Objective. Adalimumab, a fully human, antitumor necrosis factor monoclonal antibody, was evaluated for its safety and efficacy compared with placebo in the treatment of active psoriatic arthritis (PsA).Methods. Patients with moderately to severely active PsA and a history of inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks. Study visits were at baseline, weeks 2 and 4, and every 4 weeks thereafter. The primary efficacy end points were the American College of Rheumatology 20% improvement (ACR20) response at week 12 and the change in the modified total Sharp score of structural damage at week 24. Secondary end points were measures of joint disease, disability, and quality of life in all patients, as well as the severity of skin disease in those patients with psoriasis involving at least 3% of body surface area.Results. At week 12, 58% of the adalimumabtreated patients (87 of 151) achieved an ACR20 response, compared with 14% of the placebo-treated patients (23 of 162) (P < 0.001). At week 24, similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was ؊0.2 in patients receiving adalimumab and 1.0 in those receiving placebo (P < 0.001). Among the 69 adalimumabtreated patients evaluated with the Psoriasis Area and Severity Index (PASI), 59% achieved a 75% PASI improvement response at 24 weeks, compared with 1% of the 69 placebo-treated patients evaluated (P < 0.001). Disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo. Adalimumab was generally safe and welltolerated.Conclusion. Adalimumab significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active PsA.Psoriatic arthritis (PsA) is a chronic, inflammatory arthritis occurring in individuals with psoriasis. Psoriasis occurs in 2-3% of the US population (1). The reported range of prevalence of PsA in patients with psoriasis is 6-39%, depending on the population studied

Objective The recurrence rate of anti-SSA/Ro associated congenital heart block (CHB) is 17%. Reversal of 3rd degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, IVIG was evaluated as a preventative therapy for CHB. Methods A multicenter open-label study based on Simon’s 2-stage optimal design was initiated. Enrollment criteria included: maternal anti-SSA/Ro antibody, a previous child with CHB/rash,

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Background:Much new information has been reported since the last evidence-based GRAPPA recommendations for the treatment of psoriasis and psoriatic arthritis (PsA).Objectives:We aimed to compile the evidence for the efficacy and safety of established and newly developed drugs targeting the peripheral arthritis domain in PsA so as to provide information for the revised GRAPPA treatment recommendations.Methods:A working group consisting of clinicians and patient research partners (PRPs) was convened. We performed an updated systematic literature review (SLR) of randomized controlled trials (RCTs) for the treatment of PsA, including peripheral arthritis, from the date of the last GRAPPA SLR, from February 19, 2013 to August 28, 2020. The working group reviewed the evidence supporting the efficacy on peripheral arthritis for each class of drug, according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, for three patients groups: 1) naïve to treatment; 2) refractory to conventional (-c)DMARDs; and 3) with prior biological (-b)DMARD experience. We also evaluated the evidence for non-pharmacological treatments. A set of important outcomes for the peripheral arthritis domain was assessed for each class of medication. The certainty of evidence supporting each class of drugs for each patient group was evaluated. Recommendations were derived through consensus meetings.Results:87 articles from 52 RCTs were included. For patients with mild disease who are naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and PDE4i, and weakly recommends them for severe disease, where TNFi are preferred over csDMARDs. Other bDMARDs (IL-17i, IL-12/23i, IL-23i) and JAKi are strongly recommended to treat peripheral arthritis for treatment naïve patients. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i and JAKi. Certainty of evidence (GRADE) and recommendations for peripheral arthritis domain of PsA for different population groups are shown in Table 1. While the evidence supporting non-pharmacological treatments was low, we derived the recommendations from clinician/PRP expert opinion, included advocating an increase in physical activity, smoking cessation and a healthy diet to control weight gain.Conclusion:Evidence supporting drug treatment for the peripheral arthritis domain of PsA was compiled, providing required information for the revised GRAPPA treatment recommendations. Further work seeking agreement from a broader group of stakeholders is in progress.Table 1.Certainty of evidence (GRADE) and Recommendation for peripheral arthritis of PsATreatment naivecsDMARD inadequate responsebDMARD inadequate responseDrug classevidence (GRADE)Recom-mendationevidence (GRADE)Recom-mendationevidence (GRADE)Recom-mendationPDE-4iMod to highStrong for(mild/ mod disease)Conditional for(severe disease)Mod to HighStrong forbDMARD exp: ModbDMARD IR: Mod (NS)Conditional for (bDMARD exp)Conditional against (bDMARD IR)TNFiHighStrong forHighStrong forModStrong fora 2ndTNFiTNFiVs. MTXHighStrong for TNFi as 1st line for severe disease----IL-17iHighStrong forHighStrong forMod to highStrong forIL-12/23iMod to highStrong forMod to HighStrong forLowConditional forIL-23iHighStrong forHighStrong forModStrong forJAKiMod*Strong forHighStrong forMod to HighStrong forCTLA4iVery LowConditional for†LowConditional for†Mod (NS)Conditional for†Dual TNFi/ IL17iModerateNA¥ModNA¥NANA¥IL-6iVery LowConditional againstVery low to lowConditional againstNAConditional againstNS: not statistically significant; *included data from abstract; ¥ not making recommendation due to not approved and not available in market; †reserve for no alternatives. Mod: Moderate; exp: experienced; IR: inadequate response.Acknowledgements:We are grateful to the contribution of our patient research partner, Rodrigo Firmino.Disclosure of Interests:None declared.

BackgroundWe were the first in the United States to demonstrate the applicability of performing transcriptional profiling of macrophages cells isolated from ultrasound guided synovial biopsies on RA patients (Mandelin et al, A&R 20181). While the numbers of macrophages are known to corelate with response to therapy in RA patients, little is known about macrophage heterogeneity or dendritic cell (DC) involvement in disease.ObjectivesHere, we performed single cell RNA seq and bulk population RNA-seq on RA synovium and peripheral blood (classical monocytes, non-classical monocytes, and DCs) from RA patients in order to compare their genome-wide transcriptional profile within and across individuals.MethodsWe obtained blood samples and ultrasound-guided minimally invasive synovial biopsy tissue from RA patients with active disease. Using Fluorescence-Activated Cell Sorting (FACS), we isolated classical monocytes (MHCII+CD14++CD16-), non-classical monocytes (MHCII+CD14+CD16+), and dendritic cells (MHCII+CD1c+) from blood. After processing synovial tissue for single-cell suspension, we isolated CD45+ cells for single cell RNA seq and macrophages (MHCII+CD14+CD11b+CD206+) and dendritic cells (MHCII+CD1c+) by FACS. We extracted RNA from these cell populations and prepared libraries for RNA-seq. These libraries were sequenced on an Illumina NextSeq 500 and assessed for quality of RNA, sequencing, and gene detection.ResultsFor each cell population, we assessed the variability of gene expression across patients. We identified 5 different populations of macrophages that differ in their origin, response to methotrexate, differentiation status, and activation status. Additionally, as expected, the bulk population of DCs were highly variable across individuals, which this is likely due to the heterogeneity of subtypes within this population as shown in the single cell RNA seq for macrophages. In circulating monocytes, we observed varying levels of common cytokines and chemokines, such as TNF and CCL1. We also compared gene expression across cell populations to characterize transcriptional signatures that were distinctive to a given cell population. In addition to the genes previously known to be unique to dendritic cells vs. monocytes/macrophages in health, we also identified potential pathogenic factors that varied in their expression across cell types. Finally, to explore the relationship between circulating and tissue cell populations, we asked whether there were pathways that were turned on in the blood prior to extravasation into the synovium. For example, we identified genes that maintained their expression across monocytes and synovial macrophages in RA patients supporting the differentiation of the former into the latter.ConclusionTogether, these results provide a survey of myeloid cells in the blood and synovial tissue of RA patients. We aim to understand how these cells vary across patients and what clinical variables and medication status influence their transcriptional profile across individuals. Our long-term goal is...

BackgroundThe spondyloarthritides (SpA), such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are a group of rheumatologic diseases with shared genetic, pathophysiologic and clinical elements now known to be more prevalent than rheumatoid arthritis (RA). Disease characteristics and outcomes are less well studied than RA. Corrona has investigated over 4000 pts with PsA since 2003. The Corrona SpA registry was launched on 3/21/2013 to include all SpA including AS and other forms of axial and peripheral SpA and more deeply investigate PsA. Enrollment and 6 monthly follow-up data is ongoing.ObjectivesThe purpose of this analysis is to provide a profile of the demographic and clinical characteristics of the initial patients in this US registry population. The registry will be a rich resource for outcomes research as follow-up time is accrued.MethodsThus far, 35 of the Corrona investigative sites have been trained to enroll, representing a diverse geographic and private/academic mix. Data at time of enrollment into the registry for a subset of 1411 patients enrolled between 3/21/2013 and 10/17/2014 are presented in this abstract. Data are gathered on demographics, clinical characteristics, referral source, disease activity, function, quality of life, work productivity, comorbid conditions, previous and current treatments, laboratory tests, and imaging.ResultsSixty-nine percent (969/1411) of the patients enrolled in the PsA/SpA registry since 3/13 have a diagnosis of PsA. Median age among all subjects is 53 years. Forty-nine percent of all subjects are female (52% in PsA and 45% in SpA patients) and 51% are obese (BMI >30, as calculated by physician reported height and weight). One-tenth of the subjects have a history of iritis/uveitis, 6% have a history of IBD, but <1% have a history of antecedent infection. A history of fibromayalgia was reported in 9% of patients with PsA and 12% of patients with SpA. Patients with a diagnosis of PsA had a mean CDAI of 11.1 and those with diagnosis of SpA had a mean BASDAI of 3.9. At time of enrollment, 62% were on biologic therapy (majority of these on monotherapy). Eight percent of subjects were on prednisone and 48% were on NSAIDs.ConclusionsThe registry has enrolled a growing number of patients with all forms of SpA. Biologic monotherapy use is common among patients with a diagnosis of PsA or SpA. Detailed data on disease characteristics, natural history, treatment and safety outcomes will be presented.AcknowledgementsThis study is sponsored by Corrona, LLC. Initial funding for the Corrona SpA registry was provided by AbbVie. In the last two years, AbbVie, Amgen, Astra Zeneca, BMS, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB have supported Corrona LLC. through contracted subscriptions.Disclosure of InterestP. Mease Grant/research support from: Celgene, Merck, Novartis, Abbvie, Amgen, BiogenIdec, BMS, Genentech, Janssen, Lilly, Pfizer, UCB, Consultant for: Celgene, Merck, Novartis, Abbvie, Amgen, BiogenIdec, BMS, Crescendo, Genentech, J...

Rheumatoid arthritis (RA) is an autoimmune disease that primarily targets the joints, leading to synovial inflammation. Turmeric supplementation markedly reduces joint inflammation in pre‐clinical models of RA, suggesting a potential benefit in reducing joint inflammation in patients with RA. Here, we evaluate the percentage of patients eligible for a randomized controlled trial (RCT) of turmeric dietary supplements in RA, evaluating tolerability and pharmacokinetics. Recruitment materials were distributed in both rheumatology offices and community settings. Study entry eligibility criteria included having active disease (presence of inflamed and/or swollen joints), no current biologic use, as well as other health and medication criteria. Individuals were screened for basic eligibility through a telephone interview followed by a more comprehensive in‐clinic screening. In total, 200 patients were referred between September 2015 through October 2016; the majority (85%, n= 170) were self‐referred from community‐based recruitment strategies. From a pool of 171 (86%) who completed telephone screening, 40% (n=68) were disqualified from participation due to geographical location or having no clinical diagnosis of RA. Of the remaining 103 referrals, only 4% of local RA patients (n= 4) met all eligibility criteria; 15 (15%) discontinued the screening process and 84 (82%) were ineligible. Primary reasons for ineligibility included current or failed biologics (37%, n= 31) and no active disease (18%, n= 15). Other reasons included a serious comorbid medical condition (14%, n=12), unstable medication doses (13%, n= 11), high non‐steroidal anti‐inflammatory use (12%, n=10) or a history of malignancy (6%, n= 5). A greater proportion of patients referred from rheumatology practices passed telephone screening than those self‐referred from the community (20%, n= 6 vs. 8%, n= 14). Few of the patients screened met all eligibility requirements. Although uncommon, some patients did not wish to participate in the trial due to the possibility of receiving a placebo, as well as having to discontinue current turmeric supplement use. In summary, recruitment strategies that are primarily community‐based are inefficient in enrolling subjects who meet eligibility criteria for a RCT of turmeric dietary supplements in RA.Support or Funding InformationNIH (NCCIH): R34AT007837‐03