Biologic Drug Survival in Pediatric Psoriasis: A Retro-Prospective Observational Study

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Abstract

Background. Irrational selection of biological therapy leads to its inefficiency and early cancellation, aggravating the course of psoriasis and worsening the quality of life, which has negative socio-economic consequences associated with the cost of initiating and providing the patient with a new biological agent. Currently there are no clearly defined strategies and unified protocols for therapeutic tactics regarding the choice and switching of biological drugs in children with psoriasis, which requires research aimed at studying the survival of biological therapy in order to draw up evidence-based recommendations with a high evidence base. Aims — study aims to determine survival rate and significant predictors of biological therapy discontinuation. Methods. A retro-prospective observational study was conducted, which included patients with psoriasis vulgaris, aged 4 to 18 years, who had previously received or needed biological therapy. The data of patients over an 8-year period (from 2015 to 2023) were analyzed. Follow-up was performed from initiation to discontinuation of biological therapy, in cases where outcomes were unknown data was censored. Analysis of therapy survival was carried out using the Kaplan–Meier method with curve construction, the assessment of intergroup differences was carried out using a log rank test. Identification of significant predictors of biological therapy discontinuation was carried out using the Cox multivariate regression method. Results. 430 cases of biological therapy were selected from patients with psoriasis vulgaris aged 5 to 18 years. The highest survival rate of biological therapy was obtained for ustekinumab — 54.9 months, the lowest values — for etanercept (26.7 months). The survival values of adalimumab — 33.9 months and secukinumab — 34.5 months did not statistically significantly differ from each other (p = 0.387). Predictors of early discontinuation of biological therapy were established: presence of a burdened family history (HR = 3.861, p = 0.006); delayed prescription of biological therapy — > 2 years from the date of diagnosis (HR = 1.447, p = 0.045); long-term (> 6 months) use of methotrexate (HR = 3.085, p < 0.001) or cyclosporine (HR = 4.538, p < 0.001) previous to the biological treatment; the presence of comorbidity (inflammatory bowel diseases (HR = 4.938, p = 0.001), metabolic syndrome (HR = 3.947, p < 0.001) or psoriatic arthritis (HR = 2.337, p < 0.001). Conclusions. Proved the inexpediency of long-term immunosuppressive treatment with non-biological drugs and the need for early prescription of biological therapy. In the presence of a burdened family history and disease duration > 2 years since the diagnosis of psoriasis, ustekinumab or secukinumab are recommended as first-line biological therapy in children, the use of which is also associated with a longer duration of treatment and a lower risk of developing adverse events in patient with metabolic syndrome. In active Crohn’s disease, adalimumab is most recommended, followed by a possible switch to ustekinumab. Secukinumab is the drug of choice for patients diagnosed with psoriatic arthritis.

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About the authors

Nikolay N. Murashkin

National Medical Research Center of Children’s Health; I.M. Sechenov First Moscow State Medical University (Sechenov University); Central State Medical Academy of Department of Presidential Affairs

Author for correspondence.
Email: m_nn2001@mail.ru
ORCID iD: 0000-0003-2252-8570
SPIN-code: 5906-9724

MD, PhD, Professor

Россия, Moscow; Moscow; Moscow

Roman A. Ivanov

National Medical Research Center of Children’s Health; Central State Medical Academy of Department of Presidential Affairs

Email: isxiks@gmail.com
ORCID iD: 0000-0002-0081-0981
SPIN-code: 5423-8683

MD

Россия, Moscow; Moscow

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Supplementary files

Supplementary Files
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2. Fig.1. Flowchart of the selection process for cases receiving genetically engineered biological therapy. Note. GEBT - genetic engineering biological therapy; GIBP is a genetically engineered biological drug.

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3. Fig.2. Kaplan–Meier survival curves of genetically engineered biological therapy depending on the biological agent received by patients. Note. GIBT is genetic engineering biological therapy.

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4. Fig.3. Adjusted Kaplan–Meier survival curves for genetically engineered biological therapy taking into account the influence of statistically significant predictors of discontinuation. Note. GIBT is genetic engineering biological therapy.

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5. Fig.4. Survival curves of therapy depending on the biological naivety of patients, taking into account the genetically engineered biological drug received in bionaive patients (A) and patients who previously received biological therapy (B). Note. GIBT is genetic engineering biological therapy.

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6. Fig.5. Survival curves of genetically engineered biological therapy depending on whether the patient has a family history of psoriasis in patients without a family history of psoriasis (A) and patients with a family history of psoriasis (B). Note. GIBT is genetic engineering biological therapy.

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7. Fig.6. Survival curves of genetic engineering biological therapy in the general sample of cases depending on the presence of comorbid pathologies in the patient (two comorbidities: a combination of psoriatic arthritis and metabolic syndrome). Note. GIBT is genetic engineering biological therapy.

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8. Fig.7. Survival curves of genetically engineered biological therapy depending on previously received nonbiological systemic treatment. Note. GIBT is genetic engineering biological therapy.

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