Faculty Bibliography

Background/Purpose: Psoriatic Arthritis (PsA) affects up to 30% patients with psoriasis and is characterized by wide spread synovio-entheseal inflammation. Physiologically, the human gut microbiota metabolizes dietary fiber into shortchain fatty acids (FA)- which exert anti-inflammatory effects by increasing activity of regulatory T cells (Tregs).Moreover, we have previously shown decreased abundance of Akkermansia and Ruminococcus and concomitant decrease in mediumchain FA (MCFA) levels in stool of PsA patients. We therefore hypothesized that FA supplementation may have favorable effects on gut microbiome and lead to increase in tolerance, potentially serving as therapeutic target in psoriatic disease.
Method(s): Wild type (WT)animals were fed SCFA-rich diet for 14 days followed by 16S rRNA sequencing and microbiota analysis of pellet specimens.We then evaluated effects ofMCFA-rich diet in healthy subjects. Peripheral blood and stool samples were collected at days 0, 7 and 14 for 16s rRNA sequencing and FACS. Finally, we conducted a small, prospective, proof-ofprinciple study in new-onset, drug-naive psoriatic disease patients (with or without PsA). Each participant received MCFA (1 gm 4 times a day for 6 weeks). Clinical history was obtained at baseline. Skin and joint exam were performed at baseline and follow up. Serum and stool samples were collected at baseline, weeks 3, and 6 for 16S rRNA sequencing and FACS, respectively. Wilcoxon signed-rank test was used to compare differences in Tregs before and after MCFA-rich administration.
Result(s): SCFA rich diet in WT mice led to statistically significant perturbations in gut bacterial composition 14 days into intervention, with a dramatic increase in commensals (Fig 1A; p<0.001), most notably in Akkermansia(Fig 1B). MCFA administration to healthy subjects (n=7) also led to significant changes in community structure (Fig 2A; p=0.03) and associated increases in circulating Treg cells (Fig 2B; p<0.001). These findings were also observed in psoriatic disease patients (n=4) showing a significant alteration in specific taxa, including Actinobacteria (Fig 2 C; p<0.05) and Mollicutes (p=0.09) and concomitant increase in circulatory Treg cells (Fig 2D)
Conclusion(s): In both health and psoriatic disease, MCFA supplementation is associated with distinct changes in human gut microbiota composition and peripheral Treg cells. These findings rationalize the need for a larger placebo controlled, prospective trial to study the effects of MCFA in patients with psoriasis and PsA as a potential therapy alone or in combination with DMARDs. (Figure Presented)

PURPOSE OF REVIEW/OBJECTIVE:Despite a robust therapeutic landscape, significant gaps exist in the quality of care of psoriatic disease. Thus, an improved understanding of the challenges in providing quality care and the implementation of effective strategies to overcome them is needed. In this review, we summarize the burden of psoriatic disease, discuss the challenges in the care of psoriatic patients, and outline how combined dermatology-rheumatology clinics bridge many of these gaps. RECENT FINDINGS/RESULTS:Multiple challenges are faced in providing high-quality care to patients with psoriasis and psoriatic arthritis from the pre-diagnosis phase of disease to the follow-up period. Challenges are mainly driven by lack of education of patients and healthcare providers, inefficient communication between specialists, lack of a holistic approach to patients, and limitations of available therapies. The Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) is working on demonstrating the effectiveness of combined dermatology-rheumatology clinics in addressing some of these challenges. Recent findings show that combined clinic models may improve quality of care by raising awareness of psoriatic disease, fostering educational activities for both patients and physicians, and allowing for comprehensive evaluation and management of patients through improved communications between disciplines. Psoriasis and psoriatic arthritis are complex diseases that often require an interdisciplinary approach. Thus, combined dermatology-rheumatology clinics and local-regional partnerships are potentially effective in improving quality of care in psoriatic disease.

At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members received updates on several ongoing educational and research efforts. Among them were updates on GRAPPA's continued education efforts; GRAPPA's continued research efforts, including the Biomarker Project, a collaborative research effort to identify and study biomarkers of joint damage; treatment recommendations, including recommendations and core principles related to biosimilars; efforts to update GRAPPA's Website and to create a GRAPPA smart-phone application (app); and the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network.

PURPOSE OF REVIEW: Diagnosis and treatment of psoriatic arthritis (PsA) can be challenging and require a multidisciplinary approach. This review provides an overview of combined dermatology-rheumatology clinics. RECENT FINDINGS: Combined dermatology-rheumatology clinics have emerged to optimize integrated care for patients with psoriasis and PsA. There are over 20 such clinics across the USA. These clinics facilitate multidisciplinary care for patients with psoriasis and PsA and have been found to improve outcomes and enhance both patient and physician satisfaction and knowledge. Challenges presented by these clinics include appropriate scheduling for both dermatologists and rheumatologists and proving the benefits of the clinics to obtain institutional support. Combined dermatology-rheumatology clinics are a novel model of care for patients with psoriasis and PsA. They improve outcomes, patient and physician satisfaction, and efficiency. As more of these clinics are established, we must further understand their impact on outcomes and care processes.

Optimal management of patients with both psoriasis and psoriatic arthritis (PsA) necessitates collaboration among dermatologists and rheumatologists. In this manuscript, we discuss challenges and opportunities for dual care models for patients with psoriasis and PsA and the results of a survey of combined clinics based in North America.

BACKGROUND: Refractory patients with moderate-to-severe psoriatic arthritis (PsA) are commonly managed by switching between anti-TNFs.
OBJECTIVE(S): To evaluate the effectiveness of switching between anti- TNFs using a systematic review of the literature.
METHOD(S): MEDLINE- and Embase-indexed English-language publications were systematically searched from 1995-May 2015 for studies assessing real-world effectiveness outcomes of anti-TNF cycling in PsA patients.
RESULT(S): Among 1,086 unique citations identified, 48 were retrieved, and 18 studies and meeting abstracts were included. In 7 studies, 2,932 patients were tested for the association between consecutive treatment lines and effectiveness, 6 of which found significant differences between lines of anti-TNF therapy. Effectiveness measures varied widely. Only 7 of 18 measures were common across studies: ACR 20, 50, and 70, CRP, DAS28, PASI, and drug survival. In the NOR-DMARD multi-center study, significant improvement for ACR 70 (23.7% vs. 12.5%; P = 0.04) and mean change in CRP (P = 0.001) was observed for 1st-line relative to 2nd-line therapy. Likewise, in a Danish registry (DANBIO), response defined as ACR 20, 50, 70, and mean DAS28 scores were significantly improved with 1st-line vs. 2nd-line anti-TNF use. In an Italian hospital cohort, PASI 50 and 75 responses at Week 24 were also comparatively higher in the 1st line compared to 2nd line. Drug survival declined from initial anti-TNF to the 2nd and 3rd line in the DANBIO study (P < 0.0001), and from 1st line to 2nd line in a Norwegian clinical study (P < 0.001), but no drug survival loss was observed in a 12-year French cohort. When later lines were tested, no differences in CRP or PASI mean change were detected between 2nd- and 3rd-line anti-TNFs, in a second Italian hospital study. In the only study with multivariate regression testing for predictors of response, DANBIO patients were less likely to respond (ACR 20 or 50) to a second anti-TNF course if safety rather than lack of effect caused them to switch (odds ratio [OR] 0.04; P = 0.003 and OR 0.05; P = 0.03, respectively).
CONCLUSION(S): Effectiveness of anti-TNFs in 2nd-line and later has been reported in few real-world studies of PsA patients. Subsequent treatment lines may be associated with less response in some measures. Comparisons across studies are hampered by a lack of shared outcomes and studies that test for differences by treatment line. More research is needed to quantify the effectiveness of sequential anti-TNF lines in this progressive population and to compare these effects with response to drugs with a different mechanism of action