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.

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.

Fexofenadine in chronic idiopathic urticaria: a clinical and immunohistochemical evaluation.

Fexofenadine is a non-sedating selective third-generation antihistamine, which also exerts an anti-inflammatory action. The aim of this study was to evaluate the influence on the expression of inflammatory skin mediators, together with the efficacy and tolerability, of fexofenadine in chronic idiopathic urticaria (CIU). Fexofenadine 180mg was administered once daily for 4 weeks after a placebo run-in phase of 3 to 7 days. Efficacy paramaters were obtained from patients' assessment of urticaria symptoms. Non-lesional skin of patients with active CIU was studied immunohistochemically before and after treatment. The expression of the following mediators was evaluated: adhesion molecules (ICAM-1, ELAM-1, VCAM-1); mast cell proteases (chymase and tryptase) and proinflammatory cytokines (IL-1beta, IL-3, IL-6 and TNF-alpha). Of the 20 subjects enrolled, 3 dropped out of the study. Treatment proved successful in most cases (88.2%) (p <0.01) and a significant improvement of all symptoms was registered. Treatment was well-tolerated by all patients; adverse events, neither serious nor drug-related, occurred in any case. Immunochemistry revealed at the baseline a significant expression of ELAM-1, VCAM-1, tryptase, chymase, and TNF-alpha (p= 0.05) in non-lesional skin of patients compared to normal controls. After treatment with fexofenadine, there was a significant decrease in the expression of ELAM-1 (p= 0.02), VCAM-1 (p= 0.04) and tryptase (p= 0.04), whereas no relevant change was observed for the other parameters examined. This work confirms the efficacy and tolerability of fexofenadine HCl 180mg in CIU. These preliminary data show a trend towards a decrease in the expression of tryptase and some adhesion molecules after treatment, suggesting an anti-inflammatory activity of fexofenadine.

Specific IgE antibodies in twenty-eight workers with diisocyanate-induced bronchial asthma.

A specific IgE-mediated response was evaluated in twenty-eight workers exposed to TDI or MDI, with diagnosis of occupational asthma and positive to bronchial provocative challenge. The presence of anti-diisocyanate IgE was observed in 27% of subjects exposed to TDI and 83% of those exposed to MDI, particularly in individuals who experienced an acute massive exposure. An immediate-type response to bronchial provocative test was found in 66% of individuals with specific antibodies. Specific IgE are prevalent (91%) in subjects who developed symptoms before 6 years of exposure to isocyanates. The results suggest an association between the presence of specific IgE, early asthmatic symptoms and heavy episodic exposure.

Absence of IgG antibodies to TDI-HSA in a radioimmunological study.

Sera of ninety-one workers with respiratory symptoms related to occupational exposure to toluene diisocyanate (TDI) were tested by a solid phase radioimmunoassay using polyvinyl plates, in an attempt to demonstrate specific IgG antibodies to a conjugate of TDI with human serum albumin (TDI-HSA). Different conjugates were prepared. In our radioimmunoassay a TDI-HSA 1600 (1600 micrograms TDI/mg HSA), obtained at alkaline pH with borate buffer, was used; this conjugate was immunologically reactive and did not contain protein macro-aggregates. No difference in percent of binding of radiolabelled anti-human IgG to TDI-HSA coated on plastic plates was found between exposed workers (asthmatic and non-asthmatic) and fifteen normal subjects. This may suggest that either TDI-induced bronchial asthma is not mediated by IgG antibodies, or TDI-HSA conjugate is unsuitable to be detected by anti-isocyanate IgG.

Bronchial asthma due to inhaled wood dust: Tanganyika aningré.

Three cases of bronchial asthma due to wood dust from Tanganyika anigré are reported. All patients were woodworkers and had symptoms of dyspnoea, cough and wheezing, and sometimes itchiness and rhinorrhoea, after exposure to Tanganyika aningré. The intradermal skin tests were positive for antigenic extract of Tanganyika aningré. In two patients the bronchial provocation test with the wood dust and with the soluble extract inhaled by aerosol was positive showing an immediate reaction; in the same patients bronchial hyperreactivity was also found. Atopy was present in one subject. No precipitins or specific IgE were found in patient sera by the immunodiffusion technique or by RAST.

A study of short-term effect of rehabilitative therapy in chronic obstructive pulmonary disease.

51 male patients with mild degree chronic airway obstruction underwent detailed evaluation of pulmonary function tests, blood gas analysis and exercise tolerance test before and after a short-term therapy. The patients were randomly assigned to medical therapy alone or to medical and rehabilitative therapy. 23 patients treated with medical and rehabilitative therapy showed a significant decrease of respiratory rate and PaCO2 and a significant increase of TV, FEV 1.0, FEV 0.75 x 40, PaO2, SaO2 and exercise tolerance after a month of therapy. 28 patients treated with medical therapy alone showed a significant increase of VC and FEV 0.75 x 40. These data suggest that rehabilitative therapy is a valid adjunct to medical therapy in the short-term treatment of chronic airway obstruction.