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.

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.

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.

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.

Classical Kaposi's sarcoma: a survey of 163 cases observed in Bari, south Italy.

BACKGROUND: Classical Kaposi's sarcoma (KS) is a sporadic disease that is particularly prevalent in Mediterranean countries. OBJECTIVE: The aim of the study was to update clinical information about this rare condition. METHODS: A survey of 163 cases observed in the period 1971-1990 in Bari, South Italy, was carried out. All records were reviewed and, when lost to follow-up for more than 6 months, patients were called back to update personal and family histories. The age at onset averaged 64 years (range 18-85). The male-to-female ratio was 3:1. No familiar occurrence was identified, and no significant association was found with other conditions (i.e. second primary malignancies and diabetes mellitus). Death from KS occurred in 16 cases, at the mean age of 71 years, an average of 5.7 years after the onset of the disease. To assess whether the different clinical patterns of the disease in its earlier stages may give any indication of its subsequent clinical course, all cases were re-classified into three groups (low-, moderate- and high-eruptivity group) on the basis of both the extent and the rate of spread of the disease before first admission; group-stratified survival function was evaluated using Kaplan-Meier's life table method. RESULTS: Highly significant (p < 0.0001) differences were found in survival profiles of the three study groups, also when only deaths due to KS were computed. CONCLUSION: These findings provide some support to the hypothesis that three subsets of classical KS exist that have different prognoses and, consequently, need different therapeutic approaches.