Abstract
The field of rheumatology has made major contributions to medicine through the identification
of cellular and molecular targets and with the development of therapies for the treatment
of an impressive range of immune-mediated rheumatic diseases. In recent years new
milestones have been achieved. These include the recognition of an “at risk” state,
defined by distinct clusters of characteristics, including disease-specific autoantibodies
in serum and symptom complexes that include inflammatory joint pain. Studies seeking
to prevent high-risk individuals from progressing to a state of clinically apparent
arthritis have been initiated. Here, exploiting the current evidence base, an experimental
framework to inform trial design is described, taking into consideration study patient
phenotypes and highlighting the impact of risk stratification and the options available
for therapeutic intervention according to the different phases of the preclinical
syndrome. Pragmatic primary end points and suggestions for a set of risk-focused trial
outcome measures are proposed, including both clinical assessments and patient-reported
outcome measures. Rheumatoid arthritis prevention studies provide an important experimental
framework for generating deeper insights into risk stratification and for refining
trial design in the future. To this end, a research agenda is suggested, together
with some considerations for imaging and for biological sampling. This commentary
concludes with some of the operational issues that arise from such studies and addresses
some of the challenges associated with recruitment and retention of the at-risk trial
participant.
Keywords
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References
- Guidance for the Management of Rheumatoid Arthritis in Adult.
- Potential Pharmacological Targets for the Prevention of Rheumatoid Arthritis..Clin Ther. 2019; 41: 1312-1322
- Potential of lifestyle changes for reducing the risk of developing rheumatoid arthritis: is an ounce of prevention worth a pound of cure?.Clin Ther. 2019; 41: 1323-1345
- Preventing rheumatoid arthritis: a global challenge.Clin Ther. 2019; 41: 1355-1365
- Predicting Rheumatoid Arthritis in At-Risk Individuals.Clin Ther. 2019; 41: 1286-1298
- The value of ultrasonography in predicting arthritis in auto-antibody positive arthralgia patients: a prospective cohort study.Arthritis Res Ther. 2010; 12: R98
- Diagnostic test accuracy of ultrasound for synovitis in rheumatoid arthritis: systematic review and meta-analysis.Rheumatology. 2018; 57: 49-58
- Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-positive patients without clinical synovitis.Ann Rheum Dis. 2016; 75: 2060-2067
- Clinical factors, anticitrullinated peptide antibodies and MRI-detected subclinical inflammation in relation to progression from clinically suspect arthralgia to arthritis.Ann Rheum Dis. 2016; 75: 1824-1830
- EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid Arthritis.Ann Rheum Dis. 2012; 71: 638-641
- 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against Rheumatism collaborative initiative.Arthritis Rheum. 2010; 62: 2569-2581
- EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis.Ann Rheum Dis. 2017; 76: 491-496
- Epitope spreading of the anti-citrullinated protein antibody response occurs before disease onset and is associated with the disease course of early arthritis.Ann Rheum Dis. 2010; 69: 1554-1561
- Different stages of rheumatoid arthritis: features of the synovium in the preclinical phase.Ann Rheum Dis. 2011; 70: 772-777
- Features of the synovium of individuals at risk of developing rheumatoid arthritis: implications for understanding preclinical rheumatoid arthritis.Arthritis Rheumatol. 2014; 66: 513-522
- Lymph node biopsy analysis reveals an altered immunoregulatory balance already during the at-risk phase of autoantibody positive rheumatoid arthritis.Eur J Immunol. 2016; 46: 2812-2821
- A prediction rule for the development of arthritis in seropositive arthralgia patients.Ann Rheum Dis. 2013; 72: 1920-1926
- Predicting the development of clinical arthritis in anti-CCP positive individuals with non-specific musculoskeletal symptoms: a prospective observational cohort study.Ann Rheum Dis. 2015; 74: 1659-1666
Wilson JMG, Jungner G. Principles and Practice of Screening for Disease. WHO Chronicle. Geneva: World Health Organization. 22: 473 Public Health Papers, #34.
- Revisiting Wilson and Jungner in the genomic age: a review of screening criteria over the past 40 years.Bull World Health Organ. 2008; 86 (319–9)
- The public neglect of rheumatic diseases: insights from analyses of attendees in a musculoskeletal disease awareness activity.Ann Rheum Dis. 2007; 66: 697-699
- Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin.J Clin Invest. 2012; 122: 1791-1802
- Pathogenic citrulline-multispecific B cell receptor clades in rheumatoid arthritis.Arthritis Rheumatol. 2018; 70: 1933-1945
- Impact of Adverse Events Associated with Medications in the Treatment and Prevention of Rheumatoid Arthritis.Clin Ther. 2019; 41: 1376-1396
- 20 years of experience with tumour necrosis factor inhibitors: what have we learned?.Rheumatology. 2018; 57 (vii5–vii10)
- Preferences of patients and at-risk individuals for preventive approaches to rheumatoid arthritis.Clin Ther. 2019; 41: 1346-1354
- Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study.Ann Rheum Dis. 2019; 78: 179-185
- Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis-a proof of principle and exploratory trial: is dose tapering practical in good responders?.Rheumatology. 2017; 56: 2004-2014
- Regulatory considerations on the development evaluation, and approval of therapies in rheumatoid arthritis prevention.Clin Ther. 2019; 41: 1397-1400
Article info
Publication history
Published online: June 09, 2019
Accepted:
April 10,
2019
Received in revised form:
March 7,
2019
Received:
February 18,
2019
Identification
Copyright
© 2019 Published by Elsevier Inc.
