Mauro Bavetta

Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab

Our understanding of the genetic basis of predisposition to psoriasis is increasing exponentially due to the progress of genetic studies. However, so far little is known about genetic predisposition in relation to the response to psoriasis treatments. Recent data identified genetic predictors for the clinical outcome of conventional treatments such as methotrexate, acitretin and vitamin D derivatives, but few studies are available on genetic predictors of response to biologics. We hypothesized that genetic variations associated with increased risk of developing psoriasis may also act as predictors for the outcome of biologic therapy.

Efficacy and Safety of Subcutaneous Anti-Tumor Necrosis Factor-Alpha Agents, Etanercept and Adalimumab, in Elderly Patients Affected by Psoriasis and Psoriatic Arthritis: An Observational Long-Term Study

Background: In elderly patients the management of psoriasis is challenging due to contraindications and a higher risk of side effects. Objective: Our retrospective study aimed to evaluate the long-term efficacy and safety profile of subcutaneous anti-tumor necrosis factor (anti-TNF) agents in elderly psoriatic patients. Methods: The study included 89 patients (aged ≥65 years) with plaque-type psoriasis and psoriatic arthritis treated with the subcutaneous anti-TNF-α agents etanercept or adalimumab as monotherapy for a long-term continuous period. Results: Efficacy results were consistent and stable over long-term observation, as expressed by mean Psoriasis Area and Severity Index (PASI) score variation, percentage of patients achieving PASI50 and PASI75 and by the improvement of articular indices, pain visual analogue scale (Pain-VAS) and 44-Joint Disease Activity Score (DAS44-ESR). The proportion of patients achieving PASI50 was 91.80 and 82.14% at week 156 with etanercept and adalimumab treatment, respectively, while the proportion of patients achieving PASI75 was 83.61 and 71.43% at week 156 when treated with etanercept and adalimumab, respectively. The mean DAS44-ESR score decreased from 5.80 to 0.89 and from 3.43 to 1.44 at week 156 and the mean Pain-VAS score decreased from 75.10 to 3.15 and from 71.30 to 18.26 at week 156 with etanercept and adalimumab treatment, respectively. Both treatment adherence and safety profile were good. Conclusions: Our study demonstrates that subcutaneous anti-TNF-α agents are appropriate in the long-term management of elderly patients.

Evaluation of Clinical and Ultrasonographic Parameters in Psoriatic Arthritis Patients Treated with Adalimumab: A Retrospective Study

Objectives. The aim of this study was to evaluate clinical and US-PD parameters in PsA during adalimumab treatment. Methods. A retrospective study has been conducted in forty patients affected by moderate-to-severe peripheral PsA. Clinical, laboratory, and US-PD evaluations were performed at baseline, after 4, 12, and 24 weeks of treatment. They included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS), Health Assessment Questionnaire (HAQ) modified for Spondyloarthritis, Psoriasis Area Severity Index (PASI) score, the 28-joint Disease Activity Score (DAS 28), and US-PD assessment. US-PD findings were scored according to a semiquantitative scale (ranging 0–3) for synovial proliferation (SP), joint effusion (SE), bone erosions (BE), and PD. Results. Data obtained for clinical, laboratory findings and US-PD evaluation showed statistical significant improvement in all the measures performed except for BE. A significant parallel decrease in SE, SP, and PD values were demonstrated. Conclusion. This study demonstrated that US-PD is a valid technique in monitoring the response to adalimumab in moderate-to-severe PsA.

Adalimumab in the treatment of plaque-type psoriasis and psoriatic arthritis

Introduction: Psoriasis and psoriatic arthritis (PsA) are chronic immune-mediated diseases, and TNF-α (tumor necrosis factor) is a pro-inflammatory cytokine that plays a critical role in the pathogenesis of these conditions. Adalimumab is an anti-TNF-α drug widely used for the treatment of both psoriasis and PsA. Controlled clinical trials demonstrated that adalimumab is characterized by a high degree of clinical response. The aim of this review is to report the safety, efficacy, and recent findings in the treatment of psoriasis and PsA with adalimumab. Areas covered: This article reviews the results of Phase II, III, controlled, and observational clinical studies on adalimumab in the treatment of psoriasis and PsA. A systematic search was conducted using the Pubmed Medline database for primary articles. Expert opinion: Treatment of psoriasis and PsA represents a therapeutic challenge for dermatologists and rheumatologists. The efficacy, tolerability, and safety profiles suggest adalimumab as a suitable anti-psoriatic drug in the long-term treatment of psoriasis and PsA. Management of long-term treatment, loss of efficacy, and comorbidities has been described.

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

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.

Quality of life of psoriatic patients evaluated by a new psychometric assessment tool: PsoDisk

BackgroundPsoriasis is a chronic skin disorder which negatively impacts a patient’s quality of life (QoL).Arecently published assessment tool, PsoDisk, has been proposed to evaluate patient’s QoL.ObjectiveThe aim of this study was to test PsoDisk as a QoL assessment tool in psoriatic patients undergoing treatment with adalimumab.MethodsA retrospective, monocentric study, including patients who completed at least 48 weeks of both adalimumab therapy and PsoDisk assessment. PASI was assessed by the physician whereas the PsoDisk test was self-performed by the patient. Both were evaluated at each control visit throughout the study-period in order to detect changes in disease severity and the impact of quality of life, respectively.ResultsIn total, we evaluated 31 patients selected from our database. At baseline, all aspects of patients’ psycho-emotional and social lives were impaired. PASI score reduction correlated with a PsoDisk score decrease (r = 0.97; p = 0.02), reflecting an overall improvement of patient’s QoL.ConclusionPsoDisk was found to be easy to administer and intuitive for interpreting clinical results.

Detection of Adalimumab and Anti-Adalimumab Levels by ELISA: Clinical Considerations

Enabling Technology, Genomics, Proteomics Clinical Development Phases I‐III Regulatory, Quality, Manufacturing

Use of Vitamins and their Derivates in the Treatment of Cutaneous Disorders

Vitamins represent fundamental substrates for various physiologic functions occurring in human body. This review seeks to highlight their relevance in skin biology and to describe the cutaneous manifestations correlated with their deficiency.

Is weekly dose of adalimumab a simple approach for resistant psoriasis

In recent years, use of biologic agents for patients with moderateto-severe chronic plaque psoriasis (PsO) has increased for their good safety profile, no cumulative organ specific toxicity and their high sustainability (1). Response to therapy remains subjective and patients can develop resistance over time to standard therapy dose (2). Adalimumab is a fully human monoclonal antibody specific for TNF-a that has been approved for the treatment of PsO at a maintenance dose of 40mg administered subcutaneously weekly or every other week (3). Dose escalation (reducing interval or increasing dose) represent modification strategies that can be used in real life. However, before switching to another systemic agent, it is recommended to first use these mentioned strategies (4). Here, we report a case of a man of 59 years old affected by PsO and by psoriasis arthritis (PsA), previously treated with all PsO conventional treatments. On admission (December 2002), the patient presented generalized erythroderma with numerous psoriatic plaque localized on the trunk, arms and legs. Based on severity of the disease we decided to start a biological treatment. The efficacy was evaluated in the patient at baseline and then every four weeks by calculating the psoriasis activity and severity index (PASI), the dermatology life quality index (DLQI), the psoriasis disability index (PDI), disease activity score calculator for rheumatoid arthritis (DAS28).

Efficacy and safety of Adalimumab after failure of other anti-TNFα agents for plaque-type psoriasis: clinician behaviour in real life clinical practice

Abstract Introduction: During treatment with biologic agents for psoriasis (Pso) in a number of patients a failure may occur and discontinuation with transitioning to another drug or an optimization strategy, consisting in a dose-adjustment or a co-medication with a traditional systemic agent, represent two possible alternatives. Objective: The SAFARI study objective was a retrospective observation of adalimumab efficacy and safety profile after switching from other anti-TNFα agents related to clinician behavior after the failure of the first-line agent. Results: The retrospective multicenter observation demonstrated that after a first-line anti-TNFα failure adalimumab efficacy was consistent at week-12 and 24 with a further significant improvement at week-48 with a proportion of patients achieving PASI75/PASI90/PASI100 of 83.3, 71.6, and 56.9.%, respectively. Clinician strategies to extend drug-survival after first-line anti-TNFα failure, such as co-medication or dose-adjustment, were irrelevant to future drug effectiveness. Conclusions: Adalimumab profile was excellent in this 5-year retrospective observation, showing the clinical validity of interclass transitioning among anti-TNFα options.