Safety of systemic agents for the treatment of pediatric psoriasis

Inge M.G.J. Bronckers, Marieke M.B. Seyger, Dennis P. West, Irene Lara-Corrales, Megha Tollefson, Wynnis L. Tom, Marcia Hogeling, Leah Belazarian, Claus Zachariae, Emmanuel Mahé, Elaine Siegfried, Sandra Philipp, Zsuzsanna Szalai, Ruth Ann Vleugels, Kristen Holland, Ruth Murphy, Eulalia Baselga, Kelly Cordoro, Jo Lambert, Alex AlexopoulosUlrich Mrowietz, Wietske Kievit, Amy S. Paller, Psoriasis Investigator Group (PsIG), Pediatric Dermatology Research Alliance, European Working Group on Pediatric Psoriasis (EWGPP)

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE: Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited. OBJECTIVE: To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children. 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. 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. 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; 95% CI, 0.06-0.41; P < .001) or 7 days per week (OR, 0.21; 95% CI, 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 were 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. CONCLUSIONS AND RELEVANCE: Medication-related AEs occur less often with tumor 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.

Original languageEnglish (US)
Pages (from-to)1147-1157
Number of pages11
JournalJAMA Dermatology
Volume153
Issue number11
DOIs
StatePublished - Nov 1 2017

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Psoriasis
Methotrexate
Pediatrics
Safety
Folic Acid
Fumarates
Therapeutics
Tumor Necrosis Factor-alpha
Biological Factors
Cyclosporine
Acitretin
Phototherapy
North America
Transaminases
Registries
Tuberculosis
Obesity
Odds Ratio
Outcome Assessment (Health Care)
Injections

ASJC Scopus subject areas

  • Dermatology

Cite this

Bronckers, I. M. G. J., Seyger, M. M. B., West, D. P., Lara-Corrales, I., Tollefson, M., Tom, W. L., ... European Working Group on Pediatric Psoriasis (EWGPP) (2017). Safety of systemic agents for the treatment of pediatric psoriasis. JAMA Dermatology, 153(11), 1147-1157. https://doi.org/10.1001/jamadermatol.2017.3029

Safety of systemic agents for the treatment of pediatric psoriasis. / Bronckers, Inge M.G.J.; Seyger, Marieke M.B.; West, Dennis P.; Lara-Corrales, Irene; Tollefson, Megha; Tom, Wynnis L.; Hogeling, Marcia; Belazarian, Leah; Zachariae, Claus; Mahé, Emmanuel; Siegfried, Elaine; Philipp, Sandra; Szalai, Zsuzsanna; Vleugels, Ruth Ann; Holland, Kristen; Murphy, Ruth; Baselga, Eulalia; Cordoro, Kelly; Lambert, Jo; Alexopoulos, Alex; Mrowietz, Ulrich; Kievit, Wietske; Paller, Amy S.; Psoriasis Investigator Group (PsIG); Pediatric Dermatology Research Alliance; European Working Group on Pediatric Psoriasis (EWGPP).

In: JAMA Dermatology, Vol. 153, No. 11, 01.11.2017, p. 1147-1157.

Research output: Contribution to journalArticle

Bronckers, IMGJ, Seyger, MMB, West, DP, Lara-Corrales, I, Tollefson, M, Tom, WL, Hogeling, M, Belazarian, L, Zachariae, C, Mahé, 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, Psoriasis Investigator Group (PsIG), Pediatric Dermatology Research Alliance & European Working Group on Pediatric Psoriasis (EWGPP) 2017, 'Safety of systemic agents for the treatment of pediatric psoriasis', JAMA Dermatology, vol. 153, no. 11, pp. 1147-1157. https://doi.org/10.1001/jamadermatol.2017.3029
Bronckers IMGJ, Seyger MMB, West DP, Lara-Corrales I, Tollefson M, Tom WL et al. Safety of systemic agents for the treatment of pediatric psoriasis. JAMA Dermatology. 2017 Nov 1;153(11):1147-1157. https://doi.org/10.1001/jamadermatol.2017.3029
Bronckers, Inge M.G.J. ; Seyger, Marieke M.B. ; West, Dennis P. ; Lara-Corrales, Irene ; Tollefson, Megha ; Tom, Wynnis L. ; Hogeling, Marcia ; Belazarian, Leah ; Zachariae, Claus ; Mahé, Emmanuel ; Siegfried, Elaine ; Philipp, Sandra ; Szalai, Zsuzsanna ; Vleugels, Ruth Ann ; Holland, Kristen ; Murphy, Ruth ; Baselga, Eulalia ; Cordoro, Kelly ; Lambert, Jo ; Alexopoulos, Alex ; Mrowietz, Ulrich ; Kievit, Wietske ; Paller, Amy S. ; Psoriasis Investigator Group (PsIG) ; Pediatric Dermatology Research Alliance ; European Working Group on Pediatric Psoriasis (EWGPP). / Safety of systemic agents for the treatment of pediatric psoriasis. In: JAMA Dermatology. 2017 ; Vol. 153, No. 11. pp. 1147-1157.
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abstract = "IMPORTANCE: Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited. OBJECTIVE: To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children. 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. 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. 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; 95{\%} CI, 0.06-0.41; P < .001) or 7 days per week (OR, 0.21; 95{\%} CI, 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 were 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. CONCLUSIONS AND RELEVANCE: Medication-related AEs occur less often with tumor 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.",
author = "Bronckers, {Inge M.G.J.} and Seyger, {Marieke M.B.} and West, {Dennis P.} and Irene Lara-Corrales and Megha Tollefson and Tom, {Wynnis L.} and Marcia Hogeling and Leah Belazarian and Claus Zachariae and Emmanuel Mah{\'e} and Elaine Siegfried and Sandra Philipp and Zsuzsanna Szalai and Vleugels, {Ruth Ann} and Kristen Holland and Ruth Murphy and Eulalia Baselga and Kelly Cordoro and Jo Lambert and Alex Alexopoulos and Ulrich Mrowietz and Wietske Kievit and Paller, {Amy S.} and {Psoriasis Investigator Group (PsIG)} and {Pediatric Dermatology Research Alliance} and {European Working Group on Pediatric Psoriasis (EWGPP)}",
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T1 - Safety of systemic agents for the treatment of pediatric psoriasis

AU - Bronckers, Inge M.G.J.

AU - Seyger, Marieke M.B.

AU - West, Dennis P.

AU - Lara-Corrales, Irene

AU - Tollefson, Megha

AU - Tom, Wynnis L.

AU - Hogeling, Marcia

AU - Belazarian, Leah

AU - Zachariae, Claus

AU - Mahé, Emmanuel

AU - Siegfried, Elaine

AU - Philipp, Sandra

AU - Szalai, Zsuzsanna

AU - Vleugels, Ruth Ann

AU - Holland, Kristen

AU - Murphy, Ruth

AU - Baselga, Eulalia

AU - Cordoro, Kelly

AU - Lambert, Jo

AU - Alexopoulos, Alex

AU - Mrowietz, Ulrich

AU - Kievit, Wietske

AU - Paller, Amy S.

AU - Psoriasis Investigator Group (PsIG)

AU - Pediatric Dermatology Research Alliance

AU - European Working Group on Pediatric Psoriasis (EWGPP)

PY - 2017/11/1

Y1 - 2017/11/1

N2 - IMPORTANCE: Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited. OBJECTIVE: To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children. 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. 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. 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; 95% CI, 0.06-0.41; P < .001) or 7 days per week (OR, 0.21; 95% CI, 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 were 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. CONCLUSIONS AND RELEVANCE: Medication-related AEs occur less often with tumor 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.

AB - IMPORTANCE: Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited. OBJECTIVE: To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children. 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. 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. 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; 95% CI, 0.06-0.41; P < .001) or 7 days per week (OR, 0.21; 95% CI, 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 were 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. CONCLUSIONS AND RELEVANCE: Medication-related AEs occur less often with tumor 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.

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