Therapeutic goals and treatment response evaluation in moderate to severe psoriasis: an experts opinion document

Objective: To critically analyse and define therapeutic objectives, response to treatment evaluation and related decisions in psoriasis. Methods: Expert consensus meetings, a systematic and narrative reviews and a collaborative Delphi procedure were carried out. A steering committee from the Spanish Group of Psoriasis was established who based on the reviews generated a set of related statements. Subsequently, a group of 40 experts tested their agreement with the statements, through 3 Delphi rounds. Results: We found a great variability in clinical guidelines regarding to the definition of treatment goal and the response. In general, treatment failure was considered if a PASI50 is not 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 reachedThis project was promoted and funded by the Spanish Academy of Dermatology and Venereology (AEDV) with unrestricted grant from Leo Pharma

PASI 100 response rates in moderate to severe psoriasis: a systematic literature review and analysis of clinical practice guidelines

Background Response to treatments in psoriasis can be assessed using the PASI response 50, 75, 90 or 100. Achieving a PASI 100 response would mean a complete resolution of the patient's basal lesions. Therefore, PASI 100 score has been increasingly used in the context of research, but its role in daily practice is currently controversial. Objective (1) To analyze PASI 100 response rates to pharmacological treatments; (2) To examine clinical practice guidelines (CPGs) recommendations/comments on PASI 100. Methods We conducted a systematic literature review (SLR). Selection criteria concerned patients with psoriasis, reporting PASI 100. Results Overall, 65 studies were included. Patients on methotrexate achieved at 16 weeks a PASI 100 of 7.3%. For TNF inhibitors rates were: 3.7–11.1% at 12 weeks, 13.7–20% at 16 weeks, 10.7–24% at 24 weeks and 21.8–34.8% at 1 year. IL-17 inhibitors achieved 23.3–44% at 12 weeks, 44.3–57.2% at 16 weeks, 39.7–67.5% at 24 weeks and 41.4–67.5% at 1 year. And the reported by IL-12/23 inhibitors were 12%/23.8% at 12 weeks, 32.7%/50% at 16 weeks, 44% at 24 weeks and 41.8%/56.3% at 1 year. PASI 100 response is scarcely commented in the CPGs. Conclusions PASI 100 response rate is an endpoint fundamentally restricted to research

Urine metabolome profiling of immune-mediated inflammatory diseases

BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) are a group of complex and prevalent diseases where disease diagnostic and activity monitoring is highly challenging. The determination of the metabolite profiles of biological samples is becoming a powerful approach to identify new biomarkers of clinical utility. In order to identify new metabolite biomarkers of diagnosis and disease activity, we have performed the first large-scale profiling of the urine metabolome of the six most prevalent IMIDs: rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn's disease, and ulcerative colitis. METHODS: Using nuclear magnetic resonance, we analyzed the urine metabolome in a discovery cohort of 1210 patients and 100 controls. Within each IMID, two patient subgroups were recruited representing extreme disease activity (very high vs. very low). Metabolite association analysis with disease diagnosis and disease activity was performed using multivariate linear regression in order to control for the effects of clinical, epidemiological, or technical variability. After multiple test correction, the most significant metabolite biomarkers were validated in an independent cohort of 1200 patients and 200 controls. RESULTS: In the discovery cohort, we identified 28 significant associations between urine metabolite levels and disease diagnosis and three significant metabolite associations with disease activity (P FDR < 0.05). Using the validation cohort, we validated 26 of the diagnostic associations and all three metabolite associations with disease activity (P FDR < 0.05). Combining all diagnostic biomarkers using multivariate classifiers we obtained a good disease prediction accuracy in all IMIDs and particularly high in inflammatory bowel diseases. Several of the associated metabolites were found to be commonly altered in multiple IMIDs, some of which can be considered as hub biomarkers. The analysis of the metabolic reactions connecting the IMID-associated metabolites showed an over-representation of citric acid cycle, phenylalanine, and glycine-serine metabolism pathways. CONCLUSIONS: This study shows that urine is a source of biomarkers of clinical utility in IMIDs. We have found that IMIDs show similar metabolic changes, particularly between clinically similar diseases and we have found, for the first time, the presence of hub metabolites. These findings represent an important step in the development of more efficient and less invasive diagnostic and disease monitoring methods in IMIDs