2014 January-March; 2(1): 1–10. ISSN: 2282-4103
Published online 2014 April 30.

Clinical applications of PPI-TT guidelines on transitioning therapies in the treatment of moderate to severe psoriasis: an expert opinion of central Italy dermatologists

Alessandra Narcisi,1 Annalisa Arcese,1 Claudio Bonifati,2 Valentina Carboni,3 Marta Carlesimo,1 Clara De Simone,4 Magda D’Agostino,4 Maria Esposito,5 Simona Giancristoforo,6 Dario Graceffa,2 Elisa Maiani,2 Fabiana Riccardi,7 Antonio Richetta,6 Paola Tribuzi,7 Maurizio Zampetti,3 Arianna Zangrilli,5 and Antonio Costanzo1

1Dermatology Unit, NESMOS Department, “Sapienza” University of Rome, Italy
2IFO Dermatologic Institute San Gallicano, Rome, Italy
3Frascati Hospital, Frascati, Rome, Italy
4Dermatology Institute, Catholic University of Sacred Heart, Rome, Italy
5Department of Dermatology, University of Rome “Tor Vergata”, Rome, Italy
6Dermatology Clinic, “Sapienza” University of Rome, Rome, Italy
7Dermatology Unit, Viterbo Hospital, Viterbo, Italy

Address for correspondence: Antonio Costanzo, Dermatology Unit, NESMOS Department, “Sapienza” University of Rome, Italy, Phone: +39 06 33775822, Fax: +39 06 33775538, E-mail: antonio.costanzo@uniroma1.it


Optimization of treatment management in patients affected by moderate to severe psoriasis is important to achieve long-term control of the disease. The PPI-TT provided practical suggestions on management of systemic treatments for psoriasis. However, these guidelines do not take into account differences in regulations and clinical practice among European states.

Evaluate how PPI-TT guidelines can be applied to clinical practice in central Italy identifying criticisms and ways to improve them.

Experts from central Italy were invited to present clinical cases on treatment optimization and transitioning before PPI-TT guidelines were published. At a first board meeting PPI-TT guidelines were presented and clinical cases evaluated and discussed identifying discrepancies and criticisms. In a second meeting new cases were presented and discrepancies with PPI-TT were discussed.

There was a high level of agreement between clinical practice and PPI-TT guidelines, discrepancies were found in: 1) management of combination therapies, and 2) in the optimization of biologic therapies.

The experts agreed on the importance of PPI-TT guidelines as a practical guide for the management of moderate-to-severe psoriasis patients but also suggest that these can be improved to adapt them to local clinical behavior and regulations.

Keywords: psoriasis, biologic therapies, PPI-TT guidelines, transitioning therapies


The “Progressive Psoriasis Initiative Transitioning Therapies program” (PPI-TT), was established to provide a practical guideline, evidence based and agreed by experts, on the optimization and therapy in the management of moderate to severe psoriasis.

Thirty-three countries were involved in this project, that was carried out between May 2011 and June 2012. A directing committee composed by nine dermatologists from Europe and Canada supervised the project. Participating dermatologists were invited to suggest clinically relevant questions related to three main topics: the optimization of systemic therapies, transitioning from conventional systemic therapies to biologics and transitioning from one to another biologic. Principal topics were: optimization of systemic conventional therapies (Methotrexate and Cyclosporine); modalities to interrupt a conventional systemic therapy; transition from conventional therapy to biologic; combination of conventional therapy with biologic therapy; optimization of biologic therapy and transition from one to another biologic drug. A detailed description of the methodology and results was recently published by Mrowietz et al. (1).

The PPI-TT project was carried out through a modified Delphi procedure and consisted in different phases. A similar method was employed to develop other consensus-based guidelines (2, 3). The results consisted in the definition of 16 questions related to the different topics, followed by one or more answers useful for patients’ management (Table 1). Each answer had a higher or lower level of evidence according to the Oxford Centre for Evidence-Based Medicine Classification (4).

Table 1Table 1
Guidelines for therapy optimization and transitioning of the PPI-TT initiative.

The general objective of PPI-TT project was to provide a tool to guide dermatologists in the correct management of systemic therapies and in the transitioning from one to another therapy. Being an international project, however, answers provided by the consensus not always reflect the clinical practice in the different countries or regional prescribing and dosing limitations, such as those imposed by the regional health authorities in Italy.

Our project had the objective to adapt the Transitioning Therapies program to the clinical reality of center Italy with the idea to extend the results to other Italian areas.

In this manuscript we describe the results of this project consisting in the evaluation of PPI-TT guidelines use in central Italy through the analysis of real life cases by a group of experts in psoriasis management.


Nine dermatologists from 8 different hospital and university centers, all of them experts in the treatment of moderate to severe psoriasis were invited to present clinical cases on systemic therapy in psoriasis focusing on the transitioning modalities, before the results of the Psoriasis progressive Initiative Transitioning Therapies program (PPI-TT) were published. The experts presented 18 clinical cases in a “board” meeting. During the same meeting the results of the Transitioning Therapies program were explained and distributed, and the same clinical cases evaluated focusing on common points and differences with the guidelines. The experts were then invited to perform therapy optimization and transitioning on other patients, following the PPI-TT guidelines as close as possible.

At a second meeting, the same experts examined clinical cases presented by each center and agreed to publish this point-of-view paper on the use of PPI-TT guidelines in central Italy focusing on strengths and weak points.


During the first experts meeting, critical points for the application of PPI-TT guidelines in Italy were discussed. Here are the results of this discussion.

Optimization of conventional therapy
Generally, the experts found that the PPI-TT statements on the optimization of conventional treatment (Questions 1 to 7) are very useful and mostly reflect their clinical practice. However, analysis of clinical cases raised these points:
  • Some of the conventional systemic drugs toxicity evaluation modalities (Question 4) are not diffused in Italy (e.g. PIIINP and fibroscan monitoring for hepatic fibrosis evaluation during methotrexate treatment).
  • Phototherapy (Narrow band UVB and PUVA), that is considered as a conventional systemic treatment is not taken into account in this section of the PPI-TT guidelines. The experts agreed that short UV therapy course can be useful into optimize both conventional systemic drugs and biologics. However, transitioning from NB-UVB or PUVA to cyclosporine should be carefully evaluated considering the risk of developing cutaneous Squamous Cells Carcinomas (SCC) (5, 6).
  • The possibility to associate MTX with cyclosporine is not considered in PPI-TT guidelines, not even in the section dealing with transitioning from one to another drug, and there is no sufficient data on psoriasis in the literature. The experts agree that a short (4–8 weeks) combination therapy period can be performed when shifting from cyclosporine to methotrexate to avoid psoriasis rebound (7) (However it should be pointed out that this combination may be potentially harmful due to the immunosuppression induced by the combined used of these two drugs.
  • The experts agree that reaching DLQI >5 alone is not a sufficient parameter to influence the decision of restarting a systemic treatment. PASI and BSA should be considered as the main criteria for this decision.

Transition from conventional systemic to biologic
The experts think that PPI-TT suggestions on the management of the therapy transition from systemic to biologic treatment (Questions 7 to 12) are very useful and mostly reflect current clinical practice.

However, the analysis of real life clinical cases raised some problems:

  • The transitioning from cyclosporine to ustekinumab (Question 8b) could be also performed with a short overlap period (2–6 weeks) to avoid rebounds after cyclosporine discontinuation in partial responders. The PPI-TT guidelines do not consider the possibility to associate systemic steroids to biologics, particularly in those patients who suffer important disease flares after therapy discontinuation. The experts agree that 1–2 weeks of steroid therapy (prednisone 0,5–1 mg/kg/day) could enhance the clinical response to biologics and reduce immunogenicity of biologics (8, 9). The experts think that the optimal modality to associate methotrexate to biologics should be at the beginning of biologic therapy to reduce the immunogenic potential of biologic drugs (10).

Transitioning from one to another biologic
Expert discussion on the optimization of biologic therapy and transition from one biologic to another raised several considerations that should be taken into account to apply PPI-TT guidelines in Italy.
  • The most important point is that in Italy it is not allowed to change dosing and frequency of biologic administration. These can be used only following the administration schedule approved for the indications which are present in the SPC. This makes impossible to adapt biologic therapies to patients’ clinical needs, e.g. by reducing administration frequency when clinical efficacy is not optimal (11).
  • The PPI-TT guidelines do not specify criteria to choose a second biologic when the first has failed. For example, after failing a first anti-TNF can we start a second anti-TNF? In which cases should we switch biologic class? This issue is particularly important if we consider the introduction of new classes of biologic drugs (e.g. IL-17 blockers) (12, 13). Literature suggests that at least in Rheumatology, after failure of an anti-TNF because of the formation of anti-drug antibodies (ADA), a second anti-TNF drug is effective, while when the causes of failure is not linked to immunogenicity but is a “class” failure, the second biologic should belong to a different class (e.g. ustekinumab) (14, 15). It is therefore advisable to check for the presence of anti-drug antibodies before deciding which biologic to use after failure of a first one.
  • A last point of discussion identified by the experts is the lack of information on re-use of a previously used biologic. For example, after failing a first anti-TNF, and other biologics, can the first anti-TNF be reintroduced? In the opinion of the expert the reason for biologic discontinuation (e.g. first or secondary failure) as well as the kind of drug (antibody vs fusion receptor) should guide the choice to re-try a previously used drug.

During the second experts meeting 35 clinical cases of patients’ transitioning were analyzed. Experts were encouraged to perform therapy optimization and transitioning in these patients according to PPI-TT guidelines. The adherence to PPI-TT guidelines was very high, however the analysis of cases revealed that this was not always possible. Here we described the differences in patients’ management with respect to PPI-TT guidelines resulting from cases analysis and discussion.

Optimization of conventional therapy
  • - In one case methotrexate therapy was discontinued because of liver toxicity (increased liver enzymes) without performing PIIINP and fibroscan to monitor liver fibrosis.

Transition from conventional systemic to biologic
  • - In one case biologic drug (adalimumab) was added to methotrexate because of low response to MTX before reaching the maximal MTX suggested dose (20 mg/week).
  • - In two cases NB-UVB therapy was associated to etanercept treatment to increase therapeutic response. This association is not mentioned in the PPI-TT guidelines.
  • - In one case leflunomide was added to adalimumab to improve the clinical response on the arthritic component. A first try of reducing adalimumab dosing intervals was not performed because is off-label in Italy.
  • - In two cases a short course of oral prednisone (1mg/kg/day) was added to biologic drugs to control psoriasis severe flares.

Transitioning from one to another biologic
  • - In two cases the washout period (etanercept to adalimumab) was 4 weeks instead of one week.
  • - Switch to anti-TNF instead of adding MTX was performed in two patients under ustekinumab treatment who developed arthralgia (lack of data on ustekinumab in psoriatic arthritis).
  • - Two patients were shifted from etanercept to adalimumab instead of increasing etanercept to 50 mg twice weekly because this dosage is off-label in Italy after the first 12-week induction period.


Treatment optimization and management of therapy transition in moderate to severe psoriasis has a critical impact on the efficacy of long-term treatment in these patients (16). PPI-TT guidelines were implemented to serve as a practical guide for dermatologists dealing with these aspects of therapy management (1). However, differences in local laws and practice may influence the use of these guidelines at a regional level. For these reasons we developed a project aimed at evaluating how PPI-TT guidelines can be applied to dermatology centers in Italy. In this manuscript we report the results of an analysis of the PPI-TT guidelines performed by a group of experts from central Italy. Clinical cases of therapy optimization and therapy transitioning observed before the PPI-TT guidelines publication was analyzed. The experts found a very good level of correspondence between their clinical management and PPI-TT guidelines. However, they also identified some differences and points to be improved. In particular, association therapies with NB-UVB, PUVA and steroids are not deeply evaluated in the PPI-TT guidelines, and suggestions on how a second biologic drug should be chosen after failing a first one are lacking. In a second phase of the project, the experts tried to perform transitioning and treatment optimization according to the PPI-TT guidelines. Presentation of these clinical cases revealed only a few cases where clinical behavior differed from that suggested in PPI-TT guidelines. Most of these cases were related to therapeutic associations between biologics and NB-UVB, steroids and leflunomide. In other patients it was not possible to optimize biologic treatment by increasing or reducing the drug dosage because this is off-label in Italy.

In conclusion the experts agreed on the importance of PPI-TT guidelines as a practical guide for the management of moderate-to-severe psoriasis patients but also suggest that these can be improved to adapt them to local clinical behavior and regulations.


We thank Debora Cannone for optimal technical assistance. This work was supported in part by grants from National Psoriasis Foundation and FIRB-IDEAS to A.C.

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