SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.
Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.
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Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.
To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.
Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).
Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.
Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).
Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.
The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.
The International Psoriasis Council funded the study. The investigators did not list disclosures.