Injectable biologic case studies. (17/231)

OBJECTIVE: To identify strategies used by a commercial managed care organization (MCO) to affect appropriate cost-effective use and prioritize payment for biologic agents. SUMMARY: With the rapid increase in the number of biologic agents and the lack of head-to-head comparative trials, determining clinical superiority of one agent may be challenging. Four case studies are presented that highlight strategies used by a commercial MCO to manage the costs and utilization of these agents and identify a preferred biologic therapy to recommend for its internally developed prior-authorization (PA) criteria for rheumatoid arthritis, asthma, psoriasis, and multiple sclerosis. The first case illustrates how the route of drug administration, differences in distribution channels, and the need for cotherapy can impact the overall cost of therapy. The second case demonstrates the need for tight control of drug utilization when a biologic agent offers only marginal incremental clinical benefit over existing options but at a substantial increase in cost. The third case provides an example of the relationship between increased efficacy and the cost of therapy, and the fourth case demonstrates that PA criteria can be flexible with respect to drug coverage when clear therapeutic differences have not been demonstrated among drugs. CONCLUSION: As more biologic agents become available, it is critical that pharmacy decision makers critically evaluate these innovative new therapies by using the best available evidence to determine the products that provide the greatest clinical and economic value.  (+info)

Biologic therapy for brain cancers--based on cellular and immunobiology. (18/231)

The overall goal of our research projects is to develop effective immunotherapeutic regimens, particularly combining vaccine and gene therapy/ cell therapy strategies. For the development of clinically effective immunotherapy for brain cancers, the following issues are considered to be particularly important: 1) Induction of effective immune responses against tumors (afferent arm of the immune response), 2) Delivery of immune effector cells to the target tumor sites and maintaining the activity of the effector cells (efferent arm), 3) For specific and safe immunotherapy, specific brain tumor rejection antigens have to be identified, 4) Feasibility, safety and efficacy need to be tested in a series of clinical trials. The following presentation summarizes my research projects and demonstrates how each plan will fit in the whole schema of designing successful immunotherapeutic strategies for brain cancers. In this presentation, I would like to focus on our clinical and basic studies related to the vaccine strategies for patients with glioma, and modulation of tumor-microenvironment using bone-marrow derived stroma cells as vehicles for cytokine- gene delivery.  (+info)

Neutralizing antibodies to multiple sclerosis treatments. (19/231)

OBJECTIVE: This article reviews the incidence and clinical significance of neutralizing antibodies (NAbs) in patients with multiple sclerosis (MS) undergoing treatment with interferon beta (IFNbeta). Implications for practice are also discussed in light of the currently available data on the clinical consequences of NAbs in patients with MS. SUMMARY: As with other recombinant protein drugs used for the treatment of a number of diseases, antibodies commonly develop to IFNbeta products during the treatment of patients with MS. Neutralizing antibodies (NAbs) are a subset of antibodies that reduce or diminish the biologic activity of IFNbeta. Three formulations of IFNbeta are currently available for the treatment of relapsing-remitting MS: IFNbeta-1b (Betaseron), intramuscular (i.m.) IFNbeta-1a (Avonex), and subcutaneous (s.c.) IFNbeta-1a (Rebif). Individual phase III clinical trials and direct comparison studies have shown that NAbs develop more frequently during treatment with IFNbeta-1b than IFNbeta-1a and that between the 2 IFNbeta-1a products, NAbs develop more frequently during treatment with s.c. IFNbeta-1a than IM IFNbeta-1a. Data from clinical trials of IFNbeta products indicate that clinical efficacy of IFNbeta is reduced in NAb-positive patients. CONCLUSION: In light of these data, the immunogenicity of IFNbeta products should be considered prior to initiating treatment with IFNbeta. Also, ongoing laboratory monitoring of patients treated with higher-dose IFNbeta is recommended for early detection of NAbs.  (+info)

Clinical management of multiple sclerosis: the treatment paradigm and issues of patient management. (20/231)

OBJECTIVE: To summarize the conclusions of an expert panel of neurologists specializing in multiple sclerosis (MS) convened for the purpose of creating a treatment algorithm with regard to the clinical management of MS. The panel was sponsored by the Health Science Center for Continuing Medical Education and the University of Medicine and Dentistry of New Jersey and supported by an educational grant from Biogen Idec, Inc. SUMMARY: MS is a chronic demyelinating disease characterized by a variable clinical course. Currently, there is no cure for MS, and the management of MS requires lifelong treatment with disease-modifying agents. Some patients respond well to therapy for many years, whereas others may have aggressive disease that is more difficult to manage. Hence, given the variable nature in the course of MS and patients. response to treatment, neurologists must individualize care for their patients. An MS treatment algorithm was recently developed by a panel of neurologists who are MS experts to provide community neurologists with best-practice protocols for treating and managing their MS patients. The panel of experts categorized MS into 3 different stages, with patients transitioning between the stages based on their response to therapy and disease progression. Stage I represents MS early in the progression of the disease, during which platform drug therapy is recommended (i.e., interferon beta-1b [IFNbeta-1b], IFNbeta-1a, or glatiramer acetate). The results of randomized, controlled clinical trials suggest that IFNbeta is the optimal choice for platform therapy. Despite treatment with platform therapy, it is common for patients to experience some ongoing symptoms and periodic exacerbations of the disease (annual relapse rate of 0.59 to 0.84 on treatment); such relapses should not be considered treatment failures and are best managed with steroids. Stage II represents acute breakthrough disease (i.e., when the clinical activity becomes more frequent or severe). This stage is best managed by the addition of pulse corticosteroids to the platform drug. Stage III represents continued breakthrough disease and is best managed by the addition of immunosuppressants to the platform drug. CONCLUSION: The MS treatment algorithm provides an educational resource for physicians. It should assist all health care professionals involved in the management of MS patients and enhance their ability to improve quality of life for these patients over the course of the disease.  (+info)

Stepped-care approach to treating MS: a managed care treatment algorithm. (21/231)

OBJECTIVE: To introduce a model treatment algorithm for use in the managed care setting as a strategy to provide ongoing disease management and long-term care for patients with multiple sclerosis (MS), with the goal of delaying disease progression and the associated disability and cognitive dysfunction. SUMMARY: MS is a chronic inflammatory disorder of the central nervous system that is associated with progressive disability and cognitive dysfunction. Currently, management of MS involves planning an effective long-term treatment strategy that can delay the progression of the disease. This article reviews a typical stepped-care approach to treating MS that is based on the concept of a platform drug, which is an agent that provides baseline immunomodulatory action throughout the course of the disease. Considerations for selecting a platform therapy include the effect on the full spectrum of MS (disability, relapses, lesion load, and atrophy as well as patient compliance and the potential impact of neutralizing antibodies [NAbs]). Currently, 4 first-line therapies are approved for relapsing MS: the 3 interferon beta (IFNbeta) products and glatiramer acetate. Of these, the IFNbetas are generally recommended as platform therapy because all have shown significant effects on relapses, magnetic resonance imaging parameters of the disease, and because intramuscular (i.m.) IFNbeta-1a (Avonex) and subcutaneous (s.c.) IFNbeta-1a (Rebif) have been shown to slow the progression of sustained disability. Patients being treated with IFNbetas can develop NAbs to the drug, which can lead to a loss of efficacy and subsequent occurrence of breakthrough disease. The 3 different formulations of IFNbeta are associated with a varying incidence of NAbs (i.m. IFNbeta-1a, 5%; s.c. IFNbeta-1a, 24%; IFNbeta-1b [Betaseron], 45%). Antibodies also form against glatiramer acetate, although their clinical significance needs to be elucidated. As the disease progresses or has periods of aggressive activity, the stepped-care approach is to add other agents onto the platform therapy to improve control of the disease. CONCLUSION: Stepped care, as outlined in this model treatment algorithm for the managed care setting, is an effective method to achieve the fundamental goal of MS treatment, that is, to delay disease progression and the associated disability and cognitive impairment.  (+info)

Clinical update on alefacept: consideration for use in patients with psoriasis. (22/231)

OBJECTIVE: Alefacept was the first of the biologic agents to be approved for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. This fully human fusion protein inhibits the activation of and reduces levels of memory (CD45RO+) T cells, a subpopulation of lymphocytes that plays a critical role in the pathogenesis of psoriasis. The purpose of this article is to provide a clinical update on the use of this agent in patients with psoriasis. SUMMARY: A single course of alefacept, defined as 12 weekly injections followed by 12 treatment-free weeks, provides clinically meaningful improvements in the symptoms of psoriasis for a majority of patients. Patients who achieved a response have been shown to maintain the benefit for a median duration of about 7 months, without the need for systemic therapy or phototherapy. With each additional course of alefacept, the percentage of patients responding increases, confirming the incremental benefit of repeated administration. More than 1,300 patients have received alefacept in controlled clinical trials. Over multiple courses of therapy, alefacept-induced reductions in circulating lymphocyte counts were consistent and not cumulative. The incidences of serious adverse events, discontinuations, malignancies, and antialefacept antibodies were low and did not increase with subsequent courses. No relationship was observed between decreases in lymphocyte counts and incidences of infections or malignancies. No cases of opportunistic infections, including tuberculosis, have been reported. The favorable safety profile of alefacept was maintained in patients who received concomitant or prior immunosuppressants. Alefacept did not cause reactivation of tuberculosis in case studies of patients who showed a purified protein derivative reaction prior to the initiation of therapy. Immune responses to a neoantigen and recall antigen remained intact in alefacept-treated patients, suggesting that vaccinations may be possible during therapy. CONCLUSION: Alefacept is an effective intermittent therapy for psoriasis that can provide extended treatment-free and disease-free periods, which may lessen the need for treatment over time. The incremental efficacy seen with each subsequent course of alefacept suggests that physicians should administer 2 courses to determine efficacy before altering therapeutic interventions. The selective mechanism of action of alefacept affords multiple safety advantages and no apparent increased risk of infections or malignancies.  (+info)

Considerations for assessing the cost of biologic agents in the treatment of psoriasis. (23/231)

OBJECTIVE: This paper will establish the rationale for developing a long-term cost model to assess the utilization and associated economics of biologic agents in the treatment of moderate-to-severe psoriasis. This information should assist with defining the total cost of drug treatment when using biologic therapy to treat psoriasis. SUMMARY: The development of biologic therapies has effected the treatment of many chronic diseases, including psoriasis. Managed care organizations are debating the appropriate use of these injectable drugs because of the associated acquisition costs and administration requirements. Important considerations for evaluating these agents include the ability to produce off-treatment remissions, the ability to improve patients. quality of life, and safety and tolerability profiles. A remittive therapy may be a good early treatment for these patients because it offers the chance to avoid lifelong therapy. In addition, the safety and tolerability profiles of all biologic agents are substantially improved compared with conventional systemic psoriasis treatments. However, therapy must be individualized because risks vary with each agent. Thus, these differences in the biologic agents should be considered in the assessment of the economic impact and drug utilization of biologics for patients with psoriasis. CONCLUSION: The biologic agents currently used in the treatment of psoriasis offer patients new hope for safe and effective therapy. Comparison of these agents by managed care decision makers requires consideration of characteristics that differentiate the agents, including efficacy, duration of off-treatment response, and safety and tolerability.  (+info)

Mechanism of action of donor-specific transfusion in inducing tolerance: role of donor MHC molecules, donor co-stimulatory molecules, and indirect antigen presentation. (24/231)

Donor-specific transfusion (DST) can synergize with T cell co-stimulatory blockade in inducing tolerance in several transplant models, but the mechanism of action of DST is poorly characterized. This study used genetically altered mice in an established model of cardiac transplantation to study the role of MHC and co-stimulatory molecule expression on DST cells in mediating the immunomodulatory effects of DST. In addition, to examine the role of indirect antigen presentation in the effect of DST, experiments used recipient mice that do not express MHC class II molecules on peripheral antigen-presenting cells, but do have functional CD4(+) T cells (II(-)4(+)). As previously reported, treatment with DST from wild-type donors in combination with CD154 blockade induced tolerance in wild-type recipients of cardiac allografts. Tolerance in this model is also induced despite the absence of MHC class I and II, CD40, or B7 molecules on transfused cells. In contrast, eliminating the indirect pathway using II(-)4(+) recipients blocked the induction of long-term cardiac allograft survival by DST. These results indicate that the indirect antigen recognition pathway mediates the immunomodulatory effect of DST in inducing transplantation tolerance in vivo.  (+info)