of response or primary failure occurs when there is no adequate response by the end of the induction phase, according to both the physician and the patient  Lack of response or primary failure occurs when a decrease in 50% from the baseline PASI score has not been achieved (or this degree of response has been lost) after the induction phase 5 British guideline of -Review response to biologic therapy by taking into account: systemic therapy [27]  Psoriasis disease severity compared with baseline (e.g. PASI)  Agreed treatment goal  Control of PsA disease activity and/or IBD  Impact of psoriasis on the person’s physical, psychological and social functioning  Benefits vs. the risks of continued treatment  Views of the person undergoing treatment (and their family or carers, where appropriate)  Adherence to the treatment -Assess whether the minimal response criteria have been met, as defined by:  50% reduction in baseline disease severity (e.g. PASI 50 response, or percentage BSA) and clinically relevant improvement in physical, psychological or social functioning (e.g. 4-point) Abbreviations. PsA: psoriatic arthritis; IBD: inflammatory bowel disease; PASI: Psoriasis Area and Severity Index; BSA: Body Surface Area; DLQI: dermatol- ogy life quality index; PGA: Physician’s Global Assessment. treatment combinations if PASI 75 response is not agreed on a change of treatment strategy including achieved. On the other hand, if an absolute PASI score treatment modifications and combinations. 3 is not achieved, the experts only agreed on the Afterwards, we asked about the treatment decision use of combined therapy as a treatment modification. if the ideal or realistic goal was achieved in daily prac- However, when an absolute PASI score 5 is not tice. In both cases, dose reductions (dose down-titra- achieved, a treatment change even if it implies a cost tion and/or increasing the interval between doses) increase and treatment combinations are options. In could be considered as a change of treatment strat- general, treatment intensifications (dose increases) egy. There was no agreement on stopping the treat- were not considered in case of treatment failure in ment or making a change of treatment strategy. patients with moderate to severe psoriasis. We then tested treatment failure from the treat- Discussion ment goal perspective (Table 4). We formulated the same statements asking what attitude was appropriate In this study we have critically analysed therapeutic if the realistic goal was not achieved. The experts goal definitions and treatment response evaluation ANNALS OF MEDICINE 1733 Table 4. Main messages from the statements that achieved consensus regarding to treatment response and/or failure and treat- ment modifications in moderate to severe psoriasis. # Consensus (on the agreement) 1 Response to treatment could be assessed by absolute PASI 2 Sometimes, the rate of PASI improvement from baseline, complements the information from the absolute PASI and is useful to assess response to treatment 3 In general, in daily practice, absolute PASI is preferred to the rate of PASI improvement from baseline to assess response to treatment 4 The absolute PASI score 0 is the most appropriate measure to assess skin clearance 5 In daily practice, when complete clear skin is selected to assess response to treatment, the PASI 100 response or the PASI absolute score 0 can be used 6 In daily practice, if PASI 75 response is not reached with a treatment (recommended doses), a treatment change would be justified even if it implies a cost increase 7 In daily practice, if an absolute PASI score 3 is not achieved with a treatment (recommended doses), combination therapy would be justified 8 In daily practice, if an absolute PASI score 5 is not achieved with a treatment (recommended doses), it would be justified:  Treatment change, even if it implies a cost increase  Combination therapy 9 In daily practice, if the realistic goal is not achieved with a treatment (recommended doses), a change of treatment strategy it would be justified including:  Treatment change  Combination therapy 10 In daily practice, if the ideal goal is reached with a treatment (recommended doses), dose reduction (dose down-titration and/or increasing the interval between doses) could be included as a change of treatment strategy 11 In daily practice, if the realistic goal is achieved with a treatment (recommended doses), dose reduction (dose down-titration and/or increasing the interval between doses) could be included as a change of treatment strategy # Consensus (on the disagreement) 12 The rate of PASI improvement from baseline is preferred to absolute PASI to assess response to treatment 13 In daily practice, if PASI 100 response is not achieved with a treatment (recommended doses), dose changes would be justified (treatment intensification) 14 In daily practice, if an absolute PASI score 1 is not achieved with a treatment (recommended doses), a treatment change would be justified even if it implies a cost increase Abbreviations. PASI: Psoriasis Area and Severity Index. through a revision of main clinical guidelines/consen- applied to all patients with heterogeneous diseases like sus documents and through a Delphi process within a psoriasis. Therefore, the statements were conscientiously group of experts. generated looking for a balance between simplicity (clar- The treatment options for patients with moderate ity and applicability) and the coverage of a wide range to severe psoriasis have expanded greatly over the of psoriasis clinical profiles. The same way, we included past decade. Moreover the results of RCTs and clinical different objective measures like PASI or PGA and clin- practice indicate that the efficacy in many cases is out- ical scenarios trying to stablish possible general prefer- standing [4,5]. However, it has been shown that psor- ences but also including flexibility. As a consequence iasis treatment might be sub-optimal in many cases more than sixty statements were tested. Additionally, [11,12]. Published studies have depicted that psoriasis we would like to comment that the pre-established patients do not receive the appropriated care that is agreement level is extremely strict. This reinforce the required to clear their skin symptoms and to improve validity of those which reached agreement. their quality of life [11,12]. Several factors might Regarding to treatment goals, first, many clinical explain this situation, but the lack of well-defined guidelines or consensus documents have proposed, as treatment goals with an integrated demand for action overarching principle, that psoriasis ultimate or ideal could be definitely contributing to this situation [15]. goal is to achieve complete clearance and to maintain We design this project to analyse current definitions it in the long term [16–24]. However, it is also recog- and recommendations regarding to treatment goals nised that this would not be realistic in many cases as and response evaluation and to provide guide when data from RCTs and clinical practice show that not all establishing them in daily practice. For this purpose, patients respond appropriately [4,28]. In fact, the we first review national and international clinical Spanish consensus of systemic therapy includes as a guidelines/consensus documents. And afterwards, we possible goal in some cases an almost complete clear- generated several clinical statements to deeply explore ing or, failing that, a minimal and localised affected the opinion and attitudes of a group of expert derma- area, providing also criteria for the minimum efficacy tologists in this regard. Simple definitions and clinical required [18,25]. Therefore, as it was also agreed in recommendations are usually more easily imple- the Delphi, ideal and realistic goals were clearly differ- mented in daily practice but might not cover or be entiated and defined. According to the Delphi experts, 1734 I. BELINCHÓN ROMERO ET AL. ideal goals should always be considered as “the goal” Most of these documents also accepted a lower level and the first option. But for many patients realistic of improvement providing a good quality of life, and goals will be the drivers of therapeutic decisions. For at least two of them incorporated some other factors ideal objectives, a set of objective measures (e.g. abso- to take into account like patients opinion, or the lute PASI score 0) and clinical variables (e.g. an adherence to treatment [18,27]. All agree on modifica- absence of psoriasis-related symptoms) were included tions of treatment when the response rate is not in an effort to combine objective data but also reached. In our Delphi, it was first agreed that the rate patients experience and opinion. Besides, different of PASI improvement from baseline, complements the types of measures were considered appropriated like information from the absolute PASI and is useful to PASI response, absolute PASI score or skin clearance. assess response to treatment reflecting that both can And connected to the cut-offs, the experts agreed to be used but the absolute PASI is preferred. Regarding include those reflecting a complete resolution of the to the cut-offs to define treatment failure, the experts disease (0 value) but also others that reflect an agreed to established them if a PASI 75 response or “almost resolution” like an absolute PASI score 1 or an absolute PASI score 3 or 5 are not reached. But 2. From a practical point of view, it could assumed following with our principles of flexibility, it was also that an absolute PASI score 2 in the absence of psor- agreed that the lack of achievement with realistic iasis symptoms and impact on the patient (the real goals also led to a treatment failure and therefore to a centre of the treatment of psoriasis) as a situation treatment decision. We consider that with this last close to a complete clearance, and therefore an ideal statement more clinical scenarios are covered. clinical scenario. More specifically, we also developed some state- Remarkably, both, PASI 90 response and an abso- ments to assess skin clearance as nowadays there is lute PASI score 2, were a part of the ideal and realis- an increasing interest in defining and incorporating tic goals in our Delphi. This probably reflects the into clinical practice this variable. The experts agreed clinical heterogeneity of psoriasis disease and the fac- that the PASI 100 response or the PASI absolute score tors that influence and modulate each individual 0 can equally be used for this purpose. However, as patient (the context). For some patients that present mentioned before, skin clearance was considered an more severe disease, comorbidity or intolerance prob- ideal therapeutic goal. lems, a PASI 90 response would be ideal (though not The present project has some limitations that realistic), but for others this goal could perfectly be deserve further comments. In daily practice, there is a attainable. Following the same principle, although the necessity to decide whether a treatment is able to limits of a realistic goal were established in a PASI 75 improve the disease at a given point of time, however, response and an absolute PASI score 3, it was we did not include a clear time frame to evaluate the agreed that in some specific cases, achieving a PASI treatment response because our proposal was more 75 response or an absolute PASI score 5 might also conceptual and already quite extensive. The same way be a realistic goal. we did not define a sufficient/minimal/acceptable It is widely accepted (as well as in our Delphi) that improvement in an individual patient’s disease due to treatment goal should take into account patients, dis- the same reasons. Further studies will be necessary to ease, treatments characteristics and local medical address these challenging and complex questions. As environment. We would like to point out that regard- exposed, PASI was the selected objective outcome for ing to the context, in our project the experts specific- the formulation of all the statements. Although it ally added that in general, treatment goals should be presents some limitations [29], it is the most com- established regardless of the type of drug for psoriasis. monly used [30] and facilitate the implementation of Although psoriasis drugs present different efficacy and the statements. On the other hand, we did not gener- safety profiles, these are contextual factors not the ate specific recommendations on certain comorbidities main drivers of the therapeutic goal. like psoriatic arthritis beyond that they might modu- On the other hand, we also examined response to late/influence treatment goals because they deserve a treatment evaluation (success and/or failure) and detailed analysis. The same way, we did not include related clinical decisions. The definition of treatment specific recommendations for patients with psoriasis in failure was very consistent across the guidelines clin- specific areas involved (face, genital, nails) for the ical guidelines/consensus documents, and the criteria same reason. Finally, this is a qualitative study based was if an improvement of PASI of 50% is not on expert’s opinion, but taking into account the rele- achieved, in both, induction and maintenance phase. vance of the topic and the lack of specific studies all ANNALS OF MEDICINE 1735 of the exposed in this article might be very useful to References stablish a treatment framework for patients with mod- [1] Ferrandiz C, Bordas X, Garcia-Patos V, et al. erate to severe psoriasis. Prevalence of psoriasis in Spain (epiderma project: In summary, well-defined therapeutic goals and phase I). J Eur Acad Dermatol Venereol. 2001;15(1): treatment response criteria may be helpful to guide 20–23. physicians in their care of patients with psoriasis. 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