Risk of rare but serious skin reactions associated with the use of ustekinumab

HSA would like to bring the attention of healthcare professionals to overseas cases of rare but serious skin reactions, namely exfoliative dermatitis and erythrodermic psoriasis, which have been reported in patients receiving ustekinumab.

Ustekinumab (Stelara®, Johnson & Johnson Pte Ltd) is a fully human IgG1κ monoclonal antibody that has been registered locally since September 2009, for the treatment of adult patients with moderate to severe plaque psoriasis who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including cyclosporin, methotrexate, and psoralen combined with ultraviolet A (PUVA). It is also indicated for the treatment of adult patients with active psoriatic arthritis when the response to previous non-biological disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate.

Overseas cases of rare but serious skin reactions

Overseas cases of exfoliative dermatitis and erythrodermic psoriasis have been reported rarely (≥1/10,000 to <1/1,000) in psoriasis patients receiving ustekinumab.¹ These skin reactions were observed to occur within a few days of receiving ustekinumab and were severe, life-threatening reactions that could lead to hospitalisation. It is acknowledged that there could be a potential for confounding by indication in these cases. This is because ustekinumab is indicated for plaque psoriasis and patients may develop erythrodermic psoriasis as part of the natural course of their disease, presenting with symptoms that may be indistinguishable from exfoliative dermatitis. 

International regulatory actions

In September 2013, the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) initiated a safety review on exfoliative dermatitis associated with ustekinumab.² This signal was identified through routine pharmacovigilance surveillance in the United Kingdom, where 12 cases of exfoliative dermatitis and 15 cases of erythrodermic psoriasis associated with ustekinumab treatment were received. Upon completion of their review of the initial signal detection analysis as well as clinical and post-marketing data submitted by the marketing authorisation holder, PRAC concluded that the package insert (PI) for ustekinumab should be updated to include the risk of exfoliative dermatitis and skin exfoliation.³ A safety communication letter was issued to dermatologists in Europe to highlight this new potential risk.

In November 2014, Health Canada issued a safety review summary highlighting the possible link between exfoliative dermatitis and erythrodermic psoriasis and ustekinumab treatment. ⁴ In the safety review, Health Canada reported that it had received five reports of skin exfoliation (two serious and three non-serious) and one non-serious report of exfoliative dermatitis associated with the use of ustekinumab. A communication letter was issued to inform healthcare professionals about this safety concern and changes to the Canadian prescribing information were also implemented.

Local situation and HSA’s advisory

HSA has not received any local reports of exfoliative dermatitis and erythrodermic psoriasis associated with the use of ustekinumab.

In view of the seriousness of these events, the local PIs of ustekinumab-containing products have been strengthened to include warnings on these skin reactions. When prescribing ustekinumab to patients, healthcare professionals are advised to take into consideration the above safety information and signs and symptoms of erythrodermic psoriasis or exfoliative dermatitis. These may manifest as redness and shedding of the skin over a large area of the body, which may be painful and/or itchy. Increasing the awareness of patients and caregivers to the possible appearance of such skin reactions, through counselling, may facilitate prompt seeking of medical attention.

HSA will continue to monitor these signals and update healthcare professionals if new information arises.

References

1. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/ ↗ (opens in new tab)
    42613a-eng.php ↗ (opens in new tab)

2. http://www.ema.europa.eu/docs/en_GB/document_library/Minutes/ ↗ (opens in new tab)
    2013/10/WC500152672.pdf ↗ (opens in new tab)

3. http://www.ema.europa.eu/docs/en_GB/document_library/ ↗ (opens in new tab)
    PRAC_recommendation_on_signal/2014/02/WC500162042.pdf ↗ (opens in new tab)

4. http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/ ↗ (opens in new tab)
    stelara-eng.php ↗ (opens in new tab)