A phase 2 trial has shown upadacitinib provided relief from severe immune checkpoint inhibitor-related dermatitis inside four weeks in all participants, without any needing corticosteroids.

The Chinese team behind the study, published in JAMA Oncology, said the data suggested the JAK inhibitor could be another option to manage dermatitis side effects in oncology patients.

However, an Australian medical oncologist told the limbic while the data showed upadacitinib was effective, questions about the long-term effects of JAK inhibitors on oncology outcomes still remained.

The single centre, single group study enrolled 33 patients with grade 3 or 4 ICI-related dermatitis who were treatment naive with no prior exposure to corticosteroids and other immunosuppressants.

They received 15mg oral upadacitinib for 28 days, without concomitant glucocorticoids, immunosuppressants, or antihistamines. Among the study’s findings:

• 30 participants (90.9%) had complete resolution of their rashes, while 3 (9.1%) showed partial resolution,
• Close to 70% of patients saw rash resolution within seven days, compared to a reported median of 55 days with conventional corticosteroids,
• Close to 94% of patients were able to resume their immunotherapy treatments as scheduled after upadacitinib treatment.
• All patients reported pruritus improvement within one day.

Adverse events were also significantly fewer than in previous upadacitinib studies, with no serious events recorded.

“Upadacitinib could be a potential therapeutic option for managing ICI-related dermatitis,” the authors said.

“Nevertheless, future randomised clinical trials are warranted.”

Effectiveness of treatment vs future cancer outcomes

While the data showed upadacitinib had fast results, there remain uncertainties about the long-term effects of JAK inhibitors in this patient group.

Associate Professor Jenny Lee.

“The concern with JAK inhibitors is their potential to increase your risk of secondary malignancies,” medical oncologist at Chris O’Brien Lifehouse, Associate Professor Jenny Lee told the limbic.

“It’s really interesting how effective [upadacitinib] was at controlling dermatitis. But I think we need to understand better whether this could have a negative impact on the cancer itself. There’s no doubt it’s effective in managing the immune-related toxicity, but the question then becomes, what about the long-term outcome for the patient?”

Associate Professor Lee said at this stage, Australian clinicians were reserving the use of JAK inhibitors for treating patients with severe toxicities related to their cancer treatments, like myocarditis.

“Severe dermatitis defined as grade 3 or 4 dermatitis, where we have to stop treatment, is relatively uncommon. We have historically managed these patients with steroids, which can continue for months,” she said.