EblueprintOff-label uses of biologics in dermatology: Rituximab, omalizumab, infliximab, etanercept, adalimumab, efalizumab, and alefacept (Part 2 of 2)
Section snippets
Rituximab
Rituximab is a chimeric murine-human monoclonal antibody to CD20, which induces depletion of B cells in vivo.1 In 1997, rituximab became the first monoclonal antibody approved for treatment of malignancy. It is currently approved for the treatment of relapsed or refractory, low-grade or follicular, CD20+ B-cell lymphoma.2
CD20 is a B-cell–specific antigen expressed on the surface of B lymphocytes throughout differentiation from the pre-B cell to the mature B-cell stage, but not on plasma cells
Omalizumab
Omalizumab is a humanized recombinant monoclonal antibody that blocks the high-affinity Fc receptor of immunoglobulin E (IgE). Omalizumab reduces serum levels of IgE and blocks the attachment of IgE to mast cells and other immune cells, thereby preventing IgE-mediated inflammatory changes. Omalizumab is approved for the treatment of moderate to severe persistent asthma in adults and adolescents older than 12 years of age who have a positive skin test to a perennial allergen. Omalizumab has also
A review of TNF-α antagonist therapy
TNF-α is a proinflammatory cytokine released by macrophages, monocytes, and T lymphocytes as well as many tissue-specific cell types including keratinocytes and dendritic cells. It exists in both membrane-bound and soluble forms. TNF-α is known to promote inflammation by activation of nuclear factor kappa B, induction of IL-1, IL-6, and IL-8, and up-regulation of adhesion molecules produced by endothelial cells, resulting in increased leukocyte extravasation and migration.86, 87, 88 Currently,
Efalizumab
Efalizumab (Raptiva) is a humanized monoclonal antibody that binds the CD11a subunit of leukocyte function-associated antigen type 1 (LFA-1). LFA-1 is a T-cell surface molecule and intracellular adhesion molecule 1 (ICAM-1) is its partner molecule. The interaction between LFA-1 and ICAM-1 is important for many normal T-cell functions. By binding to CD11a, efalizumab reversibly blocks the interaction between LFA-1 and ICAM-1, thereby interfering with T-cell activation, T-cell migration into the
Alefacept
Alefacept (Amevive) is a recombinant dimeric fusion protein that consists of the extracellular CD2-binding portion of the LFA-3 linked to the Fc (hinge, CH2 and CH3 domains) portion of human IgG1. Alefacept binds to CD2 on memory-effector T lymphocytes, thereby inhibiting the activation and reducing the number of these cells.
Alefacept is approved for the treatment of moderate to severe plaque psoriasis, and the recommended regimen is a course of 12 weekly 15-mg intramuscular injections. The
Conclusion
Biologic immunomodulators have demonstrated efficacy in the treatment of several dermatologic diseases. When choosing a biologic therapy, it is important to consider the mechanism of action of the drug in the context of the pathophysiology of the disease as well as the medical history of the patient. Cost is another important factor, with many biologic immunomodulators costing between $10,000 and $50,000 annually. Because the safety profile of these medications appears to be much more favorable
References (314)
- et al.
Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20
Blood
(1994) - et al.
IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma
Blood
(1997) - et al.
Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma
Blood
(1994) - et al.
Long-term complete remission of severe pemphigus vulgaris with monoclonal anti-CD20 antibody therapy and immunophenotype correlations
J Am Acad Dermatol
(2004) Therapy of refractory pemphigus vulgaris with monoclonal anti-CD20 antibody (rituximab)
J Am Acad Dermatol
(2004)- et al.
Treatment of primary cutaneous B-cell lymphoma with rituximab
J Am Acad Dermatol
(2005) - et al.
CD20-negative relapse of cutaneous B-cell lymphoma after anti-CD20 monoclonal antibody therapy
J Am Acad Dermatol
(2002) - et al.
Systemic therapy with cyclophosphamide and anti-CD20 antibody (rituximab) in relapsed primary cutaneous B-cell lymphoma: a report of 7 cases
J Am Acad Dermatol
(2003) - et al.
Large B-cell lymphoma of the leg: clinical and pathologic characteristics in a North American series
J Am Acad Dermatol
(2003) - et al.
Polymyositis and dermatomyositis
Lancet
(2003)
Rituximab for steroid-refractory chronic graft-vs.-host disease
Blood
Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease
Blood
Treatment of chronic graft-versus-host disease with anti-CD20 chimeric monoclonal antibody
Biol Blood Marrow Transplant
Update on graft versus host disease
J Invest Dermatol
Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission
Blood
Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors
Blood
Effect of omalizumab in health care workers with occupational latex allergy
J Allergy Clin Immunol
Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma
J Allergy Clin Immunol
Evaluation of long-term safety of the anti-IgE antibody, omalizumab, in children with allergic asthma
Ann Allergy Asthma Immunol
Omalizumab is effective in the long-term control of severe allergic asthma
Ann Allergy Asthma Immunol
Omalizumab and the immune system: an overview of preclinical and clinical data
Ann Allergy Asthma Immunol
Failure of omalizumab for treatment of severe adult atopic dermatitis
J Am Acad Dermatol
Treatment of recalcitrant atopic dermatitis with omalizumab
J Am Acad Dermatol
Drug-induced systemic lupus erythematosus and TNF-alpha blockers
Lancet
Psoriasis and its treatment with infliximab-mediated tumor necrosis factor alpha blockade
Dermatol Clin
The treatment of psoriasis and psoriatic arthritis with etanercept: practical considerations on monotherapy, combination therapy, and safety
Dermatol Clin
Rituximab: an insider's historical perspective
Semin Oncol
Characterization of a human B lymphocyte-specific antigen
J Immunol
Rituximab: mechanisms and applications
Br J Cancer
Empowering targeted therapy: lessons from rituximab
Sci STKE
Safety of rituximab in the treatment of B cell malignancies: implications for rheumatoid arthritis
Arthritis Res Ther
The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial
Arthritis Rheum
Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program
J Clin Oncol
B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab
Arthritis Rheum
B cells as therapeutic targets for rheumatic diseases
Curr Opin Rheumatol
Rituximab therapy and autoimmune disorders: prospects for anti-B cell therapy
Arthritis Rheum
Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis
N Engl J Med
Anti-CD20 chimeric monoclonal antibody (rituximab) for the treatment of recalcitrant, life-threatening pemphigus vulgaris with implications in the pathogenesis of the disorder
J Am Acad Dermatol
Treatment of refractory pemphigus vulgaris with rituximab (anti-CD20 monoclonal antibody)
Arch Dermatol
Rapid response of treatment-resistant pemphigus foliaceus to the anti-CD20 antibody rituximab
Br J Dermatol
Treatment of pemphigus vulgaris with anti-CD20 monoclonal antibody (rituximab)
Br J Dermatol
Treatment of resistant pemphigus vulgaris with an anti-CD20 monoclonal antibody (Rituximab)
Clin Exp Dermatol
Anti-CD20 monoclonal antibody (rituximab) in the treatment of autoimmune diseases. Successful result in refractory pemphigus vulgaris: report of a case
Haematologica
Anti-CD20 monoclonal antibody (rituximab) in the treatment of pemphigus
Br J Dermatol
Response of pemphigus vulgaris to anti-CD20 antibody therapy (rituximab) may be delayed
Clin Exp Dermatol
Long-lasting remission of pemphigus vulgaris treated with rituximab
Acta Derm Venereol
Successful treatment of refractory childhood pemphigus vulgaris with anti-CD20 monoclonal antibody (rituximab)
Pediatr Dermatol
Delayed response of oral pemphigus vulgaris to rituximab treatment
Eur J Dermatol
Long-standing remission of recalcitrant juvenile pemphigus vulgaris after adjuvant therapy with rituximab
Br J Dermatol
Successful rituximab treatment of severe pemphigus vulgaris resistant to multiple immunosuppressants
Acta Derm Venereol
Cited by (0)
Funding sources: None.
Disclosure: Dr Heffernan has been a paid investigator, lecturer and/or consultant for Abbott, Amgen, Biogen-IDEC, Centocor and Genentech. Drs Heffernan and Graves have been active in industry-sponsored research.
Presented at the 63rd Annual Meeting of the American Academy of Dermatology, New Orleans, Louisianna, February 18-22, 2005.