Limited clinical utility of HLA-Cw6 genotyping for outcome prediction in psoriasis patients under ustekinumab therapy: a monocentric, retrospective analysis

“…All studies provided data about the PASI75 response rates at 6 months (24-28 weeks) of ustekinumab treatment, and response rates were higher among HLA-C*06:02-positive patients in all included studies (Figure 2). 7,8,10,11,16,[18][19][20] Randomeffects meta-analysis revealed a pooled RD of 0.24 (95% CI, 0.14-0.35; P < .001) in favor of HLA-C*06:02-positive patients. This RD signified that if 100 HLA-C*06:02-positive and 100 HLA-C*06:02-negative patients were to be treated with ustekinumab, PASI75 would be achieved in 24 more patients in the HLA-C*06:02-positive group compared with the HLA-C*06:02-negative group.…”

Section: Study and Patient Characteristicsmentioning

confidence: 99%

Association ofHLA-C*06:02Status With Differential Response to Ustekinumab in Patients With Psoriasis

et al. 2019

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IMPORTANCE 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. OBJECTIVE 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. DATA SOURCES 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. STUDY SELECTION 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 τ 2 and I 2 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. RESULTS 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 I 2 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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“… 77 Notwithstanding the difference, both genotype groups had a high PASI 75 response rates, so those HLA-C*06:02 negative should not be denied treatment with ustekinumab. 77 These finding were further confirmed by a more recent retrospective study by Anzengruber et al 78 Anyway, the great heterogeneity of the included studies does not allow a generalization; 77 for this reason, the authors suggest that a personalized therapy for psoriasis patients should rely on a set of biomarkers, rather than a single one. 77 Also, the same genotype may influence response to different biologics.…”

Section: Methodsmentioning

confidence: 90%

“… 75 Anyway, the positive association between HLA-C:06:02 positivity and response to ustekinumab was questioned in more recent studies. 77 , 78 Indeed, a recent systematic review and meta-analysis of 8 studies involving 1048 psoriasis patients was run by van Vugt et al with the aim to investigate if the HLA-C*06:02 status was associated with a differential response to ustekinumab in patients affected by psoriasis. 77 They showed that HLA-C*06:02 positive patients had a median PASI75 response rate of 92% after 6 months of ustekinumab therapy compared to a median PASI75 response rate of 67% in the HLA-C*06:02 negative patients.…”

Section: Methodsmentioning

confidence: 99%

Towards Personalized Medicine in Psoriasis: Current Progress

Camela¹,

Potestio²,

Ruggiero³

et al. 2022

PTT

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Although innovative targeted therapies have positively revolutionized psoriasis treatment shifting treatment goals to complete or almost complete skin clearance, primary or secondary lack of efficacy is still possible. Hence, identifying robust biomarkers that reflect the various clinical psoriasis phenotypes would allow stratify patients in subgroups or endotypes, and tailor treatments according to the characteristics of each individual (precision medicine). To sum up the current progress in personalized medicine for psoriasis, we performed a review on the available evidence on biomarkers predictive of response to psoriasis treatments, with focus on phototherapy and systemic agents. Relevant literature published in English was searched for using the following databases from the last five years up to March 20, 2022: PubMed, Embase, Google Scholar, EBSCO, MEDLINE, and the Cochrane library. Currently, more evidence exists towards biologicals, as justified by the huge health care costs as compared to phototherapy or conventional systemic drugs. Among them, most of the studies focused on anti-TNF and IL12/23, with still few on IL17 (mainly secukinumab). The most discussed biomarker gene is the HLA-C*02:06 status that has been shown to be associated with psoriasis, and also differential response to biologicals. Although its positivity is associated with great response to MTX, debatable results were retrieved concerning both anti-TNF and IL12/23 while it seems not to affect secukinumab response. Personalized treatment in psoriasis would provide excellent outcome minimizing the risk of side effects. To date, although several candidates were proposed and assessed, the scarcity and heterogeneity of the results do not allow the identification of the gold-standard biomarker per each treatment. Anyway, the creation of a more comprehensive panel would be more reliable for the treatment decision process.

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Limited clinical utility of HLA-Cw6 genotyping for outcome prediction in psoriasis patients under ustekinumab therapy: a monocentric, retrospective analysis

Cited by 8 publications

References 18 publications

Importance of genotyping patients for HLA-C*06:02: it provides not only pharmacogenetics implication in response to biologics drugs but also drug survival and drug-related costs information

Importance of genotyping patients for HLA-C*06:02: it provides not only pharmacogenetics implication in response to biologics drugs but also drug survival and drug-related costs information

Association ofHLA-C*06:02Status With Differential Response to Ustekinumab in Patients With Psoriasis

Towards Personalized Medicine in Psoriasis: Current Progress

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