Implementing well-being in the management of psoriasis: An expert recommendation.

Psoriasis causes detriment in a person's physical, mental and social health which impairs their quality of life (QoL). However, the current psoriasis management may not adequately address all relevant health domains. Since the goal of healthcare is to restore or maintain health, health outcomes should include all areas of the patient's overall health. Life satisfaction, QoL and patient well-being are essential to a comprehensive approach to the disease. With the inclusion of more people-centred policies, care of patients with psoriasis should evolve towards a holistic and integrated assessment of the disease impact, including subjective measures of well-being in order to encompass all aspects of health. The main objective of this expert review is to give the concept of well-being a place as an entity within the holistic therapeutic approach for patients with psoriasis. Identifying and defining common goals beyond the skin with the patient and testing them throughout the course of treatment will benefit and enhance treatment success. We propose a series of recommendations for application in clinical practice, providing tangible clinical guidance for implementing well-being in the management of psoriasis. Among the recommendations are the need to initially listen to the patient, to know their level of empowerment or what they want to achieve, their preferences in decision making, the evaluation of not only the physical but also the emotional impact of the disease (well-being), the definition of the aspects that can generate a cumulative deterioration of the disease throughout life, and a continuous assessment of the patient's preferences with the opinion of the expert clinician and the integration of the knowledge of external clinical evidence.

Psoriasis Therapy and Skin Cancer: A Review.

INTRODUCTION: psoriasis is a chronic immune-mediated disease that is associated with several comorbidities, including an increased risk of malignancies, particularly skin cancer. A large number of studies have investigated whether psoriasis itself, psoriasis-associated comorbidities, or psoriasis treatment could lead to an increased risk of neoplasms. METHODS: we reviewed the literature using the most important databases (PubMed, MEDLINE, ETHERIA). All articles pertaining to skin cancer associated with psoriasis disease and psoriasis therapy were included. In this review, we also discuss some of the potential underlying mechanisms for these associations, particularly regarding the multiple psoriasis therapies currently available, and their possible implications in higher incidences of skin cancer in these patients. CONCLUSION: evidence suggests that these patients might have a higher risk of cutaneous malignancies, especially for NMSC, compared with psoriasis-free patients. The reasons for this increased risk remain to be determined. However, high dose PUVA therapy, the immunosuppressive treatments used, and the comorbidities and habits frequently described in these patients seem to play a role in the pathogenesis of these tumors. Because of these facts, periodic screening for skin cancer is recommended in this population.

Reduced doses of biological therapies in psoriasis may increase efficiency without decreasing drug survival.

Off-label treatment with reduced doses of biological therapies for moderate-severe psoriasis is used, but its efficacy, safety, and persistence are not well known. We have compared reduced doses with standard an escalated doses and study predictive factors for a successful reduction of doses lasting more than 6 months. We included 303 subcutaneous treatments (33% with reduced doses and 29% with escalated doses). Eighty (80.8%) reduced treatments were successful. Patients with longer evolution of the disease or patients treated with drugs different from adalimumab presented an increased risk of failure. Median drug survival did not differ between the different dosing schedules. Adverse events percentage was higher in the group treated with standard doses. Unlike previous literature, ustekinumab is the drug most commonly used at reduced doses in the present study. We have found similar efficacy rates in patients with dose modification compared with patients with standard dose, without further persistence problems. Our results suggest that reduction of dose should be done early, at the time of reaching a good response (PASI 90 or PASI <3 in two consecutive visits) as this dosing seems to be safe and portends no problems regarding persistence or adverse effects.

Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry.

BACKGROUND: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. OBJECTIVE: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. METHODS: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. RESULTS: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of <1), whereas cyclosporine and infliximab had the highest, with an increased rate ratio (IRR of ≥5). LIMITATIONS: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered. CONCLUSION: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.

Pharmacogenetics Update on Biologic Therapy in Psoriasis.

Background and objectives: Psoriasis is a chronic immune-mediated skin disease caused by several complex factors, both environmental and genetic, many of which are still not fully understood. Nowadays, several groups of biological drugs are being used for psoriasis treatment. Although these therapies are very effective, they show significant variability in efficacy among individuals. Therefore, there is a need for biomarkers to predict treatment outcomes in order to guide personalized therapeutic decisions. Pharmacogenetics is the study of variations in DNA sequences related to drug response. Materials and Methods: In this article, we review pharmacogenetics studies on the treatment of moderate-to-severe psoriasis focusing on anti-interleukin (IL) 12/23 (ustekinumab) and anti-IL17 drugs (secukinumab and ixekizumab), as well as recent studies concerning anti-TNF drugs. Results: Several polymorphisms have been studied over the years in reference to anti-TNF drugs; some of the most recent studies included the performance of a genome-wide association study (GWAS) and pharmacogenetics studies focused on the optimization of a treatment regimen. Various polymorphisms in different genes have been related to ustekinumab response; among them, the most commonly studied is the HLA-C*06:02 allele. Conclusions: Although not confirmed in some studies, most studies have shown that patients carrying this allele present a significantly higher response rate to ustekinumab. Some polymorphisms have been studied in patients treated with anti-IL17 drugs, mostly related to secukinumab; however, up to now, no association has been found between any of these polymorphisms and response. Nevertheless, further studies involving larger cohorts are needed in order to confirm these results before the implementation of this biomarker in clinical practice.

Launch and preliminary analysis of Hospital de La Princesa's inter-specialists biological therapies unit.

We herein describe an inter-specialists unit for the monitoring and management of biological therapies and analyze the utilization of biological agents across specialties and diseases. Protocols and therapeutic objectives, as well as outcomes and protocol deviations, are shared and discussed periodically between specialists. All patients treated at one centre with any biological treatment from January 2000 by rheumatology, gastroenterology, dermatology, or neurology, regardless diagnosis, are identified by Clinical Pharmacy and included in an ongoing database that detects use and outcome. The drugs, survival, and reasons for discontinuation differ significantly across specialties. This approach has helped us recognizing the challenges and size of the problem of sharing expensive medications across specialties, and has served as a starting point to contribute to the better use of these compounds.

Development of clinical prediction models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis, based on the BIOBADADERM cohort.

BACKGROUND: Identifying patients likely to have very good or bad results from systemic psoriasis therapy could improve efficiency of therapy. OBJECTIVE: To develop prognostic models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis. METHODS: Multivariable logistic regression of a prospective multicenter cohort of psoriatic patients in clinical practice (6449 person-years of follow-up). We used as possible predictors demographic characteristics, comorbidities, characteristics of the psoriasis (type, PASI, arthritis), history of past therapy at entry in the cohort, and history of response to previous cycles while in the cohort. We defined good response to a treatment cycle as either cycle end due to disease remission or a cycle longer than 2 years that does not end later due to inefficacy in the follow-up period. Bad response to a treatment cycle was defined as a cycle that is finished due to inefficacy, based on the physician judgment, after more than 3 months of treatment. RESULTS: Patients with fewer previous therapies, lower body mass index, older at start of therapy, and with previous history of good responses to therapy are more likely to have positive results of therapy. However, the predictive characteristics of models are poor. CONCLUSION: Predictive models of clinical response to systemic drugs in psoriasis with the studied variables do not seem to outperform drug selection by a dermatologist.

Use of off-label doses is frequent in biologic therapy for moderate to severe psoriasis: A cross-sectional study in clinical practice.

INTRODUCTION: Biologic medications increase dramatically the burden of a chronic and high prevalent disease like psoriasis. The objective of the study was to quantify the use of dose reduction or dose escalation strategies, not reflected in the drug summary of product characteristics, in clinical practice. METHODS: An observational, cross-sectional study of a subset of patients from the Spanish Registry for Systemic Treatments in Psoriasis (BIOBADADERM) treated for over six consecutive months with the same biologic agent. RESULTS: The study included 637 patients. At the cut-off date, the initial dose had been reduced in 223 patients (35%; 95% CI: 31.3-38.9%) and escalated in 46 (7.2%; 95% CI: 5.3-9.5%). When compared with the patients treated with standard doses, the patients on reduced doses had a lower PASI score at the cut-off date (a mean 2.6 versus 1; -1.6 points) and exhibited greater improvement in PASI since the start of biologic therapy (mean reduction over baseline 75% versus 87%). By contrast, the patients receiving an escalated dose had higher PASI scores (2.6 versus 8.0) and showed less improvement in PASI (75% versus 46.8%). CONCLUSION: Off-label doses of biologic agents for psoriasis are frequent in clinical practice. This information is especially relevant for pharmacoeconomic models.

Pharmacogenetics of topical and systemic treatment of psoriasis.

Psoriasis is a chronic inflammatory skin disease. The cause of psoriasis is unknown, although genetics may play a key role in its development. Treatment of the disease varies with severity. Topical drugs, such as corticosteroids, coal tar, retinoids and vitamin D analogs, are commonly used to treat mild psoriasis. Phototherapy and systemic drugs, such as calcineurin inhibitors, methotrexate, acitretin and biological drugs, are usually used to treat moderate-to-severe psoriasis. Not all patients respond well to treatment, and some can develop severe adverse effects. Interindividual differences in several genes may explain this variation in response to treatment. Pharmacogenetics and pharmacogenomics can facilitate more personalized medicine and prevent the adverse effects associated with treatment.

Risk of serious adverse events associated with biologic and nonbiologic psoriasis systemic therapy: patients ineligible vs eligible for randomized controlled trials.

OBJECTIVE: To describe the use of systemic therapy for psoriasis (biologic and nonbiologic [classic] drugs) in patients not adequately represented in randomized controlled trials (RCTs) and the risk of serious adverse events (SAEs) in these patients. DESIGN: A registry inception cohort was used. SETTING: Thirteen dermatology departments in Spain participated. PATIENTS: A consecutive sample of patients treated with biologics and a systematic sample of patients treated with classic systemic therapy were evaluated. A total of 1042 patients (2179 person-years) were included. EXPOSURE: Inadequate representation in trials was defined as the presence of any of the following factors: elderly age (>70 years); type of psoriasis other than chronic plaque psoriasis; history of infection caused by hepatitis B, hepatitis C, or human immunodeficiency virus; history of cancer (excluding nonmelanoma skin cancer); and chronic renal or hepatic disease. MAIN OUTCOME MEASURES: Serious adverse events as defined by the International Conference on Harmonization were evaluated. RESULTS: In all, 29.8% of patients receiving systemic therapy for psoriasis would not have been eligible for RCTs. These individuals had an increased risk of SAEs (incidence rate ratio, 2.7; 95% CI, 1.5-4.7). Patients exposed to biologics had an adjusted increased risk of SAEs (incidence rate ratio, 2.3; 95% CI, 1.1-4.8) that was similar in patients eligible and ineligible for RCTs. CONCLUSIONS: Patients ineligible for RCTs are an important proportion (30%) of those receiving systemic therapy for psoriasis. These patients have a higher risk of SAEs and should be closely monitored. Patients exposed to biologics (whether these patients are eligible for RCTs or ineligible) are susceptible to the same increase in risk of SAEs, but biologics add to a higher baseline risk in patients who are ineligible for RCTs. The risk-benefit ratio in ineligible patients receiving biologics might be different from the ratio in eligible patients.

Treatment and management of psoriasis with nail involvement: a focus on biologic therapy.

Nail involvement in psoriasis is typically overlooked, although it can affect up to 50% of patients with psoriasis and cause functional impact as well as psychological stress that can significantly affect quality of life. In addition, psoriatic patients with nail disease tend to have a more severe skin condition, a higher rate of unremitting and progressive arthritis and more associated anxiety and depression. Historically, the treatment of nail psoriasis has proven difficult, with most patients feeling that the treatment for their nail disease was unsatisfactory. The current management of nail psoriasis includes topical, intralesional and systemic therapies, although little clinical evidence is available on the effectiveness of conventional treatments and, consequently, no specific treatment approach has been fully supported. Biologic agents are beginning to emerge as a viable option to treat patients with both cutaneous and nail clinical manifestations of psoriasis and psoriatic arthritis. The extra disease burden that nail symptoms place on the patient can be considered indicative of a more severe form of the disease and should be taken into consideration when assessing treatment options.