The DOE Joint Genome Institute is an integrated high-throughput sequencing facility which provides high-quality genomic sequences to the scientific community. Currently there are approximately 300 microbial genomes in the JGI production genomics facility (PGF) pipeline in Walnut Creek and to date, 160 have been completely finished. The PGF microbial finishing group is involved in improving the microbial genomic sequences that come directly out of production. The finishing team is responsible for solving misassemblies, closing gaps, improving low-quality areas in the DNA assemblies and submitting high-quality data to the annotation group which in turn submit the sequence to the public domain. The finishing pipeline at PGF starts with resolving DNA repeats using an automated pipeline developed at JGI/PGF. Low quality and gap regions in the assemblies are resolved by directed reactions mainly using primers designed by applying Autofinishing functionality of Consed and other software developed in-house. Finally, manual checks are performed to ensure a minimum consensus phred quality of 30 or above, error rate is less than 1 base per 50,000bp and 2 times coverage throughout the DNA sequence assemblies. The strategies for solving repeats, misassemblies and difficult to finish regions will be further discussed in detail in this poster.

Background

Two randomized controlled trials (reSURFACE 1 and 2) have demonstrated the effectiveness of tildrakizumab, a high-affinity, humanized, IgG1κ, anti-interleukin-23 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in the first 28 weeks.

Objectives

To examine the efficacy of tildrakizumab and its impact on quality of life (QoL) in patients with different levels of week-28 Psoriasis Area and Severity Index (PASI) improvement.

Methods

Patients treated with tildrakizumab 100 mg or 200 mg from baseline to week 28 were pooled from reSURFACE 1 and reSURFACE 2 and classified into five mutually exclusive week-28 PASI improvement groups for each dose: PASI 0-49, 50-74, 75-89, 90-99 and 100. Mean PASI improvement and Dermatology Life Quality Index (DLQI) 0/1 over time were examined for each group.

Results

Of 1156 patients, 575 were in the 100-mg and 578 in the 200-mg cohorts, respectively. At week 28, 8.3%, 14.3%, 23.8%, 30.4% and 23.1% in the 100-mg and 4.0%, 18.1%, 19.6%, 29.1% and 29.3% in the 200-mg cohort achieved PASI < 50, 50-74, 75-89, 90-99 and 100, respectively. Patients with PASI < 50 at week 28 could be identified as early as week 8, and those with week-28 PASI ≥ 90 had approximately 50% PASI improvement by week 4. Among patients achieving PASI > 50 at week 28 who continued the same dose of tildrakizumab to week 52, mean PASI improvement was maintained or improved over time. Similar results were observed for both doses. Higher proportions of patients achieved DLQI 0/1 in higher week-28 PASI groups, and DLQI 0/1 was maintained or improved to week 52. However, not all patients with PASI 100 had DLQI 0/1.

Conclusion

Patients unlikely to respond to tildrakizumab could be identified by week 8, and those likely to achieve a PASI ≥ 90 response could be identified as early as week 4. Week-28 PASI improvement level correlated with QoL improvement.