Subcutaneously Administered Efalizumab (Anti-CD11a) Improves Signs and Symptoms of Moderate to Severe Plaque Psoriasis

Gottlieb, Alice B.; Miller, Bruce; Lowe, Nicholas J.; Shapiro, William; Hudson, Charles P.; Bright, Ross; Ling, Mark; Magee, Anna; McCall, Calvin O.; Rist, Toivo; Dummer, Wolfgang; Walicke, Patricia A.; Bauer, Robert J.; White, Mark L.; Garovoy, Marvin R.

doi:10.1007/s10227-002-0118-1

Cited by 38 publications

(30 citation statements)

References 23 publications

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“…intravenous or subcutaneous). A total of 2,980 patients received treatment with efalizumab in 1 or more of 14 clinical trials (summarized in table 1; Genentech Inc., data on file) [7, 17, 18,21,22,23,24,25,26,27, 43]. Safety information is available for 762 patients who received placebo and 2,980 patients who received efalizumab.…”

Section: Methodsmentioning

confidence: 99%

“…Binding of efalizumab to leukocyte function-associated antigen 1 modulates T cell interactions known to play an important role in the pathogenesis of psoriasis [4,11,12,13,14,15], including T cell activation in the lymph nodes, T cell trafficking from the circulation into inflamed skin and T cell reactivation therein [11, 14, 16, 17]. The safety and efficacy of efalizumab for treating plaque psoriasis have been demonstrated in multiple placebo-controlled phase III trials [18,19,20,21,22,23] as well as in numerous other trials [14, 17,24,25,26,27]. Currently efalizumab has the largest safety database for a biologic used in the treatment of psoriasis.…”

Section: Introductionmentioning

confidence: 99%

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A Review of Malignancies Observed during Efalizumab (Raptiva®) Clinical Trials for Plaque Psoriasis

Toth¹,

Cather²,

Langley³

et al. 2006

Dermatology

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Background: Psoriasis is a chronic, incurable immune-mediated disease. Most therapies used for moderate to severe psoriasis are immunosuppressive. Agents that depress immune function, including traditional psoriasis therapies, have been associated with an increased incidence of malignancies. Efalizumab is a recombinant monoclonal immunoglobulin G1 (IgG1) antibody approved for use in psoriasis patients. Objectives: To evaluate the incidence of malignancy in patients receiving efalizumab during clinical trials compared with placebo-treated patients, psoriasis patients from external cohorts and the general US population. Methods: Patient data were pooled from multiple phase III placebo-controlled, open-label efalizumab clinical trials, and the incidence rate of reported malignancies was calculated as a function of patient years of observation. The results for the efalizumab-treated patients were compared with the data on psoriasis patients from insurance claims databases and a registry of events in the general population. Results: The efalizumab- and placebo-treated patients had similar incidence rates of malignancy, including lymphoproliferative disease, solid tumor, malignant melanoma and nonmelanoma skin cancer. The incidence of nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, in patients receiving efalizumab or placebo was elevated relative to the external databases. Conclusions: These results suggest that efalizumab treatment does not increase a patient’s risk for malignancy. The difference observed with nonmelanoma skin cancer may be due to biases introduced by the clinical trial methodology. Additional patient observation is necessary to ascertain whether a link exists between efalizumab therapy and nonmelanoma skin cancer above that normally observed in psoriasis patients.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Review of Malignancies Observed during Efalizumab (Raptiva®) Clinical Trials for Plaque Psoriasis

Toth¹,

Cather²,

Langley³

et al. 2006

Dermatology

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“…The journey to the current situation in psoriasis treatment started by evidencing that T-cell activity in psoriasis had real implications for the patients. Thus, depletion of T cells [9,10], costimulation [11], and inhibition of their migration from blood to skin demonstrated improvement in the clinical severity [12]. Not only memory T cells are of translational relevance in psoriasis, but also TNF-α is a key cytokine for this disease.…”

Section: An Interdisciplinary Approach To Psoriasis 62mentioning

confidence: 99%

“…It became evident that the ustekinumab clinical eicacy was related to inhibition of the IL-23 biological efect. CTLA4-Ig T cell costimulation blockade CD80, CD86 Blocking T cell activation improve psoriasis [11] LFA-3-Ig Memory T cell depletion CD2 Memory T cells are relevant in psoriasis [10] Anti-LFA-1 T cell migration and T-cell costimulation inhibitor LFA-1 Migration of T cells to psoriasis lesion is involved in disease [12] Anti-TNF-α Neutralization of biological selectively IL-23, which also has conirmed the clinical relevance of speciically blocking the IL-23/Th17 in psoriasis [16].…”

Section: Translational Research and Clinically Relevant Pathological mentioning

confidence: 99%

Human Translational Research in Psoriasis Using CLA+ T Cells

Ruiz-Romeu¹,

Santamaria‐Babí²

2017

An Interdisciplinary Approach to Psoriasis

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Focusing on the study of human memory CLA+ T cells to understand psoriasis pathology constitutes an innovative approach to explore the pathological mechanism of this chronic cutaneous inlammatory disease. CLA+ T cells can be considered peripheral cell biomarkers in the study of T-cell mediated human skin diseases. During the last few years, new evidences have been found that link streptococcal infection with IL-17 response in psoriasis by studying the interaction between Streptococcus pyogenes with CLA+ T cells and autologous epidermal cells. S. pyogenes constitutes the best clinically characterized trigger of psoriasis and by exploring its efect on CLA+ T cells and epidermal cells in psoriasis may allow understanding psoriasis by using patient's clinical samples ex vivo. Keywords: psoriasis, CLA+ T cells, translational research, Streptococcus pyogenes, IL17 CLA+ T cells and the regional cutaneous immune systemThe adaptive immune responses taking place during cutaneous chronic inlammation in psoriasis preferentially involve a subset of memory T lymphocytes, which are related to the skin and that belong to the cutaneous immune system, and constitute one of the best characterized regional immune systems of the body and known for decades [1]. In the humans, the cutaneous lymphocyte-associated antigen (CLA) is a surface cell marker that allows identifying T cells that belong to the cutaneous immune system. The CLA antigen is a carbohydrate expressed by 15% of human circulating T cells, and on most (>90%) skin-iniltrating T cells, contrary to other inlamed organs [2]. CLA is expressed preferentially on memory antigenexperienced T cells.© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.The CLA is one of the adhesion molecule that, together with chemokine receptors, allows T cells to selectively migrate to the skin, in either homeostatic or inlammatory conditions, by binding to endothelial cell wall via adhesion molecules or ligands. The molecular interactions between CLA/E-selectin, very late antigen-4 (VLA-4)/vascular cell adhesion protein-1 (VCAM-1), lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1), and chemokine ligands for chemokine, C-C motif receptor (CCR) 10, CCR4, CCR6, and CCR8 constitute a code bar system enabling skin iniltration [3].The importance of circulating CLA+ T cells for understanding the skin immune system is not only based on their capacity to selectively migrate to skin, but also on the fact that these circulating memory T cells are functionally related to the immune response taking place in the cutaneous inlamed lesions. This feature is based on the recirculating capacity of those cells between lesional skin and blood during cutaneous inlammation in psoriasis [3]. The adhesive interaction between LFA-1 ...

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“…The LFA-1: ICAM-1 interaction is a key element in stabilizing the immunologic synapse that forms between T cells and APCs and also mediates the binding of T cells to endothelial cells [2,10,11] . Blocking the costimulatory signaling process and inhibiting the interaction of these ligands pairs have been shown to be effective in the treatment of autoimmune diseases, such as psoriasis [4,7,12] . Efalizumab (Raptiva ® ) is a recombinant, humanized CD11a-specific mAb developed by Genentech Inc that can bind to CD11a, preventing LFA-1 binding to ICAM-1 [6] .…”

Section: Introductionmentioning

confidence: 99%

Tolerability, pharmacokinetics and pharmacodynamics of CMAB001, an anti-CD11a antibody, in Chinese healthy volunteers and psoriatic patients

Yan

et al. 2012

Acta Pharmacol Sin

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Aim: To evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and primary tolerability of an anti-CD11a monoclonal antibody (CMAB001) in Chinese healthy volunteers and psoriatic patients.Methods: Two open-label studies were conducted. One was a parallel-group, single-center, dose-escalation test, including 24 healthy adult volunteers from 18 to 45 years in age. All subjects randomly received a single subcutaneous injection dose of 0.5, 1.0, or 2.0 mg/kg. The other was a multiple-dose study: 10 adult psoriatic patients were administered weekly subcutaneous injections of 1.0 mg/kg for 7 weeks. Results: CMAB001 was well tolerated in the single-and multiple-dose studies. Slow absorption was observed in both studies. In the single-dose study, the concentration of CMAB001 reached its highest level 2 d later after the injection, and the C max increased in an approximate dose-proportionate manner, while the area under curve (AUC) showed much greater than dose-proportionate increase. In the multiple-dose study, the steady-state serum concentration level was attained following the 4th injection. Conclusion: CMAB001 exhibited a nonlinear pharmacokinetic profile over the dose range from 0.5 to 2.0 mg/kg, and was well tolerated in healthy volunteers and psoriatic patients.

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Subcutaneously Administered Efalizumab (Anti-CD11a) Improves Signs and Symptoms of Moderate to Severe Plaque Psoriasis

Cited by 38 publications

References 23 publications

A Review of Malignancies Observed during Efalizumab (Raptiva®) Clinical Trials for Plaque Psoriasis

A Review of Malignancies Observed during Efalizumab (Raptiva®) Clinical Trials for Plaque Psoriasis

Human Translational Research in Psoriasis Using CLA+ T Cells

Tolerability, pharmacokinetics and pharmacodynamics of CMAB001, an anti-CD11a antibody, in Chinese healthy volunteers and psoriatic patients

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