Faculty Bibliography

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.

Anti-tumor necrosis factors (Anti-TNFs) are a class of biologic disease-modifying anti-rheumatic drugs indicated for the treatment of moderate-to-severe psoriatic arthritis (PsA). Refractory patients are commonly managed by switching from one anti-TNF to another. To assess the evidence on the effectiveness of anti-TNF cycling in PsA patients, a systematic review of the literature was conducted. MEDLINE- and Embase-indexed English-language publications were systematically searched from 1995 to 2015 for studies assessing real-world effectiveness outcomes of anti-TNF cycling in PsA patients. Of 1086 citations identified, 18 studies were included; most conducted in Europe. Six of seven studies testing between lines found significant differences in effectiveness between earlier and subsequent lines of anti-TNF therapy. First-line therapy yielded better results compared with second-line therapy, and significant differences were observed between second- and third-line anti-TNF treatments. In the only study with multivariate regression testing for predictors of response, Danish registry patients were less likely to respond (American College of Rheumatology 20 % or 50 % response) 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). Effectiveness of anti-TNFs at second line and later is reported in a small number of real-world studies of PsA patients. Subsequent treatment lines may be associated with less response in some measures. More research is needed to quantify the effectiveness of sequential anti-TNF lines in this progressive population' and to compare these effects with responses to drugs with different mechanisms of action.

Background/Purpose: Psoriasis (PsO) is a chronic immune-mediated skin condition affecting ~3% of adults worldwide. Up to a third of PsO patients go on to develop psoriatic arthritis (PsA), a heterogeneous inflammatory arthritis characterized by concomitant bone erosion and osteoproliferation. Although multiple advances have been made in the pathogenesis and therapeutics of these disorders, it is currently not possible to predict which individuals will progress from PsO to PsA. The role of the microbiome as a potential trigger for autoimmunity and rheumatic disease has recently been implicated. The goal of this study was to characterize the cutaneous microbiota of patients with PsO and PsA (in both psoriatic plaques and unaffected skin) to determine if there are characteristic features related to disease phenotype. Methods: Skin swabs from subjects with PsO (n=29) and PsA (n=62) were collected from both psoriatic plaque lesions and contralateral unaffected skin. 16S rDNA was extracted per protocol (MoBio, USA) and amplicons targeting the hypervariable V4 region were sequenced using MiSeq (Illumina) to define the microbiota composition. The obtained 16S rRNA sequences were analyzed using the Quantitative Insights into Microbial Ecology (QIIME) pipeline. Taxonomic relative abundance was determined to compare their prevalence among different phenotypes using Kruskal-Wallis statistical analysis. Alpha diversity plots and weighted Unifrac analysis (beta diversity) of cutaneous bacterial communities were generated. False discovery rate analysis was applied to identify unique differentiating taxa. Results: Baseline characteristics were comparable in both groups. PsO samples had, on average, a similar number of operational taxonomic units as compared to PsA samples. Beta diversity plots did not demonstrate statistically distinct clustering of microbial communities between PsO and PsA subjects, PsO and PsA nonlesional skin, or PsO and PsA lesional skin. Staphylococcus and Corynebacterium were the most abundant genera across all samples. However, several genera were statistically more abundant in PsO compared to PsA lesions, including unclassified Bradyrhizobiaceae (p<0.0006), Rahnella (p<0.0006), unclassified Prevotellaceae (p<0.001), and Parvibaculum (p<0.002). Rothia was more abundant in PsA (p<0.02). Conclusion: Our results characterize, for the first time, the cutaneous microbial composition of individuals with PsO compared to those with PsA both in psoriatic lesions and unaffected skin. Although we did not find overall community differences among the various phenotypes, our preliminary observations point towards differences in specific genera, which are characteristically more abundant in PsO. Further in-depth analysis is required to better understand the significance of this dysbiotic process in PsA and whether it contributes to the pathogenesis of the psoriatic disease spectrum. Current efforts are devoted to incorporating healthy controls into our analysis, and analyzing the cutaneous microbiome (and metagenome) across multiple body sites, multiple visits, as well as pre- and post-immunosuppressive/biologic therapy

Background/Purpose: Previous studies have established the value of measuring complement activation products (C4d) bound to platelets (PC4d) for the diagnosis and monitoring of Systemic Lupus Erythematosus (SLE). Separately, Antiphospholipid (APL) antibodies have been associated with complement activation and PC4d expression. In this study, we sought to validate the performance characteristics of PC4d, stratified by the presence or absence of APL antibodies. Methods: This multi-centered validation cross sectional study (16 sites in the US) enrolled 402 SLE subjects fulfilling the 1982 American College of Rheumatology Criteria revised in 1997 (mean age 41 years; 91% female), 411 subjects with rheumatic and autoimmune diseases other than SLE (mean age 55, 86% female consisting of 181 rheumatoid arthritis, 90 primary fibromyalgia, 92 other rheumatic diseases, and 48 autoimmune thyroiditis or hepatitis) and 198 healthy volunteers (mean age 41 years; 66% female). PC4d densities were determined using flow cytometry (expressed as mean fluorescence intensity [MFI]). Positive PC4d consisted of PC4d levels greater than 20 net MFI. Anticardiolipin IgG, anti-Beta-2-glycoprotein 1 IgG, or anti-Phosphatidylserine/Prothrombin (PSPT) complex IgG antibodies were determined using ELISA (INOVA diagnostics, San Diego, CA). Presence of APL antibodies consisted of any of these antibodies above manufacturer cutoff. SLE Disease activity was assessed using the non-serological SLE Disease Activity Index SELENA modification (ns-SELENA-SLEDAI, without the complement and anti-dsDNA). Performance characteristics were established using sensitivity, specificity, and ROC Curve Area Under the Curve (AUC). Statistical evaluation was by t-test (for disease activity), by chi-squared test for equality of proportions (for sensitivities and specificities) and by the method of DeLong (for ROC Curve AUC). Results: PC4d was highly specific in distinguishing SLE from other rheumatic diseases (Table) and normals. Among SLE subjects, 47% (n=187) presented with at least one APL antibody as compared to 21% (n=86) of subjects with other diseases and 15% of normals. PC4d sensitivity for SLE was higher among APL positive subjects by comparison to APL negative subjects (p=0.003). Specificity was not significantly different between APL positive and negative subjects (p>0.372). ROC AUC was significantly higher among the APL positive compared to negative subjects (p=0.002). The incidence of APL antibodies among all PC4d positive subjects was 60% compared to 27% among PC4d negative subjects (p<0.001). SLE subjects presenting with positive PC4d had higher disease activity (4.1+/-0.5) than those presenting with negative PC4d (3.0+/-0.2) (p=0.03). Conclusion: We confirm that PC4d is highly specific for SLE, and is associated with disease activity. (Table Presented)

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

Introduction: Several studies have shown that obesity is more common among patients with psoriasis and psoriatic arthritis, and this correlation may be related to the systemic inflammation associated with obesity. Although bariatric surgery has been shown to improve several obesity-related comorbidities, the effects of surgical weight loss on psoriasis and psoriatic arthritis have not been adequately studied. Our objective was to investigate the effects of weight loss from bariatric surgery on psoriasis and psoriatic arthritis. Methods: A retrospective database of 9,073 bariatric surgeries performed at a single center between 2002 and 2013 was queried. Patients with a diagnosis of psoriasis prior to bariatric surgery were identified. Preoperative demographic, anthropometric, and comorbidity data were collected. Patients were contacted about their history of psoriasis, changes in symptoms after surgery, diagnosis of psoriatic arthritis, and treatment modalities for psoriasis and psoriatic arthritis pre- and postoperatively. The primary outcome was the percentage of patients who reported improvement in psoriasis after surgery. Secondary analyses were performed to define factors associated with improvement in psoriasis. Results: We identified 128 patients with a preoperative diagnosis of psoriasis. Seventy-four (58%) patients completed the study. Baseline patient characteristics are listed in Table 1. The mean time from surgery was 6.2 years, with a mean excess weight loss (EWL) of 46.5%. At the time of contact, forty-one (55%) patients reported improvement in their psoriasis, 24.3% reported improvement with subsequent relapse, 6.8% had no change, and 12.6% reported that their psoriasis progressively worsened. Sixteen (22%) patients also had a preoperative diagnosis of psoriatic arthritis; 62.5% reported improvement in their psoriatic arthritis, whereas 19% had no change and 19% worsened. In secondary analyses, lower preoperative BMI (43.7kg/m² vs. 48.4 kg/m², p=0.004) was found to be independently associated with postoperative improvement in psoriasis. Patients with severe psoriasis at the time of surgery and significant postoperative improvement, excluding those whose improvement may have been due to escalation in medication class, demonstrated greater weight loss (101.4 lb vs. 66.0 lb, p=0.025) and EWL (63.7% vs. 44.7% EWL, p=0.028). Similarly, improvement in psoriatic arthritis was associated with greater EWL, but this did not reach statistical significance (51.4 vs. 48.3, p=0.815). Conclusion: Although the natural history of psoriasis and psoriatic arthritis is typically chronic, a majority of patients experience improvement after bariatric surgery. Based on our results, there is an association between excess weight loss and symptomatic improvement in severe cases of psoriasis. Factors such as lower preoperative BMI may be used to identify those patients with a greater likelihood of remission. Additionally, ours is the first study to show an improvement in psoriatic arthritis after bariatric surgery and a possible association between surgical EWL and improvement in psoriatic arthritis. Larger prospective studies are needed to further define the true effect of surgical weight loss on psoriasis and psoriatic arthritis