Changing Trends in Drug Prescription and Causes of Treatment Discontinuation of First Biologic Over Ten Years in Psoriasis in the Spanish Biobadaderm Registry. / Cambios en las tendencias de la prescripción y causas de la interrupción en los tratamientos biológicos indicados en la psoriasis durante los primeros 10 años. Datos obtenidos del registro español Biobadaderm.

BACKGROUND AND OBJECTIVES: Current psoriasis guidelines do not usually include recommendations about first line classical or biologic treatment. The objectives of this study were: to describe shifts in the prescription of the first biological treatment, and to compare treatment withdrawal and rates of adverse events over ten years. MATERIAL AND METHODS: Biobadaderm registry was analyzed to describe: first biological prescription in bio-naïve patients, adverse events rate and reasons for drug withdrawal comparing three periods of time (2008-2010, 2011-2014, 2015-2018). RESULTS: Anti-TNF drugs were the most prescribed biological drug from 2008 to 2010. Ustekinumab has become the most prescribed first biologic since 2014. The main reasons for drug discontinuation were adverse events, lack of efficacy and remission. In each period any treatment was less likely to be discontinued due to any of these three reasons comparing to the previous period. CONCLUSIONS: The present study identifies trends in prescription of the first biological antipsoriatic drug in clinical practice from 2008 to 2018. It suggests that we have become more comfortable with the safety profile and more exigent with the efficacy of the drugs.

Description of Patients Treated with Biologic Drugs as First-Line Systemic Therapy in the BIOBADADERM Registry Between 2008 and 2016. / Descripción de los pacientes que reciben biológicos como primer tratamiento sistémico en el registro BIOBADADERM durante el periodo 2008-2016.

INTRODUCTION AND OBJECTIVES: Biologic drugs are usually prescribed as second-line treatment for psoriasis, that is, after the patient has first been treated with a conventional psoriasis drug. There are, however, cases where, depending on the characteristics of the patient or the judgement of the physician, biologics may be chosen as first-line therapy. No studies to date have analyzed the demographics or clinical characteristics of patients in this setting or the safety profile of the agents used. The main aim of this study was to characterize these aspects of first-line biologic therapy and compare them to those observed for patients receiving biologics as second-line therapy. MATERIAL AND METHOD: We conducted an observational study of 181 patients treated in various centers with a systemic biologic drug as first-line treatment for moderate to severe psoriasis between January 2008 and November 2016. All the patients were registered in the Spanish Registry of Adverse Events Associated with Biologic Drugs in Dermatology. RESULTS: The characteristics of the first- and second-line groups were very similar, although the patients receiving a biologic as first-line treatment for their psoriasis were older. No differences were observed for disease severity (assessed using the PASI) or time to diagnosis. Hypertension, diabetes, and liver disease were all more common in the first-line group. There were no differences between the groups in terms of reasons for drug withdrawal or occurrence of adverse effects. CONCLUSIONS: No major differences were found between patients with psoriasis receiving biologic drugs as first- or second-line therapy, a finding that provides further evidence of the safety of biologic therapy in patients with psoriasis.

Cumulative exposure to biological therapy and risk of cancer in patients with psoriasis: a meta-analysis of Psonet studies from Israel, Italy, Spain, the U.K. and Republic of Ireland.

BACKGROUND: Cancer risk following long-term exposure to systemic immunomodulatory therapies in patients with psoriasis is possible. OBJECTIVES: To assess a dose-response relationship between cumulative length of exposure to biological therapy and risk of cancer. METHODS: Four national studies (a healthcare database from Israel, and prospective cohorts form Italy, Spain and the U.K. and Republic of Ireland) collaborating through Psonet (European Registry of Psoriasis) participated in these nested case-control studies, including nearly 60 000 person-years of observation. 'Cases' were patients who developed an incident cancer. Patients with previous cancers and benign or in situ tumours were excluded. Four cancer-free controls were matched to each case on year of birth, sex, geographic area and registration year. Follow-up for controls was censored at the date of cancer diagnosis for the matched case. Conditional logistic regression was performed by each registry. Results were pooled using random-effects meta-analysis. RESULTS: A total of 728 cases and 2671 controls were identified. After matching, differences between cases and controls were present for the Charlson Comorbidity Index in all three registries, and in the prevalence of previous exposure to psoralen-ultraviolet A and smoking (the British Association of Dermatologists Biologic Interventions Register only). The risk of first cancers was not significantly associated with cumulative exposure to biologics (adjusted odds ratio per year of exposure 1·02, 95% confidence interval 0·92-1·13). Results were similar if squamous and basal cell carcinomas were included in the outcome. CONCLUSIONS: Cumulative length of exposure to biological therapies in patients with psoriasis in real-world clinical practice does not appear to be linked to a higher risk of cancer after several years of use.

Comparison of phenotype, comorbidities, therapy and adverse events between psoriatic patients with and without psoriatic arthritis. Biobadaderm registry.

BACKGROUND: There are a limited number of studies comparing psoriasis patients without psoriatic arthritis (PsA) to those with arthritis. Previous results are controversial. OBJECTIVES: To perform a comparative analysis of the phenotype, baseline comorbidities, therapeutic profile and incidence of adverse events (particularly overall adverse events, infections and infestations, malignancies and psychiatric disorders) among psoriatic patients with/without PsA. METHODS: All the patients on the Biobadaderm registry, a prospective inception cohort of psoriasis patients on systemic therapy, were included. Patients were divided into two groups: those with psoriasis without arthritis at the time of entry into the cohort (Pso group) and those with psoriasis and psoriatic arthritis (PsA group) at entry. Patients were followed until the censorship date (last visit in a lost-to-follow-up patient, or 10 November 2015, whichever occurred first). We excluded all the patients who developed any kind of signs and/or symptoms of joint involvement during the follow-up. A descriptive analysis was performed. We estimated incidence ratios (IRR) of adverse events during systemic treatment using a mixed-effects Poisson regression. RESULTS: We included 2120 patients: 1871 (88%) patients with psoriasis without arthritis and 249 (12%) with psoriasis and PsA. The follow-up time was 5020 patients-year in the Pso group and 762 patients-year in the PsA group. Patients with PsA had more comorbidities, particularly hypertension and liver disease; used a higher number of systemic therapies, particularly anti-TNFα drugs and combination therapy; and presented more adverse events (IRR adjusted = 1.29; 95% CI: [1.05-1.58]), particularly serious adverse events (IRR adjusted = 1.51; 95% CI: [1.01-2.26]) and infections/infestations (IRR adjusted = 1.88; 95% CI: [1.27-2.79]), independently of the associated comorbidities and present/past therapies. CONCLUSIONS: Given the differences between patients with psoriasis alone or with psoriasis associated with PsA, patients with psoriasis and PsA should be followed and managed more closely and with specific attention.

Management of Biologic Therapy in Moderate to Severe Psoriasis in Surgical Patients: Data From the Spanish Biobadaderm Registry. / Manejo de los tratamientos biológicos en pacientes con psoriasis moderada-grave sometidos a intervenciones quirúrgicas en el registro español Biobadaderm.

BACKGROUND AND OBJECTIVE: We now have considerable experience in the use of biologic agents to treat psoriasis, but doubts about management arise in certain clinical settings. Surgery is one of them. Although treatment guidelines advise that biologics be suspended before major surgery, data about actual clinical practices and associated complications are lacking. We aimed to analyze current practice in the clinical management of these cases. METHODS: Retrospective study of cases in the Biobadaderm database. We analyzed the management of biologic therapy in patients with psoriasis who underwent surgical procedures. RESULTS: Forty-eight of the 2113 patients registered in Biobadaderm underwent surgery. The largest percentage of procedures (31%) involved skin lesions. Biologic treatment was interrupted in 42% of the cases. No postsurgical complications were significantly related to treatment interruption. Likewise we detected no associations between treatment interruption and other variables, such as sex, age, or duration or severity of psoriasis. CONCLUSION: Continuity of biologic treatment and the risk of postsurgical complications were not associated in this study, although conclusions are limited by the small sample size.

Risk of adverse events in psoriasis patients receiving classic systemic drugs and biologics in a 5-year observational study of clinical practice: 2008-2013 results of the Biobadaderm registry.

BACKGROUND: Biobadaderm is the Spanish registry of psoriasis patients receiving systemic treatment in clinical practice. OBJECTIVE: To compare the safety of biologics and classic systemic treatment. METHODS: Prospective cohort of patients receiving biologics and classic systemic therapies between 2008 and 2013 in 12 hospitals are included. We registered demographic data, diagnoses, comorbidities, treatments and adverse events (AE). We obtained raw relative risks (RR) for specific AE. Multivariate analysis consisted of Cox models adjusting for age, gender, chronic hepatic disease and previous cancer. RESULTS: A total of 1030 patients received biologics (2061 AE in 3681 person-years), 926 patients classic systemic drugs (1015 AE in 1517 person-years). Ninety-three per cent of AE in both groups were non-serious, 6% serious and 0.003% fatal. The age- and gender-adjusted hazard ratio of AE was lower in the biologics group [hazard ratio 0.6 (95% CI: 0.5-0.7)].We found no differences in rates of serious and mortal AE. Some system organ class AE rates differed between both groups. As limitations: Prescription bias might affect the incidence of AE in both groups. Association of drug and AE was based on timing: associations might not be causal. CONCLUSION: Patients receiving biologics had lower risk of AE. We did not find differences in the risk of serious or fatal AE.

Chemopreventive potential of phenolic compounds in oral carcinogenesis.

OBJECTIVE: To evaluate the chemopreventive potential of phenolic compounds - potassium apigenin, cocoa, catechins, eriocitrin and rosmarinic acid in oral carcinogenesis induced in hamsters by means of the topical application of 7,12-dimethylbenz(a)anthracene(DMBA). STUDY DESIGN: An experimental study at the University of Murcia. METHODS: 50 male Syrian hamsters (Mesocricetus auratus) were divided into five groups of ten: Group I (control group): 0.5% DMBA; Group II: 0.5% DMBA+1.1mg/15ml potassium apigenin; Group III: 05% DMBA+2.5mg/15ml cocoa catechins; Group IV: 0.5% DMBA+6mg/15ml eriocitrin; Group V: 0.5% DMBA+1.3mg/15ml rosmarinic acid. The flavonoids were administered orally. All the animals were sacrificed after 12 weeks. Macroscopic, microscopic and immunohistochemical (PCNA and p53) analyses of the lesions were performed. RESULTS: All the groups treated with phenolic compounds showed lower incidences of tumour, greater differentiation and lower scores in the tumour invasion front grading system in comparison with the control group. Potassium apigenin and rosmarinic acid achieved the best results, the former considerably reduced the carcinoma tumour volumes developed and both significantly reduced the intensity and aggression of the tumours. Immunoexpression of PCNA and p53 were significantly altered during DMBA-induced oral carcinogenesis. CONCLUSIONS: Animals treated with phenolic compounds, particularly potassium apigenin and rosmarinic acid, showed a lower incidence of tumours.

Effect of the phenolic compounds apigenin and carnosic acid on oral carcinogenesis in hamster induced by DMBA.

OBJECTIVE: To investigate oral carcinogenesis in hamster induced by the topical application of 7,12-dimethyl benzanthracene (DMBA) to evaluate the different lesions produced and the possible preventive effects of the phenolic compounds apigenin (flavone) and carnosic acid (diterpene). MATERIALS AND METHODS: Thirty-two Syrian hamsters were divided into three groups: I: 0.5% DMBA (n = 12); II: 0.5% DMBA + potassium apigenin (n = 8); III: 0.5% DMBA + carnosic acid (n = 12). All the animals were sacrificed after 11 weeks, and a macroscopic and light microscopic study was made of the lesions. RESULTS: The largest number of neoplasms, showing the most aggressive biological behavior, corresponded to the control group. The group treated with potassium apigenin ranked second in tumor incidence, although the tumors were not very aggressive behavior. In the group treated with carnosic acid, only one malignancy was recorded, showing the smallest volume of all the recorded tumor lesions. CONCLUSIONS: Our findings indicate that both potassium apigenin and carnosic acid have chemoprotective effects against carcinogenesis induced by DMBA in hamster.