HLA-C*06:02 Negativity Shouldn't Bar Ustekinumab Treatment for Psoriasis

By David Douglas

April 30, 2019

NEW YORK (Reuters Health) - Although being positive for the HLA-C*06:02 genotype is associated with a better response to ustekinumab therapy in patients with plaque psoriasis, those with negative findings also do well, according to Dutch researchers.

In a paper online April 17 in JAMA Dermatology, they note that a lack of power in "small cohort studies prohibits sound conclusions about the association between this variant and response to ustekinumab."

Moreover, "the suspected pharmacogenetic mechanism for involvement of HLA-C*06:02 in the response to ustekinumab is unknown," Dr. Lieke J. van Vugt of Radboud University Medical Centre, in Nijmegen, and colleagues say.

The researchers reviewed eight studies involving 1,048 patients. All reported the association between HLA-C*06:02 status and 75% improvement in Psoriasis Area and Severity Index (PASI75) response to ustekinumab therapy.

At six months, PASI75 evaluation per genotype showed response rates of approximately 90% among HLA-C*06:02-positive patients and 65% for HLA-C*06:02-negative patients. At 3 months, the results were approximately 80% and 60%, respectively.

The researchers concede that "there was a lack of details about population demographics for the included studies, barring insight into possible causes of heterogeneity. Most important, race/ethnicity of the included patients was not explicitly mentioned in most studies."

Nevertheless, although there was a difference between the genotype groups, this may be of more statistical than clinical importance, they say. The underlying response rate was "actually high in both genotype groups. Therefore, there appears to be no rationale for excluding patients from ustekinumab therapy based on an HLA-C*06:02–negative status."

Dr. Luis R. Espinoza, chief of the section of rheumatology at LSU Health Sciences Center in New Orleans, told Reuters Health by email, "This is an interesting and relevant study whose main objective is to characterize or identify the presence of a biomarker(s), which might be useful in the selection of a biological agent for the treatment of patients with moderate to severe, and also refractory psoriasis."

"The choice of HLA-C*06:02 is an appropriate one," added Dr. Espinoza, who was not involved in the study, "taking into consideration that HLA-C*06-02 is the major disease allele at the PSORS1 locus that predisposes to early-onset disease in Caucasian populations. Information gathered, however, does not have practical relevance considering that the high degree of clinical response observed between the positive and negative groups."

He joined the researchers in noting that a main limitation of the study was "that the race/ethnicity of studied patients was not well-characterized."

Dr. Espinoza concluded, "Further studies of this nature are needed in view of the high cost of this type of therapy, and also due to the fact that a considerable proportion of psoriasis patients treated do not fully respond, develop toxicity, or eventually cease to respond."

Dr. van Vugt did not respond to requests for comments. He and two of his coauthors report ties to Janssen, which markets ustekinumab as Stelara.

SOURCE: https://bit.ly/2Pvn0Gu

JAMA Dermatol 2019.