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Gerald G. Krueger – One of the best experts on this subject based on the ideXlab platform.

  • Alefacept for severe alopecia areata: a randomized, double-blind, placebo-controlled study.
    Archives of dermatology, 2009
    Co-Authors: Bruce E. Strober, Gerald G. Krueger, Kavita Menon, Amy J. Mcmichael, Maria K. Hordinsky, Jackie M. Panko, Kimberly Siu, Jonathan L. Lustgarten, Elizabeth K. Ross, Jerry Shapiro
    Abstract:

    Objective To assess the efficacy of Alefacept for the treatment of severe alopecia areata (AA). Design Multicenter, double-blind, randomized, placebo-controlled clinical trial. Setting Academic departments of dermatology in the United States. Participants Forty-five individuals with chronic and severe AA affecting 50% to 95% of the scalp hair and resistant to previous therapies. Intervention Alefacept, a US Food and Drug Administration–approved T-cell biologic inhibitor for the treatment of moderate to severe plaque psoriasis. Main Outcome Measure Improved Severity of Alopecia Tool (SALT) score over 24 weeks. Results Participants receiving Alefacept for 12 consecutive weeks demonstrated no statistically significant improvement in AA when compared with a well-matched placebo-receiving group ( P   = .70). Conclusion Alefacept is ineffective for the treatment of severe AA.

  • a multicenter open label study of repeat courses of intramuscular Alefacept in combination with other psoriasis therapies in patients with chronic plaque psoriasis
    Journal of Dermatological Treatment, 2008
    Co-Authors: Gerald G. Krueger, Alice B. Gottlieb, Neil J. Korman, Wolfram Sterry, Peter C.m. Van De Kerkhof
    Abstract:

    Objective: To evaluate the safety and efficacy of multiple courses of Alefacept in combination with traditional psoriasis therapy for the treatment of chronic plaque psoriasis (CPP). Methods: Patients with CPP requiring systemic therapy were eligible for this study. Patients received up to three courses of intramuscular Alefacept 15 mg once weekly for 12 weeks. One concomitant psoriasis therapy (topical agents, methotrexate, cyclosporine, systemic retinoids, or ultraviolet B [UVB]) per course was allowed. The extent of disease was determined using the 7‐point Physician Global Assessment (PGA; scale ranging from 0 = clear to 6 = severe). Results: More than 73% of patients improved by ⩾ one PGA category and ⩾44% of patients improved by ⩾ two PGA categories across all concomitant treatments. Clinical responses tended to be greatest in patients who received Alefacept plus UVB. The incidences of serious infections (⩽1%) and malignancies (⩽2%) were low across all courses and all combinations. Conclusion: Multip…

  • an integrated analysis of thirteen trials summarizing thelong term safety of Alefacept in psoriasis patients who have received up to nine courses of therapy
    Clinical Therapeutics, 2005
    Co-Authors: Bernard S. Goffe, Marianne T. Sweetser, Gerald G. Krueger, Kim Papp, Mohamed Darif, David Gratton, Sophia Lee, Carmen Bozic, Barry Ticho
    Abstract:

    Abstract Background: Information on longer-term safety andtolerability is needed to confidently prescribe Alefacept therapy for chronic plaque psoriasis beyond 1 or 2 courses. Objective: The aim of this work was to further examine the safety profile of Alefacept by integrating data from clinical trials involving patients with chronic plaque psoriasis who received up to 9 courses of therapy over a 5-year period. Methods: Data from 13 clinical trials conducted in patients with plaque psoriasis were integrated because they had similar inclusion/exclusion criteria and assessments. Patients who enrolled in the analyzed trials were aged ≥15 years with chronic plaque psoriasis for ≥12 months that involved ≥10% of body surface area, and CD4+ Tlymphocyte counts above the lower limit of normal (>404 cells/μL). The incidences of adverse events (AEs), serious AEs, discontinuations for AEs, infections, serious infections, malignancies, and anti-Alefacept antibodies were summarized for each course of Alefacept. The incidence of infections was stratified according to CD4+ Tlymphocyte counts ( Results: Data from 13 clinical trials of Alefacept were integrated and summarized (multicenter, randomized, double-blind studies, n = 6; multicenter, open-label studies, n = 5; other, n = 2). The analyzed population (n = 1869) included 1291 (69.1%) men and 578 (30.9%) women, between the ages of 15 and 84 years (mean, 44.8 years), of whom 1648 (88.2%) were white. Weights ranged from 40 kg to 206 kg (mean, 90.0 kg). A total of 1369 of these patients had been included in a previous analysis. Among the most commonly reported AEs in each treatment course were headache (0%–14.2%), nasopharyngitis (7.7%–25.0%), influenza (0%–8.1%), upper resprespiratory tract infection (0%–12.5%), and pruritus (0%–7.5%). The rates of discontinuations due to AEs (0%–4.8%), serious AEs (0%–4.8%), serious infections (0%–0.9%), or malignancies (0%–4.8%) did not appear to increase with repeated exposure. Fewer than 1 % of patients in each course developed a serious infection. No opportunistic infections or infection-related deaths were reported. The incidence of infections appeared to be unrelated to CD4+ Tlymphocyte counts. Fewer than 2.5% of patients tested positive for anti-Alefacept antibodies during any course of therapy. Conclusions: This integrated analysis of data from13 trials with 1869 patients supports the safety and tolerability of Alefacept for longer-term treatment of psoriasis.

P.c.m. Van De Kerkhof – One of the best experts on this subject based on the ideXlab platform.

  • The effect of Alefacept on T-cell subsets and cells expressing NK receptors in lesional psoriatic skin: the effects of monotherapy and combination treatment with calcipotriol.
    The Journal of dermatological treatment, 2008
    Co-Authors: W.h.p.m. Vissers, M.w.f.m. Van Duijnhoven, P.e.j. Van Erp, E.m.g.j. De Jong, P.c.m. Van De Kerkhof
    Abstract:

    OBJECTIVES: To investigate the effect of weekly Alefacept monotherapy 15 mg i.m. on epidermal hyperproliferation, keratinization, T-cell subsets and cells expressing NK receptors during 12 weeks of treatment. Furthermore, the addition of calcipotriol cream to Alefacept treatment was studied and compared with Alefacept monotherapy. METHODS: Five patients participated in this study, and used weekly Alefacept 15 mg i.m. combined with calcipotriol cream up to a maximum of 100 g per week. Biopsies from two lesions (one treated and another lesion not treated with calcipotriol cream) were taken at week 0 and week 12. We investigated the number of T-cell subsets (CD4, CD8, CD45RO, CD45RA, CD2, CD25), cells expressing NK receptors (CD94 and CD161), the proliferation marker Ki-67 and the keratinization marker keratin-10. RESULTS: Alefacept monotherapy induced a statistically significant reduction of CD4+, CD45RO+ and CD2+ cells in dermis and epidermis and CD8+ cells in epidermis at week 12. Furthermore, the keratin-10 positive epidermal surface was significantly increased at week 12. The combination of Alefacept and calcipotriol cream induced a statistically significant reduction of only CD4+ and CD45RO+ cells at week 12. CONCLUSIONS: The number of memory effector T-cells in the psoriatic lesion is significantly decreased by Alefacept, and calcipotriol cream does not seem to have an additional effect on this reduction. Cells expressing NK receptors are virtually not targeted by Alefacept monotherapy or the combination.

  • explorative immunohistochemical study to evaluate the addition of a topical corticosteroid in the early phase of Alefacept treatment for psoriasis
    Archives of Dermatological Research, 2007
    Co-Authors: H J Bovenschen, E.m.g.j. De Jong, W. J. Gerritsen, D W A Van Rens, M M B Seyger, P.c.m. Van De Kerkhof
    Abstract:

    The aim of this study was to explore the additional effect of betamethasone dipropionate cream in the early phase of an intramuscular (IM) Alefacept course, on plaque severity and on modulating T-cell subsets, cells expressing NK-receptors, epidermal proliferation and keratinocyte differentiation in lesional psoriatic skin. Therefore, sixteen patients with moderate-to-severe chronic plaque psoriasis received 15 mg Alefacept IM for 12 weeks, followed by a 12-week follow-up period. The first 4 weeks, patients were randomized 1:1 to either betamethasone dipropionate, or the vehicle cream, once daily. Plaque severity (SUM) was assessed and serial biopsies were immunohistochemically stained for T-cell subsets (CD3, CD4, CD8, CD45RO, CD45RA, CD2, CD25, GITR), cells expressing NK-receptors (CD94 and CD161), epidermal proliferation (Ki67) and differentiation (K10), which were quantified using manual and digital image analysis. Alefacept monotherapy resulted in statistically significant improvement in plaque severity. Subsequently, immunohistochemical assessments on T-cell subsets, epidermal proliferation (Ki67) and keratinization (K10) revealed marked time-related improvements with respect to the mentioned parameters, without significant differences between both treatment regimens. Alefacept monotherapy induces improvement of plaque severity, which is accompanied by a reduction in activated (CD2+, CD25+, CD45RO+) dermal CD4+ and activated epidermal CD8+ T cells, epidermal proliferation and differentiation. Once daily treatment with betamethasone dipropionate cream during the first 4 weeks of an intramuscular Alefacept course did not provide substantial additional clinical and immunohistochemical improvement.

  • Therapeutic effects of a 12-week course of Alefacept on nail psoriasis.
    Journal of the European Academy of Dermatology and Venereology, 2006
    Co-Authors: J.e.m. Körver, Annechien M. G. Langewouters, P.c.m. Van De Kerkhof, Marcel C. Pasch
    Abstract:

    BACKGROUND AND OBJECTIVES: Nail psorpsoriasis is a common finding in psoriatic patients and it affects the quality of life in a great proportion of patients. Topical or systemic treatments have limited effectiveness or have a serious toxicity potential. Biologicals such as Alefacept are the most recent treatment modalities for psoriasis. In the present study we evaluated changes in nail pathology in patients with plaque psoriasis and nail involvement during treatment with Alefacept. PATIENTS AND METHODS: Digital photographs from eight patients were produced, which were analysed using the nail psorpsoriasis severity index (NAPSI). A minimal NAPSI of 15 was chosen to divide patients into a moderate to very severe nail psorpsoriasis group and a group with no or mild nail psorpsoriasis. A decrease in NAPSI of at least 25% was considered a significant response to therapy. RESULTS: In the group with at least moderate nail psorpsoriasis, two patients improved, in two patients the nail changes remained unchanged and in one patient the nail pathology was aggravated. The group with no or mild nail psorpsoriasis showed variable results. CONCLUSIONS: Although Alefacept showed some results in treating nail pathology in psoriasis, a more extensive study is required, covering both more patients and a more extensive time period. Furthermore, it would also be clinically relevant to compare the effects of Alefacept on nail psorpsoriasis with other biologicals.

Mark Lebwohl – One of the best experts on this subject based on the ideXlab platform.

  • Alefacept: where it stands today.
    Expert opinion on drug metabolism & toxicology, 2010
    Co-Authors: Jinan Chaarani, Mark Lebwohl
    Abstract:

    Importance of the field: The use of biologics that target a subset of immune cells in the treatment of immune-mediated ailments is an emerging field. Alefacept is one of the first biologics in the treatment of psoriasis. It selectively reduces CD45RO+ memory T cells and inhibits T-cell activation. Clinical data support its safety and efficacy in a substantial subset of patients with psoriasis.Areas covered in this review: This article reviews the mechanism of action and the pharmacokinetic and pharmacodynamic properties of Alefacept. It also presents the available data about its effectiveness, modes of treatment as well as safety and efficacy in the treatment of psoriasis and other immune-based dermatologic disorders.What the reader will gain: An overview of the published data about the clinical and adverse effects of Alefacept in the treatment of psoriasis and a myriad of immunologically-based disorders.Take home message: Ongoing literature supports that Alefacept is a safe alternative for the treatment …

  • The efficacy of multiple courses of Alefacept in patients with moderate to severe chronic plaque psoriasis
    Journal of the American Academy of Dermatology, 2006
    Co-Authors: Alan Menter, Mark Lebwohl, Jennifer Clay Cather, Diane Baker, Harold F. Farber, Mohamed Darif
    Abstract:

    Among patients with psoriasis who did not achieve Psoriasis Area and Severity Index 50 during the first course of Alefacept therapy, 53% achieved Psoriasis Area and Severity Index 50 during the second course (odds ratio [95% confidence interval] vs placebo 2.30 [1.26-4.19]). Alefacept provided incremental efficacy over 5 successive 12-week treatment courses.

  • Alefacept in the treatment of psoriasis in patients for whom conventional therapies are inadequate.
    Dermatology (Basel Switzerland), 2005
    Co-Authors: P.c.m. Van De Kerkhof, Enno Christophers, Mark Lebwohl, Christopher E.m. Griffiths, Gerald G. Krueger
    Abstract:

    BACKGROUND: Many patients with moderate to severe chronic plaque psoriasis fail to respond to or are not appropriate candidates for conventional systemic therapies and/or phototherapy. OBJECTIVES: To assess the efficacy, quality of life and safety of Alefacept among the proportion of patients who participated in the phase III studies and who were not suitable candidates for conventional systemic psoriasis therapies or phototherapy. METHODS: The patient’s historical responses at the baseline visit during the phase III studies of Alefacept were used to identify a subpopulation in whom the use of methotrexate, ciclosporin, retinoids, ultraviolet B or psoralen plus ultraviolet A was ineffective or inappropriate. Endpoints included Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and adverse events. RESULTS: Most patients (69%) who were treated with Alefacept in the phase III programme were not candidates for > or =1 of the above-mentioned therapies, and 41 and 21% were not candidates for > or =2 and > or =3, respectively. A reduction in PASI of > or =75% was achieved by 27, 23 and 26% of Alefacept-treated patients who were not candidates for > or =1, > or =2 and > or =3 conventional systemic psoriasis therapies or phototherapy, respectively (all p < or = 0.001 vs. placebo). The corresponding results for PASI 50 were 53, 52 and 50% (all p < or = 0.001 vs. placebo). At 2 weeks after the last dose of Alefacept, mean DLQI overall scores were reduced by -4.2, -3.9 and -5.2, respectively (all p < or = 0.001 vs. placebo). The incidence of adverse events was similar in the Alefacept and placebo groups. CONCLUSIONS: The efficacy, quality of life effects and safety of Alefacept in patients who were not candidates for conventional systemic psoriasis therapies or phototherapy were similar to those reported previously for the overall Alefacept-treated population in the phase III studies.

John Koo – One of the best experts on this subject based on the ideXlab platform.

  • Intralesional injections of Alefacept may predict systemic response to intramuscular Alefacept: results from a pilot study.
    The Journal of dermatological treatment, 2012
    Co-Authors: Tina Bhutani, Shilpa Gattu, Charles Chiang, Thao Nguyen, Emily M. Becker, Faranak Kamangar, Kristine B Zitelli, John Koo
    Abstract:

    Background: Alefacept (Amevive®) was the first biologic agent to be approved by the FDA for use in moderate to severe chronic plaque psoriasis and remains one of the safest systemic agents. However, Alefacept is the least utilized of all the biologic agents due to the finding that it is only effective in a small proportion of patients and its maximal efficacy is not seen until approximately 6 weeks after treatment completion. Objective: To determine whether intralesional injections with a biologic agent can predict who will be a responder or a non-responder to the medication. Methods: This was a single-center 22-week study consisting of three phases: i) intralesional injection to a target plaque, ii) intramuscular Alefacept injections for 12 weeks (standard dose) and iii) post-treatment follow-up. Results: There appears to be a perfect correlation between patients who show a response to an intralesional injection of Alefacept to a small, target plaque and those who eventually respond to a full 12-week sys…

  • Psoriasis responds to intralesional injections of Alefacept and may predict systemic response to intramuscular Alefacept: interim results of a single-arm, open-label study.
    The Journal of dermatological treatment, 2011
    Co-Authors: Shilpa Gattu, Kristine Busse, Tina Bhutani, Charles Chiang, Thao Nguyen, Emily M. Becker, John Koo
    Abstract:

    Abstract Background: Alefacept is a remittive treatment for generalized psoriasis but is rarely used due to its erratic efficacy. Objective: To determine if psoriasis plaques will respond to intralesional Alefacept and if this predicts a systemic response to intramuscular (IM) Alefacept. Methods: We describe a 25-week, single-center, open-label study. Patients received weekly intralesional Alefacept of increasing concentrations into target plaques for 3 weeks followed by IM injections for 12 weeks and concluded with an observation period of 9 weeks. The psoriasis area and severity index (PASI) was used to assess the efficacy of IM Alefacept. Results: Interim results are reported for the first seven patients enrolled. Two patients responded intralesionally to the most dilute 1:100 concentration of Alefacept to sterile water and achieved a 59% and 100% improvement in PASI. Five patients did not respond intralesionally to the most dilute form of Alefacept and none achieved PASI 75. Two of these five patients…

  • An open-label study of Alefacept plus ultraviolet B light as combination therapy for chronic plaque psoriasis
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2005
    Co-Authors: J P Ortonne, John Koo, A Khemis, J Choi
    Abstract:

    Background  Alefacept, a fully human LFA-3/IgG1 fusion protprotein, is a selective biological agent approved in the United States for the treatment of chronic plaque psoriasis. In phase 3 trials, clinical improvement and prolonged off-treatment remission of psoriasis correlated with reductions in circulating memory T cells. Reductions in pathogenic epidermal T cells in psoriatic lesions also have been noted following phototherapy with ultraviolet B (UVB) light. Because Alefacept and UVB target T cells in different ways, combination therapy with these two agents may lead to greater efficacy. Objectives  To determine the safety, tolerability, and efficacy trends of combination therapy with Alefacept plus UVB light in patients with chronic plaque psoriasis. Methods  In an open-label, parallel-group study conducted at two sites, one in France and one in the United States, patients with chronic plaque psoriasis who were candidates for phototherapy received 12-weekly intramuscular injections of Alefacept, 15 mg. In addition, patients were randomized to one of three treatment arms: no UVB treatment, 6-week UVB treatment, and 12-week UVB treatment. UVB treatment consisted of narrowband (NB) UVB at the site in France and broadband (BB) UVB at the site in the United States. The 12-week treatment period was followed by a 12-week follow-up period. Clinic visits occurred weekly during treatment and every 2–4 weeks during follow-up. Results  A total of 60 patients (n = 30/site) were enrolled in the study. Alefacept was well tolerated when administered in combination with UVB treatment and as monotherapy. There was no evidence of increased phototoxicity or photosensitivity with the combination. At each study site, Alefacept/UVB provided a higher overall response rate and led to a more rapid onset of response compared with Alefacept monotherapy. Of patients who achieved ≥ 50% reduction from baseline Psoriasis Area Severity Index (PASI 50) at 2 weeks after the last dose of Alefacept, 75–100% in the combination therapy groups maintained this response throughout follow-up in the absence of further psoriasis therapy. Conclusions  In patients with chronic plaque psoriasis, combination therapy with Alefacept plus short-term (6–12 weeks) UVB treatment is well tolerated with a trend toward greater and more rapid efficacy than Alefacept alone.

Marcel C. Pasch – One of the best experts on this subject based on the ideXlab platform.

  • Therapeutic effects of a 12-week course of Alefacept on nail psoriasis.
    Journal of the European Academy of Dermatology and Venereology, 2006
    Co-Authors: J.e.m. Körver, Annechien M. G. Langewouters, P.c.m. Van De Kerkhof, Marcel C. Pasch
    Abstract:

    BACKGROUND AND OBJECTIVES: Nail psoriasis is a common finding in psoriatic patients and it affects the quality of life in a great proportion of patients. Topical or systemic treatments have limited effectiveness or have a serious toxicity potential. Biologicals such as Alefacept are the most recent treatment modalities for psoriasis. In the present study we evaluated changes in nail pathology in patients with plaque psoriasis and nail involvement during treatment with Alefacept. PATIENTS AND METHODS: Digital photographs from eight patients were produced, which were analysed using the nail psoriasis severity index (NAPSI). A minimal NAPSI of 15 was chosen to divide patients into a moderate to very severe nail psoriasis group and a group with no or mild nail psoriasis. A decrease in NAPSI of at least 25% was considered a significant response to therapy. RESULTS: In the group with at least moderate nail psoriasis, two patients improved, in two patients the nail changes remained unchanged and in one patient the nail pathology was aggravated. The group with no or mild nail psoriasis showed variable results. CONCLUSIONS: Although Alefacept showed some results in treating nail pathology in psoriasis, a more extensive study is required, covering both more patients and a more extensive time period. Furthermore, it would also be clinically relevant to compare the effects of Alefacept on nail psoriasis with other biologicals.

  • Effect of calcipotriol on epidermal cell populations in Alefacept-treated psoriatic lesions.
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2006
    Co-Authors: M.w.f.m. Van Duijnhoven, J.e.m. Körver, Marcel C. Pasch, W.h.p.m. Vissers, P.e.j. Van Erp, I.m.j.j. Van Vlijmen-willems, P.c.m. Van De Kerkhof
    Abstract:

    BACKGROUND AND OBJECTIVES: The effect of the established antipsoriatic treatment with topical calcipotriol (with a maximum of 100 g per week) in addition to systemic treatment with Alefacept, a new biological agent for psoriasis, on epidermal cell populations in the psoriatic lesion was investigated using a combination of the Zenon labelling technique and microscopic image analysis. Epidermal cell populations were measured quantitatively with this sensitive method. PATIENTS/METHODS: Frozen sections of non-treated psoriatic epidermis and psoriatic epidermis treated with either Alefacept intramuscular or Alefacept intramuscular in combination with topical calcipotriol for 12 weeks were compared immunohistochemically. Antibodies against keratin 6, 10 and 15 were labelled with the Zenon technique, whereas antibodies against the Ki-67 antigen and beta-1 integrin were covalently Fluorescein Isothiocyanate (FITC)-labelled. Using image analysis, these markers were measured in the epidermis in a standardized manner. RESULTS AND CONCLUSIONS: Treatment of psoriasis with Alefacept resulted in a good clinical response in several patients and in a normalization of epidermal expression of the immunohistochemical parameters for differentiation and proliferation. The addition of topical calcipotriol resulted in a faster clinical improvement with a similar overall clinical response and a similar response of epidermal cell populations as compared to treatment with Alefacept monotherapy after 12 weeks of treatment. This study also suggests that the appearance of keratin 15 has a predictive value for the duration of remission. It can be concluded that the addition of a low-dose calcipotriol treatment does not contribute to the clinical efficacy of Alefacept, both at the clinical level and with respect to markers for epidermal proliferation and differentiation.

  • Alefacept modifies long-term disease severity and improves the response to other treatments.
    European journal of dermatology : EJD, 2005
    Co-Authors: M.w.f.m. Van Duijnhoven, Marcel C. Pasch, E.m.g.j. De Jong, W. J. Gerritsen, P.c.m. Van De Kerkhof
    Abstract:

    Alefacept treatment has been shown in several multicentre studies to result in prolonged post-treatment remission periods (median duration 241 days). This communication describes the clinical responses of 10 patients to multiple courses of 12 weekly intramuscular injections with Alefacept given in combination with available antipsoriatic treatments. It was shown that in this group of 10 patients with moderate-severe psoriasis, 8 were no longer candidates for any more long-term continuous systemic treatment with methotrexate or acitretin, 7 had no options for UVB/PUVA courses and 8 were not suitable for treatment with cyclosporine. In 5 out of these 10 patients Alefacept had resulted in a considerable long-term improvement with only mild disease expression, which lasted one year or longer. Patients indicated that these responses were outstanding as compared to the troublesome years before. Another patient reported a major improvement in the quality of life by reduction of itch. In two patients Alefacept vastly enhanced the efficacy of dithranol treatment, as compared to previous treatments. Another patient was able to discontinue methotrexate without relapsing during Alefacept, in contrast to severe rebound episodes following discontinuation of methotrexate in the past. The long-term responses of 8 out of the 10 patients described in this report indicate that Alefacept, in the context of individualised care of patients with moderate to severe psoriasis, can have an important contribution. In particular, the long-term response after stopping Alefacept makes this treatment a valuable tool, achieving prolonged disease control in at least some patients with moderate to severe psoriasis.