DC-STAMP: Regulators of Osteoclastogenesis and Response Marker in PsA

Psoriatic arthritis (PsA), an inflammatory joint disease associated with psoriasis (Ps),
affects approximately 650,000 adults in the United States and is associated with increased
morbidity and mortality. Bone damage develops in half these patients within the first two
years of the disease, often leaving them with impaired function and diminished quality of
life. The emergence of anti-Tumor Necrosis Factor therapies (TNFi) has dramatically improved
clinical response and slowed bone and cartilage degradation in PsA patients, however, only
50-60% of patients respond to these agents. To improve these outcomes, the investigators must
address two major gaps: a limited understanding of key events that underlie pathologic bone
destruction and the absence of biomarkers to predict biologic response and identify early
biologic responders to facilitate optimization of therapy.

Bone damage is mediated by osteoclasts which arise from monocyte precursors in the blood.
Osteoclast Precursors (OCPs) are dramatically increased in PsA, compared to controls,
particularly in patients with bone damage on X-ray. The number of these circulating precursor
cells dropped rapidly following treatment with TNFi. OCPs may serve as response biomarkers,
but cost, time and high variability limit these assays. Osteoclast precursors express
Dendritic Cell-Specific Transmembrane Protein (DC-STAMP), which is a seven-pass transmembrane
protein required for fusion of monocytes to form osteoclasts and giant cells. Monocyte
DC-STAMP levels dropped rapidly following treatment with TNFi. TNF receptor-associated factor
3 (TRAF3), an inhibitor of OC formation that correlates with extracellular TNF
concentrations, is elevated in OCPs from PsA patients. These markers may predict TNFi
treatment response.

The goal of this study is to examine DC-STAMP in Psoriatic Arthritis patients prior to and
after starting standard of care treatment with a TNFi or non-biologic DMARD. We will also
examine PsA patients with low disease activity on standard of care TNFi and PsA patients with
low disease activity on standard of care non-biologic DMARDs will serve as controls.

Three groups of subjects will be recruited.

1. Longitudinal: 30 subjects starting out on standard of care treatment with a TNFi or
non-biologic DMARD will take part in the longitudinal section of the study. Subjects may
be asked to have a blood draw at one additional visit before starting therapy for
additional research assays if they are DC-STAMP positive. If the longitudinal subjects
that return for an additional blood draw before starting medication have unusable sample
data, they will be replaced by additional longitudinal subjects out of the 30 enrolled
longitudinal participants to get sufficient data results of two subjects. The subjects
with unusable data will continue in the longitudinal follow up study visits as intended.

2. Cross sectional: 36 patients will take part in the cross-sectional part of the study. 18
patients on stable non-biologic DMARDS and 18 patients on stable TNFi will be compared
in the cross-sectional part. This population should be in good disease state such that
their disease is controlled and treatment will not need to be changed. If longitudinal
subjects fit the cross-sectional criteria and wish to participate, they will be
re-consented for the cross-sectional part of the study.

While 66 subjects will be studied in both the longitudinal and cross-sectional studies
combined, up to 80 PsA subjects may be consented to allow for screen failures and to
replace longitudinal subjects who withdraw or are lost to follow-up.

3. Assay Development: Up to 40 PsA or healthy subjects may be enrolled for blood draw for
assay development and to test development of techniques for ultrasound comparison and
scoring system validation.

Inclusion Criteria:

- Ability to provide written informed consent.

- Subjects can be of either gender but must be at least 18 years old.

- Subjects with PsA should fulfill CASPAR criteria.

- Longitudinal: Patients with active PsA who will be starting a TNFi or
non-biologic DMARD treatment (Subjects starting non-biologic DMARDS can have
their blood drawn within the first few days of starting therapy).

- Additional Blood Draw: Positive DC-STAMP signal at baseline

- Cross-Sectional: Patients on stable DMARDS or TNFi for more than 16 weeks.

- Healthy Subjects: Healthy controls should have no active systemic disorders or
inflammatory conditions that would confound the results of the study.

Exclusion Criteria:

- Unable to donate blood because of poor venous access or intolerance of phlebotomy.