Age affects drug survival rates of interleukin (IL)-17 and IL-23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi-country, cohort study.

BACKGROUND: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. OBJECTIVES: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. METHODS: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. CONCLUSIONS: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

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.

Prevalence of genital and oral human papillomavirus infection among psoriasis patients on biologic therapy.

Current knowledge about human papillomavirus (HPV) infection in psoriasis patients treated with biologics is limited. In this study we evaluated the prevalence of oral and genital HPV infection in psoriasis patients treated with biologics or topical therapy for at least 6 months. The presence of HPV DNA in oral rinse and genital smears was evaluated. In total, 267 patients who met the inclusion criteria and agreed to participate were enrolled: 110 (41.2%) on topical therapy, 84 (31.5%) on anti-TNF-alpha therapy, 31 (11.6%) on anti-IL-12/23 therapy and 42 (15.7%) on anti-IL-17 therapy. The presence of genital HPV infection was detected in 34.6% of men receiving anti-TNF-α treatment, in 25.0% of patients on anti-IL-12/23 and 18.8% of patients on anti-IL-17 therapy. The difference in prevalence was not statistically different from men on topical treatment (26.3%). Prevalence of oral HPV infection was higher across all of the biologic groups (11.9% for anti-TNF-α, 12.9% for anti-IL-12/23 and 19.0% for anti-IL-17) compared to patients on topical therapy (7.3%), but statistically significant only for anti-IL-17 (p < 0.05). The presence of oral HPV infection in patients treated with biologics was significantly higher (44.0%) in patients on long-term biologic treatment (>8 years) compared to patients taking biologics for a shorter period (9.1%; p < 0.01). Our results suggest that patients on biologics for psoriasis have a higher prevalence of oral HPV infection compared to patients on topical treatment. Long-term treatment with biologics seems to be associated with a higher prevalence of oral HPV infection, independent of previous conventional immunosuppressive therapy.

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.

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.

Long-term impact of adalimumab therapy on biomarkers of systemic inflammation in psoriasis: Results of a 2 year study.

Psoriasis patients are at increased risk of atherosclerosis, characterized by endothelial dysfunction, linked through systemic inflammation. Anti-TNF-a therapy seems to decrease this risk. The purpose of this study was to measure the levels of serum markers associated with systemic inflammation in psoriasis patients, compared to healthy individuals and to investigate the change in their levels after 3 months and 2 years of adalimumab therapy. We investigated four biomarkers: high-sensitivity C-reactive protein (hsCRP), oxidized low-density lipoproteins (OxLDL), E-selectin, and Interleukin 22 (IL-22). These markers were measured in healthy volunteers and in 28 patients with moderate/severe psoriasis before and after 3 and 24 months of treatment with adalimumab. Psoriasis patients had increased levels of markers in comparison to the control group. After 3 months of therapy, E-selectin decreased significantly (P < .001), as well as IL-22 (P < .001). hsCRP also decreased but did not show a statistical significance, OxLDL were slightly higher than initially. After 24 months, 17 patients were still being treated with adalimumab. In these patients, hsCRP (P < .05), E-selectin (P < .001) and IL-22 (P < .001) were significantly decreased. OxLDL remained at a higher level. The stable decrease of E-selectin, hsCRP, and IL-22 after 24 months confirms that adalimumab suppresses systemic inflammation.

Deroofing followed by thorough sinus tract excision: a modified surgical approach for hidradenitis suppurativa.

BACKGROUND AND OBJECTIVES: Deroofing has proven to be an effective method to treat mild to moderate forms of hidradenitis suppurativa (HS). The basic procedure includes removal of the sinus roof, followed by secondary intention healing, while fibrotic tissue usually stays in situ. We have tried to establish a modified method of deroofing in which meticulous removal of the fibrotic tissue results in a low recurrence rate in moderate to severe HS patients. PATIENTS AND METHODS: An open prospective study consisted of 96 deroofed lesions in 52 consecutive patients with moderate to severe HS. Patients were followed up for a minimum of 28 months. RESULTS: Recurrence occurred after a median time of 2.3 months in 14 % of locations. Recurrences according to location were as follows: 6 % in the axillary region and 25 % in the inguinal region. Postoperative bleeding was the only considerable complication and occurred in 7 % of treated locations. Seven patients were lost to follow-up. CONCLUSION: Modified deroofing followed by meticulous sinus tract removal is a surgical approach suitable for patients with moderate disease, especially in the axillary region. This results in a low recurrence rate and the same healing period as that of the standard deroofing procedure.

[Psoriasis comorbidities]. / Komorbidity psoriázy.

Psoriasis is a chronic inflammatory skin disease affecting 2-4 % of Central European population. Nowadays, we know that psoriasis is not limited to the skin but is connected with several comorbidities like, psoriatic arthritis (around 25 %), Crohn's disease, ulcerative colitis, Bechterev, non-alcoholic liver steatosis, psychiatric disorders and mainly diseases of the so called metabolic syndrome, like diabetes mellitus type 2, arterial hypertension or dyslipidemia. In the last years, new information is arising which connect psoriasis with sleep apnoe and chronic obstructive pulmonary disease.

Dead Sea ultraviolet climatotherapy for children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common, chronic, and relapsing inflammatory skin disorder. Moderate to severe cases represent an extremely disabling disease, for both children and their parents. Dead Sea climatotherapy (DSC), recognized as a natural treatment for patients with skin diseases, takes advantage of the selectively scattered ultraviolet irradiation (UV) present at the lowest terrestrial site on the earth. OBJECTIVES: To investigate the impact on short-term results of DSC in moderate to severe AD children from the Czech Republic treated 4 weeks at the Deutsches Medizinisches Zentrum (DMZ), Israel, and to correlate their results to the cumulative UVA and UVB irradiation doses received during treatment. PATIENTS AND METHODS: Seventy-two patients aged <19 years were divided into three groups and treated in March 2014, October 2014, and March 2015 with gradually increasing sun exposure during 28 consecutive days. Daily and cumulative exposure doses of UVB and UVA were calculated through patients' recorded sun exposure logs. The SCORing Atopic Dermatitis (SCORAD) index was recorded immediately after DSC and 3 months later by the same dermatologist. RESULTS: Good clinical results were observed in all groups, with overall improvement in SCORAD reaching 87.5 ± 13.4% and 71.3 ± 21.3% immediately after DSC and 3 months later, respectively. No side effects were observed during the treatments. Higher cumulative exposure times correlated with better results and enhanced remission. CONCLUSION: Dead Sea climatotherapy represents a valuable option for the treatment of AD in children. Medically controlled and prescribed sun exposure seems to directly and positively influence the results obtained.

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.

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.

Real-World Clinical, Psychosocial, and Economic Burden of Atopic Dermatitis: Results From the ESSENTIAL AD Multicountry Study.

INTRODUCTION: Limited real-world evidence exists about the burden of atopic dermatitis (AD) in patients receiving systemic or non-systemic therapies in clinical practices. ESSENTIAL AD was an observational study that aimed to fill this information gap. METHODS: ESSENTIAL AD enrolled (September 2021-June 2022) adult patients with physician-confirmed AD that was routinely managed with systemic and non-systemic treatment in a real-world setting from 15 countries in Eastern Europe, the Middle East, and Africa. Primary outcome variables were Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), and Dermatology Life Quality Index (DLQI) assessed during one office visit. RESULTS: A total of 799 enrolled patients fulfilled selection criteria and were included in the study. Patients mean (standard deviation [SD]) age was 36.3 (14.4) years, 457 (57.2%) were female, and the majority of patients were white (647 [81.0%]). Mean (SD) time since AD diagnosis was 17.6 (15.2) years (median 16.5; interquartile range [IQR] 3.3-26.8). The mean (SD) EASI, SCORAD, and DLQI total scores were 11.3 (11.3 [median 8.1; IQR 3.6-15.8]), 37.8 (17.9 [median 35.5; IQR 24.2-49.0]), and 10.6 (7.2 [median 10.0; IQR 5.0-15.0]), respectively. Patients receiving systemic treatment had significantly higher disease burden (mean [SD] EASI 13.3 [13.0]; median [IQR] 9.6 [3.9-17.9]) versus non-systemic treatment (mean [SD] 9.3 [8.7]; median [IQR] 6.8 [3.0-13.2]; P < 0.0001). Results were similar for SCORAD (39.9 [19.6] vs 35.6 [15.7]; median [IQR] 38.6 [24.7-53.1] vs 32.6 [23.9-44.6]; P = 0.0017), and DLQI total scores (11.4 [7.4] vs 9.9 [6.9]; median [IQR] 11.0 [5.0-16.0] vs 9.0 [5.0-14.0]; P = 0.0033, respectively). CONCLUSION: Patients with AD continue to have substantial disease burden despite treatment with systemic therapy, suggesting that a need for effective disease management remains, including effective therapies that improve psychological outcomes and reduce economic burden of AD, in Eastern Europe, the Middle East, and Africa.

Patients with atopic dermatitis often suffer from debilitating symptoms that impact their everyday lives. Although several treatment options are available, many patients continue to experience symptoms of disease. The ESSENTIAL AD study assessed burden of atopic dermatitis in patients receiving systemic and/or non-systemic therapies in real-life clinical practices across 15 countries in Eastern Europe, the Middle East, and Africa. The results of the study demonstrated that adult patients with atopic dermatitis continue to have substantial disease burden regardless of treatment with systemic therapy or non-systemic therapy. The findings suggest that optimal management of atopic dermatitis needs to be reassessed in Eastern Europe, the Middle East, and Africa, especially as new, more effective treatment options become available to patients.

Treatment of Severe Atopic Dermatitis with Dupilumab in Patients with Advanced Cancer.

Atopic dermatitis is a chronic inflammatory intensively pruritic skin disease. Patients with moderate-to-severe atopic dermatitis or with difficult-to-treat areas are candidates for systemic therapy, especially when topical therapy is inadequate. Currently, we have available not only conventional immunosuppressive systemic therapy, but also targeted biological therapy, which has shown a remarkable reduction in clinical severity with a good safety profile. Dupilumab has been approved to treat moderate-to-severe atopic dermatitis. Even though the therapy has been available for more than 3 years, there are still limited data regarding the treatment of patients with concomitant cancer. Previous immunosuppressive treatment for atopic dermatitis, such as cyclosporine or azathioprine, poses a safety risk for patients with malignant disease. We present a case series of three patients with advanced cancer and severe atopic dermatitis treated with dupilumab for an average of 17 months with a great response toward atopic dermatitis without cancer recurrence. One patient had colorectal cancer' the second and the third both had cancer duplicity-colorectal and kidney cancer and penile squamous cell carcinoma with prostate cancer. Our cases suggest that dupilumab can safely control atopic dermatitis in patients with advanced cancer.

Long-Term Efficacy, Safety, and Drug Survival of Guselkumab in Patients with Psoriasis: Real-World Data from the Czech Republic BIOREP Registry.

BACKGROUND: Real-world data on the long-term use of guselkumab for treatment of psoriasis are still limited. OBJECTIVE: We aimed to evaluate long-term efficacy, safety, and drug survival of guselkumab in a real-world setting. METHODS: This is a retrospective study analyzing Czech Republic registry (BIOREP) data of patients treated with guselkumab. RESULTS: In total, 333 patients were included. Improvement in Psoriasis Area and Severity Index (PASI) score was significant. Mean PASI score decreased from 16 at baseline to 0.7, 0.9, and 0.8 after 12, 24, and 36 months, respectively. Absolute PASI scores of ≤ 3 and ≤ 1 were achieved in 93.9% and 77.9%, 94.2% and 71.0%, and 94.8% and 70.7% of patients after 12, 24, and 36 months, respectively. Response PASI 90 and PASI 100 were attained in 81.8% and 57.1%, 75.4% and 50.7%, and 75.9% and 55.2% of patients after 12, 24, and 36 months, respectively. The percentage of patients achieving PASI 90 and PASI 100 responses was higher throughout the study in bio-naive and in normal-weight patients, while presence of psoriatic arthritis had no influence. Improvement in Dermatology Life Quality Index (DLQI) score was also significant; mean DLQI score decreased from 14.2 at baseline to 0.9, 1.0, and 0.7 after 12, 24, and 36 months, respectively. Patients with PASI 100 had lower mean DLQI throughout the study compared with patients with PASI 90. Major reason for discontinuation was loss of effectiveness in 7.1% of patients, while only 0.6% were due to adverse events. Overall cumulative drug survival was high, with only a minimal decline over time, reaching 91.6%, 87.0%, and 85.5% after 12, 24, and 36 months, respectively. Drug survival was not affected by previous biological treatment, patient weight, or presence of psoriatic arthritis. CONCLUSIONS: This real-world study demonstrated the long-term effectiveness, good safety profile, and high drug survival of guselkumab treatment over a period of 36 months.