Real-world data on the efficacy and safety of apremilast in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, which requires long-term, safe and effective treatment. Apremilast, a small-molecule PDE4 inhibitor, has been introduced as psoriasis (and psoriatic arthritis) treatment in Europe in 2015. OBJECTIVE: We analysed and report the efficacy and safety of apremilast in the first 51 patients with psoriasis that have undergone treatment with this novel small molecule in our outpatient clinic. METHOD: Our primary endpoint was the evaluation of clinical response to apremilast according to the percentage of Psoriasis Area Severity Index (PASI) reduction (ΔPASI) at 16 weeks after treatment initiation. Secondary endpoints were the evaluation at week 16 of (i) PASI; (ii) Dermatology Life Quality Index (DLQI); (iii) Physician Global Assessment (PGA); (iv) Psoriasis Scalp Severity Index (PSSI); and (v) the percentage of patients who achieved ΔPASI50, ΔPASI75, ΔPASI90 and ΔPASI100; (vi) adverse events (AE); (vii) reasons for drug discontinuation; and (viii) drug survival. RESULTS: About 59.3% of the patients who remained on apremilast achieved at least ΔPASI75 at week 16, while 11.1% achieved combined 50% ≤ PASI < 75% and DLQI ≤ 5 (satisfactory response) adequate enough to maintain treatment. Five patients (18.5%) also achieved ΔPASI100. Patients discontinued apremilast (28%), mostly during the first 4 weeks due to adverse events (12%) with gastrointestinal symptoms being the most common, and later due to lack of efficacy (16%). A statistically significant improvement of PASI, DLQI, PGA and PSSI scores was observed after 4 and 16 weeks of treatment relative to pretreatment measurements. CONCLUSION: Apremilast is a safe and efficacious treatment for psoriasis patients as it produces ΔPASI75 and ΔPASI50 responses combined with DLQI ≤ 5 in 16 weeks in 70.4% of the patients. These results, from a real-world setting, confirm the efficacy and safety of apremilast which has been demonstrated in large phase III clinical trials.

Association between the severity of newly diagnosed obstructive sleep apnea and subclinical carotid atherosclerosis in patients without overt cardiovascular disease.

OBJECTIVE: Obstructive Sleep Apnea (OSA) has been associated with both subclinical and accelerated atherosclerosis; however, it still remains unknown whether this association is unique or is mediated by the higher burden of co-existing cardio-metabolic disorders frequently seen in patients with OSA. PATIENTS AND METHODS: A total of 40 subjects without clinically diagnosed cardiovascular disease (CVD) referred for polysomnography test were included in the study. Subjects with apnea/hypopnea index (AHI > 15/h) were classified as moderate/severe OSA. Subclinical changes in carotid atherosclerosis were assessed using mean carotid intima-media thickness (cIMT) and presence of atheromatic plaques on both carotid arteries. The measurement was performed using B-mode ultrasonogram. Framingham risk score was used in the approximation of cardiovascular risk. RESULTS: The mean age of our cohort was 56.8 years, 70% (n = 28) of whom were males. Moderate/severe OSA was diagnosed in 21 subjects. Both groups were well matched in terms of clinical and demographic characteristics, and cardiovascular risk profile, as shown in their respective Framingham risk scores (10.4 ± 6.6 vs. 11.8 ± 8.8, p = NS). Patients with moderate/severe OSA had a higher mean AHI, 3% oxygen desaturation index, and lower minimum nocturnal oxygen saturation than controls. No significant differences were detected in terms of C-reactive protein levels. The two groups had similar cIMT (0.66 ± 0.17 vs. 0.75 ± 0.20 p = 0.33) and presence of atheromatic plaque (50% vs. 45%, p = 1.00). CONCLUSIONS: Our study suggests that among patients with similar cardiovascular risk profile and free of overt CVD, the severity of newly diagnosed OSA was not correlated with increased inflammation or subclinical carotid atherosclerosis.

The impact of obstructive sleep apnea syndrome on renin and aldosterone.

OBJECTIVE: Obstructive Sleep Apnoea Syndrome (OSAS) is a respiratory disorder characterized by recurrent airflow obstruction caused by total or partial collapse of the upper airway. OSAS is an established independent factor of cardiovascular risk together with other risk factors such as smoking and increased lipids. The aim of our study was to measure serum levels of aldosterone and renin in OSAS patients that did not suffer from arterial hypertension and compare them to matched healthy subjects in order to reveal the impact of chronic intermittent hypoxia on the renin-angiotensin-aldosterone system. PATIENTS AND METHODS: The patients that enrolled in this study were 19 OSAS patients who had undergone overnight polysomnography and had an Apnoea Hypopnoea Index (AHI) greater than 10 events/hour. They were compared to 20 healthy non-OSAS closely matched controls. Serum aldosterone and direct renin concentration were measured by radioimmunoassay. RESULTS: Aldosterone concentration follows a diurnal variation; therefore, all blood samples were obtained at the same time (6 AM). There were no significant differences in serum aldosterone levels between the two studied groups of OSAS patients and the healthy subjects group (140.6 pg/ml ± 25.2 vs. 133.2 pg/ml ± 18.5 with p = 0.223). Similar were the results for the renin levels (25.0 ± 6.9 vs. 24.9 ± 4.4 with p = 0.360). CONCLUSIONS: Our study suggests that patients with OSAS, but without existing hypertension have aldosterone and renin levels similar to healthy subjects. According to our findings a direct connection between OSAS and the development of arterial hypertension may not be established via sympathetic system activation.

Pilot study of 19 patients with severe pemphigus: prophylactic treatment with rituximab does not appear to be beneficial.

AIMS: To assess the efficacy and safety of rituximab in refractory pemphigus and the possible benefit of an additional prophylactic infusion at 6 months. METHODS: Seventeen patients with pemphigus vulgaris, 1 with pemphigus foliaceus and 1 with pemphigus vegetans were treated with 4 weekly infusions of rituximab (375 mg/m(2)). Nine patients received an additional prophylactic infusion after 6 months while the rest received no maintenance therapy. In case of recurrence, an additional single infusion was administered. RESULTS: Control of the disease was obtained after 3-8 weeks. End of the consolidation phase for all patients was observed after 16 weeks. Patients remained in full remission for 7-42 months. All immunosuppressive agents, including prednisone, were discontinued after 2-12 months. The disease relapsed in 5 out of 9 patients who received the additional prophylactic infusion, and in 3 out of 10 patients among those skipping the prophylactic additional infusion. CONCLUSION: One course of rituximab and treatment of relapses is highly effective and well tolerated in the treatment of refractory pemphigus. In this pilot study of 19 patients, the prophylactic infusion does not appear to have provided any additional benefit to the patients receiving it.

Ustekinumab induces fast response and maintenance of very severe refractory scalp psoriasis: results in two Greek patients from the psoriasis hospital-based clinic.

BACKGROUND: Scalp psoriasis, one of the most common sites of psoriasis involvement, is often difficult to control with topical agents. There is a lack of substantial evidence-based data for the efficacy and safety of systemic therapies. METHODS: Two patients from our university-based psoriasis clinic with chronic plaque psoriasis and severe recalcitrant scalp involvement were assessed by Psoriasis Area and Severity Index and Psoriasis Scalp Severity Index scores, respectively, and quality of life by the Dermatology Life Quality Index. RESULTS: We report 2 psoriasis patients with very severe scalp psoriasis who developed a fast clinical response of scalp psoriasis to ustekinumab in 8 weeks with excellent patient adherence up to 28 weeks of follow-up and positive impact on quality of life due to rapid and long-term clearing. CONCLUSION: Ustekinumab produces a fast clinical response of recalcitrant scalp psoriasis with excellent patient adherence and a positive impact on quality of life due to rapid and long-term clearing in patients with very severe scalp involvement who failed conventional topical and systemic treatment.

Sleep apnea as a comorbidity in obese psoriasis patients: a cross-sectional study. Do psoriasis characteristics and metabolic parameters play a role?

BACKGROUND: Psoriasis is associated with a variety of comorbidities such as obesity and cardiovascular disease. OBJECTIVE: In a cross-sectional study, we explored whether obstructive sleep apnea and hypopnea syndrome (OSAHS) is associated with psoriasis characteristics and metabolic parameters. METHODS: Thirty-five patients with chronic plaque psoriasis underwent a nocturnal polysomnography study and were analysed for Apnoea-Hypopnoea Index to assess OSAHS severity and Framigham score to predict the absolute risk of coronary artery disease at 10 years. The association of OSAHS with psoriasis was examined according to psoriasis characteristics (PASI and DLQI scores, disease duration and previous use of systemic treatments), metabolic parameters (Body Mass Index - BMI, waist to hip ratio - WHR, lipid profile) and other comorbidities (obesity, hypertension, arthritis and cardiovascular disease). RESULTS: There was no correlation between psoriasis characteristics and OSAHS. Psoriasis patients with OSAHS presented more frequent snoring and lower sleep quality compared with those without OSAHS. In univariate analyses, OSAHS was associated with increased BMI and hypertension in psoriasis patients. In multivariable logistic regression models, there was statistically significant evidence that only BMI and hypertension were associated with increased risk of OSAHS, adjusting for psoriasis characteristics, age and gender. Presence of metabolic syndrome, WHR, and smoking were not significant risk factors for OSAHS. In subgroup analyses, OSAHS correlated with duration of psoriasis (>8 years) in women (P = 0.021) and with Framigham score in men (P = 0.035). CONCLUSION: OSAHS may be a comorbidity in obese psoriasis patients with hypertension. Treatment with continuous positive airway pressure and weight loss interventions should be initiated.

Prasugrel versus high dose clopidogrel to overcome early high on clopidogrel platelet reactivity in patients with ST elevation myocardial infarction.

OBJECTIVE: There is a paucity of data regarding the early effectiveness of the proposed 600 mg clopidogrel loading dose (LD) on platelet reactivity (PR) in ST elevation myocardial infarction (STEMI) patients. If high on-treatment platelet reactivity (HTPR) is present, prasugrel reloading and subsequent maintenance dose (MD), might offer faster and stronger platelet inhibition than high clopidogrel MD. METHODS: In 93 STEMI patients treated by primary percutaneous coronary intervention we assessed PR using the VerifyNow P2Y12 platelet function test, 2 h following 600 mg LD of clopidogrel. All the 60 (64.5 %) patients exhibiting HTPR (defined as PR ≥ 235 P2Y12 reaction units), were randomized to 1 of 2 therapeutic strategies: reloading with prasugrel 60 mg/10 mg MD or high (150 mg) clopidogrel MD. RESULTS: The primary endpoint of PR at 24 h post randomization was lower in the prasugrel compared to the clopidogrel group (51.3, 25.7-77.0 versus 242.4, 215.8-268.9 P2Y12 reaction units, least square estimates, 95 % confidence intervals, p < 0.001). PR at 2 h and 5 days post randomization was lower in the prasugrel compared to the clopidogrel group (117.2, 70.9-163.4 and 101.6, 70.1-133.2 least square mean difference, 95 % confidence intervals, p < 0.001 for both). At all the time points of PR assessment, HTPR rates were lower in prasugrel than in clopidogrel group. CONCLUSIONS: HTPR is commonly observed early post 600 mg clopidogrel LD in STEMI patients. In this case, prasugrel 60 mg LD/10 mg MD provides faster and stronger platelet inhibition than a high clopidogrel MD regimen.

Adefovir dipivoxil added to ongoing lamivudine therapy in patients with lamivudine-resistant hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND: Long-term treatment with lamivudine is required to control viral replication in patients with hepatitis B e antigen-negative chronic hepatitis B, but is associated with a high rate of viral resistance. The role of adefovir dipivoxil in these patients has not been definitively evaluated. AIM: To address the role of adefovir in the management of patients with lamivudine-resistant hepatitis B e antigen-negative chronic hepatitis B. METHODS: Patients were assigned to receive adefovir 10 mg once daily plus ongoing lamivudine 100 mg once daily for 52 weeks. The primary end point was reduction in serum hepatitis B virus DNA level (hepatitis B virus DNA response). Secondary end points included the proportion of patients with undetectable hepatitis B virus DNA at week 52 (complete virological response) and the percentage of patients with normalization of alanine transferase level at week 52 (biochemical response). RESULTS: A total of 49 consecutive patients were enrolled in this study. After 52 weeks of treatment, all patients had an hepatitis B virus DNA response and 57.1% had complete virological response. Biochemical response occurred in 75.6% of patients. CONCLUSIONS: Administration of adefovir in patients with lamivudine-resistant chronic hepatitis B results in significant suppression of viral replication. Nevertheless, continuous therapy will probably be needed in order to maintain remission in these patients.