Faculty Bibliography

The Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) was established to optimize the clinical care of patients with psoriatic disease through multidisciplinary collaboration, education, and innovative research. This article is a report of the 2018 PPACMAN Annual Meeting held in New York City, on December 8, 2018. At this meeting, attendees discussed the benefits and challenges of combined dermatology/rheumatology clinics and PPACMAN ongoing project updates. In addition, collaborators participated in breakout sessions and plenary voting dedicated to achieving consensus on terminology for preclinical psoriatic arthritis studies, one of PPACMAN's main areas of interest. The data obtained from this voting exercise were used to draft a formal Delphi survey that is currently underway.
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From birth, humans coexist and coevolve with trillions of micro-organisms inhabiting most body surfaces and cavities, referred to as the human microbiome. Advances in sequencing technologies and computational methods have propelled the exploration of the microbiome's contribution to human health and disease, spearheaded by massive efforts such as the Human Microbiome Project and the Europe-based MetaHit Consortium. Yet, despite the accumulated body of literature and a growing awareness among patients, microbiome research in rheumatology has not had a key impact on clinical practice. Herein, we describe some of the landmark microbiome studies in autoimmunity and rheumatology, the challenges and opportunities of microbiome research and how to navigate them, advances in related fields that have overcome these pitfalls, and future directions of harnessing the microbiome for diagnostic and therapeutic purposes.

Background/UNASSIGNED:Chronic inflammatory diseases (CIDs; ankylosing spondylitis [AS], psoriatic arthritis [PsA], psoriasis [PsO], or rheumatoid arthritis [RA]) and inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) are associated with substantial economic burden. The relative increased costs among patients with CIDs and concomitant IBD compared to those without IBD is an important consideration when deciding on the clinical management of patient symptoms. Given the increasing use of novel agents for the treatment of CIDs, including those that may increase the risk of IBD in patients with CIDs, the objective of the study was to describe the incidence of IBD and to quantify healthcare resource utilization (HRU) and costs associated with IBD among patients with CIDs. Methods/UNASSIGNED:The IBM MarketScan® Research Databases (1/2010-7/2017) were used to identify adult patients with ≥2 claims with a diagnosis of either AS/PsA/PsO/RA (index date was a random claim for AS/PsA/PsO/RA). The one-year incidence rate of IBD was calculated following the index date. HRU and healthcare costs were compared between patients developing and not developing IBD in the year following the index date, adjusting for baseline characteristics. Results/UNASSIGNED: < 0.0001). Conclusion/UNASSIGNED:Higher HRU and costs were observed in patients with concomitant CID and IBD compared to patients with CID alone. Consideration should be given to treatment decisions that adequately manage CID and IBD to ensure optimal clinical and economic outcomes.

In the past three decades, extraordinary advances have been made in the understanding of the pathogenesis of, and treatment options for, inflammatory arthritides, including rheumatoid arthritis and spondyloarthritis. The use of methotrexate and subsequently biologic therapies (such as TNF inhibitors, among others) and oral small molecules have substantially improved clinical outcomes for many patients with inflammatory arthritis; for others, however, these agents do not substantially improve their symptoms. The emerging field of pharmacomicrobiomics, which investigates the effect of variations within the human gut microbiome on drugs, has already provided important insights into these therapeutics. Pharmacomicrobiomic studies have demonstrated that human gut microorganisms and their enzymatic products can affect the bioavailability, clinical efficacy and toxicity of a wide array of drugs through direct and indirect mechanisms. This discipline promises to facilitate the advent of microbiome-based precision medicine approaches in inflammatory arthritis, including strategies for predicting response to treatment and for modulating the microbiome to improve response to therapy or reduce drug toxicity.

OBJECTIVE:=0.02). CONCLUSIONS:In patients with psoriasis, platelets are activated and induce endothelial cell inflammation. Low-dose aspirin improved endothelial cell health in psoriasis via platelet COX-1 inhibition. These data demonstrate a previously unappreciated role of platelets in psoriasis and endothelial cell inflammation, which suggests that aspirin may be effective in improving vascular health in patients with psoriasis. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03228017.

BACKGROUND:Dual neutralisation of interleukin 17A (IL17A) and interleukin 17F (IL17F) is a potential novel therapeutic approach in psoriatic arthritis. We assessed bimekizumab, a monoclonal antibody that selectively neutralises IL17A and IL17F, in patients with active psoriatic arthritis. METHODS:BE ACTIVE was a randomised, double-blind, placebo-controlled, dose-ranging phase 2b study done at 41 sites in the Czech Republic, Germany, Hungary, Poland, Russia, and the USA. Eligible patients aged 18 years or older with active adult-onset psoriatic arthritis and symptoms for at least 6 months were randomly assigned (1:1:1:1:1) to placebo, 16 mg bimekizumab, 160 mg bimekizumab, 160 mg bimekizumab with a one-off 320 mg loading dose, or 320 mg bimekizumab, which were administered as subcutaneous injections every 4 weeks for 12 weeks. After 12 weeks, patients assigned to the placebo and 16 mg bimekizumab groups were randomly reassigned (1:1) to either 160 mg or 320 mg bimekizumab, and all other patients remained on their originally assigned initial dose up to 48 weeks. Both participants and researchers were blinded to treatment allocation in the first 12 weeks, and blinded to the dose of bimekizumab thereafter. The primary endpoint was the proportion of patients with at least 50% improvement in the American College of Rheumatology response criteria at week 12, which was assessed in all patients who received at least one dose of study treatment and had a valid measurement of the primary efficacy endpoint at baseline. The trial, including all follow-up, has been completed. This trial is registered with ClinicalTrials.gov, NCT02969525. FINDINGS:Between Oct 27, 2016, and July 16, 2018, 308 patients were screened, and 206 were randomly assigned: 42 to the placebo group, and 41 each to the four bimekizumab groups. At 12 weeks, compared with the placebo group, significantly more patients in the 16 mg bimekizumab (odds ratio [OR] 4·2 [95% CI 1·1-15·2]; p=0·032), 160 mg bimekizumab (8·1 [2·3-28·7]; p=0·0012), and 160 mg (loading dose) bimekizumab (9·7 [2·7-34·3]; p=0·0004) groups achieved an ACR50 response. At 12 weeks, 24 (57%) of 42 patients in the placebo group and 68 (41%) of the 164 patients in the bimekizumab groups reported treatment-emergent adverse events. Most of these adverse events were mild or moderate. Serious treatment-emergent adverse events occurred in nine patients, eight of whom were receiving bimekizumab. No deaths or cases of inflammatory bowel disease were reported. INTERPRETATION:Bimekizumab doses of 16 mg and 160 mg (with or without a 320 mg loading dose) were associated with significant improvements in ACR50 compared with placebo, with an acceptable safety profile. Our results support phase 3 investigation of bimekizumab as a treatment for psoriatic arthritis. FUNDING:UCB Pharma.

OBJECTIVE:gene with radiographic severity of symptomatic knee osteoarthritis (SKOA) and the risk of incident OA. We also explored these genetic polymorphisms in patients with new onset rheumatoid arthritis (RA). METHODS:haplotypes were also assessed for association with disease activity (DAS28) and plasma inflammatory markers in patients with RA. RESULTS:demonstrated that carriage of the TTG haplotype was associated with 4.1-fold (p=0.001) increased odds of incident rOA. Plasma IL-1Ra levels were lower in TTG carriers, while chondrocytes from TTG carriers exhibited decreased secretion of IL-1Ra. In patients with RA, the TTG haplotype was associated with increased DAS28, decreased plasma IL-1Ra and elevations of plasma inflammatory markers (hsCRP, interleukin 6 (IL-6)). CONCLUSION/CONCLUSIONS:TTG risk haplotype, associated with decreased IL-1Ra plasma levels, impairs endogenous 'anti-inflammatory' mechanisms.

OBJECTIVE:To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome of psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients. METHODS:Fecal samples from PsA/SpA patients pre- and post-treatment with tumor necrosis factor inhibitors (TNFi; n=15) or an anti-interleukin (IL)-17A monoclonal antibody inhibitor (IL-17i; n=14) underwent sequencing (16S, ITS and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL-17i (n=5) were analyzed for expression of IL-23/Th-17 related cytokines, IL-25/IL-17E-producing cells and type-2 innate lymphoid cells (ILC2s). RESULTS:There were significant shifts in abundance of specific taxa after treatment with IL-17i compared to TNFi, particularly Clostridiales (p=0.016) and Candida albicans (p=0.041). These subclinical alterations correlated with changes in bacterial community co-occurrence, metabolic pathways, IL-23/Th17-related cytokines and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL-25/IL-17E-producing tuft cells and ILC2s (p<0.05) compared to pre-IL-17i treatment levels. CONCLUSION/CONCLUSIONS:In a subgroup of SpA patients, the initiation of IL-17A blockade correlated with features of subclinical gut inflammation and intestinal dysbiosis of certain bacterial and fungal taxa, most notably C. albicans. Further, IL-17i-related CD was associated with overexpression of IL-25/IL-17E-producing tuft cells and ILC2s. These results may help to explain the potential link between inhibition of a specific IL-17 pathway and the (sub)clinical gut inflammation observed in SpA.

OBJECTIVE:To examine the construct validity of Routine Assessment of Patient Index Data (RAPID3) and Psoriatic Arthritis Impact of Disease (PSAID) in patients with psoriatic arthritis (PsA). In examining construct validity, we also addressed scores among subgroups with severe psoriasis, polyarticular disease, enthesitis and dactylitis and evaluated influences of sociodemographic factors and comorbidities (contextual factors) on these patient-reported outcomes (PROs). METHODS:Patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium (PARC) between 2014-2016. PARC is a longitudinal observational cohort study conducted at four United States institutions. In this cross-sectional study, construct validity was assessed by examining Spearman's correlation coefficients for RAPID3 and PSAID with physician-reported disease activity measures and other PROs (e.g., Short Form 12 (SF12-PCS/-MCS), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue). Contextual factors and disease subgroups were assessed in multivariable linear regression models with RAPID3 or PSAID12 as outcomes of interest and the hypothesized contextual factors as covariates. RESULTS:Among 401 patients enrolled in PARC, 347 completed RAPID3 or PSAID12. Of these, most were Caucasian females with a mean age of 51.74 (SD 14.02). RAPID3 and PSAID were highly correlated (r=0.90). These measures were also correlated with the SF12-PCS (r=-0.67) and FACIT-Fatigue (r=-0.77). Important contextual factors and disease subgroups included enthesitis, joint counts, education, insurance type, and depression. CONCLUSION/CONCLUSIONS:RAPID3 and PSAID12 have excellent construct validity in PsA and are strongly correlated despite differing items. Contextual factors (i.e., the presence of depression and obesity) should be considered when interpreting raw scores of the RAPID3 and PSAID12.