Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab

Abstract

Background:Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine.Methods:To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for ≥16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or ≥64 of ustekinumab treatment.Results:A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02–3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6–positive and HLA-Cw6–negative patients (P = 0.164).Conclusions:The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged.

Direct comparison of risankizumab and fumaric acid esters in systemic therapy–naïve patients with moderate-to-severe plaque psoriasis: a randomized controlled trial

“…Five patients in the FAE group discontinued the study drug because of an AE vs. no patients in the risankizumab group. The AEs leading to discontinuation of FAEs were mostly related to gastrointestinal tolerability, lymphopenia and flushing, which is consistent with the known safety profile of FAEs 11 . Serious infections in both groups (influenza and chronic obstructive pulmonary disease for one risankizumab patient, and arthralgia and obesity for one patient each in the FAE group) were considered serious because they resulted in hospitalization.…”

“…The most frequently prescribed first‐line systemic treatment for psoriasis in Germany is the oral formulation of fumaric acid esters (FAEs), Fumaderm ® . FAEs are approved in Germany for patients with moderate‐to‐severe plaque psoriasis 11 and reach maximum efficacy after 24 weeks of treatment 12,13 . They are also recommended by the European S3‐Guideline on the systemic treatment of psoriasis vulgaris as a first‐line treatment before biologic treatments are considered 14 .…”

Biomarkers predictive of treatment response in psoriasis and psoriatic arthritis: a systematic review

“…examined the relationship between the presence of the HLA-C*06 haplotype and subsequent response to ustekinumab. 11 They found no statistically significant difference in clinical response between HLA-C*06 positive and HLA-C*06 negative patients. Ryan et al .…”

Immunogenicity of Monoclonal Antibodies and the Potential Use of HLA Haplotypes to Predict Vulnerable Patients

“…The membrane glycoprotein CD52 is expressed by lymphocytes, monocytes, subsets of dendritic cells and subsets of epithelial cells. Inhibiting this glycoprotein causes the depletion of lymphocytes and blood dendritic cells in vivo, making it a target for mAbs designed to treat graft versus host disease in bone marrow transplantation, relapsing multiple sclerosis and chronic lymphocytic leukaemia (113). The anti-CD52 mAb used in the clinic is alemtuzumab, which is a humanized mAb.…”