HLA-C*06:02 Positivity and Smoking Linked With Reduced Drug Survival of Ustekinumab for Psoriasis

Smoking was found to modify the effect of a genotype on the response to ustekinumab in patients with psoriasis.

Patients with psoriasis who smoke and test positive for the HLA-C*06:02 genetic variant may have a higher risk for reduced drug survival with ustekinumab compared with patients who do not smoke and who test negative for HLA-C*06:02, study results published in the Journal of Investigative Dermatology suggests.

The study relied on patient data from the DermaReg. A total of 167 patients with psoriasis who were treated with ustekinumab from 2009 to 2019 were selected from this register and included in the study. Approximately 27% (n=45) and 37% (n=61) of patients smoked and were positive for the HLA-C*06:02 variant, respectively.

Drug survival was evaluated in the 167-patient cohort. All patients were censored 180 days after the last registered clinic visit, 2 years after initiation of treatment, or at the date of data extraction, whichever came first. The mean Psoriasis Area and Severity Index (PASI) during maintenance was also estimated. The mean PASI scores were estimated during maintenance, defined as treatment from 12 weeks after the start of treatment until patients were no longer receiving therapy.

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In terms of drug survival, there was no difference in patients who were HLA-C*06:02-positive and HLA-C*06:02negative (P =.11) or in patients who smoked and did not smoke (P =.55). The HLA-C*06:02 genotype was associated with reduced drug survival in patients who smoked (P <.001) but not in patients who did not smoke (P =.71). During the maintenance treatment period, patients who were negative for HLA-C*06:02 had higher mean PASI scores compared with patients positive for HLA-C*06:02, but this difference was not statistically significant (hazard ratio [HR], 1.4; 95% CI, −0.1 to 2.8).

According to an interaction analysis, there was a positive interaction on the multiplicative (HR, 9.4; 95% CI, 2.0-44.4) and additive scales (HR, 2.1; 95% CI, 0.6-3.5) for the HLA-C*06:02 variant and smoking.

Study limitations were the small number of patients, the potential residual confounding, as well as the inclusion of patients only from Sweden, which may limit the generalizability of the findings.

The investigators suggest that the interaction of HLA-C*06:02 and smoking observed in the study “appears to be clinically meaningful and has the potential to improve decision-making in clinical practice.”

Disclosure: This clinical trial was supported by Janssen-Cilag, Abbvie, Novartis, and Eli Lilly. Please see the original reference for a full list of authors’ disclosures.


Svedbom A, Nikamo P, Ståhle M, et al. Interaction between smoking and HLA-C*06:02 on the response to ustekinumab in psoriasis. J Invest Dermatol. doi:10.1016/j.jid.2020.01.013