How safe are various systemic therapies for pediatric psoriasis?

Reuters Health Information: How safe are various systemic therapies for pediatric psoriasis?

How safe are various systemic therapies for pediatric psoriasis?

Last Updated: 2017-09-22

By Marilynn Larkin

NEW YORK (Reuters Health) - For children with psoriasis, adverse events (AEs) occur less frequently with tumor necrosis factor (TNF) inhibitors than with methotrexate, but appropriate folic acid administration may mitigate the latter's gastrointestinal effects, researchers suggest.

"Our understanding of the immune changes in skin that lead to psoriasis has been increasing, and has led to a number of more 'targeted' therapies for individuals affected by moderate-to-severe psoriasis," Dr. Amy Paller of Northwestern University, in Chicago, told Reuters Health.

"Most of these (targeted therapies) are currently available for adults, but not yet for children," she said by email.

To investigate patterns of use and the relative risks of systemic agents for pediatric psoriasis, Dr. Paller and colleagues reviewed data from 20 centers in North America and Europe on children with moderate-to-severe disease who used systemic medications for at least three months from 1990 to 2014.

As reported in JAMA Dermatology, online September 13, the analysis included 203 girls and 187 boys with a mean age of 8.4 years at psoriasis diagnosis. The mean interval between diagnosis and starting systemic therapy was three years.

Methotrexate was taken by about 69% of children, biologic agents (mainly etanercept) by 27%; acitretin by 15%; cyclosporine by 8%; and fumaric acid esters by 5%. About 19% of children used more than one medication.

Close to half (48.1%) of children reported one or more AEs associated with methotrexate, mainly gastrointestinal (24.8%). Taking folic acid six days per week (odds ratio, 0.16) or every day (OR, 0.21) protected against gastrointestinal AEs more than once-weekly folic acid, regardless of the total weekly dosage. Dr. Paller noted that this finding is changing practice in Europe, where clinicians commonly administered folic acid weekly.

Methotrexate-associated hepatic transaminase elevations were associated with obesity (in 13% of children), but folic acid was not.

About 19% of children treated with TNF inhibitors had injection-site reactions, but those did not lead to discontinuation of treatment.

Children taking methotrexate were more likely than those taking TNF inhibitors to have one or more AEs related to medication, a gastrointestinal AE, a laboratory abnormality, or an AE leading to drug discontinuation; however, the methotrexate users were less likely to report a medication-related upper airway infection.

Three children on methotrexate, two on fumaric acid esters, and one on adalimumab had a serious treatment-related AE; however, the mean duration of using methotrexate or biologic agents was double that for cyclosporine or fumaric acid esters.

No children developed tuberculosis or a malignant neoplasm.

Since the study ended, Dr. Paller said, the first TNF inhibitor (etanercept) was approved for use in children ages 4 or older in the U.S.

In Europe, she added, etanercept was approved for pediatric psoriasis during the study, and both adalimumab and the IL-12/IL-23 inhibitor ustekinumab have since been approved.

"Per the results of this study," she said, "both methotrexate and TNF inhibitors appear to be safe for the majority of children."

"Given that we do not want to keep children on methotrexate for more than a few years because of concerns of greater toxicity with long-term use," Dr. Paller continued, "having alternatives - primarily the biologics - is very important."

"In addition," she noted, "there is emerging evidence that TNF inhibitors may be superior in efficacy and work faster than methotrexate."

However, she pointed out, the overall cost of a biologic is far greater than for methotrexate - even including the cost of regular methotrexate laboratory monitoring, "which is another consideration for families."

Dr. Adnan Mir, a pediatric dermatologist at Children's Health and assistant professor at UT Southwestern in Dallas, Texas, commented, "The decision to treat a child with a long-term, potentially dangerous medication is never taken lightly."

"While we try to treat children with psoriasis topically if possible, kids with severe disease often require systemic medications to improve their lives," he said in an email to Reuters Health.

"Methotrexate has been around for over 70 years and has a very well-known side effect profile, and so many dermatologists use this as their first choice in children. The authors show that newer classes of drugs may actually come with fewer side effects."

"We already know that some of these drugs - which are frequently used by pediatric rheumatologists, gastroenterologists, and other specialists - may be more effective than methotrexate in psoriasis, and so we might start seeing a shift in management strategy in the near future," he concluded.

Many of the study authors received fees from industry, including some companies that produce anti-TNF drugs.

SOURCE: http://bit.ly/2fBwyin

JAMA Dermatol 2017.

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