Genetic polymorphisms to identify patients with an optimal response to tildrakizumab in psoriasis patients from real-life clinical practice.

Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI ≤1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI ≤1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI ≤1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.

Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases.

BACKGROUND: The cutaneous manifestations of COVID-19 disease are poorly characterized. OBJECTIVES: To describe the cutaneous manifestations of COVID-19 disease and to relate them to other clinical findings. METHODS: We carried out a nationwide case collection survey of images and clinical data. Using a consensus we described five clinical patterns. We later described the association of these patterns with patient demographics, the timing in relation to symptoms of the disease, the severity and the prognosis. RESULTS: The lesions may be classified as acral areas of erythema with vesicles or pustules (pseudo-chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo-chilblain pattern frequently appears late in the evolution of the COVID-19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID-19. The severity of COVID-19 shows a gradient from less severe disease in acral lesions to more severe in the latter groups. The results are similar for confirmed and suspected cases, in terms of both clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo-chilblain and vesicular). CONCLUSIONS: We provide a description of the cutaneous manifestations associated with COVID-19 infection. These may help clinicians approach patients with the disease and recognize cases presenting with few symptoms. What is already known about this topic? Previous descriptions of cutaneous manifestations of COVID-19 were case reports and mostly lacked illustrations. What does this study add? We describe a large, representative sample of patients with unexplained skin manifestations and a diagnosis of COVID-19, using a consensus method to define morphological patterns associated with COVID-19. We describe five clinical patterns associated with different patient demographics, timing and prognosis, and provide illustrations of these patterns to allow for easy recognition.

New polymorphisms associated with response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis.

Anti-tumor necrosis factor (anti-TNF) drugs are effective against psoriasis, although 20-30% of patients are nonresponders. Few pharmacogenomic studies have been performed to predict the response to anti-TNF drugs in psoriasis. We studied 173 polymorphisms to establish an association with the response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis (N=144). We evaluated the response using PASI75 at 3, 6 and 12 months. The results of the multivariate analysis showed an association between polymorphisms in PGLYR4, ZNF816A, CTNNA2, IL12B, MAP3K1 and HLA-C genes and the response at 3 months. Besides, the results for polymorphisms in IL12B and MAP3K1 were replicated at 6 months. We also obtained significant results for IL12B polymorphism at 1 year. Moreover, polymorphisms in FCGR2A, HTR2A and CDKAL1 were significant at 6 months. This is the first study to show an association with these polymorphisms. However, these biomarkers should be validated in large-scale studies before implementation in clinical practice.

Dose Modification in Biologic Therapy for Moderate to Severe Psoriasis: A Descriptive Analysis in a Clinical Practice Setting.

INTRODUCTION: In biologic therapy, dose modification in carefully selected patients when psoriasis is in remission could reduce treatment costs and the risks associated with drug exposure. MATERIAL AND METHODS: Observational, descriptive, crosssectional study, performed in January 2014, of 112 patients with moderate to severe psoriasis who had been on biologic therapy for at least 6 months. The therapeutic objective in all cases was to achieve and maintain a 75% reduction in Psoriasis Area and Severity Index (PASI 75). All the patients had started treatment with the standard regimen. During treatment, the dose had been reduced in patients who achieved the therapeutic objective and escalated in those who failed to respond adequately to standard doses. RESULTS: At the time of the study, 42.9% of the patients were receiving the standard dose, 50% were on a reduced dose, and 7.1% were on an escalated regimen. The agent with which the dose was most often reduced was adalimumab (57.7%), and the agents with which therapy was most often escalated were ustekinumab (17.9%) and infliximab (12.5%). Patients who received reduced doses had significantly longer-standing disease (P=.049) and longer treatment duration with the same biologic agent (P=.009). In the group that did not fulfill the criteria for dose reduction, the proportion of patients with psoriatic arthritis was significantly higher (P=.023). Cost savings were as follows: 21.5% with adalimumab, 13.8% with etanercept, .9% with ustekinumab, and .55% with infliximab. CONCLUSIONS: Patients with longer-standing disease and longer treatment duration with the same biologic agent were significantly more likely to be candidates for dose reduction. The proportion of patients with psoriatic arthritis was greater in the group of patients who did not fulfill the conditions for dose reduction. The overall cost saving achieved using the dose modification algorithm described in this study was 13%. Controlled studies are needed to define the profile of the patients best suited for dose reduction strategies without loss of treatment efficacy.

Characterization and Outcomes in Patients Treated With Apremilast in Routine Clinical Practice in Spain: Results From the APPRECIATE Study. / Caracterización y resultados de pacientes tratados con apremilast en la práctica clínica habitual española: resultados del estudio APPRECIATE.

BACKGROUND AND OBJECTIVES: It is necessary to expand the knowledge in the use of apremilast in clinical practice. The APPRECIATE study (NCT02740218) aims to describe the characteristics of patients with psoriasis treated with apremilast, to evaluate their perspectives and those of dermatologists, as well as the outcomes obtained in clinical practice in Spain. METHODS: Observational, retrospective, cross-sectional, multicenter study of patients with chronic plaque psoriasis who could be contacted 6 (±1) months after apremilast initiation. The data were obtained from medical records and questionnaires from patients and physicians. RESULTS: A total of 80 patients were evaluated; at apremilast onset, they showed mean (standard deviation, SD) Psoriasis Area and Severity Index (PASI) = 8.3 (5.3), mean (SD) Dermatology Life Quality Index (DLQI) = 8.9 (6.6). At six months, 58.8% (n=47) of patients continued apremilast treatment (discontinuations due to lack of efficacy [16.3%], safety/tolerability [20.0%]). In patients continuing treatment, PASI75 was achieved by 36.7% of patients; mean (95% CI) DLQI score was 2.2 (0.7-3.6) and mean (SD) Patient Benefit Index score was 2.8 (0.8). Compliance with physicians' expectations was correlated with benefits reported by patients (r=0.636). Adverse events were reported by 56.3% of patients (the most common were diarrhoea and nausea). CONCLUSIONS: Patients receiving apremilast for 6 months in Spanish clinical practice, reported substantial improvements in their quality of life (mean DLQI reduced by more than 6 points) and disease severity (PASI75 achieved by over one-third of patients), despite less skin involvement than patients who enrolled in clinical trials.

[Clinical outcomes in patients with psoriasis following discontinuation of efalizumab due to suspension of marketing authorization]. / Evolución clínica de los pacientes psoriásicos tratados con efalizumab al suspender el fármaco.

INTRODUCTION: In February 2009, the European Medicines Agency suspended the marketing authorization for efalizumab after 3 confirmed cases of progressive multifocal leukoencephalopathy were reported. To assess the consequences of this decision, we performed a prospective follow-up study of patients in our department who were being treated with efalizumab at the time and compared clinical outcomes with data from the literature. PATIENTS AND METHODS: Thirty-two patients (28 with plaque psoriasis and 4 with palmoplantar psoriasis) were enrolled between February and March 2009. We recorded psoriasis area and severity index (PASI) scores at the moment of efalizumab discontinuation, at 6 weeks post-discontinuation, and at 3-monthly intervals thereafter. PASI scores prior to treatment with efalizumab were also noted. For patients who experienced rebounds with generalized psoriasis, we noted the time that had elapsed since efalizumab discontinuation and the treatment they were receiving. RESULTS: Even though 92.8% of the patients were considered good responders (>75% reduction in PASI score), 25% of the group (8/32) experienced rebound and 15.7% (5/32) experienced relapse. The percentage of patients in whom rebound was observed on transition therapy was 18% (2/11) for cyclosporin, 50% (1/2) for methotrexate, 50% (1/2) for adalimumab, 50% (1/2) for etanercept, and 27% (3/11) for topical treatment. CONCLUSIONS: We observed a very high rate of rebound and generalized inflammation in patients whose disease had previously been well controlled for several years.