Unmet needs in psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis with a highly variable clinical presentation that does not have a validated molecular or imaging test, making accurate diagnosis a challenge. Consequences of diagnostic delay include irreversible joint damage and significant morbidity. Over the past few decades, there have been major advances in the understanding and treatment of PsA, leading to more targeted therapies. However, there is no current method to predict optimal treatment strategy to achieve minimal disease activity and prevent medication-related adverse events in the management of early disease. PsA is also associated with other comorbidities that include metabolic syndrome and psychosocial burden; two areas that are often unaddressed in the clinical setting and have associated sequelae. This chapter focuses on key domains of unmet needs, which include diagnostic challenges, delay in diagnosis, prognostication systems and stratified medicine approaches and precision medicine strategies for established and emerging therapies.

A rare coding allele in IFIH1 is protective for psoriatic arthritis.

OBJECTIVES: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. While many common risk alleles have been reported for association with PsA as well as psoriasis, few rare coding alleles have yet been identified. METHODS: To identify rare coding variation associated with PsA risk or protection, we genotyped 41 267 variants with the exome chip and investigated association within an initial cohort of 1980 PsA cases and 5913 controls. Genotype data for an independent cohort of 2234 PsA cases and 5708 controls was also made available, allowing for a meta-analysis to be performed with the discovery dataset. RESULTS: We identified an association with the rare variant rs35667974 (p=2.39x10-6, OR=0.47), encoding an Ile923Val amino acid change in the IFIH1 gene protein product. The association was reproduced in our independent cohort, which reached a high level of significance on meta-analysis with the discovery and replication datasets (p=4.67x10-10). We identified a strong association with IFIH1 when performing multiple-variant analysis (p=6.77x10-6), and found evidence of independent effects between the rare allele and the common PsA variant at the same locus. CONCLUSION: For the first time, we report a rare coding allele in IFIH1 to be protective for PsA. This rare allele has also been identified to have the same direction of effect on type I diabetes and psoriasis. While this association further supports existing evidence for IFIH1 as a causal gene for PsA, mechanistic studies will need to be pursued to confirm that IFIH1 is indeed causal.