Real-world outcomes of children treated with dupilumab for moderate-to-severe atopic dermatitis: a single-centre retrospective observational UK study.

BACKGROUND: Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged ≥ 6 months. OBJECTIVES: The aim of this study was to examine real-world outcomes and safety of dupilumab in British children with moderate-to-severe AD attending a tertiary referral paediatric centre. METHODS: Skin and quality of life scores, adverse events and discontinuation rates were assessed. Patients aged ≤ 18 years with moderate-to-severe AD were included if they had skin scores recorded at baseline and at least one follow-up visit. Efficacy and safety were assessed using descriptive statistics. RESULTS: In this retrospective observational survey, 72 children/teenagers, with a median age of 14 years (range 7-18) were included. Oral systemic immunosuppressants had failed to control AD in 88% of children recruited. All patients commenced on dupilumab had pretreatment eczema skin scores consistent with moderate-to-severe disease, with a median Eczema Area and Severity Index (EASI) score of 25 [interquartile range (IQR) 20-31]. EASI scores decreased by a median of 94% (IQR 82-100) and remained consistently low over 10-52 months of the study, with a median EASI score at final follow-up of 2 (IQR 0-6). Of the 72 children, 8 (11%) were able to discontinue dupilumab as they were in remission. Nineteen (26%) experienced adverse events, most commonly conjunctivitis (12 patients; 17%). Eight (11%) discontinued dupilumab (six with ongoing inflammatory skin flares, one with severe allergic conjunctivitis, one with intercurrent Wilson disease). CONCLUSIONS: Dupilumab was highly effective in treating most children with moderate-to-severe AD with good safety outcomes in the real world. However, 10% of children may need alternative therapy because of drug ineffectiveness or side-effects.

Hypothyroxinemia in mechanically ventilated term infants is associated with increased use of rescue therapies.

OBJECTIVE: Although common in preterm infants, transient hypothyroxinemia (TH) has not been investigated extensively in ill term infants. The objectives of this study were to investigate serum thyroxine (T4) and thyroid-stimulating hormone (TSH) in sick term infants and to determine whether there is any association between measures of thyroid function and short-term outcome in term infants who receive mechanical ventilation. METHODS: The investigation consisted of both a prospective observational study and a retrospective cohort study. In the prospective study, T4 and TSH were measured after birth in a group of sick term infants (n = 38) and compared with a group of well term infants (n = 18). Infants in the sick group received mechanical ventilation or continuous positive airway pressure and/or had neonatal seizures. Illness severity was quantified using the Score for Neonatal Acute Physiology. The retrospective cohort study included term infants who required mechanical ventilation and were born over a 5-year period (n = 347). Routine T4 screening was collected on the fifth day of life. TH was diagnosed in infants with a T4 <10%, with a TSH <25 microIU/mL. Clinical outcomes in infants with TH were compared with infants without TH. RESULTS: In the prospective study, infants in the sick group had lower T4 on the fifth day of life as compared with infants in the well group (11.7 +/- 4.9 vs 18.9 +/- 5.4 microg/dL), and 34% of infants in the sick group had a T4 <10th percentile compared with 6% of infants in the well group. T4 on day of life 5 was inversely correlated with Score for Neonatal Acute Physiology (R = -0.52). In the retrospective study, 21% of mechanically ventilated infants developed TH and were given statistically more inhaled nitric oxide, high-frequency ventilation, vasopressors, and pharmacologic paralysis when compared with infants without TH. Moreover, infants with TH were statistically more likely to die or require transfer to an extracorporeal membrane oxygenation center compared with infants without TH. CONCLUSION: Our data show that, similar to preterm infants, ill term infants develop TH. Term infants with TH required more intensive rescue interventions, including inhaled nitric oxide and transfer to an extracorporeal membrane oxygenation center. However, whether T4 levels are a marker or a mediator of clinical outcome remains to be determined.

Are perinatal risk factors helpful in predicting and optimizing treatment strategies for transient hypothyroxinemia in very-low-birth-weight infants?

Transient hypothyroxinemia is common in premature infants and has been associated with intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), poor neurodevelopmental outcomes, and mortality. Recent trials have failed to show that supplemental thyroid hormone improves overall neurodevelopmental outcome. The objective of this article is too determine perinatal risk factors for transient hypothyroxinemia (TH). We studied a cohort of infants born between July 1993 and July 2000 who were less than 1500 g and who received a newborn screening for thyroid function ( n = 932). Total serum thyroxine (T(4)) was collected routinely on the fifth day of life. T (4) was correlated with gestational age (R = 0.59, p < 0.01). After controlling for potential confounding variables, gestational age, dopamine, and mechanical ventilation were found to be independently associated with low T (4) (overall model: r(2) = 0.41, p < 0.01). Number needed to treat (NNT) analysis showed treating all infants less than 27 weeks would lead to treating 6.3 infants for every one with a subsequent T(4) < 5 microg/dL. By combining gestational age and need for dopamine support, NNT = 2.4 for every one infant with subsequent T(4) < 5 microg/dL. Low gestational age, mechanical ventilation, and need for dopamine were associated with low T(4) levels and may be helpful in optimizing treatment strategies for TH.