Background: Efalizumab (anti-CD11a), a humanized monoclonalantibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactiva...Background: Efalizumab (anti-CD11a), a humanized monoclonalantibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes. Objectives: This multinational, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1.0 mg kg-1 once weekly for 12 weeks compared with placebo in a population that included high-need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication. Patients/methods: Patients with moderateto- severe plaque psoriasis [involvement of ≥ 10% of total body surface area and Psoriasis Area and Severity Index (PASI) ≥ 12.0 at screening] were randomized in a 2:1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving ≥ 75% PASI improvement (PASI- 75 response) at week 12 in the intention-to-treat population; secondary endpoints included changes in PASI, static Physician’ s Global Assessment, Physician’ s Global Assessment of change from baseline and percentage of body surface area affected. Results: We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high-need patients (342 received efalizumab and 184 placebo). Week 12 PASI- 75 rates were 29.5% for efalizumab compared with 2.7% for placebo among high-need patients (P < 0.0001) and 31.4% for efalizumab compared with 4.2% for placebo in the full study population (P < 0.0001). Results for all secondary efficacy endpoints showed superiority of efalizumab over placebo in both the high-need and the full populations. Efalizumab demonstrated a favourable safety profile, without evidence of systemic toxicity, in both the high-need group and the overall study population. Conclusions: The efficacy and safety of efalizumab therapy were comparable between high-need patients and themore general moderate-to-severe psoriasis patient population. In view of its demonstrated efficacy and safety profile, efalizumab represents a valuable option for the treatment of adult patients with moderate-to-severe plaque psoriasis, including high-need patients.展开更多
We examined the practicability, reproducibility and analytical sensitivity of classical immunohistochemistry (IHC) and IHC with microagitation. Two monoclonal antibodies, Ki-67 (proliferation marker) and p53 (tumor su...We examined the practicability, reproducibility and analytical sensitivity of classical immunohistochemistry (IHC) and IHC with microagitation. Two monoclonal antibodies, Ki-67 (proliferation marker) and p53 (tumor suppressor marker), we re used. Consecutive paraffin sections of biopsies of suspicious lesions of pati ents with non-melanoma skin cancer were used in the study. Reproducibility was examined using specimens from four patients in three independent experiments wit h antibodies against Ki-67 and p53. Analytical sensitivity of the two methods w as determined using serial dilutions in two independent experiments. IHC with mi croagitation could be carried out without destroying the tissue. The new techniq ue was consistent and reproducible, and no background staining was observed. The primary antibodies Ki-67 and p53 could be used at higher dilutions (four to te n times) with microagitation compared with classical IHC. Microagitation can be used for immunohistochemistry; it was reproducible, highly sensitive, and antibo dies could be used at higher dilutions. Further analyses with other antibodies u sing this technique are warranted.展开更多
文摘Background: Efalizumab (anti-CD11a), a humanized monoclonalantibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes. Objectives: This multinational, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1.0 mg kg-1 once weekly for 12 weeks compared with placebo in a population that included high-need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication. Patients/methods: Patients with moderateto- severe plaque psoriasis [involvement of ≥ 10% of total body surface area and Psoriasis Area and Severity Index (PASI) ≥ 12.0 at screening] were randomized in a 2:1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving ≥ 75% PASI improvement (PASI- 75 response) at week 12 in the intention-to-treat population; secondary endpoints included changes in PASI, static Physician’ s Global Assessment, Physician’ s Global Assessment of change from baseline and percentage of body surface area affected. Results: We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high-need patients (342 received efalizumab and 184 placebo). Week 12 PASI- 75 rates were 29.5% for efalizumab compared with 2.7% for placebo among high-need patients (P < 0.0001) and 31.4% for efalizumab compared with 4.2% for placebo in the full study population (P < 0.0001). Results for all secondary efficacy endpoints showed superiority of efalizumab over placebo in both the high-need and the full populations. Efalizumab demonstrated a favourable safety profile, without evidence of systemic toxicity, in both the high-need group and the overall study population. Conclusions: The efficacy and safety of efalizumab therapy were comparable between high-need patients and themore general moderate-to-severe psoriasis patient population. In view of its demonstrated efficacy and safety profile, efalizumab represents a valuable option for the treatment of adult patients with moderate-to-severe plaque psoriasis, including high-need patients.
文摘We examined the practicability, reproducibility and analytical sensitivity of classical immunohistochemistry (IHC) and IHC with microagitation. Two monoclonal antibodies, Ki-67 (proliferation marker) and p53 (tumor suppressor marker), we re used. Consecutive paraffin sections of biopsies of suspicious lesions of pati ents with non-melanoma skin cancer were used in the study. Reproducibility was examined using specimens from four patients in three independent experiments wit h antibodies against Ki-67 and p53. Analytical sensitivity of the two methods w as determined using serial dilutions in two independent experiments. IHC with mi croagitation could be carried out without destroying the tissue. The new techniq ue was consistent and reproducible, and no background staining was observed. The primary antibodies Ki-67 and p53 could be used at higher dilutions (four to te n times) with microagitation compared with classical IHC. Microagitation can be used for immunohistochemistry; it was reproducible, highly sensitive, and antibo dies could be used at higher dilutions. Further analyses with other antibodies u sing this technique are warranted.
