HLA Class I Alleles as a Predictor of Retention to Treatment with Il-17 Antagonists in a Cohort of Patients with Psoriatic Arthritis in Newfoundland

Objectives Psoriatic arthritis (PsA) is a chronic, immune-mediated disease with genetic and environmental components to pathogenesis. Secukinumab (Sec) and ixekizumab (Ixe), IL-17A antagonists, are biologic disease-modifying antirheumatic drugs (bDMARD) that have shown safety and efficacy in treatment of PsA. Phenotypic manifestations of PsA have been associated with specific HLA alleles.[1] The primary aim of the study was to determine whether HLA class I profiles had an association with retention to treatment with the IL-17A inhibitors secukinumab and ixekizumab. A secondary objective was to determine the percentage of patients remaining on IL-17A inhibitors for up to 3 years as well as to assess for HLA class I allele association with predictors of drug retention. Methods Data was collected prospectively and analyzed retrospectively from a Newfoundland PsA cohort started in 2007. Patients were indexed on the date they first initiated secukinumab or izekizumab. Retention was assessed at 6, 12, 24, and 36 months using clinical and laboratory data including TJC28, SJC28, health assessment questionnaire (HAQ), patient and physician global assessments, PASI scores, and CRP levels. Serologic HLA class I typing was performed. IBM SPSS v.28.0 was used to calculate Kaplan-Meier survival curves and 2-tailed Spearman correlation coefficients. Results 30 patients were included. All were b/tsDMARD experienced. 60% of patients were female. The mean BMI was 31.3 kg/m2 and 33.3% of participants had a smoking history. PsA was diagnosed at a mean age of 42.3 (21-60) years. On index, patients had a mean CRP of 11.5 mg/mL, TJC28 of 6.7, SJC28 of 4.7, and HAQ of 1.5. Overall retention was estimated at 50.3% at 36 months. 23 patients had HLA class I analysis performed. The most common haplotypes were HLA A1 (43.5%), A2 (52.2%), B8 (30.4%), B27 (39.1%), Bw4 (39.1%), and Bw6 (47.8%). HLA Bw4 was negatively associated with retention to IL-17A inhibitors secukinumab and ixekizumab with Spearman correlation coefficient (r) −0.639 (p= 0.025) (Table). Although not statistically significant, in those who discontinued IL-17A antagonists before 36 months, HLA A2 and B27 showed tendency for negative association with r −0.418 (p= 0.177) and −0.123 (p= 0.704), respectively. We did not find any definitive association with HLA class I profile and response outcome measures such as CRP or HAQ. There was also no association with discontinuation due to lack of efficacy or side effects. The small nature of the study limited the ability to assess for a difference in response to treatment with either agent. Table 2. Correlation between time to discontinuation of interleukin 17A antagonists, CRP at index, and HLA class I type. Conclusion In patients with psoriatic arthritis, HLA class I type may be associated with various responses to treatment with the IL-17A antagonists secukinumab or ixekizumab. This cohort study is limited by small sample size and has significant potential for error, but further exploration with larger studies is warranted. References [1.] Rahman P. J Rheumatol 2012;39:431-3.