Negative HLA-C*06:02 status may not be a reason to avoid ustekinumab (Stelara) therapy in patients with psoriasis, a systematic review concluded.
Following 6 months of ustekinumab treatment, there was a risk difference of 0.24 (95% CI 0.14-0.35, P<0.001) for reaching a 75% improvement in Psoriasis Area and Severity Index (PASI75) in favor of HLA-C*06:02-positive patients, reported Lieke van Vugt, MD, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues.
The median PASI75 response rate was 67% for HLA-C*06:02-negative patients, and 92% for the HLA-C*06:02-positive cohort, they reported in JAMA Dermatology.
Prior investigations highlighted that, based on HLA-C*06:02 status, psoriasis patients had a differential response to ustekinumab therapy, but these were mostly small, inconclusive cohort investigations, the researchers noted.
The current investigation suggested that patients should not be omitted from ustekinumab therapy due to a negative HLA-C*06:02 status, they stated.
“[H]eterogeneity complicated generalizability and thus implementation of our findings, which may prohibit the current use of HLA-C*06:02 as a single predictor for ustekinumab treatment response in patients with psoriasis in clinical practice,” van Vugt and colleagues wrote. “Realization of personalized treatment in psoriasis care may be dependent on finding a set of biomarkers, rather than a single marker, that in combination are strongly predictive of therapeutic response.”
The study serves as proof of concept that there is hope for genetic tests to tailor drugs for subgroups of psoriasis patients, noted Robert Brodell, MD, of the University of Mississippi Medical Center in Jackson, who was not involved in the study.
Brodell pointed out “both groups did so well that, clinically, they would both be very happy with their treatment result.” There is “no reason to use this genetic test to distinguish potential responders from non-responders,” he told MedPage Today.
The investigators reviewed eight studies. There were 937 patients included in the primary assessment of PASI75 response following 6 months of therapy, and 1,048 patients were assessed in the meta-analyses.
Studies were included if they reported the relationship between PASI75 and HLA-C*06:02 status response to ustekinumab treatment among plaque psoriasis patients following either 3 or 6 months of treatment. Observational studies and randomized clinical trials were used in the review. Selection and screening were done independently by two reviewers.
Reviewers extracted PASI75 response rates and HLA-C*06:02 genotype status. Using random-effects models, data were pooled, and heterogeneity was evaluated using I2 and τ2 statistics. Meta-Analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) reporting guidelines were followed.
Oral communications, case series, meeting summaries, case reports, and poster abstracts were excluded.
Heterogeneity testing yielded an I2 of 82%, a high number. Other study limitations included the possibility that studies of interest might have been overlooked due to language restrictions. Also, the researchers did not have details on population demographics, or patients’ ethnicity and race.
van Vugt disclosed relevant relationships with AbbVie, Celgene, Janssen, and Novartis. Co-authors disclosed multiple relevant relationships with industry.