Amevive (alefacept) / Astellas - LARVOL DELTA

Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes. (PubMed, J Immunol) - "The persistent increase of TIGIT+PD1+ effector memory CD4 T cells was specific to alefacept treatment; 2 other T cell depleting therapies, teplizumab and anti-thymocyte globulin, induced only a transient increase in this CD4 population. Our data suggest that the expanding TIGIT+PD1+ effector memory CD4 T cell population represents a promising biomarker of early treatment effects of alefacept. The nondepleting effects on proliferation and cytokine production also suggest agonistic activity by this CD2 targeted therapy."

IO biomarker • Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD2 • CD4 • CD58 • CD8 • PD-1 • TIGIT

A systematic review of case series and clinical trials investigating systemic oral or injectable therapies for the treatment of vitiligo (EADV 2024) - "Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness."

Clinical • Review • Dermatology • Immunology • Vitiligo

The Dermatology Life Quality Index (DLQI) as the Primary Outcome in Randomised Clinical Trials: A systematic review. (PubMed, Br J Dermatol) - "This study provides evidence for use of the DLQI as primary outcome in clinical trials to inform researchers' and clinicians' decisions for its further use."

Journal • Review • Dermatology

CD2-high Auto-reactive, but Not Viral-reactive, Memory CD8 T Cell Repopulation Is Hampered Following LFA3-Ig Depletion (FOCIS 2024) - "This lack of rebound among CD2-high islet-specific Tmem did not associate with clinical response, nor did it appear to be due to a natural decline over time as determined by comparison to placebo data. Together, these data suggest that islet-specific CD8 T cells are enriched for a Helios+ CD2-low Tmem subset that is not depleted by alefacept but also does not preferentially expand following treatment."

Clinical • Immunology • B3GAT1 • CD2 • CD58 • CD8

Agonistic Effect of Alefacept on TIGIT+PD1+ Effector Memory CD4 T Cells in New-onset Type 1 Diabetes (FOCIS 2024) - "Thus, anti-CD2 therapy led to expanded PD1+TIGIT+ CD4 TEM concurrent with reduced functionality. These findings indicate that alefacept had an agonistic effect and suggest that PD1+TIGIT+ CD4 TEM may represent an early biomarker of treatment with alefacept."

IO biomarker • Immunology • CD4 • CD58 • CD8 • PD-1 • TIGIT

A systematic review of case series and clinical trials investigating systemic oral or injectable therapies for the treatment of vitiligo. (PubMed, Skin Res Technol) - "Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness."

Journal • Review • Dermatology • Immunology • Vitiligo

Immune therapy – Predicting responders/non-responders (ATTD 2024) - "However, several post-hoc responder phenotypes have been seen in clinical trials using teplizumab, alefacept, anti-thymocyte globulin and more. While more robust responder phenotypes are seen post-treatment, we are beginning to test ways to turn these into 'predictive' responder signatures using in vitro testing. Thus, responder analyses are vital for the development of precision-directed enrollment criteria in clinical trials and are needed to move the field forward with haste."

Diabetes • Infectious Disease • Metabolic Disorders • Type 1 Diabetes Mellitus

Proinflammatory islet antigen reactive CD4 T cells are linked with response to alefacept in type 1 diabetes. (PubMed, JCI Insight) - "Cluster 3 cells had a proinflammatory phenotype characterized by expression of the transcription factor BHLHE40 and the cytokines GM-CSF and TNF-α, and shared TCR chains with effector memory-like clusters. Our results suggest IAR CD4 T cells as a potential baseline biomarker of response to therapies targeting the CD2 pathway and warrant investigation for other T cell-related therapies."

IO biomarker • Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD2 • CD4 • CD58 • CSF2 • TNFA

Dimethyl Fumarate in Psoriasis (EADV 2023) - "CD2 is reported to stimulate Naïve T cells via keratinocytes (Orlik et al., 2020) and is a target for a biologic (Alefacept), which reduces infiltrating T cells while activating dendritic cells and inflammatory genes (Chamian et al., 2005)... Gene expression changes significantly from baseline by week 4 in patients taking DMF, with pathways relevant to the pathogenesis of psoriasis being dis-regulated. Preliminary data also indicate patients who achieve a higher level of response may have reduced CXCR3 at week 24 although this will require validation. Future analysis will be able to compare these signals in skin and blood and perform a multiomic assessment of response layering in analyses of DNA and the proteome."

IO biomarker • Dermatology • Immunology • Oncology • Psoriasis • CCL23 • CD2 • CXCR3 • GZMK • IDO1 • KIF5C • PI3K • STAT3 • TFF3

The Dermatology Life Quality Index(DLQI): Primary Endpoint in Clinical trials -A paradigm shift! (EADV 2023) - "Most drug interventions (17/25, 68.0%) were systemic of which 5/25 (20.0%) were biologics (liraglutide, alefacept, secukinumab, ustekinumab, adalimumab). Data on ethnicity should be recorded in all future trials involving patients.This study provides evidence of the use of DLQI as a primary endpoint in RCTs: this recent development indicates acceptance of the appropriateness of PROMs as primary outcome measures, and informs and reassures researchers and clinicians over further similar use."

Clinical • Dermatology

Enrichment of PD-1+TIGIT+ CD4 effector memory cells after Alefacept treatment in Type 1 Diabetes (FOCIS 2023) - No abstract available

Immunology • CD4 • PD-1 • TIGIT

Interconnected Differentiation Trajectories of Exhausted and NK-like CD8+ T Cells Linked to Alefacept Therapy in Type 1 Diabetes (FOCIS 2023) - No abstract available

Immunology

Review of natural compounds for potential psoriasis treatment. (PubMed, Inflammopharmacology) - "Alefacept, efalizumab, Adalimumab, Ustekinumab, and Secukinumab are a few examples of chemical drugs. Its rapidly progressive infection of the central nervous system caused by the JC virus and other drugs may cause increased production of neutralising anti-drug antibodies (ADA) and the risk of infusion reactions like pruritus, flushing, hypertension, headache, and rash. So, our context intends to talk in our review about natural products or plants that may have therapeutic characteristics for this disease and may have few or no side effects on the patient's body."

Journal • Review • Cardiovascular • CNS Disorders • Dermatology • Hypertension • Immunology • Infectious Disease • Inflammation • Pain • Pruritus • Psoriasis • Rare Diseases • IL12A • IL17A • IL23A

Biologics Can Significantly Improve Dermatology Life Quality Index (DLQI) in Psoriatic Patients: A Systematic Review. (PubMed, Psoriasis (Auckl)) - "Adalimumab, alefacept, etanercept, infliximab, ustekinumab and secukinumab were included biologics. Quality of life of psoriatic patients will be improved by the studied biologics. In the future, more research is needed into biologics on patient and quality of life characteristics."

Journal • Review • Dermatology • Immunology • Psoriasis

Differential therapeutic modulation of exhaustion among autoreactive and global CD8 T cells in type 1 diabetes (T1D) (IMMUNOLOGY 2022) - "We assessed PBMCs from select T1D subjects who had variable preservation of pancreatic function two years after treatment with teplizumab (anti-CD3, n=7) or alefacept (LFA3-Ig, n=12). Overall, increases in islet-specific TEX were rarely detected in poor responders (1 of 8 subjects with detectable islet-specific cells) consistent with a lack of change in global TEX, However, in subjects with better preservation of beta cell function, islet-specific TEX increased in fewer subjects (2 of 6) than global CD8 T cells (4 of 8). Together these results indicate that islet-specific CD8 T cells only partially mirror global CD8 responses, and further research is needed to clarify the role of exhaustion and its relation to autoreactive T cells in determining outcome in therapeutic settings."

Clinical • IO biomarker • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD58 • CD8 • KLRG1 • PD-1 • TIGIT

Construction of miRNA-regulated drug-pathway network to screen drug repurposing candidates for multiple sclerosis. (PubMed, Medicine (Baltimore)) - "We analyzed the properties of the miRNA-regulated drug-pathway network through genes and uncovered a number of novel MS agents by assessing their respective Z-values.A total of 20 likely drug candidates were identified, including human immunoglobulin, aspirin, alemtuzumab, minocycline, abciximab, alefacept, palivizumab, bevacizumab, efalizumab, tositumomab, minocycline, etanercept, catumaxomab, and sarilumab. Each of these agents were then explored with regards to their likely mechanism of action in treating MS.The current investigation provides a fresh perspective on MS biological mechanisms as well as likely treatment strategies."

Journal • CNS Disorders • Multiple Sclerosis

Cost-Effectiveness of Low-dose Antithymocyte Globulin versus Other Immunotherapies for Treatment of New-Onset Type 1 Diabetes. (PubMed, Diabetes Technol Ther) - "Low-dose ATG treatment is both less costly and more effective relative to other immunotherapies and no treatment for new-onset type 1 diabetes."

HEOR • Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Risk of herpes zoster associated with biological therapies for psoriasis and psoriatic arthritis: A systematic review and meta-analysis. (PubMed, Medicine (Baltimore)) - "Few RCTs have reported HZ incidents; thus, our results require confirmation via large-scale RCTs."

Journal • Retrospective data • Review • Dermatology • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Oncology • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Varicella Zoster

"دوز و مقدار داروی Alefacept ، از فردی به فرد دیگر متفاوت است؛ دارو را دقیقاً همانطور که پزشک برایتان تجویز کرده است، استفاده نمایید. دوز این دارو بر اساس وضعیت بیمار تجویز می‌شود.امید است که این دارو زود تر موجود شود@merck" (@darudarman)

Risk of Herpes Zoster Among Psoriasis Patients Taking Biologics: A Network Meta-Analysis of Cohort Studies. (PubMed, Front Med (Lausanne)) - "We included studies referred to seven biologics (adalimumab, alefacept, efalizumab, etanercept, infliximab, rituximab, and ustekinumab) as well as methotrexate for psoriasis. Of note, the negative findings of our study do not mean the unnecessity of vaccination. More efforts must be taken to further determine HZ risk of different therapeutic strategies."

Retrospective data • Review • Dermatology • Herpes Zoster • Immunology • Infectious Disease • Psoriasis • Varicella Zoster

[VIRTUAL] Do Global Changes Induced by T Cell-targeted Therapies Reflect Alterations in the Antigen-specific CD8 T Cell Compartment? a Preliminary Report of T1D Autoantigen Response Profiles in Two Completed Clinical Trials (FOCIS 2021) - "Immune phenotyping studies during clinical trials in recent-onset type 1 diabetes have identified CD8 T-cell exhaustion profiles that correlate with better clinical outcomes in subjects who received teplizumab or alefacept therapy, targeting CD3 or CD2, respectively...When changes in these exhaustion profiles among the total CD8 T cell population were compared with islet-specific subsets for each individual, we observed a frequent lack of concordance following therapy, although this result is limited by small numbers of subjects and cells available for study. These data illustrate the need for caution in extrapolating from global profiling to the antigen-specific fraction of cell populations."

Clinical • IO biomarker • Immunology • CD2 • CD57 • CD8 • PD-1 • TIGIT

Safety and Pharmacokinetics (PK) of Alefacept in Adolescent Subjects With Moderate to Severe Psoriasis (clinicaltrials.gov) - P2; N=30; Completed; Sponsor: Astellas Pharma Inc; Active, not recruiting ➔ Completed

Clinical • Trial completion • Dermatology • Immunology • Psoriasis • CD4

Safety and Pharmacokinetics (PK) of Alefacept in Adolescent Subjects With Moderate to Severe Psoriasis (clinicaltrials.gov) - P2; N=30; Completed; Sponsor: Astellas Pharma Inc; N=50 ➔ 30

Clinical • Enrollment change • Dermatology • Immunology • Psoriasis • CD4

"دوز و مقدار داروی Alefacept ، از فردی به فرد دیگر متفاوت است؛ دارو را دقیقاً همانطور که پزشک برایتان تجویز کرده است، استفاده نمایید. دوز این دارو بر اساس وضعیت بیمار تجویز می‌شود.@merck #stopanimaltesting" (@sait11859965)

Exhausted-like CD8 T cell phenotypes linked to C-peptide preservation in alefacept-treated T1D subjects. (PubMed, JCI Insight) - "The populations were distinguished by reciprocal expression of CD8 T and NK cell markers (GZMB, CD57 and inhibitory KIR genes), versus T cell activation and differentiation markers (PD1 and CD28). These findings support previous evidence linking exhausted CD8 T cells to successful immune interventions for T1D, while suggesting multiple inhibitory mechanisms can promote this beneficial cell state."

Clinical • IO Biomarker • Journal • Cognitive Disorders • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus • CD57 • CD8 • GZMB • PD-1 • TIGIT