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BACKGROUND: Despite that brodalumab's efficacy and safety have been assessed in randomized clinical trials, real-life data remain scarce. BrIDGE was an observational, prospective, single-cohort, multicentre study that recruited patients with moderate-to severe plaque psoriasis in Greece. OBJECTIVES: The primary objective was to assess the proportion of patients who achieved Psoriasis Area and Severity Index (PASI)100 after 24 weeks. Other endpoints included: the maintenance of PASI90/100 through to 104 weeks, the short-term response [PASI75/90/100 and static Physician's Global Assessment (sPGA) 0/1] to brodalumab at 12-16 weeks and time to complete clearance. Moreover, we explored the change in quality of life [Dermatology Life Quality Index (DLQI) 0/1] and adherence to brodalumab. METHODS: Two hundred patients who were initiating treatment with or switching to brodalumab, were recruited. Analyses were conducted using the as observed data and three imputation approaches were also applied for the missing data (last observation carried forward, 'worst case' and 'best case' scenario). Continuous variables were reported using summary statistics, whereas categorical variables were reported in frequency tables. RESULTS: Based on the 'as observed data', 42.0% of patients achieved PASI100 at Week 24 after 25.9 ± 3.5 weeks and 65% of patients attained PASI100 at Week 104. In total, 70.2%, 47.5% and 32.0% achieved PASI75/90/100, respectively, whereas 72.6% of patients achieved sPGA 0/1, at Weeks 12-16. With respect to sPGA status 82.8%, 89.2% and 92.5% of patients achieved sPGA 0/1 at Weeks 24, 52 and 104, respectively. The time to achieve PASI100 at Weeks 12-16 was 13.7 ± 1.3, 52.1 ± 3.4 weeks at Week 52 and 105.5 ± 4.8 weeks at Week 104. Mean DLQI and Psoriasis Symptom Inventory (PSI) scores decreased by 11.4 ± 7.0 and 15.4 ± 6.5 points from baseline to Week 104, respectively. Adherence to treatment was equal to 98.9%. CONCLUSIONS: Brodalumab confers rapid and durable responses, as well as improvements in the quality of life of moderate-to-severe psoriasis patients.
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Anticuerpos Monoclonales Humanizados , Psoriasis , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Grecia , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Fármacos Dermatológicos/uso terapéutico , Resultado del TratamientoRESUMEN
Fixed combination calcipotriol/betamethasone (Cal/BD) aerosol foam has been shown to be effective in psoriasis treatment in clinical trials, but real-world evidence is currently sparse. The real-world CELSUS study in Greece found that Cal/BD aerosol foam treatment was effective and associated with satisfaction in psoriasis patients. Patients from the CELSUS study (N = 400) were stratified by baseline disease severity according to physician's global assessment (PGA) score (mild vs. moderate vs. severe) and by previous psoriasis treatment (naïve vs. treatment-experienced). Proportions of patients achieving treatment success (clear/almost clear [PGA 0/1]) after 4 weeks' treatment with Cal/BD aerosol foam were reported for each subgroup. Psoriasis area and severity index (PASI) and patient-reported itch, itch-related sleep loss, scaling, dry skin, and erythema numerical rating scores were reported by subgroup. At baseline, 216 (54%) patients were systemic-or-topical psoriasis treatment-naïve and 184 (46%) were treatment experienced. By disease severity, there were 135 versus 89 patients with mild, 69 versus 83 with moderate and 12 versus 12 with severe disease in the treatment-naïve versus treatment-experienced groups, respectively. In the treatment-naïve group, treatment success was achieved by 72.6%, 56.5%, and 66.7% of patients with mild, moderate, and severe disease, respectively, while the proportions in the treatment-experienced group were 60.7%, 42.2%, and 25%, respectively. Reduction from baseline in psoriasis symptoms was observed in all patient groups. The greatest reductions were observed in treatment-naïve patients with severe disease. Clinically relevant benefits were observed with Cal/BD aerosol foam in psoriasis patients, regardless of prior treatment-experience and disease severity at baseline.
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Fármacos Dermatológicos , Psoriasis , Humanos , Aerosoles , Betametasona , Calcitriol/análogos & derivados , Combinación de Medicamentos , Grecia , Satisfacción del Paciente , Psoriasis/complicaciones , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Treatment of alopecia areata is often challenging, especially for patients with extended disease. Contact immunotherapy with diphenylcyclopropenone (DPCP) has been reported as an effective topical treatment but the exact immunologic mechanism of diverting the immune response is still unknown. We investigated the efficacy of topical immunotherapy with DPCD in acute, intermediate, and chronic lesions of AA and the response rate was associated with perifollicular infiltrate of T regulatory cells. Approximately two-thirds of our patients (67.5%) had a response rate > 50% after 6 months of DPCP therapy. Patients with acute and intermediate onset of the disease were more likely to respond to the therapy. Although responders demonstrated FOXP3+ positive lymphocytes in immunohistochemistry, this association could not be confirmed by statistical significance (p = 0.052). In patients with multiple lesions, that had different chronological onset, the lesions with more recent onset responded faster than lesions of longer duration.
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Alopecia Areata , Alopecia Areata/inducido químicamente , Alopecia Areata/tratamiento farmacológico , Biomarcadores , Ciclopropanos , Humanos , Factores Inmunológicos , Inmunoterapia , Linfocitos T ReguladoresRESUMEN
Brodalumab's clinical efficacy and favorable safety profile have been demonstrated during controlled clinical trials, but real-world data remain scarce. BrIDGE, an ongoing 104 week, observational, prospective, multicenter study conducted in Greece, enrolled moderate-to-severe plaque psoriasis patients, with body surface area (BSA) > 10 or psoriasis area severity index score (PASI) > 10 and dermatology life quality index (DLQI) > 10, based on European consensus, initiating brodalumab treatment as per routine clinical practice. This interim analysis includes evaluations 12-16 weeks following treatment initiation. Key efficacy endpoints included proportion of patients achieving static Physician's Global Assessment (sPGA) score of "clear/almost clear" (0/1) and a reduction ≥75%, 90%, 100% from baseline in PASI (PASI75, PASI90, and PASI100) at weeks 12-16. Other endpoints included time to achieve PASI100, changes in self-reported DLQI and psoriasis symptom inventory (PSI) at weeks 12-16. From 200 patients (mean age 51.4 years, 70% male, mean disease duration 13.8 years) enrolled, 72.8% achieved sPGA of 0/1, whereas 70.2%, 47.5%, and 32.0% achieved corresponding PASI75, PASI90, and PASI100 responses following 12-16 weeks of brodalumab treatment, according to the "as-observed" analysis. The mean time to achieve PASI100 was 13.7 ± 1.2 weeks for the 32% who achieved PASI100. Concurrent decreases in mean DLQI and PSI were observed. Furthermore, 90% adherence to brodalumab was noted and nine adverse events were reported. Brodalumab confers substantial clinical improvements short-term as reflected by high levels of skin clearance in moderate-to-severe plaque psoriasis patients within 12-16 weeks of treatment under everyday clinical conditions, followed by improvements in symptoms and quality of life and a favorable safety profile.
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Psoriasis , Calidad de Vida , Humanos , Masculino , Persona de Mediana Edad , Femenino , Grecia , Estudios Prospectivos , Anticuerpos Monoclonales/efectos adversos , Índice de Severidad de la Enfermedad , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamente , Resultado del TratamientoRESUMEN
INTRODUCTION: Certolizumab pegol (CZP) is an anti-tumor necrosis factor alpha (TNFα) approved for the treatment of moderate to severe plaque psoriasis (PSO). However, data on its real-world use is currently limited. The objective of this study was to describe the 1-year real-world effectiveness of CZP, its impact on health-related quality of life (HRQoL), and safety outcomes in patients with moderate to severe PSO in multi-country settings. METHODS: CIMREAL, a prospective, noninterventional study, was conducted across Europe and Canada from August 2019 to December 2022. Patients were followed for 1-year, receiving CZP 400 mg initial doses at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg Q2W maintenance dosing. Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI). Safety was also evaluated. RESULTS: Overall, 399 patients with moderate to severe PSO were included. Of these, 93.7% (374/399) and 77.9% (311/399) completed months 3 and 12, respectively. Mean age (± standard deviation) was 42.9 ± 13.5 years and body mass index was 28.5 ± 6.8 kg/m2, with the majority of patients being female (68.2%). At 12 months, CZP showed substantial effectiveness, achieving PASI 75 and PASI 90 response rates (≥ 75% and ≥ 90% improvement from baseline, respectively) of 77% and 56.5%, respectively. Patients with PASI score of ≤ 3 and ≤ 2 experienced improvement from 3 months (49.8% and 41.1%, respectively) to 12 months (82.0% and 75.3%, respectively). HRQoL considerably improved, with mean DLQI scores decreasing from 12.4 to 2.3 after 12 months of treatment, and the proportion of patients with DLQI 0/1 increased from 28.6% at 3 months to 59.4% at 12 months. The 1-year probability of persistence was approximately 85%. Overall, 30.6% of the patients experienced any adverse events and 9.3% had serious adverse events. CONCLUSION: In routine clinical practice, CZP exhibited consistent effectiveness, positively impacting both skin psoriasis activity and HRQoL. The 1-year persistence of CZP was high, and no new safety signals were identified. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04053881 https://www. CLINICALTRIALS: gov/study/NCT04053881 .
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The clinical heterogeneity regarding the response profile of the antitumor necrosis factor (anti-TNF) in patients with Crohn's disease (CD) and psoriasis (PsO) is attributed, amongst others, to genetic factors that influence the regulatory mechanisms which orchestrate the inflammatory response. Here, we investigated the possible associations between the MIR146A rs2910164 and MIR155 rs767649 variants and the response to anti-TNF therapy in a Greek cohort of 103 CD and 100 PsO patients. We genotyped 103 CD patients and 100 PsO patients via the PCR-RFLP method, utilizing the de novo formation of a restriction site for the SacI enzyme considering the MIR146A rs2910164, while Tsp45I was employed for the MIR155 rs767649 variant. Additionally, we investigated the potential functional role of the rs767649 variant, exploring in silico the alteration of transcription factor binding sites (TFBSs) mapped on its genomic location. Our single-SNP analysis displayed a significant association between the rare rs767649 A allele and response to therapy (Bonferroni-corrected p value = 0.012) in patients with PsO, a result further enhanced by the alteration in the IRF2 TFBS caused by the above allele. Our results highlight the protective role of the rare rs767649 A allele in the clinical remission of PsO, implying its utilization as a pharmacogenetic biomarker.
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Enfermedad de Crohn , MicroARNs , Psoriasis , Humanos , Enfermedad de Crohn/genética , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Pruebas de Farmacogenómica , Polimorfismo Genético , Psoriasis/patología , MicroARNs/genéticaRESUMEN
OBJECTIVE: To assess the real-world clinical treatment outcomes with brodalumab in patients with moderate-to-severe plaque psoriasis in Greece. MATERIALS AND METHODS: This was a longitudinal, retrospective, real-world analysis of data from medical records of 106 patients with moderate-to-severe plaque psoriasis, treated with brodalumab for up to 24 months at four University Dermatology Centers in Greece. Efficacy assessments of psoriasis severity [Psoriasis Area and Severity Index (PASI) and Body Surface Area affected (BSA) scores] and its impact on patients' quality of life (QoL) [Dermatology Life Quality Index (DLQI) score] were evaluated at different timepoints up to 24 months. RESULTS: Treatment with brodalumab reduced both mean PASI (14.0-1.5, p < .001) and BSA scores (21.6-2.5, p < .001) across all visits. This effect was accompanied by reduction in mean DLQI score (12.8-2.1, p < .001) across all visits compared with baseline. Moreover, therapeutic efficacy was affected by prior biologic treatment exposure, as biologic naïve patients had greater reductions in all scores from baseline following treatment with brodalumab (numerical for mean PASI, significant for mean BSA and DLQI scores). CONCLUSION: Brodalumab is effective long term, improving disease severity and health-related QoL in patients with moderate-to-severe plaque psoriasis in a real-world setting.