Safety evaluation of apremilast for the treatment of psoriasis.

INTRODUCTION: Psoriasis (PSo) is a chronic inflammatory skin disease associated with co-morbidities such as hypertension, diabetes, dyslipidemia and metabolic syndrome. It is a typothypical Th1/Th17 disease that affects from 2 to 3% of the world population. Numerous are the drugs that can be used in our clinical practice; the choice of these drugs depends on the characteristics of the patient. Areas covered: Apremilast is the first oral small molecules to receive FDA approval for the treatment of adults with active psoriasis and psoriatic arthritis. It is a small-molecule that specifically inhibits the activity of cyclic AMP phosphodiesterase-4 (PDE4). Several analyses have been performed on data from phase III studies to assess apremilast safety and efficacy on psoriasis and psoriatic arthritis (PsA). Apremilast could also represent a treatment opportunity for those patients unresponsive to both systemic and biological agents or whose treatment was contraindicated. Expert opinion: For its safety profile and easy route of administration, apremilast may offer an oral treatment option for those patients that discontinue treatments because of ineffectiveness, intolerability or ineligibility to the currently available drugs.

Real-life 9-year experience with adalimumab in psoriasis and psoriatic arthritis: results of a single-centre, retrospective study.

BACKGROUND: Observational studies in daily practice are an essential complement to pivotal randomised controlled trials because their findings refer to larger and more diverse patient populations with common comorbidities, complex medical history, concomitant medications and longer follow-up periods. OBJECTIVES: To evaluate long-term clinical outcomes of the anti-TNF-α monoclonal antibody, adalimumab, in patients with psoriasis (PsO) or psoriatic arthritis (PsA) referring to an Italian dermatological centre. METHODS: Single-centre retrospective real-world investigation with an observation period of up to 9 years. RESULTS: We reviewed the records of 316 patients (117 with PsO and 199 with PsA) treated with adalimumab and followed for up to 9 years. Safety and efficacy of adalimumab were consistent with those described in randomised controlled trials (RCTs) and other observational studies. A rapid and sustained improvement of skin lesions (evaluated as Psoriasis Area and Severity Index (PASI) 75, PASI 90 and PASI 100 response rates) was observed in the majority of patients, including those with body mass index (BMI) >30 and with prior experience of biologic therapies (including other anti-TNFs). The safety profile of adalimumab was confirmed also in elderly patients (>65 years). CONCLUSION: Our real-life experience shows that the long-term treatment with adalimumab is effective and well tolerated in psoriatic patients, including overweight/obese, elderly and anti-TNF-experienced subjects.

PSOCUBE, a multidimensional assessment of psoriasis patients as a both clinically/practically sustainable and evidence-based algorithm.

BACKGROUND: There is increasing awareness of the clinical relevance of psoriasis comorbidities and of the importance of timely and effective screening for such comorbidities in the management of psoriatic patients. Previous works have focused on assessing evidence for prevalence of comorbidities and on the best available evidence for sensitivity in diagnosing suspected comorbidities. No algorithms are available, which have been tested on large numbers of physicians concerning the acceptance of such algorithms both by practicing clinical dermatologists and by their consulting specialists from other fields. OBJECTIVE: To propose a multidimensional assessment algorithm for psoriasis comorbidities which may prove at the same time enough sensitive and practically sustainable in daily clinical practice. METHODS: After an exhaustive literature search, we performed a Delphi procedure involving 50 dedicated dermatological centres to obtain a standardized assessment algorithm, which would meet requirements of sustainability and acceptability both from the point of view of Evidence-Based Medicine as well as from the point of view of practical and clinical feasibility: to meet both requirements, results from the Delphi procedure were elaborated and modified by a restricted panel of experts. RESULTS: The procedure has yielded PSOCUBE, a three-dimensional table comprising 14 clinical examination and history taking items, 32 screening laboratory and instrumental exams and 11 clinimetric scores. CONCLUSION: PSOCUBE, a simple algorithm, may be employed by practising dermatologists to perform standardized assessment procedures on psoriatic patients raising the chances of early recognition of patients at risk for comorbidities, thus fostering more effective prevention; PSOCUBE may therefore contribute to reduce the overall impact of this chronic, widespread disease.

Topical lactoferrin can improve stable psoriatic plaque.

AIM: Lactoferrin (LF), a non-haem iron binding glycoprotein, shares antimicrobial properties with innate immune system components influencing proinflammatory release of cytokines involved in psoriatic plaque development. The objective of the study was to verify if LF could provide a therapeutic application in psoriasis. METHODS: An open-label, two arms, 4-week trial was designed on 30 subjects affected by mild to moderate plaque psoriasis. All patients received oral bovine LF 100 mg. Fifteen patients (group A) were topically treated with 10% LF ointment, 15 patients (group B) with 20% LF ointment. All patients applied only ointment vehicle on contra lateral target lesion as intra-patient side to side control. Efficacy was assessed by Target Lesion Score. RESULTS: Twenty-two patients completed the study. Improvement in elevation, redness and scaling was observed on LF treated psoriatic target lesions comparing to the controlateral controls (P<0.05). There was no additional efficacy for 20% versus 10% topical applications. Oral drug alone did not exert any improvement on the control plaques receiving topical placebo. CONCLUSION: Our clinical results suggest that LF could be included as a possible safe topical therapeutic option in the treatment of psoriatic plaque.

Management of non-melanoma skin cancer in solid organ transplant recipients.

Non-melanoma skin cancer (NMSC) is the most frequent cancer observed in solid organ transplant recipients (SOTR). Early diagnosis, patient education, and modification of immunosuppression are effective measures for reduction of NMSC incidence. Many risk factors have been identified, including age at transplantation, fair skin, type of immunosuppressive drugs, cumulative sun exposure, viral infections, and various genetic markers. Skin self-examination and photoprotection should be encouraged in all transplanted patients. Long-term skin surveillance, early diagnosis and aggressive treatment of any suspicious lesion, reduction of immunosuppressive therapy, and conversion to mammalian target-of-rapamycin (m-TOR) inhibitors can be also effective measures for reduction of NMSC incidence.

High density cholesterol level as predictor of clinical response to anti-TNF-alpha therapy in psoriatic patients.

Psoriasis is a common, chronic, inflammatory, and debilitating disease of the skin. Infliximab is a human/mouse chimeric anti-TNF-alpha antibody effective in the management of psoriasis. Availability of biomarkers for prediction of response, could optimize the therapeutic approach. The aim of this study was to identify predictors of clinical response to infliximab in psoriatic patients in the long-term treatment. Patients affected with psoriasis and suitable for treatment with infliximab were prospectively enrolled. Patients treated for a period longer than 96 weeks were included in the study and divided into high responders and low responders according to infliximab efficacy (PASI 90). A logistic regression analysis was used to explore independent association between high clinical response and possible biomarkers of prediction. A total of 112 patients were included for the analysis. Multiple regression analysis showed that high levels of HDL cholesterol and the short duration of psoriasis [OR 1.11 (CI 1.05-1.18) and OR 0.94 (CI 0.89-0.99)] predicted the most effective clinical response to infliximab. Our findings, which highlight a possible role for HDL cholesterol as clinical predictor for psoriasis treatment, are particularly noteworthy in the context of clinical strategies, but also suggest a possible role for lipid metabolism in aspects of psoriasis that deserves further investigation.

Prevalence and management of panic attacks during infliximab infusion in psoriatic patients.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease associated with anxiety and depression. Infliximab (IFX) is a human/mouse chimeric anti-TNF-α antibody effective in the treatment of psoriasis. OBJECTIVE: The aim of this study was to evaluate the prevalence of panic disorders in psoriatic patients during IFX infusions. METHODS: A retrospective study was performed on patients affected with psoriasis who were treated with IFX from 2002 to 2011 at a single center. Panic disorders were defined using the clinical criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. A population of dermatological patients under treatment with IVG, rituximab, apheresis, intravenous corticosteroids and antibiotics was considered as the control group. RESULTS: A total of 141 patients were evaluated. Of these, 6 (4.25%) experienced panic attacks during the infusion; 16 (11.3%) had a medical history of panic attack and of those 5/16 (31%) experienced panic attacks during IFX infusion. In the control group panic attacks were not recorded. CONCLUSION: We describe 6 cases of patients in whom panic attacks were triggered by IFX infusion. Premedication with oral benzodiazepine and a slow rate of infusion is recommended.

Exaggerated imiquimod application site reactions in the context of systemic tumor necrosis factor-alpha inhibition: more than a coincidental occurrence?

Topical imiquimod and tumor necrosis factor (TNF)-alpha inhibitors have gained wide acceptance as safe and effective treatments for non-melanoma skin cancer (NMSC) and moderate to severe psoriasis, respectively. While mild to moderate application site reactions (ASRs) are a well-known and common phenomenon associated with imiquimod, the potential of TNF-alpha blockers to elicit cutaneous inflammatory reactions has only recently been recognized. We present two cases of severe, atypical ASRs which occurred during NMSC treatment with imiquimod in the context of infliximab administration for psoriasis, and consider the grounds supporting a non-fortuitous association. To date, no relation has ever been suggested between TNF-alpha inhibitors and increased susceptibility to developing exaggerated ASRs with imiquimod. We believe that this subject deserves further analysis; meanwhile, increased attention should be drawn to the possibility of this adverse interaction, as simultaneous treatment with TNF-alpha blockers and imiquimod is becoming increasingly frequent in daily practice.

Influence and variation of the body mass index in patients treated with etanercept for plaque-type psoriasis.

A relationship between psoriasis, pro-inflammatory cytokines and obesity has been demonstrated. Tumour necrosis factor-alpha (TNF-alpha), that is involved in the pathogenesis of psoriasis, is commonly over-expressed in obese subjects, and seems to be derived from inflammatory cells and adipocytes. The primary aim of this study is to investigate whether the Body Mass Index (BMI) of patients influences the clinical response to etanercept, a competitive inhibitor of TNF-alpha approved for the treatment of moderate-to-severe plaque-type psoriasis. The secondary aim is to evaluate whether the TNF-alpha inhibition influences the weight and BMI profile of patients. One hundred patients received 50 mg etanercept twice weekly for 12 weeks, followed by 25 mg. At weeks-12 and 24, treatment efficacy and tolerability were evaluated, as well as body weight and BMI. BMI values did not correlate with etanercept efficacy. Mean PASI score variation did not show significant differences among the BMI groups. A statistically significant weight gain and BMI variation were observed in a consistent rate of patients. Patient BMI does not influence psoriasis efficacy parameters. Although the role of anti TNF-alpha molecules on weight regulation need to be confirmed, our study shows that etanercept treatment may induce weight gain and a BMI increase.

Does metabolic syndrome influence psoriasis?

The metabolic syndrome is a combination of diabetes mellitus type 2, hypertension, central obesity and combined hyperlipidemia. The metabolic syndrome and its components have been largely associated with psoriasis. We report the case of a 66-year-old man affected with metabolic syndrome and psoriasis in which a multidisciplinary approach with endocrinologists and nutritionists led to an improvement of both conditions. After only 4 months of diet and an appropriate therapeutic regimen we observed an improvement of the hyperglycaemia, dyslipidemia, significant lose of weight, BMI switching from obesity to overweight and improvement of plaque psoriasis in absence of other treatments. We report this case to emphasise the need of a major control of the metabolic syndrome and associated comorbidities in psoriatic patients. Moreover we suggest that diet counselling and regular nutritional visits should be recommended in some patients to obtain dual benefits.

Regional distribution of psoriasis in Italy.

BACKGROUND: Psoriasis is a chronic disease affecting skin and joints; the prevalence varies considerably within ethnic groups and countries. OBJECTIVE: The aim of this study was to examine the prevalence of psoriasis across Italy and to identify regional differences. METHODS: The study was conducted in February 2006. A questionnaire was created to survey the prevalence and the geographical distribution of psoriasis in Italy. A representative sample of 3500 families from the contiguous 20 Italian regions was interviewed by a telematic panel. RESULTS: A total of 4109 individuals were interviewed. The research showed that 2.9% of Italians declared suffering from psoriasis (regional range: 0.8-4.5%); that 52% knew somebody with psoriasis; that 33% knew well the meaning of psoriasis; and that 31% of individuals affected from psoriasis defined the effect on quality of life as high. CONCLUSION: In association with the socio-cultural data, this is the first study describing the variation in prevalence of psoriasis among Italian regions.

A biological approach in a patient with psoriasis and bullous pemphigoid associated with losartan therapy.

Several cases of psoriasis associated with bullous disorders have been reported, and it is clearly recognized that bullous pemphigoid (BP) is the most common bullous disorder observed in association with psoriasis, especially after ultraviolet (UV)B and psoralen UVA therapy. Moreover, other medications have been repeatedly reported to induce bullous diseases, especially pemphigus vulgaris. We report for the first time a case of BP possibly induced by losartan, an angiotensin II antagonist, in a patient with a severe psoriatic background. Angiotensin II type 1 receptor antagonists belong to a new class of drug for hypertension or congestive heart failure with established efficacy and few side-effects. Coexistence of psoriasis vulgaris with bullous diseases represents also a difficult therapeutic challenge. This rare case of psoriasis and generalized BP triggered by a sartan drug was treated with rituximab and etanercept.

The role of neuropeptides in psoriasis.

The pathogenesis of psoriasis is incompletely understood but cutaneous neurogenic inflammation is probably involved. This involvement is suggested by a number of clinical and histological observations. Reports about the distribution of cutaneous nerves and the quantification of nerve growth factor and neuropeptides, including calcitonin gene-related peptide and vasoactive intestinal peptide, in lesional and nonlesional psoriatic skin suggest that sensory neuropeptides contribute to the development of psoriasis. This review summarizes what is known about the role of neurogenic markers in psoriasis.

A 308-nm monochromatic excimer light in the treatment of palmoplantar psoriasis.

BACKGROUND: Various reports have shown the efficacy of narrow-band UVB (311-313 nm) and excimer laser (308 nm) in the treatment of psoriasis. OBJECTIVE: To prove the efficacy of light produced by xenon-chloride excimer at 308 nm (monochromatic excimer light, MEL) in the treatment of palmoplantar psoriasis (PP). METHODS: Fifty-four patients (29 male and 25 female) affected by PP were treated with MEL every 7-14 days. A mean number of 10 sessions was performed with an increase of the dose depending on patient's skin type and response. RESULTS: All 54 patients completed the treatment. After 4 months of MEL we observed a complete remission in 31 patients, a partial remission in 13 patients, and a moderate improvement in 10 patients. CONCLUSIONS: These results suggest that MEL can be considered as a valid therapeutic option for treatment of selected forms of PP.

Efficacy of monochromatic excimer laser radiation (308 nm) in the treatment of early stage mycosis fungoides.

BACKGROUND: Various reports have recently shown the efficacy of narrowband ultraviolet (UV) B phototherapy at 311 nm in the treatment of early stage mycosis fungoides (MF). OBJECTIVES: To examine the effectiveness and tolerability of monochromatic excimer light (MEL) at 308 nm as a first treatment for early stage MF (stage IA). METHODS: Ten lesions from five patients with a clinical and histological diagnosis of MF were treated with repeated applications of MEL until complete remission was achieved or up to a maximum of 10 applications, with a cumulative dose of 308 nm UVB of between 6 and 12 J cm(-2). All patients were observed every 2 weeks for 2 months, with a 1-year follow-up. Results At present, all patients are in complete remission, with no side-effects. CONCLUSIONS: Based on these results, MEL can be considered a useful tool in the treatment of early stage MF.