Safety of Systemic Agents for the Treatment of Pediatric Psoriasis
Por:
Bronckers, IMGJ, Seyger, MMB, West, DP, Lara-Corrales, I, Tollefson, M, Tom, WL, Hogeling, M, Belazarian, L, Zachariae, C, Mahe, E, Siegfried, E, Philipp, S, Szalai, Z, Vleugels, RA, Holland, K, Murphy, R, Baselga, E, Cordoro, K, Lambert, J, Alexopoulos, A, Mrowietz, U, Kievit, W, Paller, AS, PediataDermatologyaResaAlliance, EuropeanaWorkingaGrpaPediataPsoriasis
Publicada:
1 nov 2017
Resumen:
IMPORTANCE Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited.& para;& para;OBJECTIVE To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children.& para;& para;DESIGN, SETTING, AND PARTICIPANTS A retrospective review was conducted at 20 centers in North America and Europe, and included all consecutive children with moderate to severe psoriasis who used systemic medications or phototherapy for at least 3 months from December 1,1990, to September 16,2014.& para;& para;MAIN OUTCOMES AND MEASURES The minimal core data set included age, sex, severity of psoriasis, systemic interventions, monitoring, adverse events (AEs), and reason for discontinuation.& para;& para;RESULTS For 390 children (203 girls and 187 boys; mean [SD] age at diagnosis, 8.4 [3.7] years) with psoriasis who used 1 or more systemic medications, the mean interval between diagnosis and starting systemic therapy was 3.0 years. Methotrexate was used by 270 patients (69.2 % ), biologic agents (primarily etanercept) by 106 (27.2%), acitretin by 57 (14,6%), cyclosporine by 30 (7.7%), fumaric acid esters by 19 (4.9 % ), and more than 1 medication was used by 73 (18.7%). Of 270 children taking methotrexate, 130 (48.1%) reported 1 or more AEs associated with methotrexate, primarily gastrointestinal (67 [24 ,8%]). Folic acid 6 days per week (odds ratio, 0.16; 9 5 % Cl, 0,06-0.41; P < .001) or 7 days per week (OR, 0.21; 9 5 % Cl, 0.08-0,58; P = .003) protected against gastrointestinal AEs more than once-weekly folic acid, regardless of the total weekly dosage. Methotrexate-associated hepatic transaminase elevations were associated with obesity (35 of 270 patients [13.0%]), but a folic acid regimen was not. Injection site reactions occurred in 20 of 106 patients (18.9%) treated with tumor necrosis factor inhibitors, but did not lead to discontinuation of treatment. Having 1 or more AEs related to medication, gastrointestinal AE, laboratory abnormality, or AE leading to discontinuation of the drug was more likely with methotrexate than tumor necrosis factor inhibitors, but having 1 or more infections related to medication (predominantly upper airway) was less likely. Six patients developed a serious treatment-related AE (methotrexate, 3; fumaric acid esters, 2; and adalimumab, 1), but methotrexate and biologic agents w ere taken for a mean duration that was 2-fold greater than the mean duration for cyclosporine or fumaric acid esters. No patient developed tuberculosis or a malignant neoplasm.& para;& para;CONCLUSIONS AND RELEVANCE Medication-related AEs occur less often with tum or necrosis factor inhibitors than with methotrexate. Folic acid administration 6 or 7 times per week protected more against methotrexate-induced gastrointestinal AEs than did weekly administration. A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis.
Filiaciones:
Bronckers, IMGJ:
Radboud Univ Nijmegen, Dept Dermatol, Nijmegen, Netherlands
Seyger, MMB:
Radboud Univ Nijmegen, Dept Dermatol, Nijmegen, Netherlands
West, DP:
Northwestern Univ, Dept Dermatol, 676 N St Clair,Ste 1600, Chicago, IL 60611 USA
Northwestern Univ, Dept Pediat, Chicago, IL 60611 USA
Lara-Corrales, I:
Univ Toronto, Hosp Sick Children, Dept Pediat Med, Dermatol Sect, Toronto, ON, Canada
Tollefson, M:
Mayo Clin, Dept Dermatol, Rochester, MN USA
Tom, WL:
Univ Calif San Diego, Dept Dermatol, Rady Childrens Hosp San Diego, San Diego, CA 92103 USA
Univ Calif San Diego, Dept Pediat, Rady Childrens Hosp San Diego, San Diego, CA 92103 USA
Hogeling, M:
Phoenix Childrens Hosp, Dept Dermatol, Phoenix, AZ USA
Univ Calif Los Angeles, Dept Dermatol, Los Angeles, CA USA
Belazarian, L:
Univ Massachusetts, Sch Med, Dept Dermatol, Worcester, MA USA
Zachariae, C:
Univ Copenhagen, Herlev Gentofte Hosp, Dept Dermatol & Allergy, Copenhagen, Denmark
Mahe, E:
Hop Victor Dupouy Argenteuil, Dept Dermatol, Argenteuil, France
Siegfried, E:
St Louis Univ, Sch Med, Dept Dermatol, St Louis, MO USA
St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63104 USA
Philipp, S:
Charite, Psoriasis Res & Treatment Ctr, Berlin, Germany
Szalai, Z:
Heim Pal Childrens Hosp, Dept Dermatol, Budapest, Hungary
Vleugels, RA:
Boston Childrens Hosp, Dept Dermatol, Boston, MA USA
Holland, K:
Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA
Med Coll Wisconsin, Dept Pediat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA
Murphy, R:
Nottingham Univ Hosp, Paediat Dermatol Dept, Nottingham, England
Baselga, E:
Hosp Sanat Creu & St Pau, Dept Dermatol, Barcelona, Spain
Cordoro, K:
Univ Calif San Francisco, Dept Dermatol, Med Ctr, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Pediat, Med Ctr, San Francisco, CA USA
Lambert, J:
Ghent Univ Hosp, Dept Dermatol, Ghent, Belgium
Alexopoulos, A:
Univ Athens, Med Sch, Dept Pediat, Agia Sofia Childrens Hosp, Athens, Greece
Mrowietz, U:
Univ Med Ctr Schleswig Holstein, Dept Dermatol, Campus Kiel, Kiel, Germany
Kievit, W:
Radboud Univ Nijmegen, Dept Hlth Evidence, Nijmegen, Netherlands
Paller, AS:
Northwestern Univ, Dept Dermatol, 676 N St Clair,Ste 1600, Chicago, IL 60611 USA
Northwestern Univ, Dept Pediat, Chicago, IL 60611 USA
Green Published
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