Efalizumab for severe atopic dermatitis: A pilot study in adults

Takiguchi, Rodd; Tofte, Susan J.; Simpson, Brenda; Harper, Erin; Blauvelt, Andrew; Hanifin, Jon M.; Simpson, Eric L.

doi:10.1016/j.jaad.2006.08.031

Cited by 85 publications

(62 citation statements)

References 16 publications

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“…This allowed the prediction that CD11a-targeting treatment modalities like the antipsoriatic efalizumab might be also of therapeutic efficacy in atopic dermatitis [14] . And indeed, this MELC methodology-based prediction has very recently been confirmed by some clinical studies demonstrating the positive effects of efa lizumab in atopic dermatitis [24][25][26] , although they still need to be validated under placebo-controlled conditions. Although under our given study conditions we had the opportunity to investigate only a relatively small cohort of patients, we observed 5/6 psoriasis patients in our series as responders to 12 weeks of efalizumab treatment.…”

Section: Additional Datamentioning

confidence: 81%

Topo-Proteomic in situ Analysis of Psoriatic Plaque under Efalizumab Treatment

Bonnekoh

Pommer²,

Böckelmann

et al. 2007

Skin Pharmacol Physiol

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In a pilot study 6 psoriasis patients were treated over 12 weeks with efalizumab targeting the CD11a subunit of LFA-1. The treatment was well tolerated. Five of these patients proved to be responders with an average decrease in psoriasis area and severity index (PASI) from 21.3 ± 5.4 (day 0) to 3.9 ± 0.6 (week 12). The nonresponder was subsequently successfully treated with cyclosporin. Skin biopsies were taken before and after efalizumab treatment and subjected to Multi-Epitope Ligand Cartography (MELC) robot microscopy. A MELC library of 46 antibodies including FITC-labeled efalizumab was chosen focusing upon inflammatory epitopes. Quantification of marker expression was performed using a special adaptation to the needs of skin tissue in terms of pixel events normalized to a standardized horizontal skin width of 100 µm. The before-versus-after comparison for the responders revealed at the ‘single epitope level’ of MELC analysis a significant decrease (p < 0.05) in epidermal thickness (represented by pan-cytokeratin, CD71, CD138), of the expression of common leukocyte antigen (CD45), T-cell markers (CD2, CD4, CD8, CD45R0), CD11a, efalizumab binding site (EfaBS), and CD58. At the ‘EfaBS-centered, double colocation level’ a corresponding decrease was observed for CD2, CD3, CD4, CD8, CD11a, CD13, CD26, CD44, CD45, CD45R0, CD54, CD62L, HLA-DR, and TIA-1. MELC analysis at the ‘multicombinatorial level’ revealed predominant combinatorial molecular phenotype (CMP) motifs, which showed an efalizumab treatment-dependent significant decrease. These CMP motifs were defined as toponomic combinations of lead markers for (i) leukocytes in general (CD45), (ii) T cells (CD2, CD3, CD4, CD45R0, CD45RA), (iii) macrophages (CD68), (iv) cell activation (CD13, CD26, HLA-DR), and (v) cell adhesion (CD11a, EfaBS). Thirty-five of the most relevant 50 CMP motifs were directly related to the T-cell type. A descriptive statistical analysis of the nonresponder before treatment showed a below-responder range degree of expression for CD4, CD8, CD44 (H-CAM), CD56, CD62L, HLA-DQ, and also for these epitopes in colocation with EfaBS. In the nonresponder and before treatment we observed an above-responder range degree of expression for CD54 (ICAM-1) as LFA-1 ligand. In conclusion, the topo-proteomic data provide new diversified insights into the pleiotropic cellular dynamics in psoriatic skin lesions under effective efalizumab treatment. Moreover, the data may be relevant to the future development of possible strategies for individual prediction of efalizumab treatment response or nonresponse.

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Section: Additional Datamentioning

confidence: 81%

Topo-Proteomic in situ Analysis of Psoriatic Plaque under Efalizumab Treatment

Bonnekoh

Pommer²,

Böckelmann

et al. 2007

Skin Pharmacol Physiol

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“…Paradoxically efalizumab has already been used for the treatment of atopic dermatitis [25, 26]. Recently, a prospective study researched the efficacy and tolerance of efalizumab among 10 adults presenting a severe atopic dermatitis, without placebo control, at a dose of 1 mg·kg –1 · day –1 .…”

Section: Discussionmentioning

confidence: 99%

Eczematous Dermatosis and Thrombocytosis Induced by Efalizumab: Two New Side Effects

Firmin

Roguedas

Lemasson³

et al. 2008

Dermatology

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Efalizumab was authorized to be put on the market in France starting July 21, 2005. Its efficacy and tolerance profile in plaque psoriasis at a dose of 1 mg·kg^–1 weekly in a subcutaneous injection have been studied in phase III trials. At the current moment, more than 3,500 patients have been included in clinical trials. Flu-like symptoms (fever, chills, headaches, nausea, vomiting, myalgia) are the most frequent adverse events. On the skin, a localized papular rash or the aggravation of the psoriasis in an edematous or even pustular form are the two most regularly observed complications. At the biological level, hyperlymphocytosis and a temporary increase in alkaline phosphatases without clinical consequences are the most frequent anomalies. We report 2 adverse events under efalizumab that to our knowledge have never been described: a case of an eczematous rash and a case of thrombocytosis.

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“…было отмечено снижение индекса EASI на 50% и более у 6 из 10 пациентов с тяжелой формой АД на фоне приема эфализумаба. Препарат был предложен авторами в качестве возможной аль-тернативы существующей системной терапии [112]. Однако полученные результаты противоречили дан-ным Ibler и соавт.…”

Section: антицитокиновая терапияunclassified

Biological Therapeutic Treatment of Atopic Dermatitis

Кубанова

Кубанов

Карамова

et al. 2017

Vestnik dermatologii i venerologii

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Atopic dermatitis is a chronic recurrent inflammatory disease caused, inter alia, by violations of the barrier function of the skin and pathological immune response in the form of an imbalance of Th1 and Th2 lymphocytes with increased production of IL-4, IL-5, IL-13, IL-31. Treatment of severe forms of atopic dermatitis is not an easy task due to the variability of the individual response to treatment, the short duration of the therapeutic effect and the frequent development of undesirable phenomena associated with the use of existing methods of systemic immunosuppressive therapy. The study of the pathogenesis of atopic dermatitis made it possible to identify the spectrum of molecular targets, providing the basis for researching alternative variants to the previously used systemic therapy methods – genetic engineering biological preparations. Contemporary data on the pathogenesis of atopic dermatitis as well as potential molecular targets for innovative biological preparations, the efficacy of which has been evaluated through clinical trials, are presented in the review.

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Efalizumab for severe atopic dermatitis: A pilot study in adults

Cited by 85 publications

References 16 publications

Topo-Proteomic in situ Analysis of Psoriatic Plaque under Efalizumab Treatment

Topo-Proteomic in situ Analysis of Psoriatic Plaque under Efalizumab Treatment

Eczematous Dermatosis and Thrombocytosis Induced by Efalizumab: Two New Side Effects

Biological Therapeutic Treatment of Atopic Dermatitis

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