Management of Moderate to Severe Plaque Psoriasis with Brodalumab in Daily Practice: Real-World Evidence from the LIBERO Study in the Czech Republic.

INTRODUCTION: Psoriasis is a chronic, immune-mediated inflammatory skin disease. Despite the availability of several therapies, many patients affected by this disease remain untreated, do not have adequate response, or suffer from treatment-related toxic effects. It has been shown that the interleukin (IL)-17 pathway plays a key role in the immunopathogenesis of psoriasis. Brodalumab, the first human monoclonal IgG2 antibody that selectively binds to subunit A of the human IL-17 receptor, blocking interactions with a number of cytokines of the IL-17 family, has confirmed fast onset of action, high complete clearance rates, and sustained efficacy. Nevertheless, there is only a limited amount of published real-world evidence (RWE) data. METHODS: This was an open-label, multicenter, real-world, prospective, non-interventional, non-controlled (single-arm) observational study (LIBERO-CZ) assessing the management of moderate to severe psoriasis with brodalumab in daily practice for up to 52 weeks of treatment. RESULTS: Fifty-four patients (70.4% male, mean age 46.9 ± 13.4 years, weight 95.6 ± 22.7 kg, disease duration 18.6 ± 12.7 years) were enrolled and included in the final analysis. Forty-nine of the patients completed the study and five discontinued prematurely; 51.8% of all the enrolled patients were biologic-naïve. At baseline, 28% patients were classified as severe (psoriasis area severity index (PASI) ≥ 20). Overall, the mean PASI decreased by 15.6 from 16.1 (± 5.0) at baseline to 0.5 (± 1.2) at the last visit. The primary endpoint of an absolute PASI ≤ 3 at week 12 (as observed analysis) was achieved by 95.9% of patients. The static Physician's Global Assessment (sPGA) success (defined as clear = 0 and almost clear = 1) at week 52 was achieved by 92.1% of patients. PASI 75, PASI 90, and PASI 100 were achieved by 98.0%, 87.8%, and 75.5% of patients, respectively, after approximately 52 weeks of treatment. The study also recorded very positive results concerning patient-reported outcomes. CONCLUSIONS: LIBERO-CZ confirms the fast onset and high clearance rates of brodalumab in real life in both biologic-naïve and biologic-experienced patients.

Efficacy, safety, and drug survival of patients with psoriasis treated with IL-17 inhibitors - brodalumab, ixekizumab, and secukinumab: real-world data from the Czech Republic BIOREP registry.

BACKGROUND: Real-world data on the use of interleukin-17 (IL-17) inhibitors for the treatment of psoriasis are limited. OBJECTIVE: To evaluate and compare the efficacy, safety, and drug survival of IL-17 inhibitors. METHODS: This retrospective study analyzed the BIOREP registry data of patients treated with at least one IL-17 inhibitor (secukinumab, ixekizumab, and brodalumab). RESULTS: In total, 949 patients were included. The improvement in PASI score was significant for all drugs, and the proportion of patients achieving PASI 75, 90, and 100 after both 3 and 24 months of therapy was highest for brodalumab, followed by ixekizumab and secukinumab. The Dermatology Life Quality Index score decreased to ˂3 after 3 months and to ˂2 after 24 months of therapy for all inhibitors. Loss of effectiveness was the major reason for discontinuation in 17.2% of patients, followed by adverse events in 3.2% of patients. The drug survival probability was the highest for brodalumab, followed by ixekizumab and secukinumab. Negative predictors for treatment discontinuation were obesity and the number of treatment lines, whereas a positive predictor was the presence of concomitant psoriatic arthritis; sex had no influence. CONCLUSION: This real-life study demonstrated the effectiveness and good safety profile of all currently available IL-17 inhibitors.

Real-life experience in the effectiveness, impact on quality of life and safety of dupilumab treatment in patients with moderate to severe atopic dermatitis in the Czech Republic.

OBJECTIVES: The aim of the study was to assess the effectiveness and safety of dupilumab therapy in patients with moderate-to-severe atopic dermatitis (AD) in a real-life Czech bicentric cohort. METHODS: We retrospectively analysed 50 patients with moderate-to-severe AD treated with dupilumab in two centres in the Czech Republic. Baseline characteristics, the Eczema Area and Severity Index (EASI) score and Dermatology Life Quality Index (DLQI) were collected at baseline and each 3 following months. The proportion of patients achieving EASI50, EASI75, EASI90 and EASI100 were analysed. Levels of immunoglobulin E (IgE) were collected before and after 6 and 12 months of therapy. Adverse events were recorded as well. RESULTS: Thirty-two men and 18 women with mean body mass index (BMI) of 25.7 were enrolled in our analysis. The mean age of the patients was 37.6 years and the mean time from diagnosis until the initiation of dupilumab therapy was 35.0 years. After 4 months, EASI75 was achieved by 75.7%, out of which 40.5% achieved EASI90 and 10.8% achieved complete clearance. Improvement continued with time, and the proportion of patients with EASI90 increased to 71.4% at the 6th month and at the 12th month of therapy the EASI90 was 65.2%. EASI100 was achieved by 14.3% and 13.0% at the 6th and 12th month, respectively. A marked reduction was observed in the DLQI and also in IgE levels. EASI responses were independent of BMI. No new safety issues were identified. Adverse events were experienced by 44% (22/50) of the patients and they were all mild in intensity. Conjunctivitis and herpes simplex virus infection were the most common adverse events. CONCLUSION: Our results confirmed the effectiveness and safety of dupilumab in a real-life setting in adult patients with moderate-to-severe AD in the Czech Republic. Dupilumab was well-tolerated and resulted in a significant clinical improvement in combination with improvement of quality of life.

Dupilumab for the treatment of atopic dermatitis: real-world data from the Czech Republic BIOREP registry.

BACKGROUND: Dupilumab has been approved to treat moderate-to-severe atopic dermatitis; however, the data in a real-world setting are still limited. OBJECTIVE: To analyze the effectiveness and safety of dupilumab. METHODS: This was a real-life Czech multicenter retrospective study from patients treated with dupilumab for severe AD. RESULTS: A total of 360 patients were included. At 16 weeks, 66.6, 34.1, and 5.5% of patients achieved EASI75/90 and EASI100, respectively. Improvement continued with the time, and the proportion of patients with EASI75/90 and EASI100 increased to 89.5, 55.6, and 12.9% after one year of treatment and reached 95.8, 60.4, and 27.1% in the second year of therapy, respectively. A significant reduction was observed in the DLQI scores. The most common adverse events were infections in 5.8% of patients, followed by ocular complications in 2.5% of patients. Persistence rates were 98.2% at four months to 93.1% at month 24, and lack of effectiveness was the most common reason for discontinuation. CONCLUSION: This real-life study confirmed the effectiveness and safety of dupilumab in a real-life setting during the COVID-19 pandemic. Our study revealed a higher frequency of infections and a lower conjunctivitis frequency than other real-life studies and clinical trials.

Risankizumab for the Treatment of Moderate-to-Severe Psoriasis: Real-Life Multicenter Experience from the Czech Republic.

INTRODUCTION: Risankizumab has been approved for the treatment of moderate-to-severe plaque psoriasis; however, real-life data are limited. Our objectives were to evaluate the effectiveness and safety of risankizumab and its impact on the quality of life of patients with psoriasis in a real-world setting. METHODS: We retrospectively analyzed 154 patients from 18 centers in the Czech Republic who had undergone biologic therapy with risankizumab for moderate-to-severe plaque psoriasis. Baseline characteristics included data on comorbidities, demographics, previous therapies, Dermatology Life Quality Index (DLQI) score, and Psoriasis Area and Severity Index (PASI) score. The proportion of patients achieving a 90% improvement in their PASI score from baseline (PASI 90) and complete resolution (PASI 100) after 16, 28, and 52 weeks was analyzed. RESULTS: A total of 95 men and 59 women with mean body mass index (BMI) of 29.6 were enrolled in our analysis. The mean age of the patients was 48.5 years and the mean time from diagnosis until initiation of risankizumab therapy was 22.5 years. After 16 weeks, 63.8 and 44.7% patients achieved PASI 90 and PASI 100 responses, respectively. Improvement continued with time, and the proportion of patients with PASI 90 and PASI 100 responses increased to 82.4 and 67.6%, respectively, at week 52. A significant reduction was observed over time in the DLQI. Patients achieving PASI 100 response at week 16 had a higher reduction in the DLQI score than those with PASI 90 response (- 15.9 vs. - 11.8). PASI 90 and PASI 100 responses were independent of the BMI and previous biologic therapy. No new safety issues were identified. CONCLUSIONS: In this patient population, risankizumab was effective and safe in a real-world setting, and a high number of patients achieved PASI 90 and PASI 100 responses. A higher reduction in the DLQI was seen in patients with PASI 100 response, which supports the evidence that this value should be the new therapeutic goal.

Real-World Evidence From More Than 1000 Patients Treated With Adalimumab For Moderate-to-Severe Psoriasis in the Czech Republic.

INTRODUCTION: The study aimed to evaluate the real-world effectiveness of adalimumab as well as investigate the persistence of treatment and identify factors, which may affect it. METHODS: More than 1150 patients (4363.1 patient-years) with psoriasis who had been treated with adalimumab since the start of the BIOREP registry in the Czech Republic were included in this analysis. Treatment effectiveness was defined as improvement in Psoriasis Area and Severity Index (PASI). The analysis was performed during the years 2005 and 2018. Patients were on on-label dose. RESULTS: After 12 and 96 months of therapy, 84% and 88% of patients had a 75% reduction in PASI score from baseline, respectively. Drug survival was analyzed according to the number of previous biological therapies, and results showed 75% and 58.1% survival rate for biologically naïve patients in the 20th and 80th month of treatment, respectively. The negative predictors of adalimumab survival were the female gender, obesity, baseline PASI score and the number of previous biological therapies. CONCLUSIONS: Baseline factors including PASI, number of previous biological therapies, and sex were associated with shorter adalimumab survival. This long-term study shows that adalimumab is effective and has high treatment persistence.

Demographic data, comorbidities, quality of life, and survival probability of biologic therapy associated with sex-specific differences in psoriasis in the Czech Republic.

BIOREP is a Czech registry of patients with psoriasis undergoing biological treatment. The objective of the study was to compare differences in demographic data, previous therapy, comorbidities, severity of psoriasis, quality of life, drug survival rates, and reasons for discontinuation between men and women. We analyzed a cohort of patients from the registry treated between May 2005 and January 2020. The total study population of 2472 patients (4051 treatment series) included 913 females and 1559 males. Women were significantly older than men at the onset of the biological treatment (47.8 vs 45.4 years, P < .0012) and the mean durations of psoriasis and that from its diagnosis until initiation of biological therapy, were longer in women (29.6 vs 27.2 years and 23.2 vs 20.6 years, P < .0012). Women as compared with men were also more often diagnosed with psoriatic arthritis (43.5% vs 33.0%, P < .0012). The prevalence rate of comorbidities was equivalent for both sexes except for that of depression (11.4% females vs 3.7% males, P < .0012). Both the DLQI and PASI scores were significantly different at baseline (DLQI = 16.0 and PASI = 19.5 for men vs DLQI 17.6 = and PASI = 17.7 for women, P < .0012). The survival probability with biological therapy was significantly lower in women for both biologically naïve and non-naïve patients, and there was more evidence of adverse effects in women. Our research demonstrates significant differences relative to multiple factors associated with psoriasis between men and women.

Characteristics and risk profile of psoriasis patients included in the Czech national registry BIOREP and a comparison with other registries.

BACKGROUND: BIOREP is a Czech registry of psoriatic patients on biological treatment in a clinical setting. We describe the characteristics of patients with psoriasis at the time of enrollment and present comparisons with published data from other national registries. METHODS: We analyzed the cohort of patients treated with biologics between May 2005 and May 2015. Demographic data, previous therapies, comorbidities, and severity of psoriasis were compared with data from other registries - DERMBIO, BIOBADADERM, BADBIR, and PSOBEST. RESULTS: A total of 1412 psoriatic patients initiating biological treatment were included with a predominance of males (63.4%). The mean patient age was 50.2 years, and approximately 70.5% of patients were either overweight or obese. The mean baseline Psoriasis Area and Severity Index was 19.8, and the Dermatology Life Quality Index was 16.6. More than one-third of patients (41.0%) reported a history of psoriatic arthritis, and a high proportion of patients (49.5%) with cardiovascular risk factors (hypertension [35.2%], hyperlipidemia [27.7%], diabetes mellitus [11.4%], coronary heart disease [4.9%], and obesity [15.2%]) were observed. Most of the patients had been previously treated with phototherapy (85.4%), acitretin (74.0%), methotrexate (65.7%), or cyclosporine (53.1%). CONCLUSION: BIOREP is one of the first registries of patients with psoriasis treated with biologics in Central and Eastern Europe. Our results found a similar or higher prevalence of comorbidities, long disease duration, and high impact on the quality of life among patients included in Western European registries.

Drug fever as an adverse effect of acitretin in complicated psoriasis patient.

We present a case of a 63-year old man with severe chronic plaque psoriasis and a recent history of lung cancer, wherein fever appeared suddenly after initiation of treatment with low dose acitretin. Tumor recurrence or infection was not found during extensive examinations, nevertheless the patient was empirically treated with broad-spectrum antibiotics without any effect on fever. Immediately after discontinuation of acitretin therapy, the fever disappeared. The patient was followed for next 2 years, during this period similar problems did not reappear, although there has been a relapse of psoriasis and the patient was switched later on biological treatment.

Visceral leishmaniasis with cutaneous symptoms in a patient treated with infliximab followed by fatal consequences.

Leishmaniasis is an infectious disease caused by parasitic flagellates of the genus Leishmania. The authors present a case of 44-year-old man with Crohn's disease treated successfully with infliximab. This case report shows rare visceral leishmaniasis with cutaneous symptoms in an immunocompromised patient. Skin manifestations may occur before or after the visceral infection and they are often diverse.

Juvenile generalized pustular psoriasis treated with etanercept.

An 8-year-old boy with general pustular psoriasis (GPP) and iatrogenic secondary Cushing syndrome was treated successfully with etanercept after he had failed on acitretin, methotrexate, and methylprednisolone therapy. GPP is a severe and very rare variant of psoriasis in children often accompanied by life-threatening complications. Retinoids, cyclosporine, methotrexate, or dapsone used in a small number of case series and case reports were effective. Etanercept is a recombinant human tumor necrosis factor-alpha (TNF-alpha) receptor protein fused with Fc portion of IgG1 that binds to TNF-alpha, approved by Food and Drug Administration for the treatment of moderate-to-severe plaque psoriasis in children and teens who have not responded to other psoriasis treatments. In our patient, etanercept demonstrated significant clinical response associated with long-term efficacy without acute exacerbation, excellent tolerability, and good safety profile.

Risk factors for comorbidities in Czech psoriatic patients: results of a hospital-based case-control study.

BACKGROUND: Psoriasis is now known to be associated with multiple other diseases/comorbidities - including the metabolic syndrome, atherosclerosis and gastrointestinal diseases which are all significantly higher in psoriasis patients. Research results however are highly variable and the conclusions are ambiguous. As no similar study has been performed to date in Czech psoriatic patients, this study aimed at identifying risk factors and early stages of selected diseases/comorbidities in the patients. METHODS AND RESULTS: The study was designed as a hospital-based case-control study. 131 patients with chronic plaque psoriasis formed the cases and 267 patients with other skin disorders formed the controls. A comparison was made of basic demographic and anthropometric indicators, metabolic parameters, the presence of specific antibodies (ASCA, AEP, p-ANCA, AGC, EMA, ARA, t-TG, AGA) and non-specific signs of gastrointestinal diseases. The chi squared, MWU tests and binary logistical model were used to evaluate the data. The results showed significant differences (P<0.05) for the following parameters: blood pressure, waist circumference, weight, BMI values, leucocytes values, HDL cholesterol level, glycemia and gliadine antibody IgA level. All differences were to the detriment of psoriasis patients. In the binary logistical model the following parameters were associated with psoriasis: diastolic blood pressure, leucocyte value and glycemia. For all variables included in the logistical model P≤0.001. CONCLUSIONS: The results were coherent and consistent with existing data. They indicate that psoriasis is interconnected with hypertension, higher BMI and a decreased level of HDL cholesterol. These parameters have been clearly demonstrated as risk factors for the development of cardiovascular diseases. Higher levels of gliadine IgA antibodies are one of the diagnostic markers of celiac disease. Higher values of leukocytes may be interpreted as a nonspecific indicator of gastrointestinal inflammatory diseases. The associations between psoriasis and diastolic blood pressure, BMI value and glycemia are statistically significant in the binary logistic regression model. Care for psoriatic patients should focus especially on secondary prevention of predisposing diseases.

The rare case of Alternaria alternata cutaneous and pulmonary infection in a heart transplant recipient treated by azole antifungals.

We report a case of Alternaria alternata cutaneous and pulmonary infection in a 62-year-old man after heart transplantation treated by azole antifungals. Alternaria spp. belong to a group of opportunistic dematiaceous fungi with worldwide distribution. The cutaneous form of the infection in human is very rare and occurs predominantly among immunosuppressed patients. Therefore, diagnosis is often delayed or not reached at all. Appropriate treatment is not standardized and remains a matter of discussion. According to current studies, the best results are obtained with systemic azole antifungal therapy combined with surgical intervention.

Management of lymphedema.

The basic principle of the management of lymphedema is so called complex decongestive physical therapy. This therapy is divided into two phases: (i) edema reduction phase--an initial intensive treatment phase aiming for limb volume reduction; and (ii) maintenance phase--following long-term phase to sustain a manageable limb volume. The first phase consists of a number of physical therapeutic approaches which are: manual lymph drainage, pneumatic pump drainage, low-stretch bandaging, exercises, and skin care. Long-term maintenance phase consists of self-lymph drainage, low-stretch bandaging, or compressive garments, and sometimes when indicated pneumatic pump drainage, exercises, and skin care.

Pemphigus vulgaris treated with adalimumab: case study.

The study describes the case of a patient with a clinical and histopathological diagnosis of pemphigus vulgaris accompanied by severe side-effects of combined immunosuppressive therapy, who achieved a remission of the disease with adalimumab. Pemphigus vulgaris is a chronic blistering disease of the skin and mucous membranes. Before corticosteroids were introduced, mortality was high. Corticosteroids are currently used as first-line therapy. To reduce the dose of corticosteroids, therapeutic combinations with corticosteroid-sparing immunosuppressive agents are used. The therapy brings a number of complications due to its side effects. To achieve a remission of the disease by treating our patient with combined immunosuppressives, we administered adalimumab and achieved a very good clinical response.