February 01, 2019

Biologic-naive patients who were HLA-C*06:02 positive and PsA negative exhibited a significantly poorer response to adalimumab at 12 months.

HLA-C*06:02 status is a predictive biomarker that influences response to adalimumab and ustekinumab in patients with psoriasis, according to a study published in The Journal of Allergy and Clinical Immunology.

The investigators sought to explore whether HLA-C*06:02, which is the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologic agents — the antitumor necrosis factor alpha adalimumab and the anti-interleukin-12/23 ustekinumab.

The prospective, observational study used information from participants in a national psoriasis registry. All participants were >16 years of age and were enrolled in the Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) study and the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR). BSTOP was conducted across 60 UK dermatology centers that include biologic sample collection.

 BADBIR is a pharmacovigilance register that has recruited >16,000 patients with psoriasis from the United Kingdom and Ireland who are receiving systemic conventional or biologic therapy. Longitudinal treatment and response observations, along with detailed clinical data, are included in BADBIR.

HLA alleles were imputed from genome-wide genotype data for a total of 1326 patients for whom 90% reduction in Psoriasis Area and Severity Index 90 response status was observed following 3, 6, or 12 months of treatment. Regression models of Psoriasis Area and Severity Index 90 response were developed that examined the interaction between HLA-C*06:02 and the type of drug (adalimumab or ustekinumab) administered, taking into consideration any potential confounding variables.

Results of the study demonstrated that those who were negative for HLA-C*06:02 were significantly more likely to respond to adalimumab therapy than to ustekinumab therapy at all time points, with the strongest response at 6 months (odds ratio [OR] 2.95; P =5.85×10^-7). In fact, this difference was greater in patients who were negative for HLA-C*06:02 and had psoriatic arthritis (OR 5.98; P =6.89×10^-5).

Those who had never taken biologic drugs and were positive for HLA-C*06:02 and negative for psoriatic arthritis exhibited a significantly poorer response to adalimumab at 12 months (OR 0.31; P =3.42×10^-4). Results from the HLA-wide analysis were consistent with HLA-C*06:02 itself being the primary effect allele contributing to patients’ biologic responses. This role still warrants exploration in larger samples, however, to fully investigate the possible role played by other alleles.

The researchers concluded that HLA-C*06:02 status might help inform optimal selection of first-line biologic therapy for patients with severe psoriasis.

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Reference

Dand N, Duckworth M, Baudry D, et al; BADBIR study group, the BSTOP study group and the PSORT consortium. HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis [published online December 19, 2018]. J Allergy Clin Immunol. doi: 10.1016/j.jaci.2018.11.038