Evaluation of efalizumab using safe psoriasis control

BACKGROUND: Safe Psoriasis Control (SPC) is an important comprehensive measure that is validated for the assessment of benefit:risk of psoriasis treatments, combining efficacy, quality of life, and safety measures. The objective of this analysis was to assess the benefit:risk of efalizumab, a novel biologic agent indicated for the treatment of moderate-to-severe plaque psoriasis, by applying the SPC to data from randomized, placebo-controlled clinical studies of efalizumab. METHODS: SPC was applied to week 12 data from four placebo-controlled, Phase III studies: three retrospective and one prospective, the latter including a cohort of "high-need" patients for whom existing therapies were inadequate or unsuitable. RESULTS: In the retrospective analysis, 39.4% of patients achieved SPC after 12 weeks of treatment with efalizumab, compared with 10.4% for placebo. In the prospective analysis, 34.3% of patients achieved SPC after 12 weeks of treatment with efalizumab, compared with 7.3% on placebo. Among high-need patients, 33.0% achieved SPC, compared with 3.4% on placebo. CONCLUSION: Efalizumab has a favorable benefit:risk profile using the comprehensive outcome measure SPC

The incidence of arthropathy adverse events in efalizumab-treated patients is low and similar to placebo and does not increase with long-term treatment: pooled analysis of data from Phase III clinical trials of efalizumab

A large-scale, pooled analysis of safety data from five Phase III clinical trials (including open-label extensions of two of these studies) and two Phase III open-label clinical trials of efalizumab was conducted to explore whether arthropathy adverse events (AEs) were associated with efalizumab treatment in patients with moderate-to-severe chronic plaque psoriasis. Data from patients who received subcutaneous injections of efalizumab or placebo were stratified for analysis into phases according to the nature and duration of treatment. These included: the ‘first treatment’ phase (0–12-week data from patients who received either efalizumab, 1 mg/kg once weekly, or placebo in the five placebo-controlled studies); the ‘extended treatment’ phase (13–24-week data from seven trials for all efalizumab-treated patients); and the ‘long-term treatment’ phase (data from efalizumab-treated patients who received treatment for up to 36 months in two long-term trials). Descriptive statistics were performed and the incidence of arthropathy AEs per patient-year was calculated using 95% confidence intervals (CIs). During the first treatment phase, a similar proportion of patients had an arthropathy AE in the efalizumab group (3.3%; 58/1740 patients) compared with the placebo group (3.5%; 34/979 patients); the incidence of arthropathy AEs per patient-year was 0.15 in the efalizumab group (95% CI 0.11–0.19) and 0.16 in the placebo group (95% CI 0.11–0.22). Analysis of first treatment phase data from one study (n = 793) showed that the incidence of psoriatic arthropathy per patient-year was lower in efalizumab-treated patients (0.10; 95% CI 0.05–0.18) than in those given placebo (0.17; 95% CI 0.08–0.30). During the extended treatment phase, the incidence of arthropathy remained low (0.17; 95% CI 0.14–0.22). Data from two long-term studies showed that there was no increase in the incidence of arthropathy AEs over time in patients treated with efalizumab for up to 36 months. Patients who had an arthropathy AE during treatment with efalizumab appeared to be more likely to have a history of arthropathy prior to treatment. Efalizumab does not appear to increase the risk of arthropathy AEs compared with placebo

Approaches to discontinuing efalizumab: an open-label study of therapies for managing inflammatory recurrence

BACKGROUND: Efalizumab is a humanised recombinant monoclonal IgG1 antibody for the treatment of moderate-to-severe plaque psoriasis. When treatment discontinuation is necessary, however, some patients may experience inflammatory recurrence of the disease, which can progress to rebound if untreated. This analysis evaluated approaches for managing inflammatory recurrence after discontinuation of efalizumab. METHODS: An open-label, multicentre, investigational study was performed in 41 patients with moderate-to-severe plaque psoriasis who had recently completed clinical studies with efalizumab and had developed signs of inflammatory recurrence following abrupt cessation of treatment. Patients were assigned by the attending physicians to receive one of five standardised alternative systemic psoriasis treatment regimens for 12 weeks. Efficacy of the different therapy options was assessed using the physician's global assessment (PGA) of change over time. RESULTS: More favourable PGA responses were observed in patients changing to cyclosporin (PGA of 'good', 'excellent' or 'cleared': 7/10 patients, 70.0%) or methotrexate (9/20, 45.0%), compared with those receiving systemic corticosteroids (2/8, 25.0%), retinoids (0/1, 0.0%) or combined corticosteroids plus methotrexate (0/2, 0.0%). While the majority (77.8%) of patients showed inflammatory morphology at baseline, following 12 weeks of the alternative therapies the overall prevalence of inflammatory disease was decreased to 19.2%. CONCLUSION: Inflammatory recurrence after discontinuation of efalizumab therapy is a manageable event, with a number of therapies and approaches available to physicians, including short courses of cyclosporin or methotrexate

Impact of efalizumab on patient-reported outcomes in high-need psoriasis patients: results of the international, randomized, placebo-controlled Phase III Clinical Experience Acquired with Raptiva (CLEAR) trial [NCT00256139]

BACKGROUND: Chronic psoriasis can negatively affect patients' lives. Assessing the impact of treatment on different aspects of a patient's health-related quality of life (HRQOL) is therefore important and relevant in trials of anti-psoriasis agents. The recombinant humanized IgG(1 )monoclonal antibody efalizumab targets multiple T-cell-dependent steps in the immunopathogenesis of psoriasis. Efalizumab has demonstrated safety and efficacy in several clinical trials, and improves patients' quality of life. Objective: To evaluate the impact of efalizumab on HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis, including a large cohort of High-Need patients for whom at least 2 other systemic therapies were unsuitable because of lack of efficacy, intolerance, or contraindication. METHODS: A total of 793 patients were randomized in a 2:1 ratio to receive efalizumab 1 mg/kg/wk (n = 529) or placebo (n = 264) for 12 weeks. The study population included 526 High-Need patients (342 efalizumab, 184 placebo). The treatment was evaluated by patients using the HRQOL assessment tools Short Form-36 (SF-36) and Dermatology Life Quality Index (DLQI). Other patient-reported assessments included the Psoriasis Symptom Assessment (PSA), a visual analog scale (VAS) for itching, and the Patient's Global Psoriasis Assessment (PGPA). RESULTS: Efalizumab was associated with improvements at Week 12 from baseline in patient-reported outcomes, both in the total study population and in the High-Need cohort. Among all efalizumab-treated patients, the DLQI improved by 5.7 points from baseline to Week 12, relative to an improvement of 2.3 points for placebo patients (P < .001). Corresponding improvements in DLQI in the High-Need cohort were 5.4 points for efalizumab compared to 2.3 for placebo (P < .001). Improvements from baseline on the SF-36, PSA, PGPA, and itching VAS at Week 12 were also significantly greater in efalizumab-treated patients than for placebo. CONCLUSION: A 12-week course of efalizumab improved HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis. The benefits of efalizumab therapy in High-Need patients were similar to those observed in the total study population, indicating that the beneficial impact of efalizumab on QOL is consistent regardless of disease severity, prior therapy, or contraindications to previous therapies

Minimally invasive surgery and cancer: controversies part 1

Perhaps there is no more important issue in the care of surgical patients than the appropriate use of minimally invasive surgery (MIS) for patients with cancer. Important advances in surgical technique have an impact on early perioperative morbidity, length of hospital stay, pain management, and quality of life issues, as clearly proved with MIS. However, for oncology patients, historically, the most important clinical questions have been answered in the context of prospective randomized trials. Important considerations for MIS and cancer have been addressed, such as what are the important immunologic consequences of MIS versus open surgery and what is the role of laparoscopy in the staging of gastrointestinal cancers? This review article discusses many of the key controversies in the minimally invasive treatment of cancer using the pro–con debate format

Meniscopexy for Internal Derangement of Temporomandibular Joint

The term internal derangement was first adopted to describe any pathologic entity that interfered with the smooth function of the temporomandibular joint (TMJ). The term is currently used exclusively to describe alterations in disc–fossa relations. Internal derangement of the TMJ does not always cause pain, although when the disc becomes displaced, noises and locking can occur and ligamentous, capsular or retrodiscal pain may dominate the clinical picture. Meniscopexy of TMJ was done in ten patients where clinical features suggest true internal derangement of the TMJ refractory to conservative treatment with restricted movement and pain identified as arising primarily from the joint. Magnetic resonance imaging was done to identify the cause of problem