Safety of ustekinumab in adolescent patients with moderate‐to‐severe plaque psoriasis: real‐world evidence from an ongoing European study (NCT03218488)

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Safety of ustekinumab in adolescent patients with moderate-to-severe plaque psoriasis: real-world evidence from an ongoing European study (NCT03218488) Dear Editor, The European Medicines Agency approved ustekinumab for treating adolescent psoriasis patients in 2015, 1 following the phase 3 CADMUS trial. 2 However, long-term safety and efficacy data in this population are lacking. [3][4][5] We present real-world safety data for ustekinumab in adolescents with moderate-tosevere psoriasis.
This 42-month progress report of a real-world, postapproval study (NCT03218488) comprised 70 patients enrolled between 25 October 2017 and the progress report data cut-off (8 January 2021). Included patients were ≥12 to <18 years of age with a confirmed diagnosis of moderate-to-severe psoriasis who were initiated on ustekinumab treatment within 3 months before, or 2 months after, the first assessment. Patients enrolled in an interventional clinical trial were excluded. After baseline data collection, follow-up visits were conducted every 3 months for the first year and at least every 6 months thereafter, for a maximum of 6 years or until the patient reached 18 years of age, early withdrawal or study closure. Serious infections, malignancies and adverse events related to autoimmunity were predefined serious adverse events of special interest (SAESI).
Overall, 72 treatment-related AEs were reported in 20 (28.6%) patients ( Figure 1). Fatigue, pyrexia, oropharyngeal pain and headache were the most frequent, with each being reported in six patients (8.6%); all represent previously designated adverse drug reactions for ustekinumab. 6 Thirteen serious AEs (SAEs) were reported in nine patients (12.9%), of which two were considered of special interest. The first SAESI was a case of appendicitis (serious infection) that was considered possibly related to ustekinumab; it was classified as severe and resulted in the interruption of ustekinumab treatment. The second SAESI was a case of severe worsening of preexisting plaque psoriasis (due to the relationship between plaque psoriasis worsening and autoimmunity), considered unrelated to ustekinumab. Both SAESIs resolved. The remaining SAEs were considered unrelated to ustekinumab treatment. No cases of malignancy or death were reported.
The percentage of patients reporting at least one AE during ustekinumab treatment was lower in this study compared with the similar population in the CADMUS trial (55.7% vs 89.3%). This may reflect more limited recall of AE-related information at patient visits which, for this study and the CADMUS trial, were every 6 and 3 months, respectively. This may have led to less complete capture of information, underreporting of AEs, or introduction of additional biases. 2 The relatively small sample size may reflect challenges in patient enrolment due to the relatively low prevalence of moderate-to-severe psoriasis among adolescents, the limited number of patients eligible for biologic therapy, restrictions in access due to local reimbursement policies and self-isolation, quarantine and travel restrictions related to the COVID-19 pandemic. 7 In conclusion, this study identified no new safety concerns related to ustekinumab treatment in adolescent patients, with findings being generally consistent with the known safety profile for ustekinumab. After study completion in 2032, the results will provide a better understanding of the long-term efficacy and safety profile of ustekinumab in adolescents with moderate-tosevere psoriasis.

Acknowledgements
Medical writing support was provided by Cello Health MedErgy, under the direction of the authors, and funded by Janssen.

Funding sources
This article was sponsored by Janssen. Medical writing and editorial support were funded by Janssen.

Ethical approval
This study complied with ethics requirements as specified by the Independent Ethics Committee/Institutional Review Board and by local regulations. Each participant signed a participation agreement/informed consent form in line with local regulations and trial sponsor policy before data collection. Data are n (%) unless otherwise stated. AE, adverse event. a Percentages are calculated from the total number of AEs with known data (excluding missing data). b 'Not applicable' was selected when the start date/start time of the AE was either during the screening and prior to the first injection or was after discontinuation of study drug and did not lead to discontinuation.

Editor
In the following, we report on a case of prurigo pigmentosa (PP). The case is not only exceptional, because PP is still rare outside Japan or Asian region as a whole, but also because it occurred without previously known concomitant diseases such as malnutrition, diabetes or others. A woman in her twenties presented with pruritic erythematous macules and papules with erosions arranged in a symmetrically distributed reticular pattern on the back and below the breast on both sides, increased on the right one (Fig. 1).
Symptoms had started in spring of the previous year and lasted for eight months. Topical therapy with azelaic acid, (a) (b) Figure 1 Percentage of AEs related to ustekinumab a treatment (n = 72) by (a) system organ class and by (b) preferred term. AEs designated as 'Other' had ≤3 events related to ustekinumab. a An AE related to ustekinumab is defined as an AE with a possible, probable or very likely relationship to ustekinumab. AE, adverse event.