Cathal O'Connor

Credit: CorkIndependent.com

Failure of TNFα inhibition is common among individuals with trisomy 21 and severe cases of psoriasis, new findings suggest, and ustekinumab therapy may be considered by patients and clinicians as a first-line therapy.¹

These findings were the result of a study examining the biological outcomes of severe psoriasis in patients with trisomy 21, with the goal of reviewing the outcomes of those with trisomy 21 and severe cases of psoriasis given biologic or Janus kinase inhibitors (JAKi) treatments.

The research was authored by Cathal O'Connor, from the Department of Dermatology at South Infirmary Victoria University Hospital in Ireland. O’Connor and colleagues noted that trisomy 21 is linked with autoimmunity, which is connected to abnormal monocyte and circulating cytokine populations, and this can affect the use of biologic medications.²

“There have been six published reports of biologic use for psoriasis in T21: five for TNFα-inhibitors and one for ustekinumab,” O’Connor and colleagues wrote. “There has been no report of Janus kinase inhibition (JAKi) for psoriasis in T21.”

Background and Findings

The investigators received ethical approval from the clinical research and ethics committee and the study participants were identified through database searches of 3 dermatology departments in Munster, Ireland, as well as promotion through the social media platforms of the Down Syndrome Ireland network.

The research team conducted their retrospective review using a standardized data collection sheet to gather information on patient’s prior therapies, demographics, comorbidities, and treatment response, and current therapies.

Severe psoriasis was defined by the research team as a Psoriasis Area Severity Index (PASI) score exceeding 10 or a body surface area over 10%. An adequate response to the treatment was defined by the team as a Physician Global Assessment score of 0 (indicating clear skin) or 1 (indicating nearly clear skin).

Overall, the investigators’ research included 21 total patients with a mean age of 24.7 years. Among the TNFα inhibitor trials, 90% were shown to be unsuccessful. Additionally, ustekinumab showed an adequate response in almost two-thirds of the patients in the study.

All 3 or those who received tofacitinib achieved an adequate response despite having failed at least 3 prior biologic treatments. On average, the patients underwent 2.1 biologic/JAKi therapies, and the overall survival rate was shown to be 36%.

A significant proportion—81% of patients—had to switch from their initial biologic treatment due to the treatment’s failure.

The investigators also noted that there were no instances where treatment had to be discontinued as a result of adverse events. Primary failure was observed in a larger proportion of patients compared to secondary failure , which they add showed that the lack of therapeutic efficacy was more likely due to mechanistic issues rather than immunogenicity.

“In summary, this is the largest series of biologic outcomes for severe psoriasis in T21, with almost four times the total number of cases previously reported,” they wrote. “Failure of TNFα inhibition is common; ustekinumab therapy should be considered first line, and there is an emerging role for JAK inhibition, given the interferon hyperactivation seen in these patients.”

References

1. ^{O’Connor, C, Byrne, B, Roche, D, O’Connell, G, O’Connell, M, Murphy, M, et al. Biological and JAK inhibitor therapy outcomes for severe psoriasis in trisomy 21. J Dermatol. 2023; 00: 1– 4. https://doi.org/10.1111/1346-8138.16851.}
2. ^{Huggard D, Doherty DG, Molloy EJ. Immune dysregulation in children with down syndrome. Front Pediatr. 2020; 8: 73. Published 2020 Feb 27.}