Update on Systemic Therapies for Atopic Dermatitis
Methotrexate was originally developed as a safer chemotherapeutic alternative to the folate analog, aminopterin, for the treatment of childhood acute lymphoblastic leukemia. Methotrexate is an antimetabolite that directly competes with dihydrofolic acid for the binding site of dihydrofolate reductase. The resulting decrease in tetrahydrofolate inhibits cellular proliferation by limiting the synthesis of DNA, RNA, and several amino acids. In autoimmune diseases, it appears that methotrexate may also act by suppressing intercellular adhesion molecule-1 (ICAM-1) and cutaneous lymphocyte-associated antigen on T-cells. It has been used to treat malignancy, autoimmune diseases and inflammatory disorders like psoriasis and atopic dermatitis.
Prior to 2011, there had been no randomized controlled trials (RCTs) to demonstrate the efficacy of methotrexate in the treatment of atopic dermatitis. Schram et al. conducted a study of 42 adult atopic dermatitis patients randomized to either methotrexate 10 mg weekly or azathioprine 1.5 mg/kg/day for 12 weeks. Patient dosing was titrated upward until they either achieved 25% reduction in disease activity or reached the maximum dose allowed in the study (22.5 mg/week methotrexate, 2.5 mg/kg/day azathioprine). Following this, patients entered a 12-week follow-up period in which patients and providers were allowed to either continue with their current medication or alter the treatment plan as per normal clinical practice. The two medications performed similarly in a number of disease severity measures including SCORAD, IgE (immunoglobulin E), EASI, and serum TARC both during the initial 12 weeks of treatment and in the 12-week follow-up phase. A significant improvement in SCORAD was observed in both methotrexate (42%) and azathioprine (39%) treated patients at 12 weeks. Methotrexate had a similar side-effect profile to azathioprine with the exception of lymphopenia, which was only observed in azathioprine-treated patients (P = 0.02). These same patients experienced a trend toward more infections (P = 0.19). This study suggests that methotrexate and azathioprine have similar efficacy at the doses tested, but methotrexate may have a slightly more favorable side-effect profile. It would have been nice to see the relative efficacy of these treatments when methotrexate was increased to 25 mg/week – a dose used not uncommonly to achieve clearance in patients with psoriasis.
Methotrexate
Methotrexate was originally developed as a safer chemotherapeutic alternative to the folate analog, aminopterin, for the treatment of childhood acute lymphoblastic leukemia. Methotrexate is an antimetabolite that directly competes with dihydrofolic acid for the binding site of dihydrofolate reductase. The resulting decrease in tetrahydrofolate inhibits cellular proliferation by limiting the synthesis of DNA, RNA, and several amino acids. In autoimmune diseases, it appears that methotrexate may also act by suppressing intercellular adhesion molecule-1 (ICAM-1) and cutaneous lymphocyte-associated antigen on T-cells. It has been used to treat malignancy, autoimmune diseases and inflammatory disorders like psoriasis and atopic dermatitis.
Prior to 2011, there had been no randomized controlled trials (RCTs) to demonstrate the efficacy of methotrexate in the treatment of atopic dermatitis. Schram et al. conducted a study of 42 adult atopic dermatitis patients randomized to either methotrexate 10 mg weekly or azathioprine 1.5 mg/kg/day for 12 weeks. Patient dosing was titrated upward until they either achieved 25% reduction in disease activity or reached the maximum dose allowed in the study (22.5 mg/week methotrexate, 2.5 mg/kg/day azathioprine). Following this, patients entered a 12-week follow-up period in which patients and providers were allowed to either continue with their current medication or alter the treatment plan as per normal clinical practice. The two medications performed similarly in a number of disease severity measures including SCORAD, IgE (immunoglobulin E), EASI, and serum TARC both during the initial 12 weeks of treatment and in the 12-week follow-up phase. A significant improvement in SCORAD was observed in both methotrexate (42%) and azathioprine (39%) treated patients at 12 weeks. Methotrexate had a similar side-effect profile to azathioprine with the exception of lymphopenia, which was only observed in azathioprine-treated patients (P = 0.02). These same patients experienced a trend toward more infections (P = 0.19). This study suggests that methotrexate and azathioprine have similar efficacy at the doses tested, but methotrexate may have a slightly more favorable side-effect profile. It would have been nice to see the relative efficacy of these treatments when methotrexate was increased to 25 mg/week – a dose used not uncommonly to achieve clearance in patients with psoriasis.