Effectiveness of guselkumab in patients with facial and/or genital psoriasis: Interim analysis results at Week 12 from the GULLIVER study.

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.

Brodalumab for the treatment of moderate-to-severe plaque-type psoriasis: a real-life, retrospective 24-week experience.

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.

Clusterin serum level: how does it affect psoriatic patients?

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.

Survival rate of antitumour necrosis factor-α treatments for psoriasis in routine dermatological practice: a multicentre observational study.

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.

Anti-tumor necrosis factor treatment in occult hepatitis B virus infection: a retrospective analysis of 62 patients with psoriatic disease.

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.

Treatment of psoriasis with different dosage regimens of etanercept: preliminary results from the Tαranta Plastic Study Group.

This pilot open-label study is aimed to assess clinical response in psoriasis patients receiving diverse dose regimens of etanercept, consisting of the same global cumulative dose of etanercept administered over different treatment periods. Eligible patients were assigned sequentially in a 1:1 ratio to receive: etanercept 50 mg once weekly (QW) or 50 mg twice weekly (BIW) for 12 weeks. The final analysis included a total of 72 patients. At week 12 the Psoriasis Area and Severity Index (PASI) and Skindex-29 scores notably improved in both treatment arms, without significant differences between the two groups. The rate of patients attaining a PASI improvement >or= 50% (PASI 50) at week 12 was 92% in the high-dose group. In these patients, etanercept dosage was decreased to 50 mg QW from week 13, with persistence of the PASI 50 response at week 24 in all cases. Thereafter, treatment was discontinued up to week 36 and almost 30 % of patients experienced a gradual relapse of their psoriasis within this period. In the low-dose group, the PASI 50 response was observed in 75% of patients. These responders continued to be treated with etanercept 50 mg QW up to week 36 with persistence of the PASI 50 in 100% of cases at week 24 and 93% at week 36. In the low-dose regimen, 8 patients who did not respond at week 12 underwent dose escalation to 50 mg BIW for a further 12 weeks. At week 24, six of these patients gained the PASI 50 response, 4 of whom maintained the response up to week 36, after treatment discontinuation from week 24. Our results confirm that etanercept is very effective and well-tolerated in psoriasis and that the drug dosages and treatment duration may be modulated and adapted to clinical needs in a flexible way.

Adjuvant role of a new emollient cream in patients with palmar and/or plantar psoriasis: a pilot randomized open-label study.

Emollients are considered important adjunctive tools for the therapeutic management of psoriasis patients. In spite of the widespread use, the actual impact of emollients on psoriasis is far to be completely elucidated. The objective of this study was to evaluate the effect of a new emollient cream containing milk proteins and Glycyrrhiza glabra extracts in patients with palmar and/or plantar psoriasis treated with topical corticotherapy. This pilot open parallel-group trial was carried out in 40 patients with palmar and/or plantar psoriasis. Patients were randomized to receive monotherapy with mometasone furoate ointment, applied once daily to the palmoplantar lesions until remission and for a maximum of 4 weeks (N=20), or the same topical corticotherapy in combination with the emollient cream (N=20). The emollient was applied twice a day for 4 weeks. Clinical assessments were performed at baseline and 2 and 4 weeks after the start of treatment. All patients completed the study and showed a progressive improvement of their palmo-plantar psoriasis over the treatment period, achieving at week 4 a statistical significant reduction in the severity of all clinical signs (erythema, desquamation and infiltration) and in the surface area affected. The comparison between the two groups showed no differences in the mean average duration of corticosteroid therapy, whereas a significantly greater improvement of desquamation, surface area affected, and subjective symptoms was observed at week 4 in the group treated with the corticotherapy combined with the emollient as compared to patients who received the corticotherapy alone. This pilot experience suggests the importance of the adjuvant role of particular emollients in the management of psoriasis.

A cost-effectiveness and budget impact analysis of apremilast in patients with psoriatic arthritis in Italy.

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.

A cost-effectiveness and budget impact analysis of apremilast in patients with psoriasis in the Italian setting.

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.

Is there an association between antiphospholipid antibodies and psoriasis?

Ever increasing evidence supports the association between psoriasis and cardiovascular risk. Antiphospholipid antibodies (APAs), which can occur in many autoimmune diseases, are considered prothrombotic and have been associated with atherosclerosis. The aim of this study is to evaluate the prevalence and levels of APAs in psoriasis patients. Fifty patients with moderate to severe plaque psoriasis and 48 healthy subjects were investigated for lupus anticoagulant (LAC) by screening and confirmatory coagulation tests, as well as for antibodies against cardiolipin or beta2-glycoprotein I. Levels of APAs and LAC-related parameters were similar for patients with psoriasis and normal controls (p>0.05). APAs were found in only one psoriatic patient (2%) and in none of the controls. LAC was detected in 2 patients (4%) and in one subject of the control group (2.1%). These results suggest that the prevalence of APAs is not increased in plaque psoriasis as compared to the control group. The increased cardiovascular risk observed in psoriatic patients is therefore likely to be correlated to factors different from APAs.

Efalizumab in moderate-to-severe plaque psoriasis: a retrospective case series analysis from clinical practice.

Efalizumab is an anti-CD11a humanized monoclonal antibody which is safe and effective for the treatment of plaque psoriasis. We performed a retrospective analysis on -high-need- patients with moderate-to-severe psoriasis treated with Efalizumab monotherapy for more than 2 years. Chart review of patient records also concerned information about rebound, relapse, and retreatment after temporary interruption, as well as transitioning from Efalizumab to alternative treatments. Of the 52 patients who completed the initial 12 weeks of treatment, 65% attained the PASI-50 response at week 12. A notable improvement of skin lesions on critical sites, such as palmoplantar surfaces or genitals, was also observed. Continuous treatment resulted in a sustained response in the majority of patients, with a PASI-75 response in nearly 88% of those Efalizumab-treated in the long term (week 72 onwards) and a PASI-90 in 77% of patients by weeks 120-132. In general, the treatment was well tolerated, with mild-to-moderate flu-like symptoms as the most frequent adverse events, particularly after the first two doses. Increase of leukocyte and/or lymphocyte counts was the most common laboratory test alteration during treatment, also in the long term. In our case series, Efalizumab was safe and well-tolerated even in patients with relevant comorbidities, including one patient with HBsAg carriage and five patients with latent TB.

Influence of body mass index, comorbidities and prior systemic therapies on the response of psoriasis to adalimumab: an exploratory analysis from the APHRODITE data.

Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor (TNF)-alpha, which is effective for the treatment of psoriasis and psoriatic arthritis (PsA). The aim of this study is to determine whether the response of psoriasis to adalimumab treatment might be influenced by certain particular factors, such as body mass index (BMI), history of biologic therapy, blood hypertension and metabolic comorbidities. For this reason, an exploratory analysis was conducted on 144 patients with psoriasis and concomitant PsA treated with adalimumab 40 mg every other week, evaluating the influence of such factors on the Psoriasis Area and Severity Index (PASI) response rate at week 12. Our preliminary results suggest that the response rate at week 12, in terms of both PASI-50 and PASI-75, appeared to be independent of the presence of hypertension and/or metabolic comorbidities. The PASI-50 response was observed more frequently in patients with BMI less than 30 as compared to obese patients (79% vs 58%, p = 0.02). Previous use of anti-TNF biologics did not appear to affect per se the rate of responders, although it was associated with a lower PASI-75 rate among responders.

Re-induction as a possible alternative modality of dose escalation of infliximab: a prospective evaluation in a small series of psoriatic patients.

Infliximab is an anti-tumour necrosis factor-alpha chimeric monoclonal antibody which is highly effective in psoriasis, as well as in other indications. In clinical practice, some patients may require dose escalation to overcome a reduction of the extent and/or duration of response during regular maintenance treatment, possibly due to the loss of stable serum concentrations of the drug. Common strategies of dose escalation are the increase of dose per infusion and the decrease of interval between infusions. Here we report the results of re-induction therapy with infliximab used as a dose escalation strategy in 9 patients whose psoriasis relapsed during maintenance treatment with infliximab 5 mg/kg every 8 weeks. Re-induction was well tolerated and capable of restoring response in 8 of these patients.

Infliximab in recalcitrant severe atopic eczema associated with contact allergy.

Infliximab is an anti-tumour necrosis factor (TNF)-alpha chimeric monoclonal antibody which is effective in diseases associated with a T-helper (Th) 1 response, such as rheumatoid arthritis, Crohn's disease and psoriasis. There are sporadic case reports of atopic dermatitis (AD) induced or precipitated by anti-TNF-alpha therapy, which have been attributed to the switch towards Th2-mediated reactions. We report the case of a 30-year-old man with long-standing severe AD associated with contact allergy and poorly responding to conventional treatments. The use of infliximab resulted in a dramatic amelioration of AD lesions and pruritus, persisting at follow-up examinations over a 3-year period. Probably, the unexpected response to infliximab therapy in this case might be due to some peculiar features of AD in our patient (i.e. chronic-continuous course and concomitant contact allergy) which could have been responsible for a more preponderant recruitment of Th1 cells as compared to common forms of AD.

Once-weekly administration of high-dosage Etanercept in patients with plaque psoriasis: results of a pilot experience (power study).

Etanercept is a soluble tumour necrosis factor receptor fusion protein which is approved for the treatment of plaque psoriasis at the dose of either 25mg twice weekly (BIW) or, for the initial 12 weeks, 50mg BIW. Alternative dosing regimens have not been evaluated in psoriasis. In this study, we compare the efficacy and tolerability of two etanercept dosing regimens--50mg BIW and 100mg once weekly (OW)--for 12 weeks in 108 patients with moderate-to-severe recalcitrant psoriasis. Efficacy measures included Psoriasis Area and Severity Index (PASI), severity of pruritus recorded on a visual analogue scale (VAS) and the influence on quality of life assessed by means of Dermatology Life Quality Index (DLQI). Both etanercept regimens caused a significant change in all the efficacy parameters after 4 weeks and 12 weeks, at a comparable rate. At week 12, a PASI improvement of at least 50% from baseline (PASI 50) was achieved by 74% of patients treated with 50mg BIW and 78% of patients treated with 100mg OW. A PASI 75 response was obtained in 54% and 50% of patients treated with 50mg BIW and 100mg OW, respectively. Treatment was well tolerated with similar type and frequency of adverse events between the two groups.

Biosimilar infliximab: an expert view.

CT-P13, a biosimilar of infliximab, was the first biosimilar monoclonal antibody to be approved in both the European Union and Korea. As a monoclonal antibody, CT-P13 is a large molecule with a high molecular weight, and as such it differs from other biosimilars currently in the market. The comparability exercise for CT-P13, therefore, requires special consideration, as it was the first demonstration of biosimilarity between a biosimilar monoclonal antibody and its originator. This paper summarizes current regulations on the approval of biosimilars, describes the evidence leading to the approval of CT-P13, and discusses the potential role of this molecule in the Italian scenario on the basis of the view of a group of experts.

Infliximab monotherapy for refractory psoriasis: preliminary results.

Tumour necrosis factor (TNF)-alpha plays an important role in the pathogenesis of psoriasis. Infliximab is an anti-TNF-alpha chimeric monoclonal antibody, which is licensed for the treatment of rheumatoid arthritis and Crohn's disease. Some reports have shown the efficacy of infliximab, either in monotherapy or in combination with methotrexate, for the treatment of psoriatic arthropathy and psoriasis. The efficacy and tolerability of infliximab monotherapy was evaluated in 29 patients with moderate to severe psoriasis, unresponsive to conventional treatments. Fourteen patients suffered from concomitant arthropathy. Patients received intravenous infliximab, 5mg/kg, at weeks 0, 2, and 6. After this 3-dose-induction regimen, patients were followed-up at monthly intervals and retreated with a single-dose infusion in case of relapse of signs and symptoms. Clinical assessment was performed using the psoriasis area and severity index (PASI) to monitor psoriasis activity; pruritus and joint pain were assessed on a scale of 0 to 3. A marked improvement of skin lesions and subjective symptoms was noted in the majority of patients; an excellent reduction of PASI score (> or =75%) was observed in 13.8% of cases at week 2, 71.4% at week 6 and 78.6% at week 10. During the follow-up period, some patients maintained satisfactory clinical results without requiring any additional infusions. In general, skin lesions showed a trend towards a more prolonged and sustained improvement as compared with subjective symptoms. Treatment was well tolerated and no serious adverse events occurred.