From the Journals

TNF inhibitors associated with fewer side effects than methotrexate in children with psoriasis

 

Key clinical point: More frequent administration of folic acid may attenuate the GI-related adverse effects associated with methotrexate therapy in children with psoriasis.

Major finding: Almost half (48.1%) of the children treated with methotrexate experienced one or more treatment-related adverse events, compared with 41 (38.7%) of those treated with a biologic agent (OR, 1.76; P = .03).

Data source: An international, retrospective study of 390 children with moderate to severe psoriasis compared the adverse events associated with different systemic therapies.

Disclosures: The study was supported by a grant from the International Psoriasis Council.


 

FROM JAMA DERMATOLOGY

Treatment with tumor necrosis factor (TNF) inhibitors was associated with fewer adverse events (AEs) than with methotrexate, in an international, retrospective study of children with psoriasis.

“Patients with pediatric psoriasis treated with methotrexate had a greater risk of having one or more AEs than those treated with TNF-I [tumor necrosis factor inhibitors], although fewer AEs occurred with methotrexate or TNF-I than with other drug classes,” Inge M.G.J. Bronckers, MD, of the department of dermatology at Radboud University, Nijmegen, the Netherlands, and his coauthors reported.

A sign says Psoriasis. eenevski/Thinkstock

Among those treated with methotrexate, administration of folic acid six to seven times a week was more protective against methotrexate-associated gastrointestinal AEs, than when administered only once a week. The study was published on Sept. 13 in JAMA Dermatology (2017. doi: 10.1001/jamadermatol.2017.3029).

The study evaluated 390 children with moderate to severe psoriasis, treated with at least one systemic medication at 20 centers in Canada, Europe, and the United States, during December 1990-September 2014. They were diagnosed at a mean age of about 8 years, and started systemic therapy a mean of 3 years later. Of the 390 children treated for psoriasis, 270 were treated with methotrexate and 106 were treated with biologics, most often the TNF inhibitor etanercept. The remaining treatments were acitretin, cyclosporine, and fumaric acid esters; almost 19% were treated with more than one medication.

Of those treated with methotrexate, 130 (48.1%) experienced one or more treatment-related AEs, compared with 41 (38.7%) of those treated with a biologic agent (odds ratio, 1.76; P = .03). Almost 25% of those on methotrexate had GI-related AEs, the most common AE; other AEs included elevated transaminase levels and fatigue. Among those on biologics, injection site reactions were the most common (in 18.9%); 12 patients (11.3%) of those on biologics had infections, primarily airway infections.

Compared with those on a TNF inhibitor, patients on methotrexate were more likely to experience GI-related AEs (OR, 11.49; P less than .001) or to discontinue treatment (OR, 5.69; P = .02), the investigators said. But associated infections were more common with TNF inhibitors (OR, 0.36; P = .03), compared with methotrexate. There were no cases of malignancies or tuberculosis.

Folic acid was prescribed to 239 patients receiving methotrexate in one of three regimens: once weekly; six times weekly, avoiding the methotrexate day; and seven times weekly, according to the investigators. Compared with once-weekly treatment, administration six or seven times weekly was associated with a lower probability of developing a GI-related AE (OR, 0.16; P less than .001; OR, 0.21; P = .003, respectively).

“Data are sparse on the relative use of systemic agents and their toxic effects in the pediatric population,” Dr. Bronckers and his coauthors wrote, adding that standardized guidelines and more data concerning children are needed. “Our data suggest that a weekly administration of folic acid could be replaced with a daily or six times weekly administration to reduce GI AEs, although the potential efficacy of six vs. seven times weekly dosing deserves further investigation,” they concluded.

The study was supported by a grant from the International Psoriasis Council. Of the 23 authors, 11 had financial disclosures with various pharmaceutical manufacturers.

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