Treatment to target is an emerging concept in the management of psoriasis. Professional groups in Europe and North America have offered recommendations on this topic. My views on the current guidance and future directions are outlined below.
Psoriasis affects well-being as a consequence of the functional and psychological impairment that is partially reflected on health-related quality of life (HRQOL) measures. In chronic inflammatory diseases for which no cure can be provided, the goal of treatment should be to abrogate or minimize their impact on HRQOL. Treatment should be adjusted according to the degree of achievement of this predefined goal, which should be assessed by an adequate outcome measure.
The use of treatment targets to improve outcomes has been implemented in clinical practice for the management of patients with various conditions such as hypertension, diabetes, and hyperlipidemia. In some cases, clinicians monitor blood pressure and use laboratory tests to define treatment targets associated with improved outcome, in terms of overall survival and HRQOL. Similarly, rheumatologists use composite disease activity measures to implement standardized treatment targets1 in managing patients with rheumatoid arthritis,2 spondyloarthritis, and psoriatic arthritis.3
Definition of treatment goals in psoriasis does not require biomarker surrogates. However, it should include the improvement in severity and extent of lesions as well as functional and subjective (itch, appearance, or emotional/sexual impact) impairment caused by the disease and their impact on patients’ perceived HRQOL, which is usually measured by the Dermatology Life Quality Index (DLQI).
Identifying treatment goals should include treatment targets for comorbidities, especially psoriatic arthritis, and cardiovascular risk factors that require close cooperation between rheumatologists and general practitioners to achieve therapeutic success.
True treatment targets in psoriasis have yet to be generally agreed upon. In the US, no targets have yet been currently identified. The ultimate goal of therapy is clearance of lesions and a Physician’s Global Assessment (PGA) of 0 (“clear”) has been proposed by Canadian expert dermatologists4 as the current therapeutic target in psoriasis.* A PGA of 0-1 (namely, “clear” or “almost clear”) with minimum body surface area (BSA) involvement was proposed in the Spanish guidelines on treatment of psoriasis with biologics.5 Using PGA alone misses important aspects such as the extent of the disease (BSA), visibility/location of lesions, and subjective symptoms such as itch, burning, or pain.
An improvement of at least 90% with respect to the baseline Psoriasis Area and Severity Index (PASI), namely a PASI90 or better response, is considered as treatment success by the European Medicines Agency, but PASI75 response has become accepted as a reasonable therapeutic goal.6 Absolute PASI values (with a cutoff of 5, 3, or 2) might provide a better benchmark, regardless of baseline PASI, which becomes less relevant with increasing duration of treatment.5 The lower value corresponds to a PASI90 or better response for patients with a baseline PASI ≥20. A PASI score of 5, often considered the threshold for therapeutic adjustment or switching, corresponds to a PASI75 or better response for them.
Treatment outcomes in psoriasis are clinically meaningful only if they correlate with significant improvement in HRQOL. If measured by DLQI, the achievement of a DLQI = 0-1 status, corresponds to lack of effect of the disease on patient’s HRQOL.5 DLQI does not take into account the psychological burden of disease and is subject to marked transcultural variability.7 A global question score anchor8 might be used as a substitute for DLQI in clinical practice. Similarly, Visual Analog Scales can be very convenient to assess both subjective symptoms and patient’s perception on the severity of disease and/or its impact on HRQOL.
The patient’s perspective and personal goals should also be taken into account when defining target outcomes. PASI75 response meets therapeutic expectations in most patients,9 but PASI90 response or better has a significantly higher impact on DLQI improvement and is associated with significantly higher DLQI = 0-1 response rates than PASI75.10,11 The European consensus proposal12 (in 2011) of PASI75 response as a treatment goal, irrespective of DLQI score, might fall a little bit short of current therapeutic expectations, and anything less than PASI75 response with DLQI ≥2 (which is considered a satisfactory outcome not requiring treatment modification in the consensus) might be unacceptable for patients who have achieved clearance at some time point during the induction or maintenance phase of biologic treatment.
Treatment to target is an iterative process, by which the effectiveness of the intervention must be assessed periodically and treatment must be adjusted accordingly to meet prespecified goals. Because of pharmacokinetic and pharmacodynamic reasons, biologic treatments (and conventional systemic agents) have different speeds of onset of action,13 and should therefore be assessed at the relevant time point. This can be defined as the end of the induction period, when assessment should be made in terms of effectiveness (achievement of the predefined goal) or failure (according to a predefined threshold).14 Future developments may eventually provide the means for accurate prediction of success or failure based on individual genetic markers15 and drug pharmacokinetics.16,17
During the maintenance period in a treat-to-target strategy, treatment should be adjusted with the aim of achieving and maintaining therapeutic goals that must be assessed at each visit. Decisions should be made taking into account trough serum concentrations of the drugs being used, combination treatment, adjustments of dose and administration intervals, and switching of biologics. Drug withdrawal for very responsive patients should also be considered. Perhaps this approach might be feasible for those who remain clear on minimal or even undetectable drug levels.
*In clinical trials, based on approved products, PGA scales ranging from 5-7 have commonly been used.
- Smolen JS. Treat-to-target: rationale and strategies. Clin Exp Rheumatol. 2012;30(4 suppl 73):S2-S6.
- Smolen JS, Aletaha D, Bijlsma JW, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69(4):631-637.
- Smolen JS, Braun J, Dougados M, et al. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force. Ann Rheum Dis. 2014;73(1):6-16.
- Gulliver W, Lynde C, Dutz JP, et al. Think beyond the Skin: 2014 Canadian Expert Opinion Paper on Treating to Target in Plaque Psoriasis. J Cutan Med Surg. 2015;19(1):22-27.
- Puig L, Carrascosa JM, Carretero G, et al. Spanish evidence-based guidelines on the treatment of psoriasis with biologic agents, 2013. Part 1: on efficacy and choice of treatment. Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology. Actas Dermosifiliogr. 2013;104(8):694-709.
- European Medicines Agency. Guideline on clinical investigation of medicinal products indicated for the treatment of psoriasis. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guidelin.... Accessed November 20, 2014.
- Bronsard V, Paul C, Prey S, et al. What are the best outcome measures for assessing quality of life in plaque type psoriasis? A systematic review of the literature. J Eur Acad Dermatol Venereol. 2010;24 (suppl 2):17-22.
- Hongbo Y, Thomas CL, Harrison MA, Salek MS, Finlay AY. Translating the science of quality of life into practice: What do dermatology life quality index scores mean? J Invest Dermatol. 2005;125(4):659-664.
- Schäfer I, Hacker J, Rustenbach SJ, Radtke M, Franzke N, Augustin M. Concordance of the Psoriasis Area and Severity Index (PASI) and patient-reported outcomes in psoriasis treatment. Eur J Dermatol. 2010;20(1):62-67.
- Revicki DA, Willian MK, Menter A, Saurat JH, Harnam N, Kaul M. Relationship between clinical response to therapy and health-related quality of life outcomes in patients with moderate to severe plaque psoriasis. Dermatology. 2008;216(3):260-270.
- Torii H, Sato N, Yoshinari T, Nakagawa H. Dramatic impact of a Psoriasis Area and Severity Index 90 response on the quality of life in patients with psoriasis: an analysis of Japanese clinical trials of infliximab. J Dermatol. 2012;39(3):253-259.
- Mrowietz U, Kragballe K, Reich K, et al. Definition of treatment goals for moderate to severe psoriasis: a European consensus. Arch Dermatol Res. 2011;303(1):1-10.
- Nast A, Sporbeck B, Rosumeck S, et al. Which antipsoriatic drug has the fastest onset of action? Systematic review on the rapidity of the onset of action. J Invest Dermatol. 2013;133(8):1963-1970.
- Puig L. Induction phase, primary endpoint, time to decide on primary failure, and therapeutic goals in biologic treatment of psoriasis. J Eur Acad Dermatol Venereol. 2013;27(2):e257-e260.
- Talamonti M, Botti E, Galluzzo M, et al. Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab. Br J Dermatol. 2013;169(2):458-463.
- Takahashi H, Tsuji H, Ishida-Yamamoto A, Iizuka H. Plasma trough levels of adalimumab and infliximab in terms of clinical efficacy during the treatment of psoriasis. J Dermatol. 2013;40(1):39-42.
- Mahil SK, Arkir Z, Richards G, Lewis CM, Barker JN, Smith CH. Predicting treatment response in psoriasis using serum levels of adalimumab and etanercept: a single-centre, cohort study. Br J Dermatol. 2013;169(2):306-313.