Purpose: To determine the long-term efficacy of the anti-tumor necrosis factor (TNF) agents, infliximab (IFX) and adalimumab (ADA), in pediatric luminal Crohn's disease (CD) by performing a systematic literature review. Methods: An electronic search was performed in Medline, Embase, and the Cochrane Library from inception to September 26, 2019. Eligible studies were cohort studies with observation periods that exceeded 1 year. Studies that reported time-to-event analyses were included. Events were defined as discontinuation of anti-TNF therapy for secondary loss of response. We extracted the probabilities of continuing anti-TNF therapy 1, 2, and 3 years after initiation. Results: In total, 2,464 papers were screened, 94 were selected for full text review, and 13 studies (11 on IFX, 2 on ADA) met our eligibility criteria for inclusion. After 1 year, 83-97% of patients were still receiving IFX therapy. After 2 and 3 years the probability of continuing IFX therapy decreased to 67-91% and 61-85%, respectively. In total, 5 of the 11 studies subgrouped by concomitant medication consistently showed that the probabilities of continuing IFX therapy in patients with prolonged immunomodulator use were higher than those in patients on IFX monotherapy. Conclusion: This review of real-world evidence studies confirms the long-term therapeutic benefit of IFX therapy in diverse cohorts of children with luminal CD. Moreover, it supports the view that combination therapy with an immunomodulator prolongs the durability of IFX therapy in patients who previously failed to recover following first-line therapy. The limited number of time-to-event studies in patients on ADA prevented us from drawing definite conclusions about its long-term efficacy.
Objective. The aim of this study was to describe the morphology of intervertebral discs and vertebral bodies during growth in asymptomatic children and adolescents. Summary of Background Data. Earlier studies demonstrated that spinal growth occurs predominantly in vertebral bodies. This axiom introduced a vertebral-body-focus for unravelling etiological questions and achieve growth-modulation in young spinal deformity patients. Recent studies show the importance of the intervertebral discs in the early phases and possible etiology of pediatric spinal deformities. There is presently a paucity of 3D morphometric data of spinal elements during growth. Methods. A database of 298 patients aged 0 to 21 that have received a computed tomography scan for indications not related to the spine was analyzed. Custom made software was used to semi-automatically measure intervertebral disc and vertebral body morphology, corrected for orientation in all 3 planes. Results. Vertebral body height increased from birth up to adulthood, from 4-to-14 mm in the cervical, 6 to 20 mm in the thoracic, and 9 to 28 mm in the lumbar spine. This increase was 0.70 mm/year in males, more pronounced than females with 0.62 mm/year (P ¼ 0.001). Lumbar discs increased throughout growth from 4.4 to 9.0 mm, whereas thoracic discs only increased from 3.5 to 4.9 mm at age 4 and remained stable afterwards, similarly for cervical discs. The disc transverse surface area increased greatly and consistently throughout growth. Disc slenderness was stable in the lumbar spine during growth, but decreased in the thoracic and cervical spine. Overall, discs were more slender in females, especially around early adolescence. Conclusion. The spine grows predominantly in the vertebral bodies. Thoracic discs increase in height only during the first years, whereas the transverse surface area continues to increase throughout growth, thus discs slenderness decreases. Relatively, female discs remained slenderer around growth-spurt. These measurements may assist future studies on the role of disc morphology in the etiology and treatment of spinal deformity.
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