Efficacy and safety of ustekinumab in adolescents

Roselyn Kellen,1 Nanette B Silverberg,2,3 Mark Lebwohl1 1Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Department of Dermatology, Mount Sinai St Luke’s-Roosevelt Hospital, New York, NY, USA; 3Beth Israel Medical Centers, New York, NY, USA Abstract: The biologic agent ustekinumab is a human monoclonal antibody that binds to the p40 subunit shared by interleukins (ILs) 12 and 23. The antibody is able to prevent binding of cytokines to the IL-12Rβ1 cell surface receptor and therefore may prevent IL-23 driven activation of the IL-23/Th 17 axis of inflammation. The anti-inflammatory activity has been beneficial in adult psoriasis. Ustekinumab has been approved in the United States for the treatment of adults with psoriasis and psoriatic arthritis. Approval in children and adolescents has not been granted by the US Food and Drug Administration. Subcutaneous injections of ustekinumab are administered at baseline, week 4 and every 12 weeks thereafter, a regimen that is particularly appealing to young patients who do not like more frequent injections at home. The product is attractive because, although it works through an immune system mechanism, the selective activity is such that the drug has not been associated with many of the side effects attributed to other immunosuppressive medications. Case reports of ustekinumab for pediatric psoriasis have shown promising results, and the recent Phase III CADMUS trial tested the agent in adolescents aged 12–17 years with psoriasis, using standard dose 0.75 mg/kg (≤60 kg), 45 mg (>60–≤100 kg), and 90 mg (>100 kg) or half-standard dosing 0.375 mg/kg (≤60 kg), 22.5 mg (>60–≤100 kg), and 45 mg (>100 kg) with a loading dosage at week 0 and week 4. Psoriasis area and severity index-75 was achieved in more than three-quarters of patients in full and half dosing by 12 weeks, and psoriasis area and severity index-90 in 54.1% and 61.1% of half and full dosage by 12 weeks, respectively. Ustekinumab was generally well tolerated in adolescents, with some patients developing antibodies, and nasopharyngitis being the major adverse event. Ustekinumab is a promising agent in adolescent psoriasis that appears to be well tolerated. The best monitoring plan and usage in younger patients still remain to be defined.Keywords: pediatric psoriasis, ustekinumab, IL-12, IL-23, TNF agen

Hospitalization, inpatient burden and comorbidities associated with bullous pemphigoid in the U.S.A.

BACKGROUND: Bullous pemphigoid (BP) is associated with significant disability and comorbid health disorders that may lead to or result from hospitalization. However, little is known about the inpatient burden and comorbidities of BP. OBJECTIVES: To obtain data on the inpatient burden and comorbidities of BP in the U.S.A. METHODS: We analysed data from the 2002 to 2012 National Inpatient Sample, including a representative 20% sample of all hospitalizations in the U.S.A. (72 108 077 adults). RESULTS: The prevalence of hospitalization for BP increased from 25·84 to 32·60 cases per million inpatients from 2002 to 2012. In multivariate logistic regression models with stepwise selection, increasing age, nonwhite ethnicity, higher median household income, being insured with Medicare or Medicaid, and increasing number of chronic conditions were all associated with hospitalization for BP (P < 0·05 for all). The top three primary discharge diagnoses for patients with a secondary diagnosis of BP were septicaemia (prevalence 5·51%, 95% confidence interval 5·03-5·99), pneumonia (4·60%, 4·19-5·01) and urinary tract infection (3·52%, 3·15-3·89). Patients with BP also had numerous autoimmune, infectious, cardiovascular and other comorbidities. Interestingly, BP was associated with multiple neuropsychiatric disorders, including demyelinating disorders, dementias (presenile, senile, vascular and other), paralysis, neuropathy (diabetic, other polyneuropathy), Parkinson disease, epilepsy, psychoses and depression. The mean annual age- and sex-adjusted in-hospital mortality rate was significantly higher in patients with a secondary diagnosis of BP compared with no BP (2·9%, range 2·8-3·9% vs. 2·1%, range 1·9-2·2%). Significant predictors of mortality in patients with BP included increasing age, nonwhite ethnicity and insurance with Medicaid or other payment status (P < 0·05 for all). CONCLUSIONS: Hospitalization for BP increased significantly between 2002 and 2012. Moreover, there were significant ethnic and healthcare disparities with respect to hospitalization and inpatient mortality from BP