Topical and Intralesional Therapies for Hidradenitis Suppurativa: A Systematic Literature Review.

BACKGROUND AND OBJECTIVE: Topical and intralesional (IL) treatments may be considered the first-line therapy in patients with hidradenitis suppurativa (HS); however, the evidence supporting their use is limited. The aim of our review is to evaluate the efficacy and safety profile of topical and IL treatments in patients with HS. MATERIALS AND METHODS: We designed a systematic review of the current medical literature available following the PICO(T) method. And including all types of studies (Study type [T]) of individuals with HS of any sex, age, and ethnicity (Population [P]) who received any topical or IL treatment for HS (Intervention [I]) compared to placebo, other treatments, or no treatment at all (Comparator [C]), and reported efficacy and/or safety outcomes (Outcomes [O]). Two outcomes were defined: quality of life and the no. of patients with, at least, one adverse event. The search was conducted in the Cochrane Library, MEDLINE, and EMBASE databases; study selection was performed based on pre-defined criteria. The risk of bias was determined in each study. RESULTS: We obtained a total of 11,363 references, 31 of which met the inclusion criteria. These studies included 1143 patients with HS, 62% of whom were women. A total of 10, 8, 6, 2, and 5 studies, respectively, evaluated the use of photodynamic therapy (PDT), glucocorticoids, resorcinol, topical antibiotics, and other interventions. Most articles were case series (n=25), with only five randomized clinical trials (RCTs) and one cohort study. RCTs showed improvement in disease activity with topical clindamycin and botulinum toxin (BTX) vs placebo, and PDT with methylene blue (MB) niosomal vs free MB; however, intralesional triamcinolone acetonide was not superior to placebo. The risk of bias was low in three RCTs and high in two RCTs. CONCLUSION: The quality of evidence supporting the use of topical, or IL treatments is low. However, it supports the use of topical clindamycin, PDT, and BTX. Well-designed RCTs with standardized outcomes and homogeneous populations of patients and lesions are needed to support decision-making in the routine clinical practice.

Common Approach to Metabolic-Associated Fatty Liver Disease in Patients With Psoriasis: Consensus-Based Recommendations From a Multidisciplinary Group of Experts. / Abordaje común del paciente con psoriasis y riesgo de esteatosis hepática metabólica: recomendaciones de un grupo de expertos multidisciplinar.

Recent years have seen concerted efforts to understand the relation between psoriasis and metabolic-associated fatty liver disease (MAFLD). Not only is MALFD diagnosed more often in patients with psoriasis, but its clinical course is also more aggressive. A common approach is therefore needed to enable early detection of liver disease coincident with psoriasis. Especially important is an analysis of risks and benefits of potentially hepatotoxic treatments. This consensus paper presents the recommendations of a group of experts in dermatology and hepatology regarding screening for MALFD as well as criteria for monitoring patients and referring them to hepatologists when liver disease is suspected.

Moderate to Severe Psoriasis in Older Adults: Recommendations on Management from the Psoriasis Working Group of the Spanish Academy of Dermatology and Venereology (AEDV). / Recomendaciones del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología sobre el manejo del paciente de edad avanzada con psoriasis en placas moderada-grave.

Managing moderate to severe psoriasis in older adults is complex due to factors characteristic of the later years of life, such as associated comorbidity, polypharmacy, and immunosenescence. This consensus statement discusses 17 recommendations for managing treatment for moderate to severe psoriasis in patients older than 65 years. The recommendations were proposed by a committee of 6 dermatologists who reviewed the literature. Fifty-one members of the Psoriasis Working Group of the Spanish Academy of Dermatology and Venereology (AEDV) then applied the Delphi process in 2 rounds to reach consensus on which principles to adopt. The recommendations can help to improve management, outcomes, and prognosis for older adults with moderate to severe psoriasis.

Nail Psoriasis. / Psoriasis ungueal.

Nail involvement in psoriasis is common. It is seen in up to 80% of patients with psoriatic lesions and may be the only manifestation in 6% of cases. Nail psoriasis is correlated with more severe disease, characterized by earlier onset and a higher risk of psoriatic arthritis. Accordingly, it can also result in significant functional impairment and reduced quality of life. Psoriasis involving the nail matrix causes pitting, leukonychia, red lunula and nail dystrophy, while nail bed involvement causes splinter hemorrhages, onycholysis, oil spots (salmon patches), and subungual hyperkeratosis. Common evaluation tools are the Nail Psoriasis Severity Index (NAPSI), the modified NAPSI, and the f-PGA (Physician's Global Assessment of Fingernail Psoriasis). Treatment options include topical therapy, intralesional injections, and systemic and biologic agents. Treatment should therefore be assessed on an individualized basis according to the number of nails involved, the part of the nail or nails affected, and the presence of concomitant nail and/or joint involvement.

Implementation of Recommendations for the Management of Psoriasis During Preconception, Pregnancy, Postpartum, Breastfeeding, and Perinatal Care. / Implementación de las recomendaciones sobre las actuaciones a seguir durante la edad fértil, el embarazo, el posparto, la lactancia y el cuidado perinatal en pacientes con psoriasis.

OBJECTIVE: To analyze degree of implementation of recommendations on the management of psoriasis during preconception, pregnancy, postpartum, breastfeeding, and perinatal care published by the Psoriasis Working Group of the Spanish Academy of Dermatology and Venereology (AEDV). METHODS: We designed a structured online survey consisting of closed questions. A link was emailed to all the members of the Psoriasis Working Group to collect their anonymous responses. We also collected sociodemographic, professional, and practice-related data related to the goals of the study and then compiled descriptive statistics to analyze the survey findings. RESULTS: We received 53 responses for analysis. Overall, 96% of respondents were familiar with the recommendations, but very few of them worked in multidisciplinary maternity care units or had access to specific protocols on the management of psoriasis before, during, and after pregnancy in their departments. Seventy percent of dermatologists regularly ask their patients about pregnancy plans, but only 46% ask both men and women. Women also receive more preconception advice than men (54% vs. 19%). Significant variations were observed in the type of advice given. Ninety percent of the dermatologists interrupt topical treatments during pregnancy, and nearly all suspend conventional systemic drugs with the exception of cyclosporin A. Most biologics are also being discontinued in the third trimester, with the exception of certolizumab pegol. Almost all the respondents indicated that they use topical treatments, phototherapy, and certolizumab pegol in breastfeeding mothers. The main barriers to implementing the working group's recommendations are a lack of time, a lack of support, and a lack of robust data. CONCLUSIONS: Although the AEDV psoriasis working group's recommendations are widely known, areas for improvement remain.

Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience. / Psoriasis moderada-grave en pacientes pediátricos y jóvenes: experiencia en el registro BIOBADADERM.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.

Definition of minimal disease activity in psoriasis.

OBJECTIVE: To generate an operational definition to adequately reflect the construct 'Minimal Disease Activity (MDA)' in psoriasis. METHODS: A systematic review of domains included in clinical trials of psoriasis was presented to a panel of dermatologists and patients. Further domains were elicited by panel discussions. Domains (and instruments measuring these) were items of two consecutive Delphi rounds targeting dermatologists from the Psoriasis Group of the Spanish Academy of Dermatology and Venereology and patients from the Acción Psoriasis association. The instruments selected were used to generate 388 patient vignettes. The expert group then classified these vignettes as 'No MDA/MDA/Unclassifiable'. The items were further reduced by factorial analysis. Using the classification variable as gold standard, several operational constructions were tested in regression models and ROC curves and accuracy was evaluated with area under the curve (AUC). RESULTS: The following domains were included: itching, scaling, erythema and visibility by 0-10 scales, extension by BSA, impact on quality of life by DLQI, special location and presence of arthritis as yes/no. The definition with the highest AUC and best balance between sensitivity and specificity was the one including no presence of arthritis plus at least three others below the upper limit of the 95% confidence interval (AUC, 0.897; sensitivity, 95.2%, specificity, 84.1%). CONCLUSION: This study provides, for the very first time, the construct of 'Minimal Disease Activity' in psoriasis as agreed by dermatologists and patients. MDA is defined as absence of active arthritis plus 3 out of 6: itching ≤ 1/10; scaling ≤ 2/10; redness ≤ 2/10; visibility ≤ 2/10; BSA ≤ 2; DLQI ≤ 2; and no lesions in special locations. By design, domains are representative of disease impact. This MDA definition may be used as a measure of adequate management and replace other subjective or restrictive tools.

Real-world effectiveness and safety of apremilast in psoriasis at 52 weeks: a retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Little has been published on the real-world effectiveness and safety of apremilast in psoriasis. OBJECTIVES: To evaluate the effectiveness, safety and drug survival of apremilast at 52 weeks in patients with moderate to severe plaque psoriasis or palmoplantar psoriasis in routine clinical practice. METHODS: Retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis or palmoplantar psoriasis treated with apremilast from March 2016 to March 2018. RESULTS: We studied 292 patients with plaque psoriasis and 85 patients with palmoplantar psoriasis. The mean (SD) Psoriasis Area and Severity Index (PASI) score was 10.7 (7.0) at baseline and 3.0 (4.2) at 52 weeks. After 12 months of treatment, 73.6% of patients had a PASI score of 3 or less. In terms of relative improvement by week 52, 49.7% of patients achieved PASI-75 (≥75% reduction in PASI score) and 26.5% achieved PASI-90. The mean physician global assessment score for palmoplantar psoriasis fell from 4.2 (5.2) at baseline to 1.3 (1.3) at week 52. Overall drug survival after 1 year of treatment with apremilast was 54.9 %. The main reasons for treatment discontinuation were loss of efficacy (23.9%) and adverse events (15.9%). Almost half of the patients in our series (47%) experienced at least one adverse event. The most common events were gastrointestinal problems. CONCLUSIONS: Apremilast may be a suitable alternative for the treatment of moderate to severe psoriasis and palmoplantar psoriasis. Although the drug has a good safety profile, adverse gastrointestinal effects are common.

Adverse events associated with discontinuation of the biologics/classic systemic treatments for moderate-to-severe plaque psoriasis: data from the Spanish Biologics Registry, Biobadaderm.

BACKGROUND: Little is known about the adverse events (AEs) that lead to suspension of systemic treatments for psoriasis in clinical practice. OBJECTIVE: The study aimed to investigate AEs associated with discontinuation of systemic therapy in patients with psoriasis in a clinical setting (Biobadaderm). MATERIALS AND METHODS: Multicentre, prospective, cohort study of patients with moderate-to-severe plaque psoriasis receiving systemic therapies from January 2008 to November 2015, in 12 hospitals in Spain. The incidence rate (IR) was used to compare biologics and classic systemic therapies. RESULTS: A total of 4218 courses of treatment were given to 1938 patients. A total of 447 (11%) treatments were discontinued due to AEs. The IR of AE associated with discontinuation of systemic therapies was 13 events/100 patient-years (PY) (95% CI: 12.14-13.93), 9.34 events/100 PY (95% CI: 8.44-10.33) for biologics and 19.67 (95% CI: 17.9-21.6) events/100 PY for classics (P < 0.001). Of 810 discontinuation-related AEs, 117 (14%) were serious. The highest IRs were for cyclosporine [49.18/100 PY (95% CI: 41.91-57.72)] and infliximab [26.52/100 PY (95% CI: 20.98-33.51). Ustekinumab presented the lowest IR (2.6/100 PY (95% CI: 1.83-3.69). LIMITATIONS: Observational study with potential selection bias. CONCLUSION: Biologic therapies are associated with a lower rate of discontinuation-related AEs than are classic therapies in real clinical practice. Ustekinumab showed the lowest incidence.

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.

Survival of classic and biological systemic drugs in psoriasis: results of the BIOBADADERM registry and critical analysis.

BACKGROUND: Few reported studies compare drug survival in moderate-to-severe psoriasis vulgaris. OBJECTIVES: To describe and compare drug survival of systemic drugs, including biologic agents (infliximab, etanercept, adalimumab and ustekinumab) and classical drugs (acitretin, ciclosporin and methotrexate) in moderate-to-severe psoriasis. METHODS: This was a multicenter, prospective, cohort study of patients receiving systemic therapies between 2008 and 2013 in 12 hospitals in Spain. Baseline data and drug discontinuation were collected. Drug survival is presented using Kaplan-Meier survival curves. We compared adjusted risk ratios of serious adverse events (AEs) with results of survival analysis for AEs. RESULTS: A total of 1956 patients were included for analysis (1240 exposed to biologics during follow-up and 1076 to classic therapies). Median follow-up time was 3.3 years (0.0-5.1 years). There were 2209 discontinuations out of 3640 therapy cycles started. The main reason for discontinuation was lack of efficacy (36.4%) and remission (27.2%). Biologics showed a higher drug survival than classics and the pattern of survival results for all outcomes (positive or negative) were very similar. Adjusted risk ratios of serious AEs did not agree with results of survival analysis. LIMITATIONS: A limitation is that this is an observational study with potential selection bias. CONCLUSION: Survival as a proxy measure of drug safety in psoriasis is inadequate.

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.

Safety of classic and biologic systemic therapies for the treatment of psoriasis in elderly: an observational study from national BIOBADADERM registry.

BACKGROUND: Psoriasis patients over 65 years-old (elderly) constitute a growing group, underrepresented in clinical trials, and likely to be more prone to adverse events. OBJECTIVE: To describe safety of systemic psoriasis therapy in patients over 65 years-old compared to younger patients. METHODS: Patients registered in Biobadaderm, a Spanish national registry of psoriasis patients treated with systemic therapy, were grouped in elderly (≥ 65 years old) and younger patients. Rates of adverse events were described by severity and type, and the risks compared in both groups, taking into account exposure to classic or biologic drugs, using Cox regression. RESULTS: 175 (9.8%) of 1793 patients were elderly. Overall risk of adverse events was not higher in elderly (drug group adjusted HR 1.09 (95%CI: 0.93-1.3)). Serious adverse events were more common in elderly (drug group adjusted HR 3.2 (95%CI: 2.0-5.1)). Age adjusted HR of all adverse events was lower for patients exposed to biologics compared to classic drugs in the whole sample (HR 0.7 (95%CI: 0.6-0.7)). Age did not seem to modify the effect of therapy (biologic vs. classic) in the risk of adverse events (likelihood ratio test for interaction, p = 0.12 for all adverse events, p = 0-09 for serious adverse events). CONCLUSIONS: Serious adverse events are more common in elderly patients, although they may be related to other variants that are associated with this age group and not due to the treatment itself. Use of biologics was associated with lower risk of adverse events in the whole group. We found no differences in this association between young and elderly. These results are reassuring, although uncontrolled confounding could not be excluded as an explanation for these findings, and the power of the study to detect differences was low.

Expert recommendations on treating psoriasis in special circumstances.

INTRODUCTION AND OBJECTIVES: A great amount of information on systemic and biologic therapies for moderate to severe psoriasis is now available. However, applying the evidence in numerous clinical scenarios has engendered debate; under these circumstances, the consensus of experts is useful. MATERIAL AND METHODS: A scientific committee systematically reviewed the literature relevant to 5 clinical scenarios. An online Delphi survey of dermatologists with experience treating moderate to severe psoriasis was then carried out in order to shed light on questions that remained unresolved by the available evidence. RESULTS: Twenty-three dermatologists responded to the survey and consensus was reached on 37 (56%) of the 66 statements proposed. These results led to consensus on various clinical situations even though firm evidence was lacking. Thus, intermittent therapeutic regimens and strategies for reducing the intensity of treatment are considered appropriate for optimizing biologic treatment and reducing costs. The measurement of drug and antidrug antibody levels should be included routinely when following patients on biologics to treat psoriasis. Concomitant psoriatic arthritis or a history of cardiovascular conditions will influence the choice of biologic; in these situations, an agent with anti-tumor necrosis factor properties will be preferred. Tailored management is important when the patient is pregnant or intends to conceive; drug half-life and disease severity are important factors to take into consideration in these scenarios. CONCLUSIONS: A combination of systematic review of the literature and structured discussion of expert opinion facilitates decision-making in specific clinical scenarios.

Does the treatment ladder for systemic therapy in moderate to severe psoriasis only go up? The percentage of patients with severe psoriasis on biologics increases over time.

BACKGROUND: With the advent of biologic drugs in the management of moderate to severe psoriasis, there may have been a shift in therapeutic approach from rotational strategies to a unidirectional progression from topical treatments to the highest rung of the therapeutic ladder. We studied the frequency of switching from classic to biologic therapy and vice versa in a cohort of patients with psoriasis over a period of up to 5 years. METHODS: Patients are included in the BIOBADADERM prospective registry when they are first prescribed any specific conventional or biologic systemic treatment. The data for each patient refer to the follow-up period from the time they entered the cohort until October 2013. To describe the pattern of switches from classic to biologic therapy and vice versa, we used the data in the registry on the first day of every 365-day period following the date each patient was included in the cohort. RESULTS: In total, 47.3% of the patients (926/1956) were prescribed a classic systemic drug and 52.7% (1030/1956) a biologic agent on entry into the study. Of the 741 patients who accumulated 5 years of follow-up, 21.9% (155) were receiving nonbiologic drugs and 78.1% (553) were on biologic therapy on the first day of their 5th year of follow-up. CONCLUSIONS: The proportion of patients receiving biologic therapy increased with longer follow-up.