HLA-C*06:02-positive patients on ustekinumab show higher drug survival in a real-world scenario

A real-world analysis of the BADBIR registry showed that human leukocyte antigen (HLA)-C*06:02 status is a predictive biomarker of drug survival for ustekinumab and perhaps adalimumab but not for etanercept or secukinumab. In contrast, no association was found between drug survival and HLA-C*06:02 status of patients who discontinued treatment due to adverse events.

Thus, the present study, presented by Dr Oras Alabas (University of Manchester, UK), aimed to investigate whether HLA-C*06:02 affects the discontinuation of biologics in a large cohort of psoriasis patients in the real world [3]. BADBIR is a UK pharmacovigilance register designed to assess the long-term safety of newer drugs by following a real-world population of psoriasis patients of different sex, age, ethnicity, body mass index (BMI), and comorbidities. The population consisted of patients with chronic plaque psoriasis registered to BADBIR from 2007–2020. All patients were treated with adalimumab, etanercept, secukinumab, or ustekinumab, with at least 6 months follow-up, and HLA-C*06:02 data was available for all patients. Exposure time was calculated from initiation to the discontinuation of therapy and/or was censored at the latest follow-up.

Included in the analysis were 3,199 patients, of whom 52% were HLA-C*06:02 positive. Compared with HLA-C*06:02-negative psoriasis patients, they had an earlier onset of disease (onset <40 years in 94% of HLA-C*06:02-positive vs 85% in HLA-C*06:02-negative patients; P<0.001) and were less likely to have psoriatic arthritis (21% of HLA-positive vs 29% in HLA-negative patients; P<0.001). “The HLA-C*06:02-positive patients showed a better overall drug survival on ustekinumab compared with HLA-C*06:02-negative patients (HR 0.62; 95% CI 0.44–0.87; P<0.005). The same pattern was seen in adalimumab-treated patients with non-imputed data,” Dr Alabas explained. However, only the association with ustekinumab remained significant when using imputed data.

Further, HLA-C*06:02-positive patients had a 38% lower relative risk to stop treatment owing to lack of effectiveness than HLA-C*06:02-negative patients. HLA-C*06:02 status did not influence drug survival of patients discontinuing due to adverse events.

Thus, Dr Alabas concluded that HLA-C*06:02-positive patients treated with ustekinumab and maybe with adalimumab showed a lower risk of treatment discontinuation due to a lack of effectiveness in a real-world situation.

 

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   1. Chen L, Tsai TF. Br J Dermatol 2018;178:854–62.
   
   
   2. Li K, et al. J Invest Dermatol 2016;136:2364–71.
   
   
   3. Alabas O, et al. HLA-C*06:02 allele is associated with higher drug survival in patients with psoriasis on ustekinumab: an analysis from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), on behalf of the BADBIR and BSTOP. FC14, Psoriasis from Gene to Clinic 2021, 9–11 December.

 

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Posted on 2 February, 2022