Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Effectiveness and safety of tildrakizumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Tildrakizumab is a humanized, IgG1/κ antibody that interacts with the p19 subunit of interleukin 23. It is approved for the treatment of moderate-to-severe plaque psoriasis. Real-world evidence on the effectiveness and safety of tildrakizumab is limited. OBJECTIVES: To assess the effectiveness and safety of tildrakizumab at 24 weeks in patients with moderate-to-severe plaque psoriasis in routine clinical practice. METHODS: Retrospective, observational, multicentre study including adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab under real-life conditions. Patient data were extracted from anonymized electronic medical records. Statistical analysis was performed using SPSS22. RESULTS: A total of 190 patients were included. About 53.9% were men with a mean age of 51.45 (SD 3.9) and a mean BMI of 29.13 (SD 6.21). About 79.8% (132 out of 190) of patients had previously received biological therapy (BT) and 17.3% (33 out of 191) had psoriatic arthritis. Baseline PASI was 10.7 (SD 6.53). Up to 109 patients reached Week 24 and at this point mean baseline PASI decreased to 1.7 (SD 4.8), representing an 88.79% mean PASI reduction. At 6 months, 87.1% and 40.3% of the treated patients achieved PASI ≤3 and ≤1, respectively. At Week 24 mean BSA decreased from 13.2 (SD 10.07) to 1.6 (SD 4.40) and mean DLQI went from 12.5 (SD 7.12) to 1.2 (SD 3.27). Multivariate analysis showed no differences when effectiveness was correlated with gender, obesity, psoriatic arthritis or prior exposure to BT. The rate of adverse events (AE) was 5.9% (11 out of 190), where infections were the most frequent AE (4 out of 11). One patient suffered a haemorrhagic ictus and one patient died due to causes unrelated to the study. CONCLUSION: Tildrakizumab was effective and safe in a large cohort of patients with moderate-to-severe plaque psoriasis treated in a routine clinical setting.

Efficacy and Safety of Dimethyl Fumarate in Patients with Moderate-to-Severe Plaque Psoriasis: Results from a 52-Week Open-Label Phase IV Clinical Trial (DIMESKIN 1).

INTRODUCTION: Although dimethyl fumarate (DMF) has been approved since 2017 for treatment of moderate-to-severe plaque psoriasis, limited data on its safety and efficacy are available in clinical practice. The objective was to assess the efficacy and safety of DMF in patients with moderate-to-severe plaque psoriasis through 52 weeks in conditions close to real clinical practice. METHODS: DIMESKIN 1 was a 52-week, open-label, phase IV clinical trial conducted at 36 Spanish sites. Adults with diagnosis of moderate-to-severe plaque psoriasis, treated with DMF as per its summary of product characteristics and with ≥ 1 post-baseline Psoriasis Area and Severity Index (PASI) value were included [intention-to-treat (ITT) population]. Efficacy analyses were performed for ITT population and are based on multiple imputation. RESULTS: Overall, 282 and 274 patients were included in the safety and ITT populations, respectively. At week 24, 46.0%/24.8%/10.9% of patients achieved PASI 75/90/100 response, respectively. At week 52, these percentages were 46.0%/21.9%/10.9%, respectively. Mean body surface area affected decreased from 17.4% to 6.9%/7.3% after 24/52 weeks (p < 0.001, both). A total of 42.9%/49.4% of patients had a Physician's Global Assessment 0-1 at week 24/52, respectively. Mean pruritus visual analogue scale (VAS) significantly decreased after 24 and 52 weeks (p < 0.001, both), with 56.5% and 67.6% of patients, respectively, rating a pruritus VAS < 3. At week 24/52, 61.3%/73.4% patients had a Dermatology Life Quality Index (DLQI) ≤ 5 and 34.7%/32.1% had a DLQI 0-1. The most frequent adverse events were gastrointestinal disorders (mainly diarrhea/abdominal pain in 50.0%/35.1% of patients, respectively), flushing (28.0%), and lymphopenia (31.2%), mostly mild/moderate. CONCLUSIONS: DMF significantly improves main severity and extension indexes and rates, as well as patient-reported outcomes such as pruritus and quality of life in patients with moderate-to-severe psoriasis after 24 weeks of treatment. These improvements are sustained through 52 weeks. The safety profile of DMF is similar to that previously described for fumarates. EUDRACT NUMBER: 2017-00136840.

A New Classification of the Severity of Psoriasis: What's Moderate Psoriasis?

The purpose of this study is to propose a ranking system for the severity of psoriasis. The consensus method of selecting the indices to include and the classification of real patient profiles by an expert panel to create a gold standard of severity were used. The performance of potential cut-offs was evaluated to create a ranking algorithm. The combined use of PASI, BSA, and sPGA may allow the classification of the severity of psoriatic patients. The final algorithm identifies severe patients in a single step (2 out 3 are met: PASI ≥ 11 or BSA ≥ 10 or sPGA ≥ 3), while two steps are required for mild ((2 out 3 are met: PASI ≤ 3 or BSA ≤ 5 or sPGA ≤ 2) and DLQI < 5) and moderate forms (the patient does not meet 2 out 3 (PASI ≥ 11 or BSA ≥ 10 or sPGA ≥ 3) but has a DLQI ≥ 5. A ranking algorithm is presented, consisting of different measures of disease which classifies psoriatic patients into three categories: mild, moderate, and severe.

Efficacy of dimethyl fumarate treatment for moderate-to-severe plaque psoriasis: presentation extracts from the 29th EADV virtual congress, 29-31 October 2020.

Background: The 29th EADV Virtual Congress took place between the 29th-31st of October 2020. On October 29th, there was a Session on systemic treatment in which Professors Ulrich Mrowietz and Mar Llamas-Velasco presented the latest research on the efficacy of dimethyl fumarate (DMF) treatment for moderate-to-severe plaque psoriasis (BRIDGE and DIMESKIN 1 studies, respectively). The accepted DMF abstract from Professor Matthias Augustin, on the SKILL study, is also presented here. Results: Data from either prospective interventional (BRIDGE) or non-interventional (DIMESKIN 1, SKILL) studies among patients with moderate-to-severe psoriasis showed that DMF provides a positive efficacy profile in all four body regions included in the Psoriasis Area and Severity Index assessment (head and neck, trunk, upper and lower extremities) and a particularly interesting profile (strong efficacy) in the head and neck region. These findings may be of special interest to patients with scalp psoriasis who have been using topical therapies for a long time. Patient-reported outcomes (quality of life, pruritus) also improved during the 24 weeks of DMF treatment. The safety profile of DMF was similar to the previously described with fumaric acid esters. Conclusions: In summary, these results confirm the favorable efficacy and safety profile of DMF in long-term treatment.

Hospitalization in Patients with Psoriasis: Impact of Biological Therapies on Temporal Evolution.

BACKGROUND: Psoriasis is an immunomediated disease mostly controlled at the outpatient level, although there is a low percentage of patients that require systemic drugs or even hospitalization for an adequate control. Biological drugs have represented a turning point in its treatment. So far, despite the growing interest in psoriasis and its management with biological therapies, there is a lack of studies focusing on their impact on hospitalization, a relevant issue to patients and to the sustainability of our healthcare system. OBJECTIVE: In this study, we aimed to describe the temporal evolution of the hospitalizations of patients with psoriasis throughout the period between eight years before the commercialization of the first biological drugs and present, and secondly, whether this market irruption was related to a decrease in the number of admissions. METHODS: Data was collected retrospectively from the Dermatology department of the Complexo Hospitalario Universitario de Ponte- vedra (CHUP) including patients of all ages with a diagnosis of psoriasis and at least one admission to the department of Dermatology along the study period. We established different time periods for comparing the average hospitalizations per 100,000 inhabitants-year and the average stay, considering that the first biologic drug marketed for the treatment of psoriasis was in 2004. RESULTS: Regression models indicated a significant change in the temporal trend of the hospitalization rate per 100,000 inhabitants-year starting in 2004. In all cases, a gradual and significant decrease in the number of admissions per 100,000 inhabitants-year and in the average hospitalization rate per psoriasis per 100,000 inhabitants-year along the study period were found. There was also a significant decrease in medical hospitalizations and medical hospitalizations excluding psoriasis throughout the study period. CONCLUSIONS: In our study population hospitalizations for psoriasis descended progressively and significantly from 2004. So far there are no extensive data on the impact of biological therapies on psoriasis hospitalization. J Drugs Dermatol. 2021;20(2):208-214. doi:10.36849/JDD.4931.

Intralesional corticosteroid injection for the treatment of hidradenitis suppurativa: a multicenter retrospective clinical study.

BACKGROUND AND OBJECTIVES: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the follicular unit characterized by recurrent, painful, skin lesions including inflammatory nodules, abscesses, tunnels, and mutilating scarring. Intralesional corticosteroids injection (ICI) for HS has received little attention in the scientific literature. We evaluate the clinical response of ICI in acute and chronic HS lesions and aim to identify new applications of ultrasound-assisted procedures in HS management. PATIENTS AND METHODS: An observational, retrospective, multicenter study of HS patients treated with ICI was conducted from January 1 to August 1, 2015. We collected 98 HS patients. A total of 135 individual lesions were infiltrated, including non-inflammatory nodules, inflammatory nodules abscesses and fistulous tracts. RESULTS: Complete response was reached in 95 lesions (70.37%), 34 showed partial response (25.19%) and 6 (4.44%) were non-response. A total of 105 individual lesions underwent sonographic scan before ICI. CONCLUSION: Clinical experience supported the use of ICI for individual lesions. Our results showed that ICI is a useful treatment to control in acute and recalcitrant HS lesions. Response rates improve significantly if lesions are previously evaluated with HFUS.

The effectiveness and safety of ixekizumab in psoriasis patients under clinical practice conditions: A Spanish multicentre retrospective study.

The objective of the study was to evaluate efficacy and safety of ixekizumab in psoriasis patients under clinical practice conditions. Observational, retrospective, multicentre study that included patients with ixekizumab from March 2017 to March 2019. ≥ 90% reduction in the Psoriasis Area and Severity Index (PASI 90) and absolute PASI <2 were the parameters used to assess treatment response. Adverse events (AEs) were collected. Of the 301 patients included, 111 were women (36.9%), mean age was 48.5 (±13.5) years. Mean baseline PASI score was 13.5 (±7.7). More than half of the patients (68.5%) had received at least one biological drug before. At 3 months, 208 (76.5%) patients achieved PASI <2 and 156 (57.3%) PASI 90. At 12 months, 130 (73.4%) patients achieved absolute PASI <2 and 104 (58.7%) PASI 90. Multivariate analysis revealed that prior use of biologics was influential in achieving PASI <2 at both 3 and 12 months (OR 2.82, P = .006; OR 9.51, P < .001, respectively). Sixty-five patients (21.59%) exhibited at least one AE, injection site reaction was the most common (39; 36.8%). Likewise in trials, ixekizumab displayed an excellent profile of safety and efficacy also in real-life. Effectiveness appears superior in biologic-naive patients.

Long-term Safety of Oral Systemic Therapies for Psoriasis: A Comprehensive Review of the Literature.

Oral systemic therapies are important treatment options for patients with moderate-to-severe psoriasis, either as monotherapy or in therapy-recalcitrant cases as combination therapy with phototherapy, other oral systemics or biologics. Long-term treatment is needed to maintain sufficient disease control in psoriasis, but continuous use of systemic treatments is limited by adverse events (AEs) and cumulative toxicity risks. The primary aim of this comprehensive literature review was to examine the long-term safety profiles of oral agents commonly used in the treatment of adults with psoriasis. Searches were conducted in EMBASE and PubMed up to November 2018, and 157 relevant publications were included. Long-term treatment with acitretin could be associated with skeletal toxicity and hepatotoxicity, although evidence for skeletal toxicity is mixed and hepatotoxicity is rare, particularly at low doses. Other safety issues include hyperlipidaemia and potential for teratogenicity up to 2-3 years after discontinuation of treatment. There is a paucity of data on long-term treatment with apremilast. Continued exposure to apremilast does not seem to increase the incidence of common AEs, such as gastrointestinal (GI) AEs, upper respiratory tract infections and headache, while the long-term risks for depression, suicidal thoughts and weight loss are unknown. Long-term ciclosporin treatment is associated with renal toxicity, hypertension, non-melanoma skin cancer, neurological AEs and GI AEs. Long-term methotrexate treatment is associated with hepatotoxicity, GI AEs, haematological toxicity, renal toxicity and alopecia. Finally, long-term treatment with fumaric acid esters (FAE) is associated with GI AEs, flushing, lymphocytopenia, proteinuria and elevated liver enzymes. Median drug survival estimates varied considerably: ~ 2.9-9.7 months for apremilast; ~ 5.4 months for ciclosporin; ~ 8.6 months for acitretin; ~ 12.1-21.6 months for methotrexate; and ~ 54.8 months for FAE. These long-term safety profiles may help to guide clinicians to select the optimal oral systemic treatment for the long-term treatment of psoriasis in adults.

[Teledermatology in Paediatrics. Observations in daily clinical practice]. / Teledermatología en edad pediátrica. Observaciones en la práctica clínica diaria.

INTRODUCTION: Teledermatology is a technique that is increasingly being developed. There are many studies that assess this discipline in the general population, but few studies analyse the paediatric population exclusively. The aims of this study are to describe the distribution of diseases consulted through teledermatology, the use of this technique to avoid face-to-face consultations, and the agreement between virtual and face-to-face diagnoses, in the paediatric population. MATERIAL AND METHODS: The work consisted of an observational and retrospective study of the virtual consultations made between May 2011 and January 2015 through a store-and-forward teledermatology programme, involving patients from 0 to 15 years. We collected demographic data, as well as the diagnoses made by the paediatrician who made the virtual consultation, and by the dermatologists who assessed the virtual and the face-to-face consultations, the indication given by the dermatologist who assessed the virtual consultation (discharge or referral), reason for referral, and diagnostic agreement rate. RESULTS: A total of 183 virtual consultations were analysed. The most frequent diagnoses were inflammatory diseases (39%), benign pigmented lesions (23%), and infectious diseases (20%). Almost half of the virtual consultations (48%) were referred for a face-to-face diagnosis. Diagnostic agreement between the dermatologist who evaluated the virtual consultation and the dermatologist who evaluated the face-to-face consultation was 89%, and 66% between the paediatrician who made the virtual consultation and the dermatologist who assessed it. CONCLUSIONS: Virtual consultations have a similar disease distribution to conventional (face-to-face) referrals. Approximately half of the virtual consultations do not require a subsequent face-to-face visit. The agreement rate between the diagnoses given by both dermatologists (virtual and face-to-face diagnoses) is high.

Extraparietal or lymphatic late relapse of neoplasms: confirmation by means of EUS-FNA key for the treatment.

BACKGROUND: After treatment intended to cure systemic neoplasms, a series of monitoring strategies are followed. OBJECTIVE: To analyse our experience in confirming the cases of lymphatic or extraparietal relapse in areas accessible to endoscopic ultrasonography plus fine-needle aspiration (EUS-FNA) in long-term monitoring (>1 year of treatment for the primary neoplasm) and define what implications have been derived with regards histopathological confirmation in relation to treatment. MATERIALS AND METHODS: Retrospective analysis was made of all EUS-FNA carried out in our Endoscopy Unit during the period from 1/07/2007 to 28/02/2010 by means of searches in the Endobase (Olympus) database. Medical records of patients and drug therapy were reviewed in order to check the chemotherapy used in each case. RESULTS: From a total of 154 EUS-FNA carried out in our service, we have detected histopathological confirmation of malignancy in primary neoplasm treated with initial curative intention at least 1 year before. Locations were: esophageal extraparietal involvement of a squamous cell carcinoma (one patient), perirectal adenopathy of rectal adenocarcinoma (one patient), multiple lymphatic relapse of melanoma (two patients), perigastric adenopathy relapse of gastric adenocarcinoma (one patient), pancreatic head mass secondary to initial breast ductal carcinoma (one patient). In all cases, this fact has involved a directed treatment: surgery (one patient), radiotherapy (one patient), chemotherapy (four patients). CONCLUSIONS: Confirmation by means of EUS-FNA of late relapse in any section of the digestive tract allowed a treatment to be carried out by surgery, radiotherapy, or chemotherapy.