Learning about the natural history of rheumatoid arthritis development through prospective study of subjects at high risk of rheumatoid arthritis–related autoimmunity

Deane, Kevin D.

doi:10.1002/art.34445

Cited by 11 publications

(4 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The clinical phase of rheumatoid arthritis in its natural history progresses slowly, making it difficult to compare with progression within a clinical study. However, CRP levels seem to increase even before clinical manifestation, and improvement of the degree found in this study seems unlikely to happen as spontaneous, untreated remission …”

Section: Discussionmentioning

confidence: 49%

Assessment of Placebo Response in Objective and Subjective Outcome Measures in Rheumatoid Arthritis Clinical Trials

et al. 2020

View full text Add to dashboard Cite

Key Points Question Are subjective patient-reported outcomes vs objective biomarkers associated with higher placebo responses in clinical trials? Findings In this cross-sectional study examining the placebo arms of 5 randomized clinical trials of rheumatoid arthritis including 788 patients, objective markers of inflammation and subjective pain ratings improved in a comparable clinically meaningful magnitude. Baseline values were associated with placebo response, suggesting that regression to the mean might dominate response to randomized placebo treatment. Meaning The findings of this study suggest that investigators may need to improve their understanding of natural history and baseline levels of outcomes because these factors can be important contributors to the response in placebo arms.

show abstract

Section: Discussionmentioning

confidence: 49%

Assessment of Placebo Response in Objective and Subjective Outcome Measures in Rheumatoid Arthritis Clinical Trials

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Disease development in RA starts with asymptomatic autoimmunity in susceptible subjects, which transitions to arthralgia stage as autoantibodies gain access to joints and patients start experiencing non-specific musculoskeletal symptoms without any clinical signs of synovitis. Over time, arthralgia patients progress to IA/undifferentiated arthritis (UA) when they develop clinical synovitis, and finally with increased immune cell infiltration and epitope spreading, IA/UA patients develop clinically classifiable RA [ 12 , 13 ]. Joint manifestation in RA results from synovial hyperproliferation and infiltration of immune cells into the synovium leading to bone resorption and cartilage degradation [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression

et al. 2018

View full text Add to dashboard Cite

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

show abstract

“…This is followed by asymptomatic synovitis, development of symptoms, a transition to clinically apparent RA and subsequent diagnosis, and then a chronic inflammatory phase. [6][7][8] The preclinical phase of RA is supported by studies identifying the presence of autoantibodies ≥10 years prior to presentation of clinically apparent disease in RA. 9 In this issue of the Annals of Rheumatic Disease, Kristensen et al 10 provide a population-based description of the period leading up to the diagnosis of PsA, potentially the 'preclinical phase' of PsA in their paper 'Societal costs and patients' experience of health inequities before and after diagnosis of psoriatic arthritis'.…”

mentioning

confidence: 99%

The preclinical phase of PsA: a challenge for the epidemiologist

Ogdie

2017

Ann Rheum Dis

View full text Add to dashboard Cite

Learning about the natural history of rheumatoid arthritis development through prospective study of subjects at high risk of rheumatoid arthritis–related autoimmunity

Cited by 11 publications

References 27 publications

Assessment of Placebo Response in Objective and Subjective Outcome Measures in Rheumatoid Arthritis Clinical Trials

Assessment of Placebo Response in Objective and Subjective Outcome Measures in Rheumatoid Arthritis Clinical Trials

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression

The preclinical phase of PsA: a challenge for the epidemiologist

Contact Info

Product

Resources

About