Efficacy and safety of ustekinumab in adolescents

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.

Hair and skin predict cardiomyopathies: Carvajal and erythrokeratodermia cardiomyopathy syndromes

“…Since IL-12/23 inhibition reduces circulating levels of IL-17, and prior work shows that the primary defect in EKC syndrome is inappropriate intracellular accumulation of desmosomes, reduction of IL-17 may, in part, account for improvement in the skin and heart 4. Common side effects of ustekinumab include nasopharyngitis, upper respiratory tract infections, and pharyngitis 32. No major side effects have yet been reported in patients with EKC syndrome.…”

FDA Approved Biologics: Can Etanercept and Ustekinumab be Considered a First-Line Systemic Therapy for Pediatric/Adolescents in Moderate to Severe Psoriasis? A Systematic Review

“…In large, it has shown significant clinical response though partial response can also occur due to different triggered immune-mediated pathways other than interleukin 12 and 23 immune-mediated pathways [ 28 ]. Noticeably, in comparison to other biological agents, ustekinumab requires fewer injections, resulting in easy follow-up for patients [ 2 ]. Hence, the therapeutic option should be considered specifically patient-by-patient while taking into account the impact of the disease on the patient and their family [ 29 ].…”

“…The etiology of psoriasis is yet to be established, but histological examination of its lesions indicates the association of innate and adaptive immunity. The dermis and epidermis are the main culprits in an inflammatory infiltrate of T-lymphocytes, mast cells, neutrophils, and macrophages, which leads to hyperkeratosis, epidermal acanthosis, parakeratosis, and amplification of the rete ridges [ 2 ].…”