Real-World Data on Brodalumab Treatment in Patients with Moderate-to-Severe Plaque Psoriasis: An Observational Study from the Czech Republic BIOREP Registry.

INTRODUCTION: The aim of this observational, multicenter study was to assess the real-world use of brodalumab for the treatment of moderate-to-severe plaque psoriasis in patients in the Czech Republic, using data from the BIOREP registry. METHODS: The study included 273 patients aged ≥ 18 years with moderate-to-severe psoriasis who received brodalumab. Endpoints were drug survival (time from treatment initiation to discontinuation), effectiveness [Psoriasis Area and Severity Index (PASI)], and health-related quality-of-life [Dermatology Life Quality Index (DLQI)]. RESULTS: Predicted drug survival probability was 92.4% [95% confidence interval (CI): 89.1, 95.7%] at 6 months and 84.2% (95% CI 79.5, 89.1%) at 12 months; this was maintained at 24 months [80.4% (95% CI 74.5, 86.8%)]. Younger age, higher body mass index, and no previous biologic treatment were significantly associated with longer drug survival. Absolute PASI ≤ 3 after 3 months was achieved by 89.8% of patients; 92.4%, 77.8%, and 59.1% reached PASI 75, PASI 90, and PASI 100, respectively. After 12 months, 96.5% of 141 patients had an absolute PASI ≤ 3. The proportion of patients achieving DLQI 0/1 was 87.3% at 12 months. CONCLUSION: This study demonstrated high and sustained drug survival with high rates of skin clearance and improved quality of life in patients with relatively severe disease treated with brodalumab. Improvements were observed as early as 3 months post-treatment initiation and were sustained for up to 24 months in a real-life setting.

Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study.

INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.

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.

Apremilast Use in Severe Psoriasis: Real-World Data from Central and Eastern Europe.

INTRODUCTION: The broad and sustained efficacy of apremilast for psoriasis has been demonstrated in randomized and real-world observational studies. Data from Central and Eastern Europe (CEE) are lacking. Moreover, apremilast use in this region is limited by country-specific reimbursement criteria. This is the first study to report data on the real-world use of apremilast in the region. METHODS: APPRECIATE (NCT02740218) was an observational, retrospective, cross-sectional study assessing psoriasis patients 6 (± 1) months after apremilast treatment initiation. The study aimed to describe the characteristics of patients with psoriasis receiving apremilast, estimate treatment outcomes, including Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI), and assess dermatologists' and patients' perspectives on treatment using questionnaires including the Patient Benefit Index (PBI). Adverse event reports were taken from the medical records. RESULTS: Fifty patients (Croatia: 25; Czech Republic: 20; Slovenia: 5) were enrolled. In patients continuing apremilast at 6 (± 1) months, mean (± SD) PASI score was reduced from 16.2 ± 8.7 points at treatment initiation to 3.1 ± 5.2 at 6 (± 1) months; BSA from 11.9% ± 10.3% to 0.8% ± 0.9%; DLQI from 13.7 ± 7.4 points to 1.6 ± 3.2. PASI 75 was reached by 81% of patients. Physicians reported that the overall treatment success fulfilled their expectations in more than two thirds of patients (68%). At least three-quarters of patients reported apremilast had a quite or very high benefit on the needs they identified as being most important. Apremilast was well tolerated; no serious or fatal adverse events were identified. CONCLUSION: Apremilast was effective in reducing skin involvement and improving quality of life in CEE patients having severe disease. Treatment satisfaction among physicians and patients was very high. These data add to the growing body of evidence showing consistent effectiveness of apremilast across the continuum of psoriasis disease severity and manifestations. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02740218.

Efficacy of switches within the class of IL-17 inhibitors: An analysis of data from the Czech nationwide registry of psoriatic patients receiving biological/targeted therapy (BIOREP).

The IL-17 cytokine family encompasses six different homodimers and heterodimers referred to as IL-17A-F. Due to some differences in the mechanism of IL-17 inhibition, aninsufficient effect of one IL-17 inhibitor does not necessarily imply lack of efficacy of the other agent of the same class. Aim of study was analysis of the success rate of switches among IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) in patients treated in the Czech Republic. Data were obtained from the Czech nationwide registry of psoriatic patients receiving biological/targeted therapy (BIOREP). Our analysis involved data of a total of 90 patients with severe chronic plaque psoriasis and baseline PASI scores >10 both prior to first-line biological therapy initiation and after switch to another agent of the class of IL-17 inhibitors. The most effective switch was that from secukinumab to brodalumab, with PASI 90 reached by 64.7% and 73.3% of patients at weeks 12 and 24. Among patients switched from secukinumab to ixekizumab target PASI 90 responses were achieved (at weeks 12 and 24) by 41.2% and 55.2% of patients. Among patients switched from ixekizumab to brodalumab target PASI 90 responses were achieved, at the above time points, by 30.8% and 38.5% of patients. Our analysis showed a high success rate of switches from secukinumab to ixekizumab and brodalumab, followed by the ixekizumab-to-brodalumab switch. Importantly, the therapeutic response and success rates of individual switches are independent of the patient's body weight and presence of psoriatis arthritis.

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.

Topical bimatoprost in the treatment of eyelash loss in alopecia totalis and universalis: A prospective, open-label study.

Bimatoprost is a synthetic prostaglandin structural analogue used among other indications to increase eyelash growth. The aim of this prospective, open-label study was to evaluate the safety and efficacy of topical bimatoprost in the treatment of eyelash loss in alopecia areata totalis (AT) and universalis (AU). Study subjects applied ophthalmic bimatoprost (0.3 mg/ml) solution to the eyelid margins once nightly for at least 12 weeks (mean treatment period was 30.6 weeks). A total of 16 out of 17 subjects completed the study. Only the subjects with eyelashes present at baseline experienced an increase in eyelash length and thickness. No new eyelash regrowth was induced. In patients with AT and AU topical bimatoprost affected existing eyelashes, but failed to induce regrowth of new eyelashes.

A case of cutaneous collagenous vasculopathy associated with multiple myeloma and with a pathogenic variant of the glucocerebrosidase gene.

Cutaneous collagenous vasculopathy (CCV) is an extremely rare acquired microangiopathy of unknown etiology. The authors describe a case of a 68-year-old man, a carrier of a heterozygous pathogenic variant of the glucocerebrosidase (GBA) gene, who was diagnosed with CCV, revealing uncommon fibrinogen positivity in direct immunofluorescence. The patient was subsequently diagnosed with multiple myeloma. Treatment of the myeloma with combined chemotherapy including bortezomib, followed by autologous stem cell transplantation, led to significant reduction of cutaneous lesions. To the best of the authors' knowledge, this is the first published case of CCV in a carrier of a pathogenic variant of the GBA gene, associated with multiple myeloma and with significant regression of CCV after myeloma treatment. Direct immunofluorescence examination revealed an unusual fibrinogen deposition. Hypothetical causative role of bortezomib treatment was proposed regarding significant regression of CCV.

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.

Use of dupilumab in a patient with atopic dermatitis, severe asthma, and HIV infection.

Dupilumab is a monoclonal antibody against interleukin 4 (IL-4) receptor α that blocks signaling from IL-4 and IL-13, essential mediators of T helper 2 (Th2) pathway. To date, all clinical trials investigating the use of dupilumab excluded patients with human immunodeficiency virus. Herein, we describe the safe and successful use of dupilumab in a patient with atopic dermatitis, severe therapy resistant asthma, and HIV infection.

Food Hypersensitivity Reactions to Seafish in Atopic Dermatitis Patients Older than 14 Year of Age - The Evaluation of Association with Other Allergic Diseases and Parameters.

BACKGROUND: Seafood allergy is among one of the common food allergies. Decrease in consumption of omega-3 polyunsaturated fatty acids (PUFAs), prevalent especially in oily fish, has been proposed to contribute to the increased prevalence of allergic diseases. AIM: The aim of this study was to evaluate, in atopic dermatitis (AD) patients, the relation between the occurrence of food hypersensitivity reaction (FHR) to seafish and the occurrence of other atopic diseases and parameters. METHODS: Complete dermatological and allergological examination was performed in patients included in the study; 332 patients were examined, with the average age 26.8 years (SD 9.2 years). RESULTS: The FHR to seafish was confirmed in 11% of patients. Patients suffering from FHR to seafish suffered significantly more from sensitization to fungi (in 46%), from reactions to celery (in 34%), and from persistent eczematic lesions (in 82%). CONCLUSION: FHRs to seafish in AD patients are associated with persistent eczematic lesions and with the higher occurrence of sensitization to fungi and reactions to celery. The occurrence of bronchial asthma, rhinitis, positive family history, and onset of AD under 5 years of age is higher in patients with reactions to seafish, but the difference is not statistically significant.

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.

Anti-tumour necrosis factor treatment of severe psoriasis complicated by Epstein-Barr Virus hepatitis and subsequently by chronic hepatitis.

A case is described of severe acute hepatitis in 47-year-old woman with chronic psoriasis and psoriatic arthritis treated with infliximab. Although clinical, serological and laboratory results were compatible with acute EBV hepatitis, it was difficult to differentiate between EBV infection and other non-infectious causes of hepatitis. The patient gradually developed chronic hepatitis with liver steatosis and efficient treatment with adalimumab had to be stopped. This case presents an uncommon complication that may arise from the use of biologic therapy and calls for caution in long-term management of psoriatic patients with internal comorbidities.

Management of a pemphigus with IgA and IgG antibodies and coexistent lung cancer.

Immunoglobulin A (IgA) pemphigus is a clinically distinct variant of pemphigus characterized by intercellular IgA deposition in the epidermis. Recently, an IgA/Immunoglobulin G (IgG) subset of pemphigus with IgA and IgG anti-keratinocyte cell surface antibodies has been described. Both IgA and IgA/IgG pemphigus have been associated with internal malignancies. Above all, monoclonal IgA gammopathy in patients with IgA pemphigus has been reported, and lung cancers in association with IgA/IgG pemphigus have been described. IgA pemphigus can be successfully treated with dapsone, whereas therapeutic management of IgG/IgA pemphigus is not well established yet. We report a rare case of a patient, who developed atypical pemphigus with both IgA and IgG autoantibodies and an underlying lung cancer, successfully treated with corticosteroids and dapsone.

Adalimumab treatment for hidradenitis suppurativa associated with Crohn's disease.

Hidradenitis suppurativa (HS) is a chronic, inflammatory disease characterized by recurring abscesses, nodules, and fistulas predominantly in the area of the groin and axillae. The association between HS and Crohn's disease (CD) has already been documented. We report on a case of a patient with CD associated HS, refractory to multiple local and systemic agents.A complete resolution of both diseases was finally achieved after treatment with adalimumab. Our case report supports the co-occurrence of both diseases and suggests that adalimumab approved for CD might also be a safe and effective therapeutic option in the treatment of HS.

Deep vein thrombosis and lung cancer in a patient with psoriasis under anti-tumor necrosis factor treatment: a case study.

We describe a case of a patient with severe generalized psoriasis treated with etanercept, who developed deep vein thrombosis and 1 year later developed solid lung cancer. Anti-tumor necrosis factor therapies have been a powerful addition to the therapy of psoriasis; nevertheless, the treatment might be associated with adverse events, such as venous thromboembolism or malignancies. Available data regarding these specific adverse reactions are rather conflictive; therefore, more observational studies and registry reports for long-term risk assessment are needed.