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Is HLA-C*06:02 status associated with a differential response to ustekinumab therapy in patients with psoriasis?
This systematic review and meta-analysis of 8 studies and 1048 patients showed a risk difference for achievement of 75% improvement in Psoriasis Area and Severity Index (PASI75) after 6 months of ustekinumab therapy in favor of HLA-C*06:02–positive patients. Although HLA-C*06:02–positive patients had a high PASI75 response rate after 6 months, the PASI75 response rate was also high in the HLA-C*06:02–negative group.
Based on high PASI75 response rates in both genotype groups, there appears to be no rationale for excluding patients from ustekinumab treatment based on a negative HLA-C*06:02 status.
Previous research showed a differential response to ustekinumab therapy based on HLA-C*06:02 status in patients with psoriasis but consisted mostly of small (and sometimes inconclusive) cohort studies.
To assess whether HLA-C*06:02 status is associated with a differential response to ustekinumab therapy in patients with psoriasis through a systematic review and a meta-analysis of available data.
A comprehensive search was conducted using MEDLINE, Embase, the Cochrane Library, Web of Science, and gray literature sources. Databases were searched from January 1, 2000, to May 14, 2018. Search strategies included terms and synonyms for psoriasis, HLA-C, and ustekinumab. Languages were restricted to English, French, German, and Dutch.
Studies were included if they reported the association between HLA-C*06:02 status and 75% improvement in Psoriasis Area and Severity Index (PASI75) response to ustekinumab therapy in patients with plaque psoriasis after 6 and/or 3 months of treatment. Randomized clinical trials and observational studies were included. Screening and selection were performed independently by 2 reviewers.
Data Extraction and Synthesis
HLA-C*06:02 genotype status and PASI75 response rates were extracted by 2 reviewers. Data were pooled using random-effects models. Heterogeneity was assessed using the τ2 and I2 statistic. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed.
Main Outcome and Measure
The primary outcome was the risk difference of achieving PASI75 after 6 months of ustekinumab therapy between HLA-C*06:02–positive and HLA-C*06:02–negative patients.
A total of 8 studies were reviewed; 1048 patients were included for meta-analyses, and 937 patients were included for the primary analysis of PASI75 response after 6 months of treatment. Random-effects meta-analysis showed a risk difference of 0.24 (95% CI, 0.14-0.35; P < .001) in favor of HLA-C*06:02–positive patients. The median PASI75 response rate in the HLA-C*06:02–positive group was 92% (pooled, 89%; range, 62%-98%). For HLA-C*06:02–negative patients, the median response rate was 67% (pooled, 62%; range, 40%-84%). Substantial heterogeneity may have been present, with an I2 of 82%.
Conclusions and Relevance
The meta-analysis showed a differential response to ustekinumab therapy based on HLA-C*06:02 status in patients with psoriasis. Although HLA-C*06:02–positive patients had high PASI75 response rates after 6 months, the PASI75 response rate was also high in the HLA-C*06:02–negative group. There appears to be no rationale for excluding patients from ustekinumab treatment based on a negative HLA-C*06:02 status.
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Accepted for Publication: January 15, 2019.
Corresponding Author: Lieke J. van Vugt, MD, Department of Dermatology, Radboud University Medical Centre, Radboud Institute of Health Sciences, PO Box 9101, 6500 HB Nijmegen, the Netherlands (firstname.lastname@example.org).
Published Online: April 17, 2019. doi:10.1001/jamadermatol.2019.0098
Author Contributions: Dr van Vugt had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: All authors.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: van Vugt, van den Reek, Hannink.
Administrative, technical, or material support: Coenen, de Jong.
Supervision: van den Reek, Hannink, Coenen, de Jong.
Conflict of Interest Disclosures: All funding received by the authors goes to the independent research fund of the Department of Dermatology of Radboud University Medical Center, Nijmegen, the Netherlands. Dr van Vugt reported carrying out clinical trials for AbbVie, Celgene, Janssen, and Novartis. Dr van den Reek reported carrying out clinical trials for AbbVie and Janssen, receiving speaking fees from AbbVie and Eli Lilly and Company, and receiving reimbursement for attending a symposium from Janssen, Pfizer, and AbbVie. Dr de Jong reported receiving research grants for the independent research fund of the Department of Dermatology of the Radboud University Medical Center, Nijmegen, the Netherlands, from AbbVie, Pfizer, and Janssen Pharmaceutica and acting as consultant and/or paid speaker for and/or participated in research sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Janssen Pharmaceutica, Novartis, Eli Lily and Company, Celgene, and Leo Pharma. No other disclosures were reported.
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