Treatment of recalcitrant atopic dermatitis with omalizumab

Journal of Drugs in Dermatology, March, 2006 by Frank Victor

Treatment of Recalcitrant Atopic Dermatitis with Omalizumab.

Lane JE, MD, et al. Journal of the American Academy of Dermatology. 2006;54:68-72.

Summary

The authors present a case series of 3 patients with recalcitrant atopic dermatitis treated with omalizumab in an effort to evaluate its efficacy and safety in this patient population. For all patients, administration

of omalizumab occurred every 2 weeks. Treatment duration for all patients was 22 weeks. Patient one was a 10-year-old African-American female with atopic dermatitis recalcitrant to emollients, topical corticosteroids, topical tacrolimus, nonsedating and sedating antihistamines, systemic corticosteroids, leukotriene inhibitors, and oyclosporine. Serum IgE level was 1990 IU/mL. Treatment with omalizumab commenced at a dose of 300 mg subcutaneously. At 4 weeks, the dosage was increased to 450 mg and remained there for the duration of treatment. Concurrent medications included trimethoprim-sulfamethoxazole, triamcinolone and tacrolimus ointments, hydroxyzine, and montelukast. During the first 2 weeks of treatment with omalizumab, the patient improved significantly and continued to improve.

Patient 2 was a 13-year-old Caucasian male with atopic dermatitis for 11 years, comprising a body surface area of 80% at initial evaluation. Prior therapies included all of those used in patient one. Serum IgE level was 6120 IU/mL. Treatment with omalizumab began at a dose of 150 mg subcutaneously. At 4 weeks, the dose was increased to 300 mg. The dose was further increased to 450 mg at week 6 and remained there for the duration of treatment. Concurrent medications included trimethoprim-sulfamethoxazole, triamcinolone and tacrolimus ointments, hydroxyzine, cetirizine, and montelukast. The patient was noted to have a 50% improvement by the physician global assessment after the fourth treatment and continued to improve.

Patient 3 was a 12-year-old Caucasian male with chronic atopic dermatitis, also with an affected body surface area of 80% at initial evaluation. Prior therapies included oral corticosteroids. Serum IgE level was 2890 IU/mL. After initiating treatment with hydroxyzine, montelukast, and topical tacrolimus, and achieving only mild improvement, treatment with omalizumab began at 150 mg subcutaneously. At 8 weeks, the dose was increased to 300 mg subcutaneously. For the remainder of the treatment period a dose of 150 mg or 300 mg was given subcutaneously every 2 weeks, determined by the severity of the patient's disease. Concurrent medications included hydroxyzine, montelukast, and topical tacrolimus. The patient experienced marked improvement. No laboratory abnormalities were noted in any of the patients throughout the treatment period.

Comment

The authors present a series of 3 patients with recalcitrant atopic dermatitis treated with omalizumab. Omalizumab is humanized, recombinant, monoclonal antibody to IgE. Omalizumab has been shown to reduce serum levels of IgE by binding to free IgE. (1) Omalizumab binds IgE at the same site where the Fc[epsilon]RI does. Fc[epsilon]RI is the high affinity receptor for IgE and is expressed on mast cells as well as mononuclear antigen-presenting cells including Langerhans' cells, dermal dendritic cells, and macrophages. (2) In vivo studies of this receptor have shown that antigen-presenting cells can generate an allergen-specific T-cell response 100 to 1,000 times greater when IgE is bound to this receptor compared to when IgE is not bound to it, supporting the biologic potency of this receptor in the inflammatory cascade. (2) Although other IgE receptors are known, experiments have shown Fc[epsilon]RI is responsible for the cellular binding of IgE. (3) In addition to decreasing serum IgE levels, omalizumab has been shown to down-regulate expression of Fc[epsilon]RI on basophils. (1)

Given omalizumab's efficacy in treating asthma as well as its ability to decrease serum IgE and down-regulate Fc[epsilon]RI expression, it might be efficacious in treating other atopic diatheses such as atopic dermatitis. While the above 3 patients all were noted to have had improvement in their disease, other reports have not been as encouraging.

Krathen et al reported 3 cases of severe adult atopic dermatitis treated with omalizumab. (4) Patients included 2 males, ages 34 and 48, and one female, age 36. Patients were described as having "chronic severe lichenified" atopic dermatitis. Patients had serum IgE levels of 23,000 IU/mL, 5,440 IU/mL, and 24,400 IU/mL, respectively. All had failed to control their disease with prior therapies including topical and oral corticosteroids. In one patient, prior treatments included azathioprine, mycophenolate mofetil, thalidomide, and methotrexate. Despite subcutaneous injection of 450 mg of omalizumab every other week for 4 months, no improvement was noted in any of the patients. The difference in efficacy of omalizumab between these 2 case series may be due to several variables.

The case series of Lane et al treated younger patients who presumably, given their age, had less chronicity of disease than those patients treated by Krathen et al. This difference uncovers 2 variables. First, one would assume that the younger patients weigh less than the adult patients. As the dosage of omalizumab is partly based on the patient's weight, it is possible that the adult patients who failed treatment received a smaller dose of drug than that needed to have an effect. In addition, as the dosage of omalizumab is also based on the serum IgE level, it is again possible that the adult patients received too little drug, given 2 of the 3 patients had serum IgE levels exceeding 20,000 IU/mL.