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Background: There are limited long-term, ‘real-world’ data on ustekinumab, or the effect of dose adjustment in suboptimal responders. Objectives: We describe 52-week data from TRANSIT, which initiated ustekinumab by licensed regimen and investigated exploratory dose adjustment. Methods: Patients with moderate-to-severe psoriasis and inadequate methotrexate response received ustekinumab, with immediate or gradual methotrexate withdrawal. Outcomes were similar between treatment arms at week 12 (primary endpoint), so week 52 data were pooled. Patients weighing ≤ 100 kg or > 100 kg were administered ustekinumab 45 or 90 mg, respectively. Patients weighing ≤ 100 kg without 75% improvement in Psoriasis Area and Severity Index (PASI 75) response at weeks 28 or 40 received a dose adjustment to 90 mg. The primary analysis used observed data. Results: Overall, 391 and 98 patients received ustekinumab 45 and 90 mg, respectively. Forty-four patients (9%) discontinued before week 52 (0·4% due to adverse events). At week 52 (in the overall population), 369 patients (83%) achieved a PASI score ≤ 5, and 341 patients (77%) achieved PASI 75; the median PASI score decreased from 15 at baseline to 1·8. At weeks 28 and 40, 84 and 31 patients, respectively, did not achieve PASI 75 and received a dose adjustment; by week 52, 35/82 (43%) and 15/31 (48%) of these patients, respectively, achieved PASI 75 (two discontinued between weeks 28 and 40). Conclusions: Ustekinumab showed sustained 1-year efficacy and was well tolerated when initially administered according to label. Adjusting the ustekinumab dose to 90 mg may result in clinically meaningful improvement in response in patients weighing ≤ 100 kg with suboptimal initial response.

Cyclosporine (CsA) is an effective and safe therapeutic option in various dermatoses in both adults and children. Over the last 25 years, Italian dermatologists have gained relevant experience about the use of CsA in the treatment of psoriasis and atopic dermatitis, and an Italian Consensus Conference has recently provided recommendations in adult patients. A comparison between these real-world indications and current European guidelines is hereby provided.

Recent results have identified critical components of the T cell response involved in the initiation and amplification phases of psoriasis. However the link between T cell responses arising in the skin and the systemic inflammation associated with severe psoriasis is largely unknown. We hypothesized that specific subsets of memory T cells recirculating from the skin could play a role. We therefore dissected the circulating memory T cell compartment in patients by analyzing the T-CM, T-EM and T-eff phenotype, the pattern of CCR4 and CCR5 chemokine receptor expression and the expression of the tissue homing molecule CD103. For each subset we calculated the correlation with the Psoriasis Area and Severity Index (PASI) and with the extent of systemic inflammation measured as serum level of the prototypic short pentraxin, C reactive protein (CRP). Validation was performed by comparison with gene expression data in psoriatic plaques. We found that circulating CD103(+)CCR4(+)CCR5(+) and CCR4(+)CCR6(-) CD8(+) T-eff cells, were highly correlated with CRP levels as well as with the validated index PASI, reflecting a link between skin involvement and systemic inflammation in patients with severe psoriasis. In addition we observed a contraction of circulating CCR5(+) T cells in psoriasis patients, with a highly significant inverse correlation between CCR5(+)CD4 T cells and the PASI score. Increased expression of CCR5 and CCL5 genes in psoriatic skin lesions was consistent with an accumulation of CCR5(+) cells in psoriatic plaques indicating a role for CCR5/CCL5 axis in disease pathogenesis. (C) 2016 Elsevier Ltd. All rights reserved.

Background and Objectives: Biologic therapies are considered to be cost effective by leading Health Technology Assessment (HTA) agencies and, therefore, eligible for reimbursement by public health services. However, biologic therapies entail sizable incremental costs and, besides, have a considerable financial impact that in Italy amounts to 13.7 % of the national health service's pharmaceutical expenditure. In the reimbursability decision process, an important role is played by both the drug efficacy data observed in pre-licensing RCTs and the economic modelling assumptions, as they give evidence on cost effectiveness. The administration of therapies in real practice settings is likely to produce a significant deviation from the results predicted by the models, theoretically outweighing the assumption on which the decision process is founded. This is a matter of concern for public health services and, consequently, an interesting topic to investigate. Methods: To overcome the lack of knowledge concerning the actual cost effectiveness of biologic therapies for the treatment of plaque psoriasis in the clinical practice setting in Italy, an observational study was conducted in 12 specialist centres on patients switching to biologic therapy within a 6-month enrolment window. Results: The study confirms in clinical practice the efficacy of the switch to biologic therapies, analysed using a number of clinical [Psoriasis Area and Severity Index (PASI), pain visual analogue scale (VAS) and itching VAS] and quality-of-life parameters. A general health-related quality of life (HR-QOL) improvement, with a 0.23 quality-adjusted life-year (QALY) mean gain per patient, has been reported in the 6-month observation period. The direct medical costs to treat plaque psoriasis with biologic therapies amount to €15,073.7 per year (prior to their enrolment, the same patients cost €2,166.2 on an annual basis). After the switch to biologic agents, the cost per QALY during the first year of treatment amounts to €28,656.3. Conclusion: At least in the short-term, the clinical practice of the specialised Italian centres taking part in the study confirms that switching patients to a biologic drug produces an incremental cost-effectiveness ratio comparable with the values predicted by the HTA bodies

Objective Adalimumab has proven effective in psoriasis; however, secondary failure may result from the drug9s immunogenicity. Prevalence data on the immunogenicity of biologicals, and of adalimumab in particular, are highly variable. We investigated the prevalence of anti-adalimumab antibodies and the association with clinical indexes and tumour necrosis factor α (TNFα) serum levels in psoriatic patients. Design Case–control, longitudinal. Setting Single centre. Participants Patient groups: I (n=20) receiving biological therapies after switching from adalimumab; II (n=30) ongoing adalimumab therapy; III (n=30) novel adalimumab therapy; IV (n=15) biological therapies other than adalimumab. Healthy subjects : (group V; n=15) never treated with immunosuppressants or biologicals. Interventions All groups were tested at enrolment. Group II was also tested at 12 months, and group III at 1, 3, and 6 months. Primary and secondary outcome measures Standard clinical evaluations (Psoriasis Area Severity Index (PASI)), blood samples and two-site ELISA-based measurement of serum adalimumab trough levels, anti-adalimumab antibodies and TNFα. Results The false-positive rate was 23% for adalimumab detection and 22% for anti-adalimumab antibodies in patients naive to adalimumab. Spurious positivity for anti-adalimumab antibodies (one-time-point positivity in group III during follow-up) accounted for 33% of the total. The prevalence of anti-drug antibodies was highest (87%) in group I patients. No correlations were found between the presence of anti-adalimumab antibodies or adalimumab levels and changes in PASI scores. Conclusions High variability of results, high prevalence of false-positives and lack of association between anti-adalimumab antibodies and TNFα level/PASI score limit this assay9s usefulness. Accurate clinical evaluation is key to early identification of treatment failures.

Introduction: Erlotinib is useful in advanced non-small cell lung cancer although compliance and efficacy are diminished by skin rash in a high proportion of patients, often necessitating dose reduction or drug withdrawal. No effective treatment for the rash is available. Methods: We carried out a preliminary investigation on isotretinoin and clindamycin. Among 56 advanced lung cancer patients treated with erlotinib, 31 (53%) developed rash. Seven (35%) of the 20 G2/G3 cases agreed to treatment with clindamycin (450 mg/d, days 1–10; 300 mg/d, days 11–20) plus isotretinoin (20 mg/d, days 11–20) after being informed of the experimental nature of the combination. Results: In 6 of 7 (86%) patients, the rash resolved (G1/G0) without dose reduction; in the other patient (G3), the erlotinib dose also had to be reduced. Median time to resolution was 14 days (range 7–20 days). No rash-treatment adverse events occurred during 20 days of administration. Conclusions: Isotretinoin plus clindamycin promises to be the first effective treatment for erlotinib rash and is being tested further.