Background
Brodalumab was efficacious and safe in moderate‐to‐severe plaque‐type psoriasis in the AMAGINE trials; published reports under real‐life conditions are limited.
Objectives
To evaluate the ...effectiveness and safety of brodalumab in patients with moderate‐to‐severe plaque‐type psoriasis in a real‐world setting.
Methods
This observational, retrospective study enrolled adult patients (≥18 years) with moderate‐to‐severe plaque‐type psoriasis who underwent 24 weeks of treatment with brodalumab at 17 Italian dermatological centres. Baseline data included demographics, comorbidities, age of onset and duration of psoriasis and previous treatments. Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), static PGA of Genitalia, Dermatology Life Quality Index and patient satisfaction were assessed at weeks 0, 4, 12 and 24; adverse events were recorded.
Results
Seventy‐eight patients (mean age 47.9 years, 71.8% male, average disease duration 16.8 years) were enrolled. A rapid and significant reduction in mean PASI score was observed after 4 weeks of treatment, decreasing further at weeks 12 and 24 (all P < 0.0001 vs. baseline). A higher number of cardiometabolic comorbidities and previous therapies were negatively associated with the achievement of PASI 90 at all assessments. Brodalumab was effective in bio‐experienced patients, including those who had failed on anti‐interleukin (IL)‐17 therapies. Quality of life and patient satisfaction increased significantly during treatment (P < 0.0001 and P < 0.01 vs. baseline, respectively). Treatment was interrupted in 9 (11.5%) patients due to adverse events (n = 4), lack of efficacy (n = 3), lost to follow‐up (n = 1) and surgical procedure (n = 1).
Conclusions
Brodalumab is effective and safe in the treatment of moderate‐to‐severe psoriasis in a real‐world setting, including in patients with failure to anti‐IL17 therapies.
Summary
Background
Adherence is an overall marker of treatment success, and it depends on multiple factors including efficacy and safety. Despite the wide use of tumour necrosis factor (TNF)‐α ...blockers in the treatment of plaque‐type psoriasis, few data regarding treatment adherence in routine clinical practice are available.
Objectives
To estimate the long‐term survival rate of anti‐TNF‐α therapy in a cohort of patients with psoriasis in routine clinical practice; to evaluate the reasons for and predictors of treatment discontinuation.
Methods
The Outcome and Survival rate Concerning Anti‐TNF Routine treatment (OSCAR) study was based on a retrospective analysis to estimate the long‐term survival rate of the first anti‐TNF‐α treatment in patients with psoriasis, from three Italian academic referral centres. Adult patients (n = 650) with plaque psoriasis treated with a first course of adalimumab, etanercept or infliximab for ≥ 3 months were included.
Results
Global adherence to anti‐TNF‐α treatments after 28·9 ± 15·4 months (867 ± 462 days) of observation was 72·6%. Etanercept showed a longer survival (mean 51·4 months, 1565 days; P < 0·001) compared with infliximab (36·8 months, 1120 days) and adalimumab (34·7 months, 1056 days). Treatment discontinuation due to primary and secondary inefficacy was observed in 5·2% and 14·5% of patients, respectively, whereas discontinuation due to adverse events was reported in 29 subjects (4·5%). Independent predictors of treatment withdrawal were female gender hazards ratio (HR) 1·3, treatment with adalimumab or infliximab compared with etanercept (HR 2·7 and 1·7, respectively), and the concomitant use of traditional systemic treatment, as a rescue therapy, compared with monotherapy (HR 1·9).
Conclusions
Overall survival of anti‐TNF‐α agents in psoriasis is elevated, with drug discontinuation mostly due to inefficacy. Etanercept showed a longer adherence compared with adalimumab and infliximab.
What's already known about this topic?
Very few studies have analysed long‐term efficacy and safety of antitumour necrosis factor (anti‐TNF)‐α agents in plaque psoriasis.
Treatment adherence is an overall marker of treatment success, and it depends on multiple factors including efficacy, safety, patients’ satisfaction and dermatologists’ confidence with the treatment.
Survival rate is a standardized method for estimating treatment adherence.
What does this study add?
Adherence to anti‐TNF‐α agents after 2 years was > 70%.
The risk of drug discontinuation was significantly higher in women than in men, in case of treatment with adalimumab and infliximab compared with etanercept, and in patients who required a traditional systemic treatment as a rescue therapy, compared with patients treated exclusively with TNF‐α blockers.
Aims: The aim of this study was to conduct a cost-effectiveness analysis, as well as a budget impact analysis, on the use of apremilast for the treatment of adult patients with moderate-to-severe ...plaque psoriasis (defined as a psoriasis area severity index PASI ≥ 10), who failed to respond to, had a contraindication to, or were intolerant to other systemic therapies, within the Italian National Health Service (NHS).
Materials and methods: A Markov state-transition cohort model adapted to the Italian context was used to compare the costs of the currently available treatments and of the patients' quality of life with two alternative treatment sequences, with or without apremilast as pre-biologic therapy. Moreover, a budget impact model was developed based on the population of patients treated for psoriasis in Italy, who would be eligible for treatment with apremilast.
Results: Over 5 years, the cost-effectiveness analysis showed that the strategy of using apremilast before biologic therapy was dominant compared with the sequence of biologic treatments without apremilast. In addition, it is important to underline that the use of apremilast slightly increases the quality-adjusted life years gained over 5 years. Furthermore, within the budget impact analysis, the strategy including apremilast would lead to a saving of €16 million within 3 years. Savings would mainly be related to a reduction in pharmaceutical spending, hospital admissions and other drug administration-related costs.
Conclusion: These models proved to be robust to variation in parameters and it suggested that the use of apremilast would lead to savings to the Italian healthcare system with potential benefits in terms of patients' quality of life.
Aims: The aim of this study was to conduct a cost-effectiveness analysis, as well as a budget impact analysis, on the use of apremilast for the treatment of adult patients with psoriatic arthritis ...(PsA), within the Italian National Health Service (NHS).
Methods: A Markov state transition cohort model, which was adapted to the Italian context, was used to compare the costs of the currently available treatments and of the patients' quality of life with two alternative treatment sequences, with or without apremilast as pre-biologic therapy. Moreover, a budget impact model was developed based on the population of patients treated for PsA in Italy, who can be eligible for treatment with apremilast. The eligible population was represented by adult patients with PsA who had an inadequate response to or were intolerant to previous disease-modifying antirheumatic drugs (DMARDs), for the approved indication, and for the treatment studied in the economic analytic model.
Results: This cost-effectiveness analysis estimated that the strategy of using apremilast before biologic therapy is cost-effective, with an incremental cost-effectiveness ratio of €32,263.00 per QALY gained which is slightly over the normal threshold found in other Italian economic studies, which usually considers a 40-year-period. Conversely, the budget impact analysis was conducted over 3 years, and it led to an estimated annual saving of €1.6 million, €4.6 million and €5.5 million in the first, second and third year of apremilast commercialization, respectively, for a total saving of €11.75 million in 3 years.
Limitations: Limitations of this analysis include the absence of head-to-head trials comparing therapies included in the economic model, the lack of comparative long-term data on treatment efficacy, and the assumption of complete independence between the considered response rates to therapy.
Conclusion: The use of apremilast as a first option before the use of biologic agents may represent a cost-effective treatment strategy for patients with PsA who fail to respond to, or are intolerant to, previous DMARD therapy. In addition, based on a budget impact perspective, the use of apremilast may lead to cost savings to the Italian healthcare system.
Abstract Background Facial (FP) and genital psoriasis (GP) significantly affect patients' quality of life. Despite the advances in treatments, limited data on efficacy and safety are available on ...these difficult‐to‐treat areas. Guselkumab is an interleukin (IL)‐23 inhibitor which has been proven effective in treating patients with moderate‐to‐severe plaque psoriasis. Objectives The aim of this interim analysis was to report the efficacy and safety of guselkumab in the treatment of patients with FP and/or GP. Materials and Methods GULLIVER is a 52‐week Italian observational study to evaluate the effectiveness and safety of guselkumab in a real‐life setting in patients with FP and/or GP. Adult patients with facial and/or genital moderate‐to‐severe psoriasis (sPGA score ≥ 3) were included. The primary endpoint of this analysis was the percentage of patients achieving a facial or genital sPGA score of 0 (clear) or 1 (almost clear), at Week 12. The change in the score of the facial or genital sPGA components in patients with a score ≥3 for each sPGA component was assessed. PASI score in patients with a baseline PASI above or below 10 was evaluated. Results Overall, 351 patients were included in the study; 83.3% of FP and 76.5% of GP patients achieved the primary endpoint. Similar response rates were observed for the facial or genital sPGA components in patients with a baseline facial or genital sPGA score ≥3 in each component. Among patients with a baseline PASI score >10, mean PASI score improved from 19.0 (SD 8.3) to 2.2 (SD 4.8). Forty‐four AEs were observed in 32 patients; two mild and transient AEs (fatigue and nausea) were considered treatment related. No SAEs were observed. Conclusions Guselkumab, showing to be effective and safe in treating FP and GP, may be a valid therapeutic option for patients with psoriasis localized in these difficult‐to‐treat areas.
Psoriasis, a common systemic inflammatory disorder, presents with gender-related differences in the quality of life (QoL) and treatment outcomes. This post hoc analysis from the Phase 3b SUPREME ...study explored gender-related differences in patient characteristics and efficacy of secukinumab 300 mg on Psoriasis Area and Severity Index (PASI) 75/90/100 and impact on QoL using the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis through week 24.
The proportion of patients achieving PASI 75/90/100 was computed using a nonresponder imputation approach. Differences between cohorts were analyzed using a logistic regression model. The mean change from baseline in DLQI was computed using the Wilcoxon test.
Among the 433 patients (males: 71.6%), females had a higher DLQI than males at baseline (13.1 vs 9.5;
<0.0001). Males had a slightly higher response for PASI 90 than females at week 16 (80.7% vs 78.1%;
=0.0779) and 24 (83.2% vs 79.7%;
=0.0319). No differences were observed between genders in PASI 100/75 responses at week 24. Both genders showed an improvement in DLQI with secukinumab at week 24 (-10.9 vs -8.1, respectively, in females vs males;
=0.0004).
In summary, secukinumab was effective in the treatment of psoriasis, irrespective of gender.
Psoriasis is a chronic inflammatory skin disease with systemic involvement that might predispose to many psoriasis-related comorbidities, such as metabolic syndrome and cardiovascular disorders. ...Clusterin (Clu), also known as apolipoprotein J (ApoJ), is a highly conserved disulfide-linked heterodimeric glycoprotein implicated in a great variety of physiological and pathophysiological processes including lipid transportation, tissue remodeling, senescence, cell interaction, stress response, inflammation, apoptosis, diabetes mellitus and metabolic syndrome. Serum levels of Clu were assessed in 15 patients with moderate-to-severe psoriasis defined by the presence of a Psoriasis Area and a Severity Index (PASI) value of 10 or more. It was found that the Clu value was significantly higher in patients than in healthy subjects (p <0.001). Our data confirm that the association of psoriatic disease with some comorbidities, especially metabolic and cardiovascular disease, might support the correlation with increased circulating Clu. In particular, it should be pointed out that, according to the recent literature, the Clu could also have a protective role in the comorbidity of psoriasis patients. In addition, it has been published that Clu protects cardiomyocytes against ischemic cell death and is a potential therapeutic agent in the treatment of myocardial infarction; therefore it can be assumed that an artificial enhancement of Clu in the blood could limit the severity of damage also in respect to skin lesions. Although the increase in serum level of Clu was found in all patients with psoriasis, more studies on a larger cohort of patient samples is necessary to confirm the significance of high serum levels of clusterin/ApoJ and to suggest the use of this glycoprotein as an additional new marker in psoriasis pathogenesis. It could be a possibility to improve the prognosis in patients with psoriasis.
One of the problems possibly related to the use of biological agents targeting tumor necrosis factor (TNF)-alpha is the increased risk of infections, including the activation of hepatitis B virus ...(HBV). HBV activation can occur in carriers of hepatitis B surface antigen (HBsAg), but the risk may also involve the HBsAg-negative (anti-HBc ± anti-HBs) occult carriers. Precise data on the safety of anti-TNF and/or other immunosuppressive drugs in HBV occult carriers are not available. We performed a retrospective analysis of 62 psoriatic patients with occult HBV infection treated with anti-TNF biological agents over a period of approximately 4 years: 44 subjects were treated with etanercept, 8 with infliximab and 10 with adalimumab. During the observational treatment period, no signs of HBV activation were observed. Only in one patient the reappearance of HBsAg, without detectable HBV-DNA, was noted before retreatment with etanercept and after 10 months from discontinuation of the previous course. In this patient etanercept was re-administered in association with lamivudine without any adverse event. Our results suggest the overall safety of treatment with anti-TNF drugs in HBV occult carriers, although a careful and constant monitoring of virological markers is required in such patients during treatment with anti-TNF drugs in order to have an early recognition of viral reactivation.
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